ALXN Alexion Pharmaceuticals Inc.

156.7
+0.05  (+0%)
Previous Close 156.65
Open 156.5
52 Week Low 72.67
52 Week High 160.03
Market Cap $34,273,512,849
Shares 218,720,567
Float 209,923,998
Enterprise Value $34,744,312,848
Volume 2,106,122
Av. Daily Volume 2,679,956
Stock charts supplied by TradingView

Upcoming Catalysts

Drug Stage Catalyst Date
ALXN1840 (WTX101)
Wilson disease
Phase 3
Phase 3
Premium membership is required to view catalyst dates, analyst ratings, earnings dates and cash burn data. Click here to unlock and sign up to a 14-day FREE TRIAL.
ALXN2050
Paroxysmal nocturnal hemoglobinuria (PNH)
Phase 2
Phase 2
Lorem ipsum dolor sit amet, consectetur adipiscing elit. Quisque sapien.
ULTOMIRIS (ravulizumab-cwvz)
Generalized myasthenia gravis (gMG)
Phase 3
Phase 3
Lorem ipsum dolor sit amet, consectetur adipiscing elit. Quisque sapien.
ULTOMIRIS
Neuromyelitis Optica Spectrum Disorder (NMOSD)
Phase 3
Phase 3
Lorem ipsum dolor sit amet, consectetur adipiscing elit. Quisque sapien.
ULTOMIRIS (ravulizumab) - CHAMPION-ALS
Amyotrophic lateral sclerosis (ALS)
Phase 3
Phase 3
Lorem ipsum dolor sit amet, consectetur adipiscing elit. Quisque sapien.
CAEL‐101
AL amyloidosis
Phase 3
Phase 3
Lorem ipsum dolor sit amet, consectetur adipiscing elit. Quisque sapien.
ALXN2040 add-on therapy
Paroxysmal nocturnal hemoglobinuria (PNH)
Phase 3
Phase 3
Lorem ipsum dolor sit amet, consectetur adipiscing elit. Quisque sapien.

Drug Pipeline

Drug Stage Notes
ULTOMIRIS (ravulizumab-cwvz)
COVID-19 Coronavirus
Phase 3
Phase 3
Independent data monitoring committee recommended pausing enrollment due to lack of efficacy in pre-specified interim analysis - January 13, 2021.
ULTOMIRIS
Hematopoietic stem cell transplant-related thrombotic microangiopathy (HSCT-TMA)
Phase 3
Phase 3
Phase 3 trial initiated 4Q 2020.
ALXN1830
Warm autoimmune hemolytic anemia (WAIHA)
Phase 1/2
Phase 1/2
Phase 2/3 trial to be initiated 2H 2021.
AG10 / BBP-265
ATTR-PN
Phase 2
Phase 2
Phase 3 trial has been initiated.
Eculizumab
Neuromyelitis Optica Spectrum Disorder (NMOSD) - children
Phase 2/3
Phase 2/3
Phase 2/3 trial underway.
Cerdulatinib (PRT2070)
Refractory non-Hodgkin lymphoma and chronic lymphocytic leukemia - cancer
Phase 2
Phase 2
Phase 2a data presented at ASH December 9, 2019. ORR 48%; 76% in combo cohort.
Elamipretide
Leber’s hereditary optic neuropathy (LHON)
Phase 2
Phase 2
Phase 2 trial did not meet primary endpoint.
ULTOMIRIS (ravulizumab-cwvz) subcutaneous
Paroxysmal nocturnal hemoglobinuria (PNH) and atypical Hemolytic Uremic Syndrome (aHUS)
Phase 3
Phase 3
Phase 3 trial met primary endpoint - June 24, 2020. Regulatory filing due 3Q 2021.
ALXN2040
C3 Glomerulopathy (C3G)
Phase 2
Phase 2
Development discontinued - noted July 29, 2020.
Bevyxxa (betrixaban)
Venous thromboembolism (VTE) Prevention
Approved
Approved
FDA Approval noted June 23, 2017.
Andexxa
Factor Xa inhibitor reversal agent
Approved
Approved
Prior Approval Supplement (PAS) FDA Approval announced December 31, 2018.
ULTOMIRIS (ravulizumab-cwvz)
atypical Hemolytic Uremic Syndrome (aHUS)
Approved
Approved
FDA Approval announced October 18, 2019.
Eculizumab
Generalized myasthenia gravis (gMG) - children
Phase 3
Phase 3
Phase 3 trial has commenced - noted October 23, 2019.
Eculizumab
Relapsing Neuromyelitis Optica Spectrum Disorder (NMOSD)
Approved
Approved
FDA Approval announced June 27, 2019.
ULTOMIRIS (ravulizumab-cwvz)
Paroxysmal nocturnal hemoglobinuria (PNH)
Approved
Approved
FDA approval announced December 21, 2018.
Eculizumab
Refractory generalized myasthenia gravis (gMG)
Approved
Approved
Approval announced October 23, 2017.

Latest News

  1. – Independent data monitoring committee recommends pausing study enrollment due to lack of efficacy in pre-specified interim analysis –

    – Company will conduct further analysis of trial data to determine next steps –

    – No new safety findings were observed for ULTOMIRIS use in COVID-19 –

    Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) today announced the decision to pause further enrollment in the global Phase 3 study of ULTOMIRIS® (ravulizumab-cwvz) in adults with severe COVID-19 requiring mechanical ventilation. This decision is based on the recommendation of an independent data monitoring committee (IDMC), following their review of data from a pre-specified interim analysis. The IDMC recommended that additional enrollment be paused, pending…

    – Independent data monitoring committee recommends pausing study enrollment due to lack of efficacy in pre-specified interim analysis –

    – Company will conduct further analysis of trial data to determine next steps –

    – No new safety findings were observed for ULTOMIRIS use in COVID-19 –

    Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) today announced the decision to pause further enrollment in the global Phase 3 study of ULTOMIRIS® (ravulizumab-cwvz) in adults with severe COVID-19 requiring mechanical ventilation. This decision is based on the recommendation of an independent data monitoring committee (IDMC), following their review of data from a pre-specified interim analysis. The IDMC recommended that additional enrollment be paused, pending further analysis of the data, due to lack of efficacy when ULTOMIRIS was added to best supportive care, compared to best supportive care alone. There were no new safety findings observed. The study will continue for patients already enrolled, including completion of all study visits and planned ULTOMIRIS dosing according to the study protocol.

    "We would like to thank the patients and their families, as well as investigators and healthcare professionals, who were essential to this study. We greatly value their contributions to help investigate potential ways to address this devastating pandemic," said John Orloff, M.D., Executive Vice President and Head of Research & Development at Alexion. "While initial anecdotal reports from compassionate use cases were promising, these results demonstrate the importance of conducting controlled clinical trials to fully evaluate the potential of new treatment approaches and generate the necessary evidence to make informed decisions. We are disappointed in this initial outcome, but plan to further analyze the data to identify potential subgroups who may benefit and to determine next steps. In addition, we remain fully committed to our efforts to serve the rare disease community and to continuing to provide ULTOMIRIS to the patients who currently rely on it."

    The IDMC's recommendation was based on a pre-planned interim analysis of the primary endpoint – survival at Day 29 – once 122 patients completed the 29-day primary evaluation period. No secondary endpoints were analyzed as part of the interim analysis.

    In the UK, the TACTIC-R platform study led by Cambridge University Hospitals NHS Foundation Trust, which includes an ULTOMIRIS cohort, is evaluating the potential of earlier immune modulatory treatment (hospitalized patients not requiring mechanical ventilation) in preventing progression of the virus, including reducing the need for ICU admission and ventilation. This independent study remains ongoing.

    About ULTOMIRIS® (ravulizumab-cwvz)

    ULTOMIRIS® (ravulizumab--cwvz) is the first and only long-acting C5 complement inhibitor. The medication works by inhibiting the C5 protein in the terminal complement cascade, a part of the body's immune system. When activated in an uncontrolled manner, the complement cascade over-responds, leading the body to attack its own healthy cells. ULTOMIRIS is administered intravenously every eight weeks or, for pediatric patients less than 20 kg, every four weeks, following a loading dose. ULTOMIRIS is approved in the United States (U.S.), European Union (EU) and Japan as a treatment for adults with paroxysmal nocturnal hemoglobinuria (PNH). It is also approved in the U.S. and Japan for atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA) in adult and pediatric (one month of age and older) patients, as well as in the EU for the treatment of adults and children with a body weight of at least 10 kg with aHUS.

    INDICATIONS & IMPORTANT SAFETY INFORMATION for ULTOMIRIS® (ravulizumab-cwvz)

    INDICATIONS

    What is ULTOMIRIS?

    ULTOMIRIS is a prescription medicine used to treat:

    • adults with a disease called Paroxysmal Nocturnal Hemoglobinuria (PNH).
    • adults and children 1 month of age and older with a disease called atypical Hemolytic Uremic Syndrome (aHUS). ULTOMIRIS is not used in treating people with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS).

    It is not known if ULTOMIRIS is safe and effective in children with PNH.

    It is not known if ULTOMIRIS is safe and effective in children younger than 1 month of age.

    IMPORTANT SAFETY INFORMATION

    What is the most important information I should know about ULTOMIRIS?

    ULTOMIRIS is a medicine that affects your immune system and can lower the ability of your immune system to fight infections.

    • ULTOMIRIS increases your chance of getting serious and life-threatening meningococcal infections that may quickly become life-threatening and cause death if not recognized and treated early.
    1. You must receive meningococcal vaccines at least 2 weeks before your first dose of ULTOMIRIS if you are not vaccinated.
    2. If your doctor decided that urgent treatment with ULTOMIRIS is needed, you should receive meningococcal vaccination as soon as possible.
    3. If you have not been vaccinated and ULTOMIRIS therapy must be initiated immediately, you should also receive 2 weeks of antibiotics with your vaccinations.
    4. If you had a meningococcal vaccine in the past, you might need additional vaccination. Your doctor will decide if you need additional vaccination.
    5. Meningococcal vaccines reduce but do not prevent all meningococcal infections. Call your doctor or get emergency medical care right away if you get any of these signs and symptoms of a meningococcal infection: headache with nausea or vomiting, headache and fever, headache with a stiff neck or stiff back, fever, fever and a rash, confusion, muscle aches with flu-like symptoms and eyes sensitive to light.

    Your doctor will give you a Patient Safety Card about the risk of meningococcal infection. Carry it with you at all times during treatment and for 8 months after your last ULTOMIRIS dose. It is important to show this card to any doctor or nurse to help them diagnose and treat you quickly.

    ULTOMIRIS is only available through a program called the ULTOMIRIS REMS. Before you can receive ULTOMIRIS, your doctor must: enroll in the ULTOMIRIS REMS program; counsel you about the risk of meningococcal infection; give you information and a Patient Safety Card about the symptoms and your risk of meningococcal infection (as discussed above); and make sure that you are vaccinated with a meningococcal vaccine, and if needed, get revaccinated with the meningococcal vaccine. Ask your doctor if you are not sure if you need to be revaccinated.

    ULTOMIRIS may also increase the risk of other types of serious infections. Make sure your child receives vaccinations against Streptococcus pneumoniae and Haemophilis influenzae type b (Hib) if treated with ULTOMIRIS. Call your doctor right away if you have any new signs or symptoms of infection.

