ALNY Alnylam Pharmaceuticals Inc.

Upcoming Catalysts

Drug Pipeline

Latest News

1. 29 July 2021 Alnylam and PeptiDream Enter into Collaboration Agreement to Discover and Develop Peptide-siRNA Conjugates for Targeted Delivery of RNAi Therapeutics to a Broader Range of Extrahepatic Tissues

   − Agreement Combines PeptiDream's Peptide Discovery Platform to Identify High Affinity Peptide Ligands with Alnylam's Expertise in siRNA-Conjugate-Based Delivery and in Developing and Commercializing RNAi Therapeutics −

   Alnylam Pharmaceuticals, Inc. (NASDAQ:ALNY), the leading RNAi therapeutics company, and PeptiDream, Inc. (Tokyo Stock Exchange: 4587), the leading peptide-based drug discovery company with its proprietary Peptide Discovery Platform System (PDPS), announced today a license and collaboration agreement to discover and develop peptide-siRNA conjugates to create multiple opportunities to deliver RNAi therapeutics to tissues outside the liver. Through this collaboration, the companies will collaborate to select and optimize peptides…

   − Agreement Combines PeptiDream's Peptide Discovery Platform to Identify High Affinity Peptide Ligands with Alnylam's Expertise in siRNA-Conjugate-Based Delivery and in Developing and Commercializing RNAi Therapeutics −

   Alnylam Pharmaceuticals, Inc. (NASDAQ:ALNY), the leading RNAi therapeutics company, and PeptiDream, Inc. (Tokyo Stock Exchange: 4587), the leading peptide-based drug discovery company with its proprietary Peptide Discovery Platform System (PDPS), announced today a license and collaboration agreement to discover and develop peptide-siRNA conjugates to create multiple opportunities to deliver RNAi therapeutics to tissues outside the liver. Through this collaboration, the companies will collaborate to select and optimize peptides for targeted delivery of small interfering RNA (siRNA) molecules to a wide range of cell types and tissues via specific interactions with receptors expressed on the target cells.

   Under the terms of the alliance, Alnylam will select a set of receptors for PeptiDream's peptide discovery platform. PeptiDream will select, optimize, and synthesize peptides for each receptor. Alnylam will then generate peptide-siRNA conjugates and perform in vitro and in vivo studies to support final peptide selection. The collaboration has the potential to yield multiple treatment opportunities by targeting disease causing mRNA transcripts in a wide variety of tissue types.

   "Having solved delivery of RNAi therapeutics to the liver and made substantial preclinical progress on in vivo delivery to the CNS, eye, and lung, we are now adding to our suite of delivery technologies that have the potential to enable efficient delivery of siRNA to even broader tissue types throughout the human body," said Kevin Fitzgerald, Ph.D., Chief Scientific Officer of Alnylam. "We are excited to enter into this collaborative research agreement with PeptiDream, an industry leader in the discovery and optimization of peptide ligands against a wide variety of receptors. Through this collaboration, we hope to identify robust ligand-receptor pairs for extrahepatic tissue delivery, similar to the GalNAc-ASGPR pair that we have pioneered for effective liver delivery."

   "We look forward to partnering with Alnylam to leverage our PDPS technology and peptide discovery capabilities to identify novel ligands against Alnylam selected target receptors that can facilitate delivery of drug payloads to a broad range of extrahepatic tissues," said Patrick C. Reid Ph.D., President and Representative Director of PeptiDream. "This deal further expands on our strategy of using peptides to deliver a variety of therapeutic payloads (as peptide drug-conjugates) to disease cells/tissues in a targeted fashion. We hope this partnership will enable the creation of innovative peptide-siRNA conjugates in a variety of diseases and unlock many new therapeutic opportunities."

   Under the terms of the agreement, PeptiDream will receive an upfront payment from Alnylam as well as R&D funding over the term of the research collaboration, as provided in the agreement. PeptiDream may also receive payments based on the achievement of specified development, regulatory, and commercial milestones potentially totaling up to $2.2 billion (¥244 billion^*1). In addition, PeptiDream is eligible to receive low-to-mid single digit royalties on sales on any such　Alnylam products.

   *1: USD/ JPY currency conversion rate: 110.9

   About RNAi

   RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines, known as RNAi therapeutics, is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, function upstream of today's medicines by potently silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.

   About Alnylam Pharmaceuticals

   Alnylam (NASDAQ:ALNY) is leading the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare genetic, cardio-metabolic, hepatic infectious, and central nervous system (CNS)/ocular diseases. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach for the treatment of a wide range of severe and debilitating diseases. Founded in 2002, Alnylam is delivering on a bold vision to turn scientific possibility into reality, with a robust RNAi therapeutics platform. Alnylam's commercial RNAi therapeutic products are ONPATTRO® (patisiran), GIVLAARI® (givosiran), OXLUMO® (lumasiran), and Leqvio® (inclisiran) being developed and commercialized by Alnylam's partner, Novartis. Alnylam has a deep pipeline of investigational medicines, including six product candidates that are in late-stage development. Alnylam is executing on its "Alnylam P⁵x25" strategy to deliver transformative medicines in both rare and common diseases benefiting patients around the world through sustainable innovation and exceptional financial performance, resulting in a leading biotech profile. Alnylam is headquartered in Cambridge, MA. For more information about our people, science and pipeline, please visit www.alnylam.com and engage with us on Twitter at @Alnylam, on LinkedIn, or on Instagram.

