MiMedx Comments on Flawed Osiris Data Review

MARIETTA, Ga., May 3, 2016 /PRNewswire/ -- MiMedx Group, Inc. (NASDAQ: MDXG), the leading regenerative medicine company utilizing human amniotic tissue and patent-protected processes to develop and market advanced products and therapies for the Wound Care, Surgical, Orthopedic, Spine, Sports Medicine, Ophthalmic, and Dental sectors of healthcare, responded today to highlight the substantive deficiencies and serious flaws in a recent data review reported by Osiris Therapeutics, Inc.

This Osiris clinical review entitled "A Retrospective, Single-Center, Non-Randomized, Cross-Sectional Comparative Effectiveness Study Evaluating Surface Area Reduction, Volume Reduction and Closure Rates in Acute and Chronic Wounds Managed with Grafix® versus EpiFix®," was the topic of a press release issued by Osiris on May 2, 2016. The deliberate use of inadequate clinical study standards to produce a totally biased report has prompted MiMedx to respond to the Osiris press release. In the Company's response, MiMedx will not refer to this retrospective database analysis review as a "study" since it does not meet any of the established criteria to be referred to as such.

Parker H. "Pete" Petit, Chairman and CEO commented "It is unfortunate that a company issues a press release on what clinicians and scientists would normally define as retrospective 'Level III' data which has significant flaws, but then calls it 'real world.' Incidentally, 'Level III' data is the lowest level of clinical analysis. One of our other small competitors did something similar about a year ago, and it was discredited.  When a physician picks and chooses cases with random criteria to make retrospective comparisons, that is not science.  At MiMedx, we call that pseudoscience." 

Petit continued, "MiMedx now has over 25 peer reviewed and published clinical and scientific studies and papers on our allografts, more than 30 additional articles on the use of our amniotic membrane products published in peer-reviewed journals and more than 120 posters and abstracts presented at national meetings by physicians that chronicle the clinical and cost effectiveness of our Dehydrated Human Amnion/Chorion Membrane (dHACM) allografts. MiMedx has published a book entitled A Primer On Amniotic Membrane Regenerative Healing to help this sector of healthcare improve the scientific and clinical approaches necessary to truly evaluate new technology. We have 16 clinical studies, primarily randomized controlled trials ('RCTs'), underway in various parts of the country at this time.  We will continue to bring real science and clinical studies showing efficacy in various settings in order to raise the level of expertise in advanced wound care.  I would again encourage all corporate entities in advanced wound care to do the same.  It is a disservice to our patients, who we serve, and the physician community, who is so dedicated in caring for them, to have this type of pseudoscience being touted."

Dr. Thomas J.  Koob, Chief Scientific Officer, stated, "Good science requires that proper comparisons are the basis for unequivocal conclusions.  The Osiris review lacks both proper comparisons and unequivocal conclusions.  While real world experience is crucial to understand efficacy of any product, the real world experience must not be biased by subjectively determined cases to be reviewed or by the investigator analyzing the data. The Osiris press release claims that an independent third party clinical research organization analyzed the data, which is the appropriate way to conduct a study.  However, the independent organization for this review could only analyze the data that were provided to them.  If the data in a retrospective review like this are selected with bias, as it appears in this case, by a single physician, then the independence of the analysis is irrelevant."

Koob continued, "This single-site review is seriously flawed with unsound design, a lack of adequate or relevant controls, and faulty use of inadequate clinical study standards to make comparative effectiveness claims. Here are just a few examples:

• All types of wounds from acute, chronic and head-to-toe were included with no way to match and compare treatments and results;
• Comorbidities, infections, type of wound, history and wound age were not addressed and no statement of how they influenced the cases that were picked;
• The review results end point of 12 weeks was ill defined;
• Wounds were stated to have at least one treatment with one of the products, but no statements if any more placements were made to all or some of the wounds. There is no way to tell how many applications of the products were accomplished. This is crucial since proper scientific comparisons rely on equivalent treatments. One can bias this kind of review by selecting one patient pool that was treated once versus another patient pool that was treated more than once. The Osiris press release and review fail to detail the number of treatments on the patients used in each group. No conclusions can be drawn from this review since the treatment parameters are not defined;
• The number of treatments is crucial for understanding the economics of the treatment protocol, and this is lacking in this review; and
• There is no statement or discussion regarding patients lost to follow-up, discontinuation or other medical reasons or ancillary treatments in conjunction with the reviewed treatments."

Bill Taylor, President and COO, said, "The Osiris review is lacking integrity. In fact, after reviewing our allograft usage at this 70-bed hospital, it would appear that based on the number of EpiFix allografts used in this facility, it is unlikely that the clinicians used our product per the 'instructions for use.' If they did, there would have been a higher usage rate of the product. Also, our records indicate that the hospital had not used EpiFix during the last nine months of the Osiris review period. This is just one more factor that raises questions about the validity of this Osiris review."

