Home › Blog › MiMedx Reports Results of FDA Trials: Does This Spell Trouble?

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Does amniotic tissue help knee arthritis pain? That’s been an open question for some time. Thankfully this question is beginning to get answered by FDA clinical trials, the earliest of which are now beginning to report results. One such report this week could spell trouble for the other half dozen companies involved in knee arthritis clinical trials. Let’s dig in.

Amniotic Stem Cells?

Commercially sold amniotic tissue has no stem cells, which is a topic I have covered many times. See my video if you need an update on all of that:

Does Amniotic Tissue Work to Treat Pain?

This is a tough one to answer as we have very little clinical research about amniotic tissue injections used to treat knee arthritis. Let’s review what’s published to date:

• A 12-month Randomized Controlled Trial (RCT) showed good results for an amniotic product called ReNu (1). This was used to treat moderate knee arthritis with good results that beat hyaluronic acid (2). IMHO, the ReNu study has serious problems as I have pointed out.
• A small RCT on the use of amniotic injections to treat plantar fasciitis showed good short-term results compared to steroid shots (3).

The MiMedx MSK Studies

MiMedx was one of the companies that early on decided to fund not one, but several FDA trials for the use of amniotic injections to treat pain. So whatever the outcome of those trials, they are to be congratulated for spending that money when other companies wouldn’t. These are the MiMedx studies listed on Clinicaltrials.gov:

• A 60 person randomized controlled trial (RCT) to treat knee arthritis (OA) with three groups: High dose amniotic fluid (4 ml), low-dose amniotic fluid (2 ml), and saline.
• A 466 person RCT to treat knee OA with 40 mg micronized amniotic tissue versus saline (FDA trial). 
• A 276 RCT to treat plantar fasciitis with 40 mg micronized amniotic tissue versus saline (FDA trial). 

The Recent MiMedx Press Release

This is what the company said in a press release about their two larger studies listed above:

“MARIETTA, Ga., Sept. 13, 2021 (GLOBE NEWSWIRE) — MiMedx Group, Inc. (Nasdaq: MDXG) (“MIMEDX” or the “Company”), an industry leader in utilizing amniotic tissue as a platform for regenerative medicine, today announced top-line results from two late-stage musculoskeletal clinical trials of the Company’s micronized dehydrated Human Amnion Chorion Membrane (mdHACM): a Phase 2B clinical trial for the treatment of Knee Osteoarthritis (KOA) and a Phase 3 clinical trial for the treatment of Plantar Fasciitis (PF).

Top-line results from an interim analysis of the six-month efficacy data for the Phase 2B clinical trial for KOA did not meet primary endpoints, but did reveal varied efficacy signals between patient cohorts evaluated pre- and post- a blinded interim analysis performed in mid-2019, prompting the Company to plan for confirmatory efficacy studies for the KOA indication. The Phase 3 PF study did not meet its primary endpoint, and the Company will not pursue a BLA for this indication at this time. Throughout both studies, the mdHACM product was found safe and well-tolerated.”

So the knee arthritis study has mixed results and the plantar fasciitis study showed the product didn’t work.

Why the Knee OA Study Results Are Significant

Two days ago I blogged on the results of the ReNu knee arthritis studies. That amniotic product is similar to the MiMedx injectable used in the above knee study. What was interesting there was when I took that study apart at 6-months, there were very mixed results for the product compared to saline. Meaning, you could have described those results as “did not meet primary endpoints, but did reveal varied efficacy signals between patient cohorts evaluated pre- and post- a blinded interim analysis” exactly as MiMedx did above. Meaning IMHO, Organogenesis, the makers of ReNu had to do some creative statistical analysis to make it appear that the results of the 6-month study were a home run. Forget about what was happening at 12-months, where the company had lost almost 80% of its control group. I suspect that MiMedx knows that FDA will never allow that kind of drop-out if they continue this study, so this may be an opportunity to retool the study.