    Who should not receive ULTOMIRIS?

    Do not receive ULTOMIRIS if you have a meningococcal infection or have not been vaccinated against meningococcal infection unless your doctor decides that urgent treatment with ULTOMIRIS is needed.

    Before you receive ULTOMIRIS, tell your doctor about all of your medical conditions, including if you: have an infection or fever, are pregnant or plan to become pregnant, and are breastfeeding or plan to breastfeed. It is not known if ULTOMIRIS will harm your unborn baby or if it passes into your breast milk. You should not breastfeed during treatment and for 8 months after your final dose of ULTOMIRIS.

    Tell your doctor about all the vaccines you receive and medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements which could affect your treatment.

    If you have PNH and you stop receiving ULTOMIRIS, your doctor will need to monitor you closely for at least 16 weeks after you stop ULTOMIRIS. Stopping ULTOMIRIS may cause breakdown of your red blood cells due to PNH. Symptoms or problems that can happen due to red blood cell breakdown include: drop in your red blood cell count, tiredness, blood in your urine, stomach-area (abdomen) pain, shortness of breath, blood clots, trouble swallowing, and erectile dysfunction (ED) in males.

    If you have aHUS, your doctor will need to monitor you closely for at least 12 months after stopping treatment for signs of worsening aHUS or problems related to a type of abnormal clotting and breakdown of your red blood cells called thrombotic microangiopathy (TMA). Symptoms or problems that can happen with TMA may include: confusion or loss of consciousness, seizures, chest pain (angina), difficulty breathing and blood clots or stroke.

    What are the possible side effects of ULTOMIRIS?

    ULTOMIRIS can cause serious side effects including infusion-related reactions. Symptoms of an infusion-related reaction with ULTOMIRIS may include lower back pain, pain with the infusion, feeling faint or discomfort in your arms or legs. Tell your doctor or nurse right away if you develop these symptoms, or any other symptoms during your ULTOMIRIS infusion that may mean you are having a serious infusion reaction, including: chest pain, trouble breathing or shortness of breath, swelling of your face, tongue, or throat, and feel faint or pass out.

    The most common side effects of ULTOMIRIS in people treated for PNH are upper respiratory infection and headache.

    The most common side effects of ULTOMIRIS in people with aHUS are upper respiratory infection, diarrhea, nausea, vomiting, headache, high blood pressure and fever.

    Tell your doctor about any side effect that bothers you or that does not go away. These are not all the possible side effects of ULTOMIRIS. For more information, ask your doctor or pharmacist. Call your doctor right away if you miss an ULTOMIRIS infusion or for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

    Please see the accompanying full Prescribing Information and Medication Guide for ULTOMIRIS, including Boxed WARNING regarding serious and life-threatening meningococcal infections/sepsis.

    About Alexion

    Alexion is a global biopharmaceutical company focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and commercialization of life-changing medicines. As a leader in rare diseases for more than 25 years, Alexion has developed and commercializes two approved complement inhibitors to treat patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), as well as the first and only approved complement inhibitor to treat anti-acetylcholine receptor (AchR) antibody-positive generalized myasthenia gravis (gMG) and neuromyelitis optica spectrum disorder (NMOSD). Alexion also has two highly innovative enzyme replacement therapies for patients with life-threatening and ultra-rare metabolic disorders, hypophosphatasia (HPP) and lysosomal acid lipase deficiency (LAL-D) as well as the first and only approved Factor Xa inhibitor reversal agent. In addition, the company is developing several mid-to-late-stage therapies, including a copper-binding agent for Wilson disease, an anti-neonatal Fc receptor (FcRn) antibody for rare Immunoglobulin G (IgG)-mediated diseases and an oral Factor D inhibitor as well as several early-stage therapies, including one for light chain (AL) amyloidosis, a second oral Factor D inhibitor and a third complement inhibitor. Alexion focuses its research efforts on novel molecules and targets in the complement cascade and its development efforts on the core therapeutic areas of hematology, nephrology, neurology, metabolic disorders, cardiology and ophthalmology. Headquartered in Boston, Massachusetts, Alexion has offices around the globe and serves patients in more than 50 countries. This press release and further information about Alexion can be found at: www.alexion.com.

    [ALXN-G]

    Forward-Looking Statement

    This press release may include statements that are or may be deemed to be forward-looking statements. These forward-looking statements may be identified by the use of forward-looking terminology, including the terms "believes", "estimates", "envisages", "plans", "projects", "anticipates", "targets", "aims", "expects", "intends", "may", "will" or "should" or, in each case, their negative or other variations or comparable terminology, or by discussions of strategy, plans, objectives, goals, future events or intentions and include, but are not limited to the plans of Alexion with respect to ULTOMIRIS as a potential treatment for severe COVID-19 patients. Economic, competitive, governmental, technological and other factors that may affect Alexion's operations are discussed in the section entitled "Risk Factors," Alexion's Quarterly Report on Form 10-Q for the Period ended 30 September 2020, as amended by any subsequent filings made with the SEC. These forward-looking statements include all matters that are not historical facts and involve predictions. Forward-looking statements may and often do differ materially from actual results. Any forward-looking statements reflect Alexion's current views with respect to future events and are subject to risks relating to future events and other risks, uncertainties and assumptions relating to Alexion's results of operations, financial position, liquidity, prospects, growth or strategies and the industries in which they operate. Forward-looking statements speak only as of the date they are made and cannot be relied upon as a guide to future performance. Save as required by law or regulation, Alexion disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements in this press release that may occur due to any change in its expectations or to reflect events or circumstances after the date of this press release.

    View Full Article Hide Full Article
  2.  - Continued advancement of pipeline, including initiation of three Phase 3 development programs and two novel IND filings in Q4 2020 -

    - Expects to exceed the high end of 2020 revenue guidance, given at Q3 2020 results, of $5.9-$5.95 billion -

    - Recently announced acquisition agreement will enhance AstraZeneca's presence in immunology and provides opportunity to expand on Alexion's innovative complement-technology platforms -

    Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) today announced recent commercial, clinical and financial progress and upcoming 2021 milestones, which will be detailed today in the company's presentation at the 39th Annual J.P. Morgan Healthcare Conference.

    "Over the course of past year, Alexion has continued to execute…

     - Continued advancement of pipeline, including initiation of three Phase 3 development programs and two novel IND filings in Q4 2020 -

    - Expects to exceed the high end of 2020 revenue guidance, given at Q3 2020 results, of $5.9-$5.95 billion -

    - Recently announced acquisition agreement will enhance AstraZeneca's presence in immunology and provides opportunity to expand on Alexion's innovative complement-technology platforms -

    Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) today announced recent commercial, clinical and financial progress and upcoming 2021 milestones, which will be detailed today in the company's presentation at the 39th Annual J.P. Morgan Healthcare Conference.

    "Over the course of past year, Alexion has continued to execute on its value-creation strategy and delivered on the potential of its robust portfolio and clinical pipeline, giving us great momentum as we enter 2021. I am very proud of the hard work of all our teams who continue to be so dedicated to serving patients across the globe," said Ludwig Hantson, Ph.D., Chief Executive Officer at Alexion. "For almost 30 years, Alexion has been committed to transforming the lives of those impacted by rare diseases and devastating conditions, and the company remains focused on advancing its innovative therapies and pipeline to drive value for patients and shareholders once we are part of AstraZeneca."

    Robust Portfolio Positions Alexion for Growth

    Alexion continues to expand into additional therapeutic areas, with a pipeline of more than 20 development programs across seven rare disease franchises. The company has the ambition to deliver double-digit topline growth through 2025, targeting $9 to $10 billion in global revenue. This revenue target is expected to be driven by the continued growth of Alexion's neurology franchise; expansion of ANDEXXA/ONDEXXYA® [coagulation factor Xa (recombinant), inactivated-zhzo] into new indications and geographies; sustainable paroxysmal nocturnal hemoglobinuria (PNH) and growing atypical hemolytic uremic syndrome (aHUS) and metabolics businesses; and initial revenue contributions from 10 potential new launches by 2023.

    Amidst COVID-19 pressures throughout 2020, Alexion added more than 700 U.S. neurology patients over the course of the year, and now serves nearly 2,600 patients in the U.S. The company remains on track to reach its stated long-term ambition to treat roughly 7,500 people with generalized myasthenia gravis (gMG) and neuromyelitis optica spectrum disorder (NMOSD) in the United States by year end 2025.

    Continued Pipeline Progress

    Alexion remains confident in the sustainability and growth potential of its innovative pipeline. Over the course of 2020, the company has built upon, and expanded its expertise in terminal complement inhibition and other areas. Select pipeline updates, since third quarter results were reported in October 2020, regarding promising individual programs and broader platform opportunities include:

    • Completion of enrollment in the Phase 3 trial of ULTOMIRIS in gMG, with top-line data expected in the second half of 2021.
    • Continued progress in advancing Phase 3 ULTOMIRIS trials in NMOSD and amyotrophic lateral sclerosis (ALS), which are now over 80 percent and 50 percent enrolled, respectively.
    • Dosing is underway in Phase 3 trials of ULTOMIRIS in hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA), ALXN2060 (AG10) in ATTR cardiomyopathy in Japan, CAEL-101 in AL amyloidosis and ALXN2040 in paroxysmal nocturnal hemoglobinuria (PNH) patients with extravascular hemolysis (EVH).
    • The Clinical Trial Approval (CTA) scheme for ALXN1820 (bi-specific anti-properdin mini-body) and the Investigational New Drug (IND) application for ALXN1850 (next generation asfotase alfa) have been accepted, in Australia and the U.S., respectively, with Phase 1 studies expected to begin in the first half of 2021.

    Financial Execution Supports Strong Performance

    Despite the effects of COVID-19, Alexion continued to support its commitment to disciplined financial management and strong commercial performance, demonstrating the dedication and resilience of our colleagues around the globe. Subject to completion of the review of the financial results, the company expects to exceed the high end of 2020 full-year revenue guidance of $5.9 to $5.95 billion that it provided in its 2020 third quarter results.

    AstraZeneca and Alexion Combination

    On December 12, 2020, AstraZeneca and Alexion announced that the companies entered into a definitive agreement for AstraZeneca to acquire Alexion, in which Alexion shareholders will receive $60 in cash and 2.1243 AstraZeneca American Depositary Shares (ADSs) for each Alexion share. Based on AstraZeneca's reference average ADR price of $54.14 at the time of the announcement, this implied total consideration to Alexion shareholders of $39 billion or $175 per share. The acquisition has the potential to advance the shared science-led mission of both companies to leverage complementary approaches to developing life-changing medicines. The proposed combination will broaden Alexion's footprint, enabling the company to help more patients, pursue innovative science in new areas and expand its therapies in additional geographies. In addition, the transaction delivers significant value for Alexion's shareholders, who will have an important stake in the combined company's future results. Subject to receipt of regulatory clearances and the approval by AstraZeneca and Alexion shareholders, the companies expect the acquisition to close in the third quarter of 2021.

    Presentation at the 39th Annual J.P. Morgan Healthcare Conference

    Alexion will webcast its corporate presentation, given by Aradhana Sarin, M.D., Chief Financial Officer, at the 39th Annual J.P. Morgan Healthcare Conference today, Tuesday, January 12, 2021 at 7:30 a.m. Eastern Time. Audio webcasts of the presentations will be available live at: http://ir.alexion.com. Archived versions of the remarks will also be available through the company's website for a limited time following the conferences.