   About PeptiDream, Inc.

   PeptiDream Inc. is a public (TSE: 4587) biopharmaceutical company founded in 2006 employing its proprietary Peptide Discovery Platform System (PDPS), a state-of-the-art highly versatile discovery platform which enables the production of highly diverse (trillions) non-standard peptide libraries with high efficiency, for the identification of highly potent and selective hit candidates, which then can be developed into peptide-based, small molecule-based or peptide-drug conjugate therapeutics. PeptiDream aspires to be a world leader in drug discovery and development to address unmet medical needs and improve the quality of life of patients worldwide. For further information, please visit https://www.peptidream.com.

   Alnylam Forward Looking Statements

   Various statements in this release concerning Alnylam's expectations, plans, aspirations, and goals, including those related to the license and collaboration agreement with PeptiDream and the opportunity to discover and develop robust peptide-siRNA conjugates to create multiple opportunities to deliver RNAi therapeutics to a wide variety of tissue types outside the liver, the potential for payment of milestones and royalties to PeptiDream in the future, and the planned achievement of our "Alnylam P⁵x25" strategy, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation: the direct or indirect impact of the COVID-19 global pandemic or any future pandemic on Alnylam's business, results of operations and financial condition and the effectiveness or timeliness of Alnylam's efforts to mitigate the impact of the pandemic; Alnylam's ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for its product candidates; actions or advice of regulatory agencies and Alnylam's ability to obtain and maintain regulatory approval for its product candidates, as well as favorable pricing and reimbursement; successfully launching, marketing and selling its approved products globally; delays, interruptions or failures in the manufacture and supply of its product candidates or its marketed products; obtaining, maintaining and protecting intellectual property; Alnylam's ability to successfully expand the indication for ONPATTRO (or vutrisiran, if approved) in the future; Alnylam's ability to manage its growth and operating expenses through disciplined investment in operations and its ability to achieve a self-sustainable financial profile in the future without the need for future equity financing; Alnylam's ability to maintain strategic business collaborations; Alnylam's dependence on third parties for the development and commercialization of certain products, including Novartis, Regeneron and Vir; the outcome of litigation; the risk of government investigations; and unexpected expenditures; as well as those risks more fully discussed in the "Risk Factors" filed with Alnylam's most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) and in its other SEC filings. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.

   

   View source version on businesswire.com: https://www.businesswire.com/news/home/20210729006108/en/

   View Full Article Hide Full Article
2. 29 July 2021 Alnylam Reports Positive Topline Results from ILLUMINATE-C Phase 3 Study of Lumasiran in Patients with Advanced Primary Hyperoxaluria Type 1

   - Results Showed Substantial Reductions in Plasma Oxalate Relative to Baseline in PH1 Patients with Severe Renal Impairment, Including Those on Dialysis, and an Encouraging Safety and Tolerability Profile -

   - Alnylam Intends to File Supplemental Regulatory Applications with the U.S. Food and Drug Administration and the European Medicines Agency Based on ILLUMINATE-C Results in Late 2021 -

   Alnylam Pharmaceuticals, Inc. (NASDAQ:ALNY), the leading RNAi therapeutics company, announced today positive topline results from the ILLUMINATE-C Phase 3 open-label study of lumasiran in patients of all ages with advanced primary hyperoxaluria type 1 (PH1) associated with progressive decline in renal function. Lumasiran is an RNAi therapeutic targeting…

   - Results Showed Substantial Reductions in Plasma Oxalate Relative to Baseline in PH1 Patients with Severe Renal Impairment, Including Those on Dialysis, and an Encouraging Safety and Tolerability Profile -

   - Alnylam Intends to File Supplemental Regulatory Applications with the U.S. Food and Drug Administration and the European Medicines Agency Based on ILLUMINATE-C Results in Late 2021 -

   Alnylam Pharmaceuticals, Inc. (NASDAQ:ALNY), the leading RNAi therapeutics company, announced today positive topline results from the ILLUMINATE-C Phase 3 open-label study of lumasiran in patients of all ages with advanced primary hyperoxaluria type 1 (PH1) associated with progressive decline in renal function. Lumasiran is an RNAi therapeutic targeting hydroxyacid oxidase 1 (HAO1) – the gene encoding glycolate oxidase (GO) – that is being investigated for the treatment of adult and pediatric patients with advanced PH1. Results of the primary analysis at six months demonstrated substantial reduction in plasma oxalate from baseline in patients (N=21) with advanced disease, including those on hemodialysis. Elevated plasma oxalate is directly related to the pathophysiology of oxalosis and results in systemic deposition of oxalate in extra-renal tissues, potentially leading to bone fractures, cardiomyopathy, impaired erythropoiesis, vision loss, skin ulcers, and other serious manifestations¹. The safety and tolerability profile of lumasiran following six months of treatment is encouraging across all ages, with no drug related serious adverse events (SAEs) and injection site reactions (ISRs) as the most common adverse event (AE).

