The following profile of Regenicin is a combination of two separate profiles that I wrote about in late January 2011. As a disclosure I do NOT and have never owned any stock of RGIN and have not received any compensation for this article.
Regenicin, Inc. (OTC: RGIN) – Part 1: History of Permaderm
What is Permaderm?
The Cultured Skin Substitute (CSS) is a combination of outer and inner layers of skin cells. A small (business card size) biopsy of skin is taken from the patient to begin the cell culture. The skin cells are isolated and put in a special mixture of nutrients and growth factors that supports their growth. After about three weeks, the cells organize to form small sheets of CSS (3”x3”) with the physical strength of 2-3 wet paper towels. The process allows for generation of CSS of about 100 times the size of the original skin biopsy (100 business cards). From about 1% of the body, thisprocess can generate enough CSS generated to cover the entire body of a burn patient. These CSS grafts are then taken to the operating room where surgeons apply them to a burn wound, similar to the autografting method. The CSS grafts applied in the operating room are treated similarly to auto-grafts, though somewhat more fragile until the blood supply is established.
Who has been developing Permaderm…for the last 20 years?
Dr Steven Boyce, a Research Associate Professor at the University of Cincinnati College of Medicine and is Professor/ Director, Skin Substitute Laboratories, Shriners Hospitals for Children.
Permaderm has been developed for over 20 years since 1990. In 1990 Dr Boyce said, “Shriners Hospitals and the University of Cincinnati are working closely with the U.S. Food and Drug Administration (FDA) to gain approval for this method as a valid alternative to conventional skin grafts.”
Dr Boyce founded Cutanogen Corporation in 1997, which was sold to Cambrex in 2006. Permaderm was its main product and was sold together with the company for “$1.5 million to be fully paid at closing with additional purchase price payments of up to $4.8 million subject to the achievement of certain regulatory and commercial milestones.” This seems an extraordinary low amount if there is indeed value in Permaderm. They stated that they expected “to market upon its anticipated regulatory approval in 2006…and that it intends to begin a pivotal trial for PermaDerm cultured skin by the end of 2006. The trial is estimated to take approximately fifteen months. Upon completion of the analysis of the pivotal trial data, the Company expects to submit the results to the FDA in its application for Premarket Approval (PMA) for commercial sale.”
Warning letters issued by FDA in 2006/07 following Investigational Device Exemption Application
In 2006 and 2007 THREE warning letters were issued by the FDA. Although parts of the documents are blacked out it is clear from looking here that all correspondence refers to Permaderm (scroll down about three-quarters and you will find “Permaderm”).
The FDA alleged to him that, “you did not conduct the study according to the investigator agreement that you signed on June 26, 1999, and you did not follow the protocol provided to you by the sponsor on November 1, 1999. Instead of conducting the study according to the protocol, you revised or removed sections of the protocol prior to obtaining approval from the sponsor.” There were many other issues which you can read in the link above.
Dr Boyce is also mentioned in this letter by the FDA.
“This letter also requests prompt corrective action to address the violations cited and discusses Dr. Boyce’s written response, dated October 6, 2006, to the noted violations. ” “The protocol required all subjects to receive both CSS and autografts, in order to compare the two treatments. Subjects (redacted) only received the CSS dressing. Since one of the objectives of the study is to perform direct comparisons of CSS and conventional skin autograft, it was important for the subjects to receive both dressings at the same time.”
“Failure to report and accurately document unanticipated and anticipated adverse device events to the sponsor and the reviewing IRB.” The letter also stated that the FDA inspection report “revealed serious violations” of regulations regarding Investigational Device Exemptions and Protection of Human Subjects by failing to obtain informed consent and failing to maintain accurate and complete
case histories for each subject.
“Failure to report and accurately document unanticipated and anticipated adverse device events to the sponsor and the reviewing IRB”
“Ten subjects needed to be regrafted with the CSS or with an autograft after the CSS failed on certain burned areas. None of the ten subjects’ unanticipated adverse events were listed in the subjects’ case report forms (CRFs) nor were they reported to the IRB or sponsor as per regulation.”
“ At least (redacted) subjects’ records audited indicated that anticipated adverse events were experienced including development of necrotic tissue, pneumonia, and elevated temperatures, which were not reported to the Sponsor or the lRB as per regulation.”
“Failure to maintain accurate and complete case histories for each subject.”
“On [redacted] subject [redacted] had positive cultures for [redacted] of her which resulted in clinical sepsis. She was treated with triple antibiotic therapy of [redacted] and [redacted]. This event was not recorded on the adverse event case report forms (CRF) and there was no documentation of reporting this event to the sponsor, IRB, and FDA.”