    About Alexion

    Alexion is a global biopharmaceutical company focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and commercialization of life-changing medicines. As a leader in rare diseases for more than 25 years, Alexion has developed and commercializes two approved complement inhibitors to treat patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), as well as the first and only approved complement inhibitor to treat anti-acetylcholine receptor (AchR) antibody-positive generalized myasthenia gravis (gMG) and neuromyelitis optica spectrum disorder (NMOSD). Alexion also has two highly innovative enzyme replacement therapies for patients with life-threatening and ultra-rare metabolic disorders, hypophosphatasia (HPP) and lysosomal acid lipase deficiency (LAL-D) as well as the first and only approved Factor Xa inhibitor reversal agent. In addition, the company is developing several mid-to-late-stage therapies, including a copper-binding agent for Wilson disease, an anti-neonatal Fc receptor (FcRn) antibody for rare Immunoglobulin G (IgG)-mediated diseases and an oral Factor D inhibitor as well as several early-stage therapies, including one for light chain (AL) amyloidosis, a second oral Factor D inhibitor and a third complement inhibitor. Alexion focuses its research efforts on novel molecules and targets in the complement cascade and its development efforts on the core therapeutic areas of hematology, nephrology, neurology, metabolic disorders, cardiology and ophthalmology. Headquartered in Boston, Massachusetts, Alexion has offices around the globe and serves patients in more than 50 countries. This press release and further information about Alexion can be found at: www.alexion.com.

    [ALXN-G]

    Additional Information and Where to Find It

    In connection with the proposed transaction, AstraZeneca PLC ("AstraZeneca") intends to file with the SEC a registration statement on Form F-4 that will include a proxy statement of Alexion and that also constitutes a prospectus of AstraZeneca. Each of Alexion and AstraZeneca may also file other relevant documents with the U.S. Securities and Exchange Commission ("SEC") regarding the proposed transaction. This document is not a substitute for the proxy statement/prospectus or registration statement or any other document that Alexion or AstraZeneca may file with the SEC. The definitive proxy statement/prospectus (if and when available) will be mailed to stockholders of Alexion. INVESTORS AND SECURITY HOLDERS ARE URGED TO READ THE REGISTRATION STATEMENT, PROXY STATEMENT/PROSPECTUS AND ANY OTHER RELEVANT DOCUMENTS THAT MAY BE FILED WITH THE SEC, AS WELL AS ANY AMENDMENTS OR SUPPLEMENTS TO THESE DOCUMENTS, CAREFULLY AND IN THEIR ENTIRETY IF AND WHEN THEY BECOME AVAILABLE BECAUSE THEY CONTAIN OR WILL CONTAIN IMPORTANT INFORMATION ABOUT THE PROPOSED TRANSACTION. Investors and security holders will be able to obtain free copies of the registration statement and proxy statement/prospectus (if and when available) and other documents containing important information about Alexion, AstraZeneca and the proposed transaction, once such documents are filed with the SEC through the website maintained by the SEC at http://www.sec.gov. Copies of the documents filed with the SEC by Alexion will be available free of charge on Alexion's website at http://www.alexion.com or by contacting Alexion's Investor Relations Department by email at . Copies of the documents filed with the SEC by AstraZeneca will be available free of charge on AstraZeneca's website at https://www.astrazeneca.com/investor-relations.html or by contacting AstraZeneca's Investor Relations department by email at .

    Participants in the Solicitation

    Alexion, AstraZeneca, their respective directors and certain of their executive officers and other employees may be deemed to be participants in the solicitation of proxies from Alexion's stockholders in connection with the proposed transaction. Information regarding the persons who may, under the rules of the SEC, be deemed participants in the solicitation of Alexion stockholders in connection with the proposed mergers, including a description of their direct or indirect interests, by security holdings or otherwise, will be set forth in the proxy statement/prospectus when it is filed with the SEC. Information about Alexion's directors and executive officers is available in Alexion's proxy statement for its 2020 annual meeting of stockholders, which was filed with the SEC on March 26, 2020, Alexion's Annual Report on Form 10-K for the fiscal year ended December 31, 2019, which was filed with the SEC on February 4, 2020, and other documents subsequently filed by Alexion with the SEC. Information about AstraZeneca's directors and executive officers is available in AstraZeneca's Form 20-F filed with the SEC on March 3, 2020, and other documents subsequently filed by AstraZeneca with the SEC.

    No Offer or Solicitation

    This communication is not intended to and shall not constitute an offer to buy or sell or the solicitation of an offer to buy or sell any securities, or a solicitation of any vote or approval, nor shall there be any sale of securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction. No offering of securities shall be made, except by means of a prospectus meeting the requirements of Section 10 of the U.S. Securities Act of 1933, as amended.

    Forward Looking Statements

    This communication contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. You can generally identify forward-looking statements by the use of forward-looking terminology such as "anticipate," "believe," "continue," "could," "estimate," "expect," "explore," "evaluate," "intend," "may," "might," "plan," "potential," "predict," "project," "seek," "should," or "will," or the negative thereof or other variations thereon or comparable terminology. These forward-looking statements are only predictions and involve known and unknown risks and uncertainties, many of which are beyond Alexion's and AstraZeneca's control. Statements in this communication regarding Alexion, AstraZeneca and the combined company that are forward-looking, including anticipated revenue for Alexion for fiscal year 2020, future revenue for Alexion (including in 2025), 10 potential new launches by 2023, projections as to the anticipated benefits of the proposed transaction, the impact of the proposed transaction on Alexion's and AstraZeneca's businesses and future financial and operating results, the amount and timing of synergies from the proposed transaction, the terms and scope of the expected financing for the proposed transaction, the aggregate amount of indebtedness of the combined company following the closing of the proposed transaction, are based on management's estimates, assumptions and projections, and are subject to significant uncertainties and other factors, many of which are beyond Alexion's and AstraZeneca's control. These factors include, among other things, market factors, competitive product development and approvals, pricing controls and pressures (including changes in rules and practices of managed care groups and institutional and governmental purchasers), economic conditions such as interest rate and currency exchange rate fluctuations, judicial decisions, claims and concerns that may arise regarding the safety and efficacy of in-line products and product candidates, changes to wholesaler inventory levels, variability in data provided by third parties, changes in, and interpretation of, governmental regulations and legislation affecting domestic or foreign operations, including tax obligations, changes to business or tax planning strategies, difficulties and delays in product development, manufacturing or sales including any potential future recalls, patent positions and the ultimate outcome of any litigation matter. Additional information concerning these risks, uncertainties and assumptions can be found in Alexion's and AstraZeneca's respective filings with the SEC, including the risk factors discussed in Alexion's most recent Annual Report on Form 10-K, as updated by its Quarterly Reports on Form 10-Q, in AstraZeneca's most recent Annual Report on Form 20-F and in each company's future filings with the SEC. Important risk factors could cause actual future results and other future events to differ materially from those currently estimated by management, including, but not limited to, the risks that: a condition to the closing the proposed acquisition may not be satisfied; a regulatory approval that may be required for the proposed acquisition is delayed, is not obtained or is obtained subject to conditions that are not anticipated; AstraZeneca is unable to achieve the synergies and value creation contemplated by the proposed acquisition; AstraZeneca is unable to promptly and effectively integrate Alexion's businesses; management's time and attention is diverted on transaction related issues; disruption from the transaction makes it more difficult to maintain business, contractual and operational relationships; the credit ratings of the combined company declines following the proposed acquisition; legal proceedings are instituted against Alexion, AstraZeneca or the combined company; Alexion, AstraZeneca or the combined company is unable to retain key personnel; and the announcement or the consummation of the proposed acquisition has a negative effect on the market price of the capital stock of Alexion or AstraZeneca or on Alexion's or AstraZeneca's operating results. No assurances can be given that any of the events anticipated by the forward-looking statements will transpire or occur, or if any of them do occur, what impact they will have on the results of operations, financial condition or cash flows of Alexion or AstraZeneca. Should any risks and uncertainties develop into actual events, these developments could have a material adverse effect on the proposed transaction and/or Alexion or AstraZeneca, AstraZeneca's ability to successfully complete the proposed transaction and/or realize the expected benefits from the proposed transaction. You are cautioned not to rely on Alexion's and AstraZeneca's forward-looking statements. These forward-looking statements are and will be based upon management's then-current views and assumptions regarding future events and operating performance, and are applicable only as of the dates of such statements. Neither Alexion nor AstraZeneca assumes any duty to update or revise forward-looking statements, whether as a result of new information, future events or otherwise, as of any future date.

    View Full Article Hide Full Article
  3. Alexion Pharmaceuticals (NASDAQ:ALXN) today announced that management will present virtually at the 39th Annual J.P. Morgan Healthcare Conference on Tuesday, January 12th at 7:30 a.m. ET.

    Audio webcasts of the presentations will be available live at: http://ir.alexion.com. Archived versions of the remarks will also be available through the Company's website for a limited time following the conferences.

    [ALXN-G]

    Alexion Pharmaceuticals (NASDAQ:ALXN) today announced that management will present virtually at the 39th Annual J.P. Morgan Healthcare Conference on Tuesday, January 12th at 7:30 a.m. ET.

    Audio webcasts of the presentations will be available live at: http://ir.alexion.com. Archived versions of the remarks will also be available through the Company's website for a limited time following the conferences.

    [ALXN-G]

    View Full Article Hide Full Article
  4. Greater scientific presence in immunology by adding Alexion's innovative complement-technology platforms and strong pipeline 

    Dedicated rare disease unit to be headquartered in Boston

     Geographical presence to be enhanced with broad coverage across primary, speciality and highly specialised care

     Double-digit revenue growth through 2025; acquisition strengthens AstraZeneca's broad-based revenue and the company will further globalise Alexion's portfolio 

    Enhanced operating margin and cash flow to enable rapid debt reduction with an ambition to increase the dividend

    The acquisition will be immediately core earnings-accretive and value-enhancing, and is aligned with stated capital-allocation priorities

    AstraZeneca and Alexion Pharmaceuticals…

    Greater scientific presence in immunology by adding Alexion's innovative complement-technology platforms and strong pipeline 

    Dedicated rare disease unit to be headquartered in Boston

     Geographical presence to be enhanced with broad coverage across primary, speciality and highly specialised care

     Double-digit revenue growth through 2025; acquisition strengthens AstraZeneca's broad-based revenue and the company will further globalise Alexion's portfolio 

    Enhanced operating margin and cash flow to enable rapid debt reduction with an ambition to increase the dividend

    The acquisition will be immediately core earnings-accretive and value-enhancing, and is aligned with stated capital-allocation priorities

    AstraZeneca and Alexion Pharmaceuticals, Inc. (Alexion) have entered into a definitive agreement for AstraZeneca to acquire Alexion.

    This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20201212005016/en/

    Alexion shareholders will receive $60 in cash and 2.1243 AstraZeneca American Depositary Shares (ADSs) (each ADS representing one-half of one (1/2) ordinary share of AstraZeneca, as evidenced by American Depositary Receipts (ADRs)) for each Alexion share. Based on AstraZeneca's reference average ADR price of $54.14, this implies total consideration to Alexion shareholders of $39bn or $175 per share.