   "People with advanced PH1 suffer from severely impaired kidney function and may require an intensive dialysis regimen as a bridge to receiving a combined liver/kidney transplant – a procedure associated with high morbidity and lifelong immunosuppression. In ILLUMINATE-C, lumasiran reduced elevated levels of plasma oxalate that can lead to the morbidity and mortality associated with systemic oxalosis in this particularly vulnerable patient population," said Jeroen Valkenburg, General Manager, Lumasiran program at Alnylam. "Through the ILLUMINATE clinical program, we are hoping to establish that lumasiran may be a therapeutic option for PH1 patients regardless of age or disease severity, including patients on hemodialysis. We look forward to reporting complete data from the ILLUMINATE-C study at a medical congress later this year."

   "Patients with PH1 face devastating health challenges, especially those approaching or experiencing kidney failure, and these new results from the ILLUMINATE clinical development program signal hope to some of the sickest and most severely impacted individuals in this patient community," said Kim Hollander, Executive Director of the Oxalosis and Hyperoxaluria Foundation. "We're thankful that Alnylam continues to drive forth research that may benefit the PH1 community and for conducting a study that has the potential to help those who have the most severe form of the disease."

   Results

   ILLUMINATE-C (NCT04152200) is a single arm, open-label, multinational Phase 3 study evaluating the safety and efficacy of lumasiran in PH1 patients of all ages with severe renal impairment (eGFR ≤ 45 mL/min/1.73m² or elevated serum creatinine for patients <12 months of age), and conducted at 13 study sites across 10 countries around the world. Cohort A enrolled six patients with advanced PH1 who do not yet require dialysis, and Cohort B enrolled 15 patients who are hemodialysis-dependent. The dosing regimen is based on weight with three monthly starting doses followed by ongoing monthly or quarterly doses. The primary efficacy endpoint for Cohort A was the percent change in plasma oxalate from baseline to month six, and the primary endpoint for Cohort B was the percent change in pre-dialysis plasma oxalate from baseline to month six. Key secondary endpoints are designed to evaluate additional measures of plasma oxalate and changes in urinary oxalate. Renal function, frequency and mode of dialysis, frequency of renal stone events, and measures of systemic oxalosis, including clinical manifestations, will also be evaluated in the extension period of the study.

   At six months, treatment with lumasiran resulted in a substantial reduction in plasma oxalate from baseline in both dialysis-independent and -dependent patients. Lumasiran also demonstrated positive results across key secondary endpoints, including measures of urinary oxalate (for patients in Cohort A) and additional measures of plasma oxalate. There were no deaths and no drug related SAEs among enrolled patients. There were two treatment discontinuations due to adverse events in the extension period of the study, neither of which was drug related. The most common drug related AEs (occurring in 10 percent or more of patients) were ISRs reported in five patients (23.8 percent), all of which were mild.

   Based on these results, the Company plans to submit a Supplemental New Drug Application (sNDA) for lumasiran with the U.S. Food and Drug Administration (FDA) and a Type II Variation with the European Medicines Agency (EMA) in late 2021. In November 2020, lumasiran was approved by the FDA for the treatment of PH1 to lower urinary oxalate levels in pediatric and adult patients and by the EMA for the treatment of PH1 in all age groups. Lumasiran is marketed in the U.S. and EU as OXLUMO^®. ILLUMINATE-C topline results will be discussed during Alnylam's Second Quarter Earnings Conference Call on August 3rd at 8:30 am ET, and full results are expected to be presented at a medical meeting later this year.

   About Lumasiran

   Lumasiran is a subcutaneously administered RNAi therapeutic targeting hydroxyacid oxidase 1 (HAO1) in development for the treatment of primary hyperoxaluria type 1 (PH1). HAO1 encodes glycolate oxidase (GO). Thus, by silencing HAO1 and depleting the GO enzyme, lumasiran inhibits production of oxalate – the metabolite that directly contributes to the pathophysiology of PH1. Lumasiran utilizes Alnylam's Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate technology, which enables subcutaneous dosing with increased potency and durability and a wide therapeutic index. Lumasiran has received regulatory approvals from the U.S. Food and Drug Administration (FDA) for the treatment of PH1 to lower urinary oxalate levels in pediatric and adult patients and from the European Medicines Agency (EMA) for the treatment of PH1 in all age groups under the brand name OXLUMO^®.

   IMPORTANT SAFETY INFORMATION for OXLUMO (lumasiran)

   Adverse Reactions

   The most common adverse reaction that occurred in patients treated with OXLUMO was injection site reaction (38%). Symptoms included erythema, pain, pruritus, and swelling.

   Pregnancy and Lactation

   No data are available on the use of OXLUMO in pregnant women. No data are available on the presence of OXLUMO in human milk or its effects on breastfed infants or milk production. Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for OXLUMO and any potential adverse effects on the breastfed child from OXLUMO or the underlying maternal condition.

   For additional information about OXLUMO, please see the full Prescribing Information.

   About Primary Hyperoxaluria Type 1 (PH1)

   PH1 is an ultra-rare genetic disease that affects an estimated one to three individuals per million in the United States and Europe. PH1 is characterized by oxalate overproduction in the liver. The excess oxalate results in the deposition of calcium oxalate crystals in the kidneys and urinary tract and can lead to the formation of painful and recurrent kidney stones and nephrocalcinosis. Renal damage is caused by a combination of tubular toxicity from oxalate, calcium oxalate deposition in the kidneys, and urinary obstruction by calcium oxalate stones. PH1 is associated with a progressive decline in kidney function, which exacerbates the disease as the excess oxalate can no longer be effectively excreted, resulting in subsequent accumulation and deposition of oxalate in bones, eyes, skin, and heart, leading to severe illness and death.