“failure to ensure adequate monitoring of the investigation and failure to include written procedures for monitoring the investigation in the investigational plan.”
“failure to label the device as investigational.”
“failure to maintain accurate, complete and current device shipment and disposition records.”
FDA Shuts Down Permaderm Program in 2007
In January 2007 the FDA informed the University of Cincinnati College of Medicine that the review of their IDE was suspended and placed it on Integrity hold. “The decision is based, in part, on the fact that the inspections of your investigational sites suggest that the clinical data and information in the above referenced submission may be unreliable.” The FDA went on to say that Permaderm could be used compassionately on a case by case basis if permitted by the FDA.
Morley Foundation conducts audit for FDA – March 2010
The report slammed those involved in the trials. Some of the major issues were;
- Those conducting tests were incompetent.
- Most serious adverse effects were not reported but the audit succeeded in revealing more.
- Poor documentation
- Lack of following protocols
- Performing compassionate treatment without FDA Approval
- Despite under integrity hold Dr Boyce continued to give poster sessions and presentations promoting Permaderm, including a presentation to the Armed Forces Institute for
- Regenerative Medicine All Hands meeting on January 14, 2009. The FDA ordered Dr Boyce to cease conducting such activities.
As a result of the Morley Audit and the Integrity Hold, the FDA put a halt to use of compassionate use in June 2010. Alfred Real, 8, was prevented from accessing Permaderm after his family received a letter from the FDA denying them access to the treatment. The boy received third degree burns to 80% of his body so his family took him to Shriners Hospitals for Children after been “told” that he could have compassionate treatment there. However, they were DENIED compassionate use by the FDA.
“According to the letter, dated June 15,2010, the family was denied due to concerns that the device used in the procedure may produce inaccurate data. The letter further states that in past investigations performed by the FDA, data integrity was an issue. The letter cites issues involving failure to report adverse affects the device may have, as well as failure to monitor clinical studies.”
A full copy of the letter can be seen in Appendix A
In July 2010, the University of Cincinnati received approval to use Permaderm as a one-off case on the condition that they took full responsibility for the safety of the boy.
“The U.S. Department of Defense recently awarded more than $18 million in funding to a unit of Lonza Group, Ltd. for the development and commercialization of the therapeutic candidate, PermaDerm™ for the treatment of severe burns among U.S. troops and civilians. The initial trial will contain 10 patients, both male and female, between the ages of 18 and 40, who suffer third-degree burns. These trials and future trials will take place at the United States Army Institute of Surgical Research at Fort Sam Houston and at a second site to be determined.”
Expectations – Letter from Randall McCoy, CEO (issued mid 2010)
Humanitarian Device Exemption with Pre-market Approval Following.
FDA sanctioned and reported trials of 100 plus patients treated at Shriners Hospitals or affiliates.
Manufacturing process transferred from University of Cincinnati to GMP facility in Maryland Lonza in 2007.
Pre HDE meeting completed. No outstanding issues. Compatibility trials need completed with mice or rats for HDE application submission. HDE application 75% written.
Time to Market:
One year from HDE approval.
US Market for HDE label use $50M
Insight into their CEO, Randall McCoy and McCoy LLC
“Randall McCoy has served as our Chief Executive Officer and sole director since July 2010. Prior to joining the Company, Mr. McCoy served as President of McCoy Enterprises LLC since its founding in May 2002.”
At the time of writing, McCoy LLC, pictured here, was operating out of 10 High Court, Little Falls, NJ 07424
McCoy LLC has been involved with PermaDerm from at least as far back as 2009. They merged with Cavit Sciences Inc. Cavit noted in their press release that, “McCoy has been working on getting final FDA approval for their Cultured Skin Substitute (PermaDerm[TM]). Their CSS has already been given Orphan Drug Status by the FDA and will be indicated for children under 12 years old with 50% or more bodysurface burned”
Windstar Inc (WDST)
In July 2010 McCoy found a shell company called Windstar Inc. On page 4 we learn that they “are engaged in the business of developing, producing, and marketing an effective and inexpensive air purification device” for use in a kitchen. The company listed $0 cash and $0 assets and 22,500 in liabilities.
McCoy purchased the shell on July 15 and paid the shell’s owners $14,250 for 1.2m shares and an additional 225,000 in a debt conversion exchange, for a 60% share in the company. He also had a relative who owns some shares so in total his family come out with a 69.9% stake or 1,660,125 shares out of a total 2,375,000 shares.