    The boards of directors of both companies have unanimously approved the acquisition. Subject to receipt of regulatory clearances and approval by shareholders of both companies, the acquisition is expected to close in Q3 2021, and upon completion, Alexion shareholders will own c.15% of the combined company.

    Pascal Soriot, Chief Executive Officer, AstraZeneca, said: "Alexion has established itself as a leader in complement biology, bringing life-changing benefits to patients with rare diseases. This acquisition allows us to enhance our presence in immunology. We look forward to welcoming our new colleagues at Alexion so that we can together build on our combined expertise in immunology and precision medicines to drive innovation that delivers life-changing medicines for more patients."

    Ludwig Hantson, Ph.D., Chief Executive Officer, Alexion, said: "For nearly 30 years Alexion has worked to develop and deliver transformative medicines to patients around the world with rare and devastating diseases. I am incredibly proud of what our organisation has accomplished and am grateful to our employees for their contributions. This transaction marks the start of an exciting new chapter for Alexion. We bring to AstraZeneca a strong portfolio, innovative rare disease pipeline, a talented global workforce and strong manufacturing capabilities in biologics. We remain committed to continuing to serve the patients who rely on our medicines and firmly believe the combined organisation will be well positioned to accelerate innovation and deliver enhanced value for our shareholders, patients and the rare disease communities."

    Strategic rationale

    Both companies share the same dedication to science and innovation to deliver life-changing medicines. The capabilities of both organisations will create a company with great strengths across a range of technology platforms, with the ability to bring innovative medicines to millions of people worldwide. The combined company will also have an enhanced global footprint and broad coverage across primary, speciality and highly specialised care.

    Scientific leadership - accelerated presence in immunology

    AstraZeneca has built a growing scientific presence in oncology, and in cardiovascular, renal and metabolism, and respiratory diseases, with a focus on organ protection. AstraZeneca has developed a broad range of technologies, initially focused on small molecules and biologics and with a growing focus in precision medicine, genomics, oligonucleotides and epigenetics. More recently, AstraZeneca has increased its efforts in immunology research and the development of medicines for immune-mediated diseases.

    Alexion has pioneered complement inhibition for a broad spectrum of immune-mediated rare diseases caused by uncontrolled activation of the complement system, a vital part of the immune system. Alexion's franchise includes Soliris (eculizumab), a first-in-class anti-complement component 5 (C5) monoclonal antibody. The medicine is approved in many countries for the treatment of patients with paroxysmal nocturnal haemoglobinuria (PNH), atypical haemolytic uremic syndrome, generalized myasthenia gravis and neuromyelitis optica spectrum disorder. More recently, Alexion launched Ultomiris (ravulizumab), a second-generation C5 monoclonal antibody with a more convenient dosing regimen.

    Alexion's immunology expertise extends to other targets in the complement cascade beyond C5 as well as additional modalities, with its deep pipeline including Factor D small-molecule inhibitors of the alternative pathway of the complement system, an antibody blocking neonatal Fc receptor (FcRn)-mediated recycling, and a bi-specific mini-body targeting C5, among others. The FcRn extends the half-life and hence the availability of pathogenic immunoglobulin G (IgG) antibodies.

    AstraZeneca, with Alexion's R&D team, will work to build on Alexion's pipeline of 11 molecules across more than 20 clinical-development programmes across the spectrum of indications, in rare diseases and beyond.

    Alexion's leading expertise in complement biology will accelerate AstraZeneca's growing presence in immunology. The acquisition adds a new technology platform to AstraZeneca's science and innovation-driven strategy. The complement cascade is pivotal to the innate immune system. It plays a crucial role in many inflammatory and autoimmune diseases across multiple therapy areas, including haematology, nephrology, neurology, metabolic disorders, cardiology, ophthalmology and acute care. In contrast, AstraZeneca's capabilities in genomics, precision medicine and oligonucleotides can be leveraged to develop medicines targeting less-frequent diseases. Combining AstraZeneca's capabilities in precision medicine and Alexion's expertise in rare-disease development and commercialisation will enable the new company to develop a portfolio of medicines addressing the large unmet needs of patients suffering from rare diseases.

    The combined companies will bring together two rapidly converging, patient-centric models of care delivery with combined strengths in immunology, biologics, genomics and oligonucleotides to drive future medicine innovation. AstraZeneca intends to establish Boston, Massachusetts, US as its headquarters for rare diseases, capitalising on talent in the greater Boston area.

    Industry-leading revenue growth; enhanced geographical presence and broad coverage across primary, specialised and highly specialised care

    AstraZeneca's acquisition of Alexion, with its strong commercial portfolio and robust pipeline, will support its long-term ambition to develop novel medicines in areas of immunology with high unmet medical needs. Alexion achieved impressive revenue growth over the last few years, with revenues of $5.0bn in 2019 (21% year-on-year growth). Alexion has exhibited skilful commercial execution in building its 'blockbuster' C5 franchise. The success of the franchise is demonstrated by the effective transition of over 70% of PNH patients from Soliris to Ultomiris in less than two years of launch in its key markets, including the US, Japan and Germany, as well as the strong pipeline of additional indications for Ultomiris.

    Rare diseases is a high-growth therapy area with rapid innovation and significant unmet medical need. Over 7,000 rare diseases are known today, and only c.5% have US Food and Drug Administration-approved treatments.1 The global rare disease market is forecasted to grow by a low double digit percentage in the future.2

    AstraZeneca intends to build on its geographical footprint and extensive emerging markets presence to accelerate the worldwide expansion of Alexion's portfolio.

    The two companies have been on converging paths, AstraZeneca expanding its presence from primary to speciality care, whereas Alexion has been progressing from ultra-orphan to orphan and speciality conditions.

    The acquisition strengthens AstraZeneca's industry-leading growth, underpinned by its broad portfolio of medicines, which will enable the new company to bring innovative medicines to a broad range of healthcare practitioners in primary, speciality and highly specialised care.

    The combined company is expected to deliver double-digit average annual revenue growth through 2025.

    Financial benefits

    Enhanced revenue growth, operating margin and cash-flow generation

    The acquisition is expected to improve the combined Group's profitability, with the core operating margin significantly enhanced in the short term, and with continued expansion thereafter. This uplift is supported by increased scale and expected recurring run-rate pre-tax synergies of c.$500m per year from the combined Group (by end of the third year following completion of the acquisition). AstraZeneca expects to generate significant value from the acquisition by extending Alexion's commercial reach through leveraging AstraZeneca's global presence and accelerating the development of Alexion's pipeline.

    The acquisition also strengthens AstraZeneca's cash-flow generation, providing additional flexibility to reinvest in R&D and rapid debt reduction, with an ambition to increase the dividend.

    Immediately earnings-accretive and value-enhancing acquisition, in line with stated capital-allocation priorities

    The acquisition is expected to deliver robust and sustainable accretion to AstraZeneca's core earnings per share (EPS) from the outset, with double-digit percentage accretion anticipated in the first three years following the completion of the acquisition.

    The acquisition of Alexion is consistent with AstraZeneca's capital-allocation priorities. The combined company is expected to maintain a strong, investment-grade credit rating, and the acquisition supports AstraZeneca's progressive dividend policy. The combination represents a significant step in AstraZeneca's strategic and financial-growth plans.

    Webinar and conference call

    A webinar and conference call for investors and analysts will begin at 2:00 pm UK time today, please join 10-15 minutes prior to the scheduled start time.

    UK: +44 203 481 5237

    Sweden: +46 8 5052 0017

    US: +1 301 715 8592

    Webinar ID: 995 4603 8702

    Password: 12121220

    Click here for available international numbers.

    The presentation will be available at astrazeneca.com before the call takes place, and replay details after the call.

    Details of the acquisition

    Key terms

    The acquisition will be undertaken through a US statutory merger in which Alexion shareholders will receive $60 in cash and 2.1243 new AstraZeneca ADSs listed on the Nasdaq exchange for each of their Alexion shares. The cash and ADS consideration represents an c.45% premium to Alexion shareholders based on the closing stock price of Alexion on 11 December 2020 and a c.43% premium, based on the 30-day volume-weighted average closing stock price of $122.04 before this announcement. If they elect, Alexion shareholders may receive their allocation of AstraZeneca ADSs in the form of a corresponding number of ordinary shares of AstraZeneca in addition to the cash consideration.

    Based on AstraZeneca's reference average ADR price of $54.14, this implies total consideration to Alexion shareholders of $39bn or $175 per share.

    Financing

    To support the financing of the offer consideration, AstraZeneca has entered into a new committed $17.5bn bridge-financing facility, provided by Morgan Stanley, J.P. Morgan Securities plc and Goldman Sachs. The bridge-financing facility is available for an initial term of 12 months from the earlier of the date of completion of the acquisition and 12 December 2021 with up to two six-month extensions available at the discretion of AstraZeneca. The initial bridge financing facility is intended to cover the financing of the cash portion of the acquisition consideration and associated acquisition costs and to refinance the existing term loan and revolving credit facilities of Alexion. In due course, AstraZeneca intends to refinance the initial bridge-financing facility through a combination of new medium-term bank loan facilities, debt-capital market issuances and business cash flows.

    The acquisition is expected to significantly enhance cash generation, which will support rapid debt reduction and overall deleveraging. AstraZeneca remains committed to maintaining a strong investment-grade credit rating. The dividend policy remains unchanged with a commitment to a progressive dividend policy; dividend cover is expected to be materially enhanced as a result of the acquisition.

    Further information on synergies

    The acquisition is expected to realise recurring run-rate pre-tax synergies of c.$500m per year from the combined Group, generated from commercial and manufacturing efficiencies as well as savings in central costs, with full run-rate expected to be achieved by end of the third year following completion of the acquisition.

    To realise the total synergies, AstraZeneca expects to incur one-time cash costs of c.$650m, during the first three years following completion.

    Management and employees

    Members of Alexion's current senior management team will lead the future rare-disease activities. Under the terms of the acquisition agreement, AstraZeneca has agreed that for 12 months following closing, it will provide the Alexion employees with the same level of salary as such employees had before closing, incentive compensation opportunities that are in the aggregate no less favourable than those provided before closing and substantially comparable benefits to those provided before closing.

    Governance

    The companies will mutually agree on two individuals from the Alexion board of directors who will join the AstraZeneca board as directors upon closing of the acquisition.

    Closing conditions

    Closing of the acquisition is subject to approval by AstraZeneca and Alexion shareholders, certain regulatory approvals, approval of the new AstraZeneca shares for listing with the Financial Conduct Authority and to trading on the London Stock Exchange, and other customary closing conditions.

    The acquisition is a Class 1 transaction for AstraZeneca and as such, will require the approval of its shareholders to comply with the UK Listing Rules. A shareholder circular, together with notice of the relevant shareholder meeting, will be distributed to shareholders in the first half of 2021. The Alexion proxy statement is also expected to be published in the first half of 2021.

    Subject to the satisfaction of the closing conditions to the proposed acquisition, the companies expect the acquisition to close in Q3 2021.

    Termination

    The acquisition terms provide that Alexion will be liable to pay a break fee of up to $1.2bn to AstraZeneca in certain specified circumstances (including a change of Alexion's board recommendation or completion of an alternative acquisition). AstraZeneca will also be required to pay Alexion a break fee of $1.4bn in certain specified circumstances, including a change of AstraZeneca's board recommendation.