   About RNAi

   RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines, known as RNAi therapeutics, is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, function upstream of today's medicines by potently silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing or disease pathway proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.

   About Alnylam Pharmaceuticals

   Alnylam (NASDAQ:ALNY) is leading the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare genetic, cardio-metabolic, hepatic infectious, and central nervous system (CNS)/ocular diseases. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach for the treatment of a wide range of severe and debilitating diseases. Founded in 2002, Alnylam is delivering on a bold vision to turn scientific possibility into reality, with a robust RNAi therapeutics platform. Alnylam's commercial RNAi therapeutic products are ONPATTRO^® (patisiran), GIVLAARI^® (givosiran), OXLUMO^® (lumasiran), and Leqvio^® (inclisiran) being developed and commercialized by Alnylam's partner Novartis. Alnylam has a deep pipeline of investigational medicines, including six product candidates that are in late-stage development. Alnylam is executing on its "Alnylam P⁵x25" strategy to deliver transformative medicines in both rare and common diseases benefiting patients around the world through sustainable innovation and exceptional financial performance, resulting in a leading biotech profile. Alnylam is headquartered in Cambridge, MA. For more information about our people, science and pipeline, please visit www.alnylam.com and engage with us on Twitter at @Alnylam, on LinkedIn, or on Instagram.

   Alnylam Forward Looking Statements

   Various statements in this release concerning Alnylam's future expectations, plans and prospects, including, without limitation, Alnylam's views with respect to the safety and efficacy of lumasiran as demonstrated in the ILLUMINATE-C Phase 3 study and the potential for lumasiran to be a therapeutic option for PH1 regardless of age or disease severity, including for patients on hemodialysis, expectations regarding the timing of the presentation of full results from the ILLUMINATE-C Phase 3 study, and the timing and planned filing of supplemental applications with FDA and EMA based on the ILLUMINATE-C results, and Alnylam's aspiration to become a leading biotech company, and the planned achievement of its "Alnylam P⁵x25" strategy, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation: the direct or indirect impact of the COVID-19 global pandemic or any future pandemic on Alnylam's business, results of operations and financial condition and the effectiveness or timeliness of Alnylam's efforts to mitigate the impact of the pandemic; Alnylam's ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for its product candidates; actions or advice of regulatory agencies and Alnylam's ability to obtain and maintain regulatory approval for its product candidates, as well as favorable pricing and reimbursement; successfully launching, marketing and selling its approved products globally; delays, interruptions or failures in the manufacture and supply of its product candidates or its marketed products; obtaining, maintaining and protecting intellectual property; Alnylam's ability to successfully expand the indication for ONPATTRO in the future; Alnylam's ability to manage its growth and operating expenses through disciplined investment in operations and its ability to achieve a self-sustainable financial profile in the future without the need for future equity financing; Alnylam's ability to maintain strategic business collaborations; Alnylam's dependence on third parties for the development and commercialization of certain products, including Novartis, Sanofi, Regeneron and Vir; the outcome of litigation; the potential impact of current and the risk of future government investigations; and unexpected expenditures; as well as those risks more fully discussed in the "Risk Factors" filed with Alnylam's most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) and in its other SEC filings. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.

   This release discusses the use of a previously approved RNAi therapeutic in continued development and is not intended to convey conclusions about efficacy or safety as to these uses. There is no guarantee that the data described in this release will result in expanded use of this commercial product, will successfully complete clinical development or will gain health authority approval.

   Footnote:
   
   ¹ Milliner et al., End Points for Clinical Trials in Primary Hyperoxaluria. Clin J Am Soc Nephrol. 2020; 15(7):1056-1065.

   

   View source version on businesswire.com: https://www.businesswire.com/news/home/20210729005079/en/

   View Full Article Hide Full Article
3. 21 July 2021 Alnylam to Webcast Conference Call Discussing Second Quarter 2021 Financial Results

   Alnylam Pharmaceuticals, Inc. (NASDAQ:ALNY), the leading RNAi therapeutics company, announced today that it will report financial results for the second quarter ending June 30, 2021 on Tuesday, August 3, 2021, before the U.S. financial markets open.

   Management will provide an update on the Company and discuss second quarter 2021 results as well as expectations for the future via conference call on Tuesday, August 3, 2021 at 8:30 am ET. To access the call, please dial 877-312-7507 (domestic) or +1-631-813-4828 (international) five minutes prior to the start time and refer to conference ID 8870516. A replay of the call will be available beginning at 11:30 am ET on the day of the call. To access the replay, please dial 855-859-2056 (domestic…

   Alnylam Pharmaceuticals, Inc. (NASDAQ:ALNY), the leading RNAi therapeutics company, announced today that it will report financial results for the second quarter ending June 30, 2021 on Tuesday, August 3, 2021, before the U.S. financial markets open.

   Management will provide an update on the Company and discuss second quarter 2021 results as well as expectations for the future via conference call on Tuesday, August 3, 2021 at 8:30 am ET. To access the call, please dial 877-312-7507 (domestic) or +1-631-813-4828 (international) five minutes prior to the start time and refer to conference ID 8870516. A replay of the call will be available beginning at 11:30 am ET on the day of the call. To access the replay, please dial 855-859-2056 (domestic) or +1-404-537-3406 (international) and refer to conference ID 8870516.