The company then enforced a 34:1 forward split which resulted in 80,750,000 total shares with McCoy owning 56,444,250 shares. Trading under the ticker WDST you will see that it starts trading for the first month in August/September over $2, so his $14,250 investment was worth over $100m!
Increase in Authorised Shares
‘On October 27, 2010 a majority of our shareholders and our board of directors approved an amendment to Article 1 of our Articles of Incorporation to increase our total authorized common stock from 90,000,000 shares to 200,000,000 shares.”
Note that the CEO owned more than 50% at the time of the “majority” vote.
How much has the CEO been selling?
“Our CEO, Randall McCoy further agreed to restrict the sale of 11,288,850 shares of his common stock representing 20% of the number of shares of common stock beneficially owned by him, until such time as we receive approval from the FDA for the commercial sale of PermaDerm™.”
In other words, he can still freely sell the other 80%. According to their 10-K filing released in January 2011, Randall McCoy owned 44,021,640. (pg 29). A reminder that he owned 56,444,250 at the time of the forward split, which yields net sales of 12m shares, netting approximatley $15m if you look at the chart between July and December 2010. His initial investment was $14,000.
“On or around July 15, 2010, the Company’s headquarters was moved to the personal residence of Mr. McCoy. In addition, on or around November 1, 2010, the Company began utilizing space in New York City in the offices of an entity controlled by Mr. McCoy. No rent is charged for either premises.”
Change in ticker
The company began trading as RGIN when they changed their ticker on November 10, 2010.
APPENDIX A – FDA Letter denying compassionate use
University of Cincinnati College of Medicine
℅ Jane Strasser, Ph.D.
Associate Vice President
Office of Research Compliance and
University Hall Room 510
PO Box 2100567
Cincinnati, Ohio 45221
Autologous Cultured Skin Substitute
Dated: June 15, 2010
Received: June 16, 2010
Dear Dr. Strasser:
The Food and Drug Administration (FDA) has reviewed the supplement to your investigational device exemptions (IDE) application requesting approval to treat a patient outside the clinical protocol, that is, “compassionate use.” We regret to inform you that your request is not approved and you may not treat this patient with the above cited investigational device. This is based on the following
As stated in the “Guidance on IDE Policies and Procedures January 20, 1998” concerning compassionate use of an investigational device, the IDE supplement requesting compassionate use should discuss: 1) the patient’s condition and the circumstances necessitating treatment and 2) why alternatives therapies are unsatisfactory and the probable risk of using the investigational device is no greater than the probable risk from the disease or condition. From our review of the submitted and other available information, we conclude that while none of the available alternative treatments (i.e., human cadaver skin, Integra Dermal Regeneration Template, TransCyte or Biologic dressings such as porcine xenograft) is an ideal skin substitute; the medical community has experience with these products and most of these products have been adopted in burn units.
Given the availability of the above-mentioned alternatives and the lack of sufficient credible information about the investigational device (see below), FDA cannot assume that the probable risk of using the investigational device is not greater than the probable risk from the disease condition. FDA would welcome the opportunity to learn more about the safety of this product, if you can identify clinicians who are knowledgeable about Autologous Cultured Skin Substitute. Because considerable concern exists about the validity of the data generated under this IDE, we believe that these knowledgeable clinicians should be independent from the two investigators performing this study and their understanding of the product should be derived from experience other than this IDE study or publications by Drs. Kagan or Boyce.
If you submit information correcting the deficiency, we will reevaluate your application. The information should be identified as an IDE amendment referencing the IDE number above, and must be submitted in triplicate to:
U.S. Food and Drug Administration
Center for Devices and Radiological Health
Document Mail Center – WO66-G609
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
You should also give serious consideration to the following item which is considered essential for any future requests for compassionate use of this device. As stated above, an important element in granting compassionate use of an investigational device is an explanation of why the probable risk of using the investigational device is no greater than the probable risk from the disease or condition. Please be advised that FDA has considerable concern about the absence of sufficient credible scientific evidence to perform a meaningful assessment of the probable risk of using this investigational device. During the course of this IDE, FDA has observed recurring problems with data integrity including:
failures to maintain accurate, complete, and current records regarding each subject’s case history and exposure to the device, including all relevant observations;
failures to report unanticipated adverse device effects to the sponsor and reviewing IRB;
failures to maintain accurate, complete, and current records regarding the receipt, use, and disposition of a study device and failure to maintain each subject’s case history and exposure to the device, including all relevant observations;
failures of the investigator to maintain records of protocol deviations; and,
failures to obtain approval of significant changes to the protocol from the sponsor and reviewing IRB.