    Recommendation

    The boards of directors of both Alexion and AstraZeneca have unanimously approved the proposed acquisition and resolved to recommend that their respective shareholders vote in favour of it.

    Advisors to AstraZeneca

    Evercore Partners International LLP ("Evercore"), and Centerview Partners UK LLP ("Centerview Partners") are acting as lead financial advisers. Ondra LLP ("Ondra") are providing advice as part of their ongoing financial advisory services. Morgan Stanley & Co. International plc ("Morgan Stanley") and Morgan Stanley Bank International Limited and J.P. Morgan are acting as financial advisors and lead debt financing underwriters. Goldman Sachs Bank USA is acting as lead debt financing underwriter. Morgan Stanley and Goldman Sachs International are joint corporate brokers. Evercore is acting as sponsor in relation to the transaction described in this announcement. Freshfields Bruckhaus Deringer is acting as legal counsel.

    Advisors to Alexion

    Bank of America Securities is serving as financial advisor to Alexion, and Wachtell, Lipton, Rosen & Katz is serving as legal counsel.

    Alexion

    Alexion is a global biopharmaceutical company focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and commercialisation of life-changing medicines. As a leader in rare diseases for more than 25 years, Alexion has developed and commercialises two approved complement inhibitors to treat patients with PNH and atypical haemolytic uremic syndrome, as well as the first and only approved complement inhibitor to treat anti-acetylcholine receptor antibody-positive generalised myasthenia gravis and neuromyelitis optica spectrum disorder. Alexion also has two highly innovative enzyme replacement therapies for patients with life-threatening and ultra-rare metabolic disorders, hypophosphatasia and lysosomal acid lipase deficiency as well as the first and only approved Factor Xa inhibitor reversal agent. In addition, Alexion is developing several mid-to-late-stage therapies, including a copper-binding agent for Wilson disease, FcRn antibody for rare IgG-mediated diseases and an oral Factor D inhibitor as well as several early-stage therapies, including one for light chain amyloidosis, a second oral Factor D inhibitor and a third complement inhibitor. Alexion focuses its research efforts on novel molecules and targets in the complement cascade and its development efforts on haematology, nephrology, neurology, metabolic disorders, cardiology, ophthalmology and acute care. Headquartered in Boston, Massachusetts, Alexion has offices around the globe and serves patients in more than 50 countries. During 2019, Alexion generated a total revenue of $5bn and profit before tax of $2.2bn. As of 30 September 2020, Alexion had gross assets of $17.5bn. Alexion's executive officers are Ludwig Hantson (Chief Executive Officer), Aradhana Sarin (Chief Financial Officer), Tanisha Carino (Chief Corporate Affairs Officer), Ellen Chiniara (Chief Legal Officer and Corporate Secretary), Indrani Franchini (Chief Compliance Officer), Brian Goff (Chief Commercial and Global Operations Officer), and John Orloff (Head of Research and Development). This press release and further information about Alexion can be found at www.alexion.com.

    [ALXN-G]

    Evercore, Centerview Partners and Ondra, each of which is authorised and regulated by the Financial Conduct Authority in the United Kingdom, are each acting exclusively for AstraZeneca and no one else in connection with the transaction and the matters referred to in this document and will not regard any other person as a client in relation to the matters set out in this document and will not be responsible to anyone other than AstraZeneca for providing the protections afforded to their respective clients, nor for providing advice in relation to the transaction or any other matter referred to in this document. Neither Evercore, Centerview Partners nor Ondra, nor any of their respective subsidiaries, holding companies, branches or affiliates owes or accepts any duty, liability or responsibility whatsoever (whether direct or indirect, whether in contract, in tort, under statute or otherwise) to any person who is not a client in connection with the transaction or any statement contained herein or otherwise. Apart from the responsibilities and liabilities, if any, which may be imposed on each of Evercore, Centerview Partners and Ondra by the Financial Services and Markets Act 2000 (FSMA), or the regulatory regime established thereunder, or under the regulatory regime of any jurisdiction where exclusion of liability under the relevant regulatory regime would be illegal, void or unenforceable, neither Evercore, Centerview Partners nor Ondra, nor any of their respective affiliates accepts any responsibility or liability whatsoever for the contents of this announcement, and no representation, express or implied, is made by it, or purported to be made on its behalf, in relation to the contents of this announcement, including its accuracy, completeness or verification of any other statement made or purported to be made by it, or on its behalf, in connection with AstraZeneca or the matters described in this announcement. To the fullest extent permitted by applicable law, each of Evercore, Centerview Partners and Ondra and each of their respective affiliates accordingly disclaim all and any responsibility or liability whether arising in tort, contract or otherwise (save as referred to above) which they might otherwise have in respect of this announcement or any statement contained therein.

    Morgan Stanley & Co. International plc ("Morgan Stanley") and J.P. Morgan Securities plc (which conducts its UK investment banking business as J.P. Morgan Cazenove) ("J.P. Morgan Cazenove") each of which are authorised by the Prudential Regulation Authority and regulated by the Financial Conduct Authority and Prudential Regulation Authority in the UK are each acting as financial adviser exclusively for AstraZeneca and no one else in connection with the matters set out in this announcement. In connection with such matters, Morgan Stanley and J.P. Morgan Cazenove, each of their respective affiliates and their respective directors, officers, employees and agents will not regard any other person as a client, nor will they be responsible to any other person for providing the protections afforded to their respective clients or for providing advice in connection with the contents of this announcement or any other matter referred to herein.

    Goldman Sachs International, which is authorised and regulated by the Financial Conduct Authority in the United Kingdom, and Goldman Sachs Bank USA, which is authorised and regulated by the Board of Governors of the Federal Reserve System (Federal Reserve Board), the FDIC and the New York State Department of Financial Services, are each acting exclusively for AstraZeneca and no one else in connection with the transaction and the matters referred to in this document and will not regard any other person as a client in relation to the matters set out in this document and will not be responsible to anyone other than AstraZeneca for providing the protections afforded to their respective clients, nor for providing advice in relation to the transaction or any other matter referred to in this document. Neither Goldman Sachs International, nor Goldman Sachs Bank USA, nor any of their respective subsidiaries, holding companies, branches or affiliates owes or accepts any duty, liability or responsibility whatsoever (whether direct or indirect, whether in contract, in tort, under statute or otherwise) to any person who is not a client in connection with the transaction or any statement contained herein or otherwise. Apart from the responsibilities and liabilities, if any, which may be imposed on Goldman Sachs International and/or Goldman Sachs Bank USA under the regulatory regime of any jurisdiction where exclusion of liability under the relevant regulatory regime would be illegal, void or unenforceable, neither Goldman Sachs International, nor Goldman Sachs Bank USA, nor any of their respective affiliates accepts any responsibility or liability whatsoever for the contents of this announcement, and no representation, express or implied, is made by it, or purported to be made on its behalf, in relation to the contents of this announcement, including its accuracy, completeness or verification of any other statement made or purported to be made by them, or on their behalf, in connection with AstraZeneca or the matters described in this announcement. To the fullest extent permitted by applicable law, Goldman Sachs International, Goldman Sachs Bank USA and each of their respective affiliates accordingly disclaim all and any responsibility or liability whether arising in tort, contract or otherwise (save as referred to above) which they might otherwise have in respect of this announcement or any statement contained therein.

    Important additional information

    Neither this announcement nor any copy of it may be taken or transmitted directly or indirectly into or from any jurisdiction where to do so would constitute a violation of the relevant laws or regulations of such jurisdiction. Any failure to comply with this restriction may constitute a violation of such laws or regulations. Persons into whose possession this announcement or other information referred to herein should inform themselves about, and observe, any restrictions in such laws or regulations.

    This announcement has been prepared for the purpose of complying with the applicable law and regulation of the United Kingdom and the United States and information disclosed may not be the same as that which would have been disclosed if this announcement had been prepared in accordance with the laws and regulations of jurisdictions outside the United Kingdom or the United States.

    In connection with the proposed acquisition, AstraZeneca intends to file a registration statement on Form F-4 with the SEC, which will include a document that serves as a prospectus of AstraZeneca and a proxy statement of Alexion (the "proxy statement/prospectus"), Alexion intends to file a proxy statement with the SEC (the "proxy statement") and each party will file other documents regarding the proposed acquisition with the SEC. Investors and security holders of Alexion are urged to carefully read the entire registration statement and proxy statement/prospectus or proxy statement and other relevant documents filed with the SEC when they become available because they will contain important information. A proxy statement/prospectus or a proxy statement will be sent to Alexion's shareholders. Investors and security holders will be able to obtain the registration statement and the proxy statement/prospectus or the proxy statement free of charge from the SEC's website or from AstraZeneca or Alexion as described in the paragraphs below.

    Participants in the solicitation

    Alexion, AstraZeneca and certain of their directors, executive officers and employees may be deemed participants in the solicitation of proxies from Alexion shareholders in connection with the proposed transaction. Information regarding the persons who may, under the rules of the SEC, be deemed participants in the solicitation of the shareholders of Alexion in connection with the proposed transaction, including a description of their direct or indirect interests, by security holdings or otherwise, will be set forth in the proxy statement/prospectus or proxy statement when it is filed with the SEC. Information about the directors and executive officers of Alexion and their ownership of Alexion shares is set forth in the definitive proxy statement for Alexion's 2020 special meeting of shareholders, as previously filed with the SEC on March 26, 2020. Free copies of these documents may be obtained as described in the paragraphs above.

    Forward-looking statements

    This announcement may include statements that are or may be deemed to be forward-looking statements. These forward-looking statements may be identified by the use of forward-looking terminology, including the terms "believes", "estimates", "envisages", "plans", "projects", "anticipates", "targets", "aims", "expects", "intends", "may", "will" or "should" or, in each case, their negative or other variations or comparable terminology, or by discussions of strategy, plans, objectives, goals, future events or intentions and include, but are not limited to the ability of the parties to consummate the proposed acquisition on a timely basis or at all, the ability of the parties to satisfy the conditions precedent to consummation of the proposed acquisition, including the ability to secure the required regulatory approvals on the terms expected, at all or in a timely manner, the ability of AstraZeneca to successfully integrate Alexion's operations, and the ability of AstraZeneca to implement its plans, forecasts and other expectations with respect to Alexion's business after the completion of the proposed acquisition and realise expected synergies. Economic, competitive, governmental, technological and other factors that may affect AstraZeneca's and Alexion's operations are discussed in the section entitled "Risk Factors," in each of AstraZeneca's Annual Report on Form 20-F for the year ended 31 December 2019, and Alexion's Annual Report on Form 10-K for the year ended 31 December 2019, in each case as amended by any subsequent filings made with the SEC. These forward-looking statements include all matters that are not historical facts and involve predictions. Forward-looking statements may and often do differ materially from actual results. Any forward-looking statements reflect AstraZeneca's and Alexion's current views with respect to future events and are subject to risks relating to future events and other risks, uncertainties and assumptions relating to AstraZeneca's or Alexion's results of operations, financial position, liquidity, prospects, growth or strategies and the industries in which they operate. Forward-looking statements speak only as of the date they are made and cannot be relied upon as a guide to future performance. Save as required by law or regulation, AstraZeneca and Alexion disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements in this announcement that may occur due to any change in their expectations or to reflect events or circumstances after the date of this announcement.