   A live audio webcast of the call will be available on the Investors section of the Company's website at www.alnylam.com/events. An archived webcast will be available on the Alnylam website approximately two hours after the event.

   About Alnylam Pharmaceuticals

   Alnylam (NASDAQ:ALNY) is leading the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare genetic, cardio-metabolic, hepatic infectious, and central nervous system (CNS)/ocular diseases. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach for the treatment of a wide range of severe and debilitating diseases. Founded in 2002, Alnylam is delivering on a bold vision to turn scientific possibility into reality, with a robust RNAi therapeutics platform. Alnylam's commercial RNAi therapeutic products are ONPATTRO^® (patisiran), GIVLAARI^® (givosiran), OXLUMO^® (lumasiran), and Leqvio^® (inclisiran) being developed and commercialized by Alnylam's partner Novartis. Alnylam has a deep pipeline of investigational medicines, including six product candidates that are in late-stage development. Alnylam is executing on its "Alnylam P⁵x25" strategy to deliver transformative medicines in both rare and common diseases benefiting patients around the world through sustainable innovation and exceptional financial performance, resulting in a leading biotech profile. Alnylam is headquartered in Cambridge, MA. For more information about our people, science and pipeline, please visit www.alnylam.com and engage with us on Twitter at @Alnylam, on LinkedIn, or on Instagram.

   

   View source version on businesswire.com: https://www.businesswire.com/news/home/20210721005191/en/

   View Full Article Hide Full Article
4. 30 June 2021 Alnylam Initiates KARDIA-1 Phase 2 Study of Zilebesiran (ALN-AGT) in Patients with Mild-to-Moderate Hypertension

   – KARDIA-1 will Evaluate Efficacy and Safety of Quarterly and Biannual Regimens of Zilebesiran as Monotherapy –

   Alnylam Pharmaceuticals, Inc. (NASDAQ:ALNY), the leading RNAi therapeutics company, today announced initiation of KARDIA-1, a global Phase 2 study evaluating the efficacy and safety of zilebesiran (pronounced "zile-BEE-siran" and formerly known as ALN-AGT), an investigational subcutaneous RNAi therapeutic targeting liver-expressed angiotensinogen (AGT) in development for the treatment of hypertension. KARDIA-1 will evaluate zilebesiran as monotherapy across different doses administered quarterly and biannually. The Company will host an "RNAi Roundtable" webinar today at 10:00 a.m. ET to discuss the zilebesiran program.

   The primary…

   – KARDIA-1 will Evaluate Efficacy and Safety of Quarterly and Biannual Regimens of Zilebesiran as Monotherapy –

   Alnylam Pharmaceuticals, Inc. (NASDAQ:ALNY), the leading RNAi therapeutics company, today announced initiation of KARDIA-1, a global Phase 2 study evaluating the efficacy and safety of zilebesiran (pronounced "zile-BEE-siran" and formerly known as ALN-AGT), an investigational subcutaneous RNAi therapeutic targeting liver-expressed angiotensinogen (AGT) in development for the treatment of hypertension. KARDIA-1 will evaluate zilebesiran as monotherapy across different doses administered quarterly and biannually. The Company will host an "RNAi Roundtable" webinar today at 10:00 a.m. ET to discuss the zilebesiran program.

   The primary endpoint of KARDIA-1 is the change from baseline in systolic blood pressure as measured by 24-hour ambulatory blood pressure monitoring after three months of treatment. Additional endpoints will include change from baseline in blood pressure at six months, time-averaged reduction of blood pressure as a measure of tonic control, and safety. The study initiation is based on encouraging Phase 1 data, including results presented earlier this year at the 2021 Joint Meeting of the European Society of Hypertension (ESH) and the International Society of Hypertension (ISH). KARDIA-1 has been activated at clinical sites in the U.S. and will also be conducted at sites in Europe.

   "According to the World Health Organization, hypertension is the largest modifiable risk factor for cardiovascular morbidity and mortality. Despite the availability of numerous anti-hypertensive medications, tonic control of blood pressure remains elusive and represents a major unmet need, elevating the risk of fatal and nonfatal cardiovascular events, primarily stroke and heart attack. In addition, lack of patient adherence to therapy with daily oral medications further contributes to the challenges of inadequate blood pressure control," said Weinong Guo, M.D., Ph.D., Senior Vice President of Clinical Development at Alnylam. "The initiation of KARDIA-1, along with the planned start of the KARDIA-2 Phase 2 study later this year, signifies Alnylam's commitment to advance zilebesiran as a potential treatment to help address the worldwide burden of uncontrolled hypertension."

   Additional details about the RNAi Roundtable can be found on the Capella section of the Company's website here.