What These Two study Results of Micronized Amniotic Tissue Mean for the Industry

As I have written before, the main competitor for these products is PRP, which has excellent RCT research support for treating knee OA. Amniotic products usually cost about $800 for the 40 mg dose (that was the higher cost after they had committed to a BLA). My guess is that the three studies above would cost about 50-100 million to run here in the U.S. (including getting the FDA to sign off on a BLA). Let’s take the lower number at $50,000,000. If you amortized selling 50,000 vials for 5 years (that would be gangbuster sales), that’s $200 a vial. Hence, let’s set the 40mg dose at $1,000 to make the company whole. That’s well above the average doctor’s cost for PRP.

How much will doctors and insurance companies be willing to pay for the convenience of an off-the-shelf injectable knee OA product compared to PRP which takes staff time and drawing blood? My guess is that if there were equivalent results (which have NOT been seen yet in these amniotic injection trials), perhaps a $100-200 premium. Would the insurance market bear twice as much? I doubt it.

What if the product turns out to be less effective than PRP? Then the product is not marketable in my opinion. That’s a HUGE problem.

Why Are These Companies Having these Problems?

The idea is that these products are rich in growth factors that can help joints heal or reduce breakdown. However, when we looked at the GF levels in these types of products, that’s only partially true. What we saw were low levels of the growth factors involved in cartilage healing and higher levels of factors involved in tendon healing. Hence, if you had to render a guess based on the in-vitro data, these products should be able to help rotator cuff tears more than help knee arthritis.

Who Else Has Pending FDA or Other Clinical Trials?

These are the trial results we have yet to see for knee arthritis and injections of amniotic products (per www.clinicaltrials.gov):

• Organogenesis (makers of ReNu) are performing a RCT against saline on 474 patients. 
• The University of Utah is testing 60 patients in a RCT of micronized amniotic membrane against steroid injections.
• Illinois Center for Orthopaedic Research and Education is testing amniotic fluid injection in 90 patients with an RCT against saline. 
• BioD is testing 90 patients in a RCT with amniotic fluid against steroid injections. 

The upshot? So far, things don’t look good for the idea that amniotic products can help knee OA and achieve an FDA approval and outcompete PRP. However, we’ll see what the next clinical trials report. I would love to be wrong, as that would mean more tools in the proverbial toolbox!

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References:

(1) Gomoll AH, Farr J, Cole BJ, Flanigan DC, Lattermann C, Mandelbaum BR, Strickland SM, Zaslav KR, Kimmerling KA, Mowry KC. Safety and Efficacy of an Amniotic Suspension Allograft Injection Over 12 Months in a Single-Blinded, Randomized Controlled Trial for Symptomatic Osteoarthritis of the Knee. Arthroscopy. 2021 Jul;37(7):2246-2257. doi: 10.1016/j.arthro.2021.02.044. Epub 2021 Mar 12. PMID: 33716121.

(2) Mojica ES, Markus DH, Blaeser AM, Hurley ET, Jazrawi LM, Campbell KA, Strauss EJ. Estimated Time to Maximum Medical Improvement of Intra-articular Injections in the Treatment of Knee Osteoarthritis – A Systematic Review. Arthroscopy. 2021 Aug 27:S0749-8063(21)00777-5. doi: 10.1016/j.arthro.2021.08.026. Epub ahead of print. PMID: 34461219.

(3) Hanselman AE, Tidwell JE, Santrock RD. Cryopreserved human amniotic membrane injection for plantar fasciitis: a randomized, controlled, double-blind pilot study. Foot Ankle Int. 2015 Feb;36(2):151-8. doi: 10.1177/1071100714552824. Epub 2014 Sep 23. PMID: 25249320.

Chris Centeno, MD is a specialist in regenerative medicine and the new field of Interventional Orthopedics. Centeno pioneered orthopedic stem cell procedures in 2005 and is responsible for a large amount of the published research on stem cell use for orthopedic applications. View Profile