    Nothing in this announcement should be construed as a profit estimate or profit forecast. No statement in this announcement, including statements that the acquisition is accretive to core EPS, or enhancing to core operating margins should be interpreted to mean that earnings per share or core operating margins of AstraZeneca or Alexion for the current or future financial years would necessarily match or exceed the historical published earnings per share or core operating margins of AstraZeneca or Alexion.

    Completion of the proposed acquisition is subject to the satisfaction of several conditions as more fully described in this announcement. Consequently, there can be no certainty that the completion of the proposed acquisition will be forthcoming.

    This announcement is not a prospectus for the purposes of the UK Prospectus Regulation Rules or the EU Prospectus Regulation. It has been prepared solely for the proposed acquisition referred to in this announcement. A circular is expected to be published by AstraZeneca in connection with the proposed acquisition in due course.

    Certain figures contained in this announcement, including financial information, have been subject to rounding adjustments. Accordingly, in certain instances, the sum or percentage change of the numbers contained in this announcement may not conform precisely with the total figure given. Except as explicitly stated in this announcement, none of the contents of AstraZeneca's or Alexion's websites, nor any website accessible by hyperlinks on AstraZeneca's or Alexion's websites, is incorporated in or forms part of, this announcement.

    AstraZeneca

    AstraZeneca (NASDAQ:AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.

    AstraZeneca contacts

    For details on how to contact the Investor Relations Team, please click here. For Media contacts, click here.

    Alexion contacts

    For Media enquiries, Megan Goulart, +18573388634, and for Investor Relations, Chris Stevo, +18573389309.

    Notes

    Unless otherwise stated: financial information relating to AstraZeneca has been extracted or derived from the audited results for the twelve months ended 12 December 2019; and financial information relating to Alexion has been extracted or derived from the audited results for the twelve months ended 31 December 2019, and the unaudited results for the nine months ended 30 September 2020.

    All Alexion financial information in this announcement is presented following US GAAP and may be different in the Circular, which will be prepared under IFRS and AstraZeneca's accounting policies.

    Core EPS is a non-GAAP financial measure and adjusted from reported GAAP EPS to exclude certain significant items such as amortisation and impairment of intangible assets, charges and provisions related to global restructuring programmes and other specified items per AstraZeneca annual filings.

    Non-GAAP results, determined in accordance with Alexion's internal policies, exclude the impact of the following GAAP items: share-based compensation expense, fair value adjustment of inventory acquired, amortisation of purchased intangible assets, changes in fair value of contingent consideration, restructuring and related expenses, upfront payments related to licenses and other strategic agreements, acquired in-process research and development, impairment of purchased intangible assets, gains and losses related to strategic equity investments, litigation charges, gain or loss on the sale of a business or asset, gain or loss related to purchase options, contingent milestone payments associated with acquisitions of legal entities accounted for as asset acquisitions, acquisition-related costs and certain adjustments to income tax expense. These non-GAAP financial measures are not intended to be considered in isolation or as a substitute for, or superior to, the financial measures prepared and presented in accordance with GAAP and should be reviewed in conjunction with the relevant GAAP financial measures.

    Sources of information and bases of calculation

    (i) As at 9 December 2020, there were 218,720,567 Alexion shares outstanding. The International Securities Identification Number for the Alexion Shares is US0153511094.

    (ii) Any references to the issued and to be issued ordinary share capital of Alexion are based on:

    • the 218,720,567 Alexion Shares referred to in paragraph (i) above; and
    • 6,202,972 Alexion Shares which may be issued on or after the date of this announcement to satisfy the exercise of stock options and restricted and performance stock awards outstanding under the Alexion Share Plans, estimated based on the total consideration of $175 per Alexion share and calculated in accordance with the Treasury Stock Method.

    (iii) As at 9 December 2020 there were 1,312,660,216 AstraZeneca Ordinary Shares in issue of which all shares have voting rights attached.

    (iv) The value placed by the acquisition on the entire issued and to be issued ordinary share capital of Alexion is to be calculated:

    • by reference to an equivalent value of $54.14 per AstraZeneca reference ADS; and
    • on the basis of the issued and to be issued share capital of Alexion (as set out in paragraph (ii) above).

    (vi) The share capital of the combined Group (being 1,551,562,753) has been calculated as the sum of:

    • 1,312,660,216 AstraZeneca Shares, being the number of AstraZeneca Shares in issue as at 9 December 2020; and
    • 238,902,537 New AstraZeneca Ordinary Shares which would be issued pursuant to the terms of the acquisition (being 2.1243 New AstraZeneca ADSs per Alexion Share multiplied by the issued and to be issued share capital of Alexion as set out in paragraph (ii) above).

    (vii) The percentage of the share capital of the combined Group that will be owned by Alexion Shareholders is calculated by dividing the number of New AstraZeneca Shares to be issued pursuant to the terms of the acquisition referred to in paragraph (vi) above by the issued share capital of the combined Group (as set out in paragraph (vi) above) and multiplying the resulting sum by 100 to product a percentage.

    (viii) Unless otherwise stated all prices and closing prices for Alexion Shares and AstraZeneca Shares are derived from Bloomberg.

    (ix) The volume weighted average price of an Alexion Share is derived from Bloomberg by reference to the volume weighted average price over the last 30 Alexion trading days up to 11 December 2020 (being the last Business Day prior to announcement of an offer for Alexion).

    Adrian Kemp

    Company Secretary

    AstraZeneca PLC

    ________________

    1 A rare disease is a disease impacting less than 200,000 patients (as defined in the US Orphan Drug Act 1983).

    2 EvaluatePharma, World Preview 2020, Outlook to 2026.

    This announcement contains inside information

    NOT FOR RELEASE, PUBLICATION OR DISTRIBUTION, IN WHOLE OR IN PART, DIRECTLY OR INDIRECTLY, IN OR INTO OR FROM ANY JURISDICTION WHERE TO DO SO WOULD CONSTITUTE A VIOLATION OF THE RELEVANT LAWS OR REGULATIONS OF SUCH JURISDICTION.

    THIS IS AN ANNOUNCEMENT AND NOT A CIRCULAR OR PROSPECTUS OR EQUIVALENT DOCUMENT FOR THE PURPOSES OF THE UK PROSPECTUS REGULATION RULES OR THE EU PROSPECTUS REGULATION. THIS ANNOUNCEMENT DOES NOT CONSTITUTE OR FORM PART OF, AND SHOULD NOT BE CONSTRUED AS, ANY OFFER, INVITATION OR RECOMMENDATION TO PURCHASE, SELL OR SUBSCRIBE FOR ANY SECURITIES IN ANY JURISDICTION AND NEITHER THE ISSUE OF THE INFORMATION NOR ANYTHING CONTAINED HEREIN SHALL FORM THE BASIS OF OR BE RELIED UPON IN CONNECTION WITH, OR ACT AS AN INDUCEMENT TO ENTER INTO, ANY INVESTMENT ACTIVITY. INVESTORS AND PROSPECTIVE INVESTORS SHOULD NOT MAKE ANY INVESTMENT DECISION ON THE BASIS OF ITS CONTENTS. A CIRCULAR IN RELATION TO THE PROPOSED ACQUISITION DESCRIBED IN THIS ANNOUNCEMENT IS EXPECTED TO BE PUBLISHED IN DUE COURSE.

    View Full Article Hide Full Article
  5. – The new 100 mg/mL formulation will reduce infusion time by approximately 60%, lessening the burden on patients –

    – ULTOMIRIS is approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) –

    Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) today announced that the European Commission (EC) has approved the new 100 mg/mL intravenous (IV) formulation of ULTOMIRIS® (ravulizumab) for the treatment of two ultra-rare diseases – paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). ULTOMIRIS is the first and only long-acting C5 inhibitor administered to patients every eight weeks or every four weeks for pediatric patients less than 20 kg. ULTOMIRIS 100 mg/mL…

    – The new 100 mg/mL formulation will reduce infusion time by approximately 60%, lessening the burden on patients –

    – ULTOMIRIS is approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) –

    Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) today announced that the European Commission (EC) has approved the new 100 mg/mL intravenous (IV) formulation of ULTOMIRIS® (ravulizumab) for the treatment of two ultra-rare diseases – paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). ULTOMIRIS is the first and only long-acting C5 inhibitor administered to patients every eight weeks or every four weeks for pediatric patients less than 20 kg. ULTOMIRIS 100 mg/mL is an advancement in the treatment experience for patients with aHUS and PNH by reducing average annual infusion times by approximately 60 percent compared to ULTOMIRIS 10 mg/mL, while delivering comparable safety and efficacy. With ULTOMIRIS 100 mg/mL, most patients will spend six hours or less a year receiving treatment.

    "ULTOMIRIS has already provided patients with greater flexibility and this new formulation is another step forward in reducing the overall treatment burden," said Professor Alexander Röth, Department of Hematology and Stem Cell Transplantation, University Hospital Essen, Essen, Germany. "With this new formulation, patients will experience comparable safety and efficacy to the original formulation while spending significantly less time per year receiving treatment, which has the potential to make a meaningful difference in their lives."

    PNH is a blood disorder characterized by complement-mediated destruction of the red blood cells that can cause a wide range of debilitating symptoms and complications, including thrombosis, which can occur throughout the body, and result in organ damage and premature death.1 Atypical HUS can cause progressive injury to vital organs, primarily the kidneys, via damage to the walls of blood vessels and blood clots.2 Affecting both adults and children, aHUS patients can present in critical condition, often requiring supportive care, including dialysis, in an intensive care unit. The prognosis of both aHUS and PNH can be poor in many cases, so a timely and accurate diagnosis—in addition to appropriate treatment—is critical to improving patient outcomes.

    "The European Commission's approval of ULTOMIRIS in this new formulation will provide a meaningful benefit to patients' quality of life," said John Orloff, M.D., Executive Vice President and Head of Research & Development at Alexion. "This new formulation demonstrates Alexion's continued commitment to innovating for patients and their families. In addition, it lessens the overall burden on healthcare systems and practitioners with reduced infusion times, and on patients, who will only spend six hours or less a year receiving their treatment."

    The European Commission approval is based on a comprehensive chemistry, manufacturing and control submission and a supplementary clinical data set showing that the safety, pharmacokinetics and immunogenicity following administration of ULTOMIRIS 10 mg/mL and ULTOMIRIS 100 mg/mL were comparable. Similarly, the data set showed no relevant changes in the efficacy measure of mean lactate dehydrogenase (LDH) levels across the two formulations. The new proposed formulation requires an infusion time of 0.4 to 1.3 hours (25 to 75 minutes) depending on body weight, reducing the infusion time by approximately 60 percent compared with the currently available 10 mg/mL IV formulation, which ranges from 1.3 to 3.3 hours (77 to 194 minutes) depending on body weight.

    ULTOMIRIS 100 mg/mL was approved by the U.S. Food and Drug Administration (FDA) in October 2020, and a regulatory filing is under review in Japan.