   About KARDIA-1 Phase 2 Study

   The KARDIA-1 Phase 2 trial is a randomized, double-blind (DB), placebo-controlled, dose-ranging study to evaluate the efficacy and safety of zilebesiran as monotherapy in adults with mild-to-moderate hypertension. This global, multicenter trial will enroll approximately 375 adults with untreated hypertension or who are on stable therapy with one or more anti-hypertensive medications. Any patients taking prior anti-hypertensive medications will complete at least a four-week wash-out before randomization. Study participants will be randomized to one of five treatment arms during a 12-month DB period and DB extension period: 1) 150 mg zilebesiran subcutaneously once every six months; 2) 300 mg zilebesiran subcutaneously once every six months; 3) 300 mg zilebesiran subcutaneously once every three months; 4) 600 mg zilebesiran subcutaneously once every six months; or 5) placebo. Patients who receive placebo will be randomized to one of the four initial zilebesiran dose regimens beginning at month six. The study's primary efficacy endpoint is the change from baseline in systolic blood pressure, assessed by 24-hour ambulatory blood pressure monitoring, after three months of treatment. In addition to the evaluation of the safety of zilebesiran, key secondary and exploratory endpoints in this study include additional measures of blood pressure reduction at six months, time-adjusted change in blood pressure, and change in daytime average and night-time average blood pressure. For more information on KARDIA-1 (NCT04936035), please visit clinicaltrials.gov, email or call 877-256-9526 in North America and +31 20 369 7861 in Europe.

   About Zilebesiran

   Formerly known as ALN-AGT, zilebesiran (pronounced "zile-BEE-siran") is an investigational, subcutaneously administered RNAi therapeutic targeting angiotensinogen (AGT) in development for the treatment of hypertension in high unmet need populations. AGT is the most upstream precursor in the Renin-Angiotensin-Aldosterone System (RAAS), a cascade which has a demonstrated role in blood pressure regulation and its inhibition has well-established anti-hypertensive effects. Zilebesiran inhibits the synthesis of AGT in the liver, potentially leading to durable reductions in AGT protein and ultimately, in the vasoconstrictor angiotensin (Ang) II. Zilebesiran utilizes Alnylam's Enhanced Stabilization Chemistry Plus (ESC+) GalNAc-conjugate technology, which enables subcutaneous dosing with increased selectivity and a wide therapeutic index. The safety and efficacy of zilebesiran have not been established or evaluated by the FDA, EMA or any other health authority.

   About Hypertension

   Hypertension is a complex multifactorial disease clinically defined by most major guidelines as a systolic blood pressure (SBP) of above 140 mm Hg and/or a diastolic blood pressure (DBP) greater than 90 mm Hg, though AHA/ACC guidelines have a lower threshold of a SBP above 130 mm Hg and/or a DBP greater than 80 mm Hg. More than one billion people worldwide live with hypertension.ⁱ In the U.S. alone, approximately 47 percent of adults live with hypertension, with more than half of patients on medication remaining above the blood pressure target level. Despite the availability of anti-hypertensive medications, there remains a significant unmet medical need, especially given the poor rates of adherence to existing daily oral medications and daily peak and trough effects, resulting in inconsistent blood pressure control and an increased risk for stroke, heart attack and premature death.ⁱⁱ In particular, there are a number of high unmet need settings where novel approaches to hypertension warrant additional development focus, including patients with poor medication adherence, difficult-to-treat and resistant hypertension, and in patients with high cardiovascular risk.

   About RNAi

   RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines, known as RNAi therapeutics, is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, function upstream of today's medicines by potently silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.

   About Alnylam Pharmaceuticals

   Alnylam (NASDAQ:ALNY) is leading the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare genetic, cardio-metabolic, hepatic infectious, and central nervous system (CNS)/ocular diseases. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach for the treatment of a wide range of severe and debilitating diseases. Founded in 2002, Alnylam is delivering on a bold vision to turn scientific possibility into reality, with a robust RNAi therapeutics platform. Alnylam's commercial RNAi therapeutic products are ONPATTRO® (patisiran), GIVLAARI® (givosiran), OXLUMO® (lumasiran), and Leqvio® (inclisiran) being developed and commercialized by Alnylam's partner Novartis. Alnylam has a deep pipeline of investigational medicines, including six product candidates that are in late-stage development. Alnylam is executing on its "Alnylam P⁵x25" strategy to deliver transformative medicines in both rare and common diseases benefiting patients around the world through sustainable innovation and exceptional financial performance, resulting in a leading biotech profile. Alnylam is headquartered in Cambridge, MA. For more information about our people, science and pipeline, please visit www.alnylam.com and engage with us on Twitter at @Alnylam, on LinkedIn, or on Instagram.

   Alnylam Forward Looking Statements

   Various statements in this release concerning Alnylam's expectations, plans, aspirations, and goals, including those related to encouraging results from our Phase 1 study of zilebesiran (formerly known as ALN-AGT), the design and conduct of our KARDIA-1 Phase 2 study of zilebesiran and the planned activation of the study at sites in Europe following U.S. initiation, our commitment to advancing zilebesiran as a potential [treatment to help] address the worldwide burden of uncontrolled hypertension, our aspiration to become a leading biotech company, and the planned achievement of our "Alnylam P⁵x25" strategy, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation: the direct or indirect impact of the COVID-19 global pandemic or any future pandemic on Alnylam's business, results of operations and financial condition and the effectiveness or timeliness of Alnylam's efforts to mitigate the impact of the pandemic; Alnylam's ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for its product candidates; actions or advice of regulatory agencies and Alnylam's ability to obtain and maintain regulatory approval for its product candidates, as well as favorable pricing and reimbursement; successfully launching, marketing and selling its approved products globally; delays, interruptions or failures in the manufacture and supply of its product candidates or its marketed products; obtaining, maintaining and protecting intellectual property; Alnylam's ability to successfully expand the indication for ONPATTRO (or vutrisiran, if approved) in the future; Alnylam's ability to manage its growth and operating expenses through disciplined investment in operations and its ability to achieve a self-sustainable financial profile in the future without the need for future equity financing; Alnylam's ability to maintain strategic business collaborations; Alnylam's dependence on third parties for the development and commercialization of certain products, including Novartis, Regeneron and Vir; the outcome of litigation; the risk of government investigations; and unexpected expenditures; as well as those risks more fully discussed in the "Risk Factors" filed with Alnylam's most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) and in its other SEC filings. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.