We have also observed system wide failures in the methods for conducting and managing clinical trials. Such problems include:
failure to ensure investigator compliance with the signed investigator agreement; investigational plan, and applicable federal regulations, (e.g., diagnostic procedures/assessments were not performed and unanticipated adverse device effects were
not documented and reported);
a lack monitoring procedures and the absence of monitoring clinical studies;
deficient records of device accountability; and
failure to submit IDE progress reports at regular intervals and at least yearly to FDA and reviewing IRBs.
These observations are based on our initial inspection of your facility from March 7 to June 21, 2006, the annual reports submitted to your IDE, and a review of the Independent Third Party Audit submitted by the Morley Foundation to FDA on March 25, 2010. The latter document indicates that these failures in data collection and oversight have continued during period after the Integrity Hold Letter was issued in 2007 and while your clinical site was undergoing an Independent Audit in 2008-2009.
Regarding patient safety, a few issues cited in the audit report include:
The auditors determined that only 5 of 24 subjects which should have received additional informed consent information, were properly re-consented, (page 10).
Auditors found that the sites did not understand the reporting of adverse events (page 44).
Based on the definition of unanticipated adverse device effects and serious adverse effects developed by your Data Safety Monitoring Board (DSMB), 1782 out of a total of 7331 adverse events were reported. An additional 5547 AEs were extracted by the auditors based on the DSMB-generated list of adverse event reports (page 77).
In the 2007 annual report (i.e., after issuance of the Warning and Integrity Hold letters), only 8 adverse events (AEs) were reported. During the independent audit a total of 695 reportable AEs were identified. In the 2008 annual report 36 unanticipated adverse device events were reported. In contrast, the auditors identified 760 such events (page 144).
The case report forms (CRFs) for 33 of 44 subjects audited from 2003 – 2009 were not properly completed. Individual pages were incomplete and follow- up visits were not documented, even when subjects were being seen in the outpatient clinic (page 16).
Less than half of the subjects had results from the pre-treatment serum antibody tests (page 40) and 119 of 159 antibody tests required by the protocol at POD 28 were not performed (page 60). This led auditors to conclude that “the results of the serum antibody studies were virtually impossible to identify. The records were maintained in an extremely poor manner
and not sufficient for auditor review” (page 40).
While documentation states that the principal investigators (PIs) did not check the “Post Operative Date Completion for all Sets” CRFs until the subject completed the initial year, some of these “checks” were signed up to two or three years after the closure of the
subject’s initial year on study. (page 44)
Regarding microbial cultures, the auditors noted a decline in data collection the longer the time period after treatment. For example, the number of completed samples was 120/159 (pre-operation), 119/159 (POD 0), 111/159 (POD7) and 77/159 (POD 14) (page 52).
The audit report states (page 177) that a uniform protocol was not used at all of the study sites. Dr. Boyce stated that the same protocol was not used at each of the Burn centers and protocols had variations that were site specific. This suggests that the study was performed with protocols that were not reviewed or approved by FDA.
There was no evidence that appropriate data safety monitoring was put into place as part of the research plan, thereby ensuring that appropriate risk assessments were being made as part of the screening process (page 22).
Regarding device quality assurance testing the auditors determined that: 1) only 67/155 (43%) histological exams were completed and could be verified by source documents, 2) there was not sufficient documentation with respect to the storage, shipment, handling or disposition of the device used in the study and 3) while sterility tests were to be performedboth five days before and on the day of surgery, only 10/159 (6%) tests were completed five days before surgery. The majority of the sterility tests were performed 7-10 days beforesurgery. 43 of 159 tests (27%) were not done on the day of surgery. Five additional samples had incomplete data or could not be verified. (page 121 – 122)
For this reason, FDA believes it is appropriate to stop further enrollment of compassionate use subjects until: 1) you have submitted a Corrective Action Plan (CAP) that addresses the concerns cited in our Warning Letter of January 12, 2007, our Integrity Hold Letter of February 2, 2007, and the Independent Audit Report 2) FDA has completed its review of this CAP, and 3) FDA has
determined that the CAP is being appropriately implemented (e.g., via site inspection and/or document review).
If you have any questions regarding the compliance issues associated with your application, please contact Sonali P. Gunawardhana, LL.M., J.D., M.P.H. at (301) 796-5635 or firstname.lastname@example.org. If you have any questions regarding the premarket reviewissues associated with your application, please contact Charles N. Durfor, Ph.D. at (301) 796-6970 or
Mark N. Melkerson
Division of Surgical, Orthopedic
and Restorative Devices
Office of Device Evaluation
Center for Devices and
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January 29, 2011