    Alexion continues to innovate with ULTOMIRIS, with the goal of improving the patient experience. We plan to submit regulatory filings in the U.S. and EU in the third quarter of 2021 for an ULTOMIRIS subcutaneous formulation and device combination for PNH and aHUS that can be self-administered at home, pending completion of the ongoing Phase 3 study and collection of 12-month safety data. In addition, the collective ULTOMIRIS clinical development programs present an opportunity to expand treatment for rare diseases across hematology, nephrology, neurology, and for the treatment of severe COVID-19, with seven Phase 3 programs that are ongoing or have planned clinical trial initiations in 2020.

    About Paroxysmal Nocturnal Hemoglobinuria (PNH)

    PNH is a serious ultra-rare blood disorder with devastating consequences. It is characterized by the destruction of red blood cells, which is also referred to as hemolysis. PNH occurs when the complement system—a part of the body's immune system—over-responds, leading the body to attack its own red blood cells. PNH often goes unrecognized, with delays in diagnosis from one to more than five years. Patients with PNH may experience a range of symptoms, such as fatigue, difficulty swallowing, shortness of breath, abdominal pain, erectile dysfunction, dark-colored urine and anemia. The most devastating consequence of chronic hemolysis is the formation of blood clots, which can occur in blood vessels throughout the body, damage vital organs, and potentially lead to premature death. PNH can strike men and women of all races, backgrounds and ages without warning, with an average age of onset in the early 30s.

    About Atypical Hemolytic Uremic Syndrome (aHUS)

    aHUS is an ultra-rare disease that can cause progressive injury to vital organs, primarily the kidneys, via damage to the walls of blood vessels and blood clots. aHUS occurs when the complement system—a part of the body's immune system—over-responds, leading the body to attack its own healthy cells. aHUS can cause sudden organ failure or a slow loss of function over time—potentially resulting in the need for a transplant, and in some cases, death. aHUS affects both adults and children, and many patients present in critical condition, often requiring supportive care, including dialysis, in an intensive care unit. The prognosis of aHUS can be poor in many cases, so a timely and accurate diagnosis—in addition to treatment—is critical to improving patient outcomes. Available tests can help distinguish aHUS from other hemolytic diseases with similar symptoms.

    About ULTOMIRIS®

    ULTOMIRIS® (ravulizumab) is the first and only long-acting C5 complement inhibitor. The medication works by inhibiting the C5 protein in the terminal complement cascade, a part of the body's immune system. When activated in an uncontrolled manner, the complement cascade over-responds, leading the body to attack its own healthy cells. ULTOMIRIS is administered intravenously every eight weeks or, for pediatric patients less than 20 kg, every four weeks, following a loading dose. ULTOMIRIS is approved in the United States (U.S.), European Union (EU) and Japan as a treatment for adults with paroxysmal nocturnal hemoglobinuria (PNH). It is also approved in the U.S. and Japan for atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA) in adult and pediatric (one month of age and older) patients, as well as in the EU for the treatment of adults and children with a body weight of at least 10 kg with aHUS. In the U.S., ULTOMIRIS is available in two formulations with the same mechanism of action and consistent safety and efficacy. The ULTOMIRIS 100 mg/mL formulation reduces average annual infusion time for patients with aHUS and PNH by approximately 60 percent (to approximately 45 minutes for adults in the average weight cohort) compared to the ULTOMIRIS 10 mg/mL formulation. To learn more about the regulatory status of ULTOMIRIS in the countries that we serve, please visit www.alexion.com.

    About Alexion

    Alexion is a global biopharmaceutical company focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and commercialization of life-changing medicines. As a leader in rare diseases for more than 25 years, Alexion has developed and commercializes two approved complement inhibitors to treat patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), as well as the first and only approved complement inhibitor to treat anti-acetylcholine receptor (AchR) antibody-positive generalized myasthenia gravis (gMG) and neuromyelitis optica spectrum disorder (NMOSD). Alexion also has two highly innovative enzyme replacement therapies for patients with life-threatening and ultra-rare metabolic disorders, hypophosphatasia (HPP) and lysosomal acid lipase deficiency (LAL-D) as well as the first and only approved Factor Xa inhibitor reversal agent. In addition, the company is developing several mid-to-late-stage therapies, including a copper-binding agent for Wilson disease, an anti-neonatal Fc receptor (FcRn) antibody for rare Immunoglobulin G (IgG)-mediated diseases and an oral Factor D inhibitor as well as several early-stage therapies, including one for light chain (AL) amyloidosis, a second oral Factor D inhibitor and a third complement inhibitor. Alexion focuses its research efforts on novel molecules and targets in the complement cascade and its development efforts on hematology, nephrology, neurology, metabolic disorders, cardiology, ophthalmology and acute care. Headquartered in Boston, Massachusetts, Alexion has offices around the globe and serves patients in more than 50 countries. This press release and further information about Alexion can be found at: www.alexion.com.

    [ALXN-P]

    Forward-Looking Statement

    This press release contains forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Alexion, including statements related to: the safety, efficacy and benefits of the 100 mg/mL ULTOMIRIS formulation as a treatment for PNH and aHUS; that ULTOMIRIS 100 mg/mL formulation reduces infusion time as compared to the 10 mg/mL formulation of ULTOMIRIS by approximately 60% with comparable safety and efficacy; with ULTOMIRIS 100 mg/mL, most patients will spend six hours or less a year receiving treatment; this new formulation is another step forward in reducing the overall treatment burden; patients will experience comparable safety and efficacy to the original formulation while spending significantly less time per year receiving treatment; that shorter infusion times will make a meaningful difference in patient lives; that this new formulation demonstrates Alexion's continued commitment to innovating for patients and their families; that 100 mg/mL ULTOMIRIS lessens the overall burden on healthcare systems and practitioners with reduced infusion times, and on patients, who will only spend six hours or less a year receiving their treatment; Alexion plans to submit regulatory filings in the U.S. and EU in the third quarter of 2021 for an ULTOMIRIS subcutaneous formulation and device combination for PNH and aHUS that can be self-administered at home; the collective ULTOMIRIS clinical development programs present an opportunity to expand treatment for rare diseases across hematology, nephrology, neurology, and for the treatment of severe COVID-19; and that Alexion has seven Phase 3 programs that are ongoing or have planned clinical trial initiations in 2020. Forward-looking statements are subject to factors that may cause Alexion's results and plans to differ materially from those expected by these forward looking statements, including for example: the anticipated safety profile and the benefits of the ULTOMIRIS 100 mg/ml formulation may not be realized (and the results of the clinical trials may not be indicative of future results); results of clinical trials may not be sufficient to satisfy regulatory authorities; results in clinical trials may not be indicative of results from later stage or larger clinical trials (or in broader patient populations); the possibility that results of clinical trials are not predictive of safety and efficacy and potency of our products (or we fail to adequately operate or manage our clinical trials) which could cause us to discontinue sales of the product (or halt trials, delay or prevent us from making regulatory approval filings or result in denial of approval of our product candidates); the severity of the impact of the COVID-19 pandemic on Alexion's business, including on commercial and clinical development programs; unexpected delays in clinical trials; unexpected concerns regarding products and product candidates that may arise from additional data or analysis obtained during clinical trials or obtained once used by patients following product approval; future product improvements may not be realized due to expense or feasibility or other factors; delays (expected or unexpected) in the time it takes regulatory agencies to review and make determinations on applications for the marketing approval of our products; inability to timely submit (or failure to submit) future applications for regulatory approval for our products and product candidates; inability to timely initiate (or failure to initiate) and complete future clinical trials due to safety issues, IRB decisions, CMC-related issues, expense or unfavorable results from earlier trials (among other reasons); our dependence on sales from our principal product (SOLIRIS); future competition from biosimilars and novel products; decisions of regulatory authorities regarding the adequacy of our research, marketing approval or material limitations on the marketing of our products; delays or failure of product candidates to obtain regulatory approval; delays or the inability to launch product candidates due to regulatory restrictions, anticipated expense or other matters; interruptions or failures in the manufacture and supply of our products and our product candidates; failure to satisfactorily address matters raised by regulatory agencies regarding our products and product candidates; uncertainty of long-term success in developing, licensing or acquiring other product candidates or additional indications for existing products; inability to complete acquisitions or grow the product pipeline through acquisitions (including due to failure to obtain antitrust approvals); the possibility that current rates of adoption of our products are not sustained; the adequacy of our pharmacovigilance and drug safety reporting processes; failure to protect and enforce our data, intellectual property and proprietary rights and the risks and uncertainties relating to intellectual property claims, lawsuits and challenges against us (including intellectual property lawsuits relating to ULTOMIRIS brought by third parties); the risk that third party payors (including governmental agencies) will not reimburse or continue to reimburse for the use of our products at acceptable rates or at all; failure to realize the benefits and potential of investments, collaborations, licenses and acquisitions; the possibility that expected tax benefits will not be realized or that tax liabilities exceed current expectations; potential declines in sovereign credit ratings or sovereign defaults in countries where we sell our products; delay of collection or reduction in reimbursement due to adverse economic conditions or changes in government and private insurer regulations and approaches to reimbursement; adverse impacts on our supply chain, clinical trials, manufacturing operations, financial results, liquidity, hospitals, pharmacies and health care systems from natural disasters and global pandemics, including COVID-19; uncertainties surrounding legal proceedings, company investigations and government investigations; the risk that estimates regarding the number of patients with PNH, aHUS, gMG, NMOSD, HPP and LAL-D and other indications we are pursuing (as well as patients requiring a Factor Xa inhibitor reversal agent) are inaccurate; the risks of changing foreign exchange rates; risks relating to the potential effects of the Company's restructuring; risks related to the acquisitions of Portola Pharmaceuticals, Achillion and other companies and co-development efforts; and a variety of other risks set forth from time to time in Alexion's filings with the SEC, including but not limited to the risks discussed in Alexion's Quarterly Report on Form 10-Q for the period ended September 30, 2020 and in our other filings with the SEC. Alexion disclaims any obligation to update any of these forward-looking statements to reflect events or circumstances after the date hereof, except when a duty arises under law.

    References

    1. Peacock-Young B, Macrae F, Newton J, et al. Haematologica 2018. Volume 103(1):9-1
    2. Yan K, Desai K, Gullapalli L, et al. Epidemiology of Atypical Hemolytic Uremic Syndrome: A Systematic Literature Review. Clin Epidemiol. 2020;12:295-305

    Short ULTOMIRIS SmPC – June 2020

    ULTOMIRIS (ravulizumab) Prescribing Information

    Please refer to the SmPC for further information before prescribing.

    ULTOMIRIS 300 mg concentrate for solution for infusion

    Qualitative and quantitative composition: One vial of 30 mL contains 30 0mg of ravulizumab, produced in Chinese hamster ovary (CHO) cell culture by recombinant DNA technology. After dilution, the final concentration of the solution to be infused is 5 mg/mL. Excipient(s) with known effect: Sodium (5 mmol per vial). Clear to translucent, slight whitish colour, pH 7.0 solution.

    Therapeutic indication: Treatment of adult patients with paroxysmal nocturnal haemoglobinuria (PNH) in patients with haemolysis with clinical symptom(s) indicative of high disease activity and in patients who are clinically stable after having been treated with eculizumab for at least the past 6 months. Treatment of patients with a body weight of 10 kg or above with atypical haemolytic uremic syndrome (aHUS) who are complement inhibitor treatment-naïve or have received eculizumab for at least 3 months and have evidence of response to eculizumab.