   This release is not intended to convey conclusions about efficacy or safety as to any investigational uses or dosing regimens of any investigational RNAi therapeutics. There is no guarantee that any investigational therapeutics or dosing regimens for such therapeutics will successfully complete clinical development or gain health authority approval.

   __________________________________
   
   ⁱ Hypertension. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/hypertension. Published September 2019. Accessed June 2021.
   
   ⁱⁱ Carey, R. M., Muntner, P., Bosworth, H. B., & Whelton, P. K. (2018). Prevention and Control of Hypertension: JACC Health Promotion Series. Journal of the American College of Cardiology, 72(11), 1278–1293. https://doi.org/10.1016/j.jacc.2018.07.008

   

   View source version on businesswire.com: https://www.businesswire.com/news/home/20210630005138/en/

   View Full Article Hide Full Article
5. 24 June 2021 Alnylam Announces U.S. Food and Drug Administration Acceptance of New Drug Application for Investigational Vutrisiran for the Treatment of the Polyneuropathy of Hereditary ATTR Amyloidosis

   – PDUFA Date Set for April 14, 2022 –

   Alnylam Pharmaceuticals, Inc. (NASDAQ:ALNY), the leading RNAi therapeutics company, announced today that the U.S. Food and Drug Administration (FDA) has accepted the Company's New Drug Application (NDA) for vutrisiran, an investigational RNAi therapeutic for the treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults. The FDA has set an action date of April 14, 2022 under the Prescription Drug User Fee Act (PDUFA), and the Agency has indicated that they are not currently planning an advisory committee meeting as part of the NDA review.

   "We are excited that the FDA has accepted our NDA for vutrisiran, which was based on 9-month results from the HELIOS-A study…

   – PDUFA Date Set for April 14, 2022 –

   Alnylam Pharmaceuticals, Inc. (NASDAQ:ALNY), the leading RNAi therapeutics company, announced today that the U.S. Food and Drug Administration (FDA) has accepted the Company's New Drug Application (NDA) for vutrisiran, an investigational RNAi therapeutic for the treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults. The FDA has set an action date of April 14, 2022 under the Prescription Drug User Fee Act (PDUFA), and the Agency has indicated that they are not currently planning an advisory committee meeting as part of the NDA review.

   "We are excited that the FDA has accepted our NDA for vutrisiran, which was based on 9-month results from the HELIOS-A study. Today's announcement marks another important milestone as we work to make vutrisiran available to hATTR amyloidosis patients with polyneuropathy," said Rena Denoncourt, Vice President, TTR Franchise Lead. "If approved, once-quarterly, subcutaneously administered vutrisiran may represent a new treatment option that potentially reverses polyneuropathy manifestations of disease."

   Vutrisiran has been granted Orphan Drug Designation in the U.S. and the European Union (EU) for the treatment of ATTR amyloidosis. Vutrisiran has also been granted a Fast-Track designation in the U.S. for the treatment of the polyneuropathy of hATTR amyloidosis in adults. The Company plans to also submit regulatory filings in the EU, Brazil, and Japan in 2021 based on the HELIOS-A results.

   About Vutrisiran

   Vutrisiran is an investigational, subcutaneously administered RNAi therapeutic in development for the treatment of ATTR amyloidosis, which encompasses both hereditary (hATTR) and wild-type (wtATTR) amyloidosis. It is designed to target and silence specific messenger RNA, blocking the production of wild-type and variant transthyretin (TTR) protein before it is made. Quarterly administration of vutrisiran may help to reduce deposition and facilitate the clearance of TTR amyloid deposits in tissues and potentially restore function to these tissues. Vutrisiran utilizes Alnylam's Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate delivery platform, designed for increased potency and high metabolic stability that may allow for infrequent subcutaneous injections. The safety and efficacy of vutrisiran have not been evaluated by the U.S. Food and Drug Administration, European Medicines Agency or any other health authority.