Dr. Donald E. Fetterolf, Chief Medical Officer, noted, "Retrospective reviews conducted at a single center such as this small hospital are not likely to be statistically representative, especially when preselection was likely occurring. Proper research should identify inclusion and exclusion criteria, better match cohorts, and make severity adjustment for populations, which was not the case here.  Without that logic, or an underlying algorithm that contains the inclusion and exclusion criteria required in clinical research, the likelihood of comparable populations for a true comparison is low, and would clearly result in disparate populations in key wound size and volume parameters.  Nonrandomized, noncomparable, highly variable study groups created without a protocol can easily reflect any number of incorrect findings, good or bad.  Stating there was a 'blinded statistical analysis' done after the fact is meaningless in the face of nonexistent study design.  By definition, 'comparative effectiveness research' seeks to truly compare equivalent groups for differences in effectiveness and/or cost.  That discipline did not occur here.  The accepted standard for asserting a comparative effectiveness study is the RCT, which is the highest level of evidence and is referred to by scientists and clinicians as 'Level I' data."

Petit added, "MiMedx has conducted a comparative study and a follow-up publication of that study against Apligraf®, a product from a smaller competitor, Organogenesis.  Those are published peer reviewed studies that have credibility because they are RCTs.  If Osiris really wants a comparison between the clinical effectiveness of our products, they should conduct a prospective comparative RCT as we have done, which produces 'Level I' evidence.  At the same time, they should conduct an economic analysis that includes the cost associated with their inefficient logistical requirements and the cost associated with maintaining freezers and the complex requirements of thawing their product prior to application."

Petit concluded, "I am afraid the Osiris definition of 'real world' is where a paid physician retrospectively picks and chooses patients with bias to place in the review and then sends the data for 'independent' analysis.  Again, this is not science, and I do not believe it is something that health plans or the Centers for Medicare and Medicaid ('CMS') would even consider reviewing.  Manufacturers and processors of skin substitutes need to upgrade their practices in terms of providing clinical and scientific evidence. No credible clinical conclusions can be drawn from this retrospective 'Level III' review with so many unmatched, uncontrolled and subjective variables. I do not think any credible investigator would entertain conducting this type of review and calling it a 'study' with so many faulty and unsound protocols. This review calls into question Osiris' clinical and scientific integrity, and I believe this will ultimately be a professional embarrassment for them." 

About MiMedx

MiMedx® is an integrated developer, processor and marketer of patent protected and proprietary regenerative biomaterial products and bioimplants processed from human amniotic membrane and other birth tissues and human skin and bone.  "Innovations in Regenerative Biomaterials" is the framework behind our mission to give physicians products and tissues to help the body heal itself.  Our biomaterial platform technologies are AmnioFix®, EpiFix®, OrthoFlo, Physio®, AlloBurn™, and CollaFix™. AmnioFix and EpiFix are our tissue technologies processed from human amniotic membrane derived from donated placentas. Elected in advance of delivery through our donor program, a mother delivering a healthy baby via scheduled full-term Caesarean section birth may donate the placenta in lieu of having it discarded as medical waste.  We process the human amniotic membrane utilizing our proprietary PURION® Process, to produce a safe and effective implant. MiMedx is the leading supplier of amniotic tissue, having supplied over 600,000 allografts to date for application in the Wound Care, Burn, Surgical, Orthopedic, Spine, Sports Medicine, Ophthalmic and Dental sectors of healthcare.  We recently introduced OrthoFlo, an amniotic fluid derived allograft for homologous use.  Amniotic fluid is donated by a consenting mother delivering a full-term healthy baby by scheduled Caesarean section.  Through the recent acquisition of Stability Biologics,  our newest proprietary platforms include Physio, a unique bone grafting material comprised of 100% bone tissue with no added carrier, thus maximizing bone forming potential, a  demineralized bone matrix (DBM) to complement our product portfolio offerings within the Orthopedic market and AlloBurn, a skin product for burns.  CollaFix, our next technology platform we plan to commercialize, is our collagen fiber technology, developed with our patented cross-linking polymers, designed to mimic the natural composition, structure and mechanical properties of musculoskeletal tissues in order to augment their repair.  CollaFix is the only biological, biodegradable, biomimetic technology that matches human tendon in strength and stiffness.  The Company's wholly-owned subsidiary, Stability Biologics, LLC, is accredited by the American Association of Tissue Banks (AATB) and registered with the FDA. The Company distinguishes its revenue in two primary regenerative medicine specialties of "Wound Care" and "SSO."  The Company defines SSO as surgical, sports medicine and orthopedics with spinal procedures included in orthopedics and abdominal, and lower pelvic procedures included in surgical.

Safe Harbor Statement

This press release includes statements that look forward in time or that express management's beliefs, expectations or hopes. Such statements are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to that MiMedx will continue to bring real science and clinical studies showing efficacy in various settings, and the significance of MiMedx's published peer reviewed studies. These statements are based on current information and belief, and are not guarantees of future performance. Among the risks and uncertainties that could cause actual results to differ materially from those indicated by such forward-looking statements include that MiMedx may decide not to continue conducting clinical and scientific studies, or its studies in the future may not show efficacy, the Company's published peer reviewed studies may not have the same significance in the future, other products or new products may perform better than the Company's products in future studies, and the risk factors detailed from time to time in the Company's periodic Securities and Exchange Commission filings, including, without limitation, its 10-K filing for the fiscal year ended December 31, 2015. By making these forward-looking statements, the Company does not undertake to update them in any manner except as may be required by the Company's disclosure obligations in filings it makes with the Securities and Exchange Commission under the federal securities laws.

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SOURCE MiMedx Group, Inc.