    Posology and method of administration. Posology: The recommended dosing regimen consists of a loading dose followed by maintenance dosing, administered by intravenous infusion. The doses to be administered are based on the patient's body weight. For adult patients (≥ 18 years of age), maintenance doses should be administered at a once every 8 week interval, starting 2 weeks after loading dose administration. Dosing schedule is allowed to occasionally vary by ± 7 days of the scheduled infusion day (except for the first maintenance dose of ravulizumab) but the subsequent dose should be administered according to the original schedule. For patients switching from eculizumab to ravulizumab, the loading dose of ravulizumab should be administered 2 weeks after the last eculizumab infusion, and then maintenance doses are administered once every 8 weeks, starting 2 weeks after loading dose administration. Ravulizumab has not been studied in patients with PNH who weigh less than 40 kg. There is no experience of concomitant PE/PI (plasmapheresis or plasma exchange, or fresh frozen plasma infusion) use with ravulizumab. Administration of PE/PI may reduce ravulizumab serum levels. In aHUS, ravulizumab treatment to resolve TMA manifestations should be for a minimum duration of 6 months, beyond which length of treatment needs to be considered for each patient individually. Patients who are at higher risk for TMA recurrence, as determined by the treating healthcare provider (or clinically indicated), may require chronic therapy. Special Populations: Paediatric patients with aHUS with body weight ≥ 40 kg are treated in accordance with the adult dosing recommendations. The weight-based doses and dosing intervals for paediatric patients ≥ 10 kg to 20 kg is once every 4 week interval, for paediatric patients ≥ 20 kg to 40 kg once every 8 weeks, starting 2 weeks after loading dose administration. Data to support safety and efficacy of ravulizumab for patients with body weight below 10 kg are limited. No recommendation on a posology can be made for patients below 10 kg body weight (please refer to the SmPC for currently available data). The safety and efficacy of ravulizumab in children with PNH aged 0 to < 18 years have not been established. No data are available. Method of administration: For intravenous infusion only. ULTOMIRIS must be diluted to a final concentration of 5 mg/mL. This medicinal product must be administered through a 0.2 μm filter and should not be administered as an intravenous push or bolus injection. ULTOMIRIS must be diluted prior to administration by intravenous infusion over a minimal period of 1.7 to 2.4 hours depending of body weight (please refer to the SmPC).

    Contraindications: Hypersensitivity to the active substance or to any of the excipients; in patients with unresolved Neisseria meningitidis infection at treatment initiation; in patients who are not currently vaccinated against Neisseria meningitidis unless they receive prophylactic treatment with appropriate antibiotics until 2 weeks after vaccination. Special warnings and precautions for use. Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Serious meningococcal infection: Due to its mechanism of action, the use of ravulizumab increases the patient's susceptibility to meningococcal infection/sepsis (Neisseria meningitidis). Meningococcal disease due to any serogroup may occur. To reduce this risk of infection, all patients must be vaccinated against meningococcal infections at least two weeks prior to initiating ravulizumab unless the risk of delaying ravulizumab therapy outweighs the risk of developing a meningococcal infection. Patients who initiate ravulizumab treatment less than 2 weeks after receiving a meningococcal vaccine, must receive treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination. Vaccines against serogroups A, C, Y, W135 and B where available, are recommended in preventing the commonly pathogenic meningococcal serogroups. Patients must be vaccinated or revaccinated according to current national guidelines for vaccination use. If the patient is being switched from eculizumab treatment, physicians should verify that meningococcal vaccination is current according to national guidelines for vaccination use. Vaccination may not be sufficient to prevent meningococcal infection. Consideration should be given to official guidance on the appropriate use of antibacterial agents. Cases of serious meningococcal infections/sepsis have been reported in patients treated with ravulizumab. Cases of serious or fatal meningococcal infections/sepsis have been reported in patients treated with other terminal complement inhibitors. All patients should be monitored for early signs of meningococcal infection and sepsis, evaluated immediately if infection is suspected, and treated with appropriate antibiotics. Patients should be informed of these signs and symptoms and steps should be taken to seek medical care immediately. Physicians should provide patients with a patient information brochure and a patient safety card. Immunization: Prior to initiating ravulizumab therapy, it is recommended that PNH and aHUS patients initiate immunizations according to current immunization guidelines. Vaccination may further activate complement. As a result, patients with complement-mediated diseases, including PNH and aHUS, may experience increased signs and symptoms of their underlying disease, such as haemolysis. Therefore, patients should be closely monitored for disease symptoms after recommended vaccination. Patients below the age of 18 years old must be vaccinated against Haemophilus influenzae and pneumococcal infections, and strictly need to adhere to the national vaccination recommendations for each age group. Other systemic infections: Ravulizumab therapy should be administered with caution to patients with active systemic infections. Ravulizumab blocks terminal complement activation; therefore, patients may have increased susceptibility to infections caused by Neisseria species and encapsulated bacteria. Serious infections with Neisseria species (other than Neisseria meningitidis), including disseminated gonococcal infections, have been reported. Patients should be provided with information from the Package Leaflet to increase their awareness of potential serious infections and their signs and symptoms. Physicians should advise patients about gonorrhea prevention. Infusion reactions: Administration of ravulizumab may result in infusion reactions. In clinical trials, with PNH and aHUS [(4 out of 296 in patients with PNH) and (4 of 89 patients with aHUS)] patients experienced infusion reactions which were mild in severity and transient [e.g., lower back pain, drop in blood pressure, elevation in blood pressure, limb discomfort, drug hypersensitivity (allergic reaction), and dysgeusia(bad taste)]. In case of infusion reaction, infusion of ravulizumab should be interrupted and appropriate supportive measures should be instituted if signs of cardiovascular instability or respiratory compromise occur.

    Treatment discontinuation for PNH: If patients with PNH discontinue treatment with ravulizumab, they should be closely monitored for signs and symptoms of serious intravascular haemolysis, identified by elevated LDH (lactate dehydrogenase) levels along with sudden decrease in PNH clone size or haemoglobin, or re-appearance of symptoms such as fatigue, haemoglobinuria, abdominal pain, shortness of breath (dyspnoea), major adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction. Any patient who discontinues ravulizumab should be monitored for at least 16 weeks to detect haemolysis and other reactions. If signs and symptoms of haemolysis occur after discontinuation, including elevated LDH, consider restarting treatment with ravulizumab. Treatment discontinuation for aHUS: There are no specific data on ravulizumab discontinuation. In a long-term prospective observational study, discontinuation of complement C5 inhibitor treatment (eculizumab) resulted in a 13.5-fold higher rate of TMA recurrence and showed a trend toward reduced renal function compared to patients who continued treatment. If patients must discontinue treatment with ravulizumab, they should be monitored closely for signs and symptoms of TMA on an on-going basis. However, monitoring may be insufficient to predict or prevent severe TMA complications. TMA complications post-discontinuation can be identified if any of the following is observed: (i) At least two of the following laboratory results observed concurrently: a decrease in platelet count of 25% or more as compared to either baseline or to peak platelet count during ravulizumab treatment; an increase in serum creatinine of 25% or more as compared to baseline or to nadir during ravulizumab treatment; or, an increase in serum LDH of 25% or more as compared to baseline or to nadir during ravulizumab treatment (results should be confirmed by a second measurement), or (ii) any one of the following symptoms of TMA: a change in mental status or seizures or other extra-renal TMA manifestations including cardiovascular abnormalities, pericarditis, gastrointestinal symptoms/diarrhoea; or thrombosis. If TMA complications occur after ravulizumab discontinuation, consider reinitiation of ravulizumab treatment beginning with the loading dose and maintenance dose. This medicinal product when diluted with sodium chloride 9 mg/mL (0.9 %) solution for injection contains 2.65 g sodium per 720 mL at the maximal dose, equivalent to 133 % of the WHO recommended maximum daily intake of 2 g sodium for an adult. Interaction with other medicinal products and other forms of interaction: No interaction studies have been performed. Chronic intravenous human immunoglobulin (IVIg) treatment may interfere with the endosomal neonatal Fc receptor (FcRn) recycling mechanism of monoclonal antibodies such as ravulizumab and thereby decrease serum ravulizumab concentrations. Fertility, pregnancy and lactation. Women of childbearing potential: Women of childbearing potential should use effective contraception methods during treatment and up to 8 months after treatment. Pregnancy: There are no clinical data from the use of ravulizumab in pregnant women. Nonclinical reproductive toxicology studies were not conducted with ravulizumab. Reproductive toxicology studies were conducted in mice using the murine surrogate molecule BB5.1, which assessed effect of C5 blockade on the reproductive system. No specific test-article related reproductive toxicities were identified in these studies. Human IgG are known to cross the human placental barrier, and thus ravulizumab may potentially cause terminal complement inhibition in the foetal circulation. Animal studies are insufficient with respect to reproductive toxicity. In pregnant women the use of ravulizumab may be considered following an assessment of the risks and benefits. Breast-feeding: It is unknown whether ravulizumab is excreted into human milk. Nonclinical reproductive toxicology studies conducted in mice with the murine surrogate molecule BB5.1 identified no adverse effect to pups resulting from consuming milk from treated dams. A risk to infants cannot be excluded. Since many medicinal products and immunoglobulins are secreted into human milk, and because of the potential for serious adverse reactions in nursing infants, breast-feeding should be discontinued during treatment with ravulizumab and up to 8 months after treatment. Fertility: No specific non-clinical study on fertility has been conducted with ravulizumab. Nonclinical reproductive toxicology studies conducted in mice with a murine surrogate molecule (BB5.1) identified no adverse effect on fertility of the treated females or males.

    Undesirable effects. Summary of the safety profile: The most common adverse drug reactions (very common frequency) are diarrhea, nausea, vomiting, nasopharyngitis and headache. The most serious adverse reactions in patients in clinical trials are meningococcal infection and meningococcal sepsis. Tabulated list of adverse reactions: Very common adverse reactions observed from PNH and aHUS clinical trials (≥1/10): Upper respiratory tract infection, Nasopharyngitis, Headache, Diarrhoea, Nausea, Pyrexia, Fatigue. Common adverse reactions (≥1/100 to <1/10): Dizziness, Abdominal pain, Vomiting, Dyspepsia, Rash, Pruritus, Arthralgia, Back pain, Myalgia, Muscle spasms, Influenza like illness, Asthenia. Uncommon adverse reactions (≥1/1,000 to <1/100): Meningococcal infection, Chills. In paediatric patients with evidence of aHUS (aged 10 months to less than 18 years) included in the clinical study, the safety profile of ravulizumab appeared similar to that observed in adult patients with evidence of aHUS. The safety profiles in the different paediatric subsets of age appear similar. The safety data for patient below 2 years of age is limited to four patients. The most common adverse reaction reported in paediatric patients was pyrexia. The safety of ravulizumab in children with PNH aged 0 to < 18 years have not been established. No data are available.

    Storage: 2°C – 8°C. Marketing Authorization Holder: Alexion Europe SAS, 1-15, 103-105 rue Anatole France, 92300 Levallois-Perret, FRANCE.

    Marketing Authorisation Number: EU/1/19/1371/001. Date of First Authorisation: {02 July 2019}. Date of revision: {25 June 2020}. Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMA) http://www.ema.europa.eu/.

    View Full Article Hide Full Article
View All Alexion Pharmaceuticals Inc. News