   About the HELIOS-A Phase 3 Study

   HELIOS-A (NCT03759379) is a Phase 3 global, randomized, open-label study to evaluate the efficacy and safety of vutrisiran. The study enrolled 164 patients with hATTR amyloidosis with polyneuropathy at 57 sites in 22 countries. Patients were randomized 3:1 to receive either 25mg of vutrisiran (N=122) via subcutaneous injection once every three months or 0.3 mg/kg of patisiran (N=42) via intravenous infusion once every three weeks (as a reference comparator) for 18 months. The efficacy results of vutrisiran in HELIOS-A are compared to the placebo group from the landmark APOLLO Phase 3 study, which evaluated the efficacy and safety of patisiran in a patient population similar to that studied in HELIOS-A. The primary endpoint is the change from baseline in mNIS+7 score at nine months. Secondary endpoints at 9 months are the change from baseline in the Norfolk QoL-DN score and the timed 10-MWT. Changes from baseline in NT-proBNP were evaluated as an exploratory endpoint at nine months. Additional secondary endpoints at 18 months will be evaluated in the HELIOS-A study, including change from baseline in mNIS+7, Norfolk QoL-DN, 10-MWT, modified body mass index (mBMI), Rasch-built Overall Disability Scale (R-ODS), and serum transthyretin (TTR) levels. Additional exploratory cardiac endpoint data at the 18-month time point will be evaluated, including NT-proBNP, echocardiographic measures and cardiac amyloid assessments with technetium scintigraphy imaging. Following the 18-month treatment period, all patients are eligible to receive vutrisiran for an additional 18 months as part of the randomized treatment extension where they will receive either 25mg vutrisiran once quarterly or 50mg vutrisiran once every six months.

   About hATTR Amyloidosis

   Hereditary transthyretin-mediated (hATTR) amyloidosis is an inherited, progressively debilitating, and fatal disease caused by variants (i.e., mutations) in the TTR gene. TTR protein is primarily produced in the liver and is normally a carrier of vitamin A. Variants in the TTR gene cause abnormal amyloid proteins to accumulate and damage body organs and tissue, such as the peripheral nerves and heart, resulting in intractable peripheral sensory-motor neuropathy, autonomic neuropathy, and/or cardiomyopathy, as well as other disease manifestations. hATTR amyloidosis, represents a major unmet medical need with significant morbidity and mortality affecting approximately 50,000 people worldwide. The median survival is 4.7 years following diagnosis, with a reduced survival (3.4 years) for patients presenting with cardiomyopathy.

   About RNAi

   RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines, known as RNAi therapeutics, is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, function upstream of today's medicines by potently silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.

   About Alnylam Pharmaceuticals

   Alnylam (NASDAQ:ALNY) is leading the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare genetic, cardio-metabolic, hepatic infectious, and central nervous system (CNS)/ocular diseases. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach for the treatment of a wide range of severe and debilitating diseases. Founded in 2002, Alnylam is delivering on a bold vision to turn scientific possibility into reality, with a robust RNAi therapeutics platform. Alnylam's commercial RNAi therapeutic products are ONPATTRO^® (patisiran), GIVLAARI^® (givosiran), OXLUMO^® (lumasiran), and Leqvio^® (inclisiran) being developed and commercialized by Alnylam's partner, Novartis. Alnylam has a deep pipeline of investigational medicines, including six product candidates that are in late-stage development. Alnylam is executing on its "Alnylam P⁵x25" strategy to deliver transformative medicines in both rare and common diseases benefiting patients around the world through sustainable innovation and exceptional financial performance, resulting in a leading biotech profile. Alnylam is headquartered in Cambridge, MA. For more information about our people, science and pipeline, please visit www.alnylam.com and engage with us on Twitter at @Alnylam, on LinkedIn, or on Instagram.

   Alnylam Forward Looking Statements

   Various statements in this release concerning Alnylam's expectations, plans, aspirations, and goals, including those related to the investigational therapeutic vutrisiran and its potential as a low-dose, once quarterly, subcutaneously administered treatment option with encouraging safety profile for patients with hATTR amyloidosis with polyneuropathy that has the potential to reverse polyneuropathy manifestations of disease, the expected timing for FDA review of the NDA for vutrisiran, our progress toward building in the future a franchise of medicines for the treatment of ATTR amyloidosis, our aspiration to become a leading biotech company, and the planned achievement of our "Alnylam P⁵x25" strategy, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation: the direct or indirect impact of the COVID-19 global pandemic or any future pandemic on Alnylam's business, results of operations and financial condition and the effectiveness or timeliness of Alnylam's efforts to mitigate the impact of the pandemic; Alnylam's ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for its product candidates; actions or advice of regulatory agencies and Alnylam's ability to obtain and maintain regulatory approval for its product candidates, as well as favorable pricing and reimbursement; successfully launching, marketing and selling its approved products globally; delays, interruptions or failures in the manufacture and supply of its product candidates or its marketed products; obtaining, maintaining and protecting intellectual property; Alnylam's ability to successfully expand the indication for ONPATTRO (or vutrisiran, if approved) in the future; Alnylam's ability to manage its growth and operating expenses through disciplined investment in operations and its ability to achieve a self-sustainable financial profile in the future without the need for future equity financing; Alnylam's ability to maintain strategic business collaborations; Alnylam's dependence on third parties for the development and commercialization of certain products, including Novartis, Regeneron and Vir; the outcome of litigation; the risk of government investigations; and unexpected expenditures; as well as those risks more fully discussed in the "Risk Factors" filed with Alnylam's most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) and in its other SEC filings. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.

   This release is not intended to convey conclusions about efficacy or safety as to any investigational uses or dosing regimens of any investigational RNAi therapeutics. There is no guarantee that any investigational therapeutics or dosing regimens for such therapeutics will successfully complete clinical development or gain health authority approval.

   

   View source version on businesswire.com: https://www.businesswire.com/news/home/20210624005230/en/

   View Full Article Hide Full Article