"United Health Product’s PRs Describing Its HemoStyp PMA Application Process Are Bizarre, Suggesting A Denial Is Likely UEEC’s announcement of the PMA submission was released on 10/4/19 stating:
UEEC today announced that it has submitted a Premarket Approval (PMA) application for Class III approval to the FDA for HemoStyp.
This was seemingly very significant news about an important milestone concluding clinical study data analysis and submission. The text of the announcement was, however, very generic and reserved. It further states:
The PMA program confirms the safety and efficacy of a product. If approved, UHP expects that HemoStyp will be authorized for use in surgical procedures in abdominal, cardiovascular, thoracic and vascular surgeries per UHP's PMA filed Instructions For Use.
This October 4th PR mentions nothing about the results of the clinical studies, simply noting that the FDA submission has occurred.
A pre-market application (PMA) application is a very detailed and stringent process. As described in drugwatch.com, the PMA includes:
Source: drugwatch.com
Therefore, the October 4th PMA submission should have included clinical data, including a statistical analysis of its results.
Then, on 10/18/19, a relevant, yet bizarre, PR was announced, claiming positive results of the HemoStyp clinical study. We are puzzled because this announcement comes two weeks after the PMA submission on 10/4/19.
The PR says the final analysis report has been received, and it is from an independent reviewer (does “independent” mean that UEEC didn't pay for this analysis?). It further states:
In summary the independent statistical reviewer (website here) stated:
“For the primary analysis comparing HemoStyp versus Surgicel for hemostasis in 10 minutes, both non-inferiority and superiority were satisfied in both ITT population and PP population. For the secondary analysis, HemoStyp was significantly better than Surgicel with respect to the percentage achieving hemostasis at 2 minutes, 5 minutes, and 10 minutes.”
It further states:
UEEC... today announced that it has received the final report from an independent review of the results of its human clinical trial.
The way the above sentence is worded, it seems as though UEEC had just received the statistical results on October 18 or a day before. It doesn't say that this report was received and sent to the FDA 2 weeks earlier on October 4th. But if it was in fact sent to the FDA in tandem with the October 4th submission, then it is strangely communicated.
Why would they do the analysis after they already sent the application? There is such a thing as a PMA Amendment if the applicant is revising existing information or providing additional information. But UEEC didn’t say that they were doing a PMA Amendment. It is sometimes required to continue statistical analysis after the PMA submission if the clinical study is continuing and the longer patient follow-up is recorded. But according to the UEEC protocol, the follow-up was 30 days and that was finished long ago.
Because this “independent” statistical reviewer apparently gave its analysis after UEEC already submitted its application to the FDA, we would take it with a grain of salt. If it were a relevant review, it should have been included in the PMA application on October 4th. If this analysis was not included, we also wonder then what analysis was included and why the results of that analysis were not mentioned in the PR from October 4th.
But what is the most alarming to us in the 10/18/19 announcement is that the PR went silent on the very important product safety outcomes. From the UEEC clinical protocol, described on its clinicaltrials.gov page we learned about four secondary study outcomes:
Source: clinicaltrials.gov
While the Primary outcome and the Secondary outcome #1 in the UEEC study protocol are efficacy related, the Secondary #2, #3, and #4 outcomes are all safety outcomes and are of critical importance for FDA approval. The October 18th PR only addresses success of the Primary outcome and Secondary outcome #1. The PR didn't say if the study has shown a non-inferiority or superiority of HemoStyp vs Surgicel in the secondary outcomes #2-4. The history of UEEC only disclosing positive news makes us believe that the omission of results relevant to outcomes #2-4 could have been on purpose, because the clinical study likely showed the inferior performance of HemoStyp vs Surgicel in these outcome measures.
The statistician was very specific to claim non-inferiority and superiority of HemoStyp only in the initial hemostasis after application of HemoStyp to the wound. It is silent on what has happened after the initial hemostasis was achieved.
HemoStyp, according to UEEC, quickly dissolves in an aqueous environment due to its unique degradation properties. We can find this on the company’s website.
From UEEC’s product testing page:
The data obtained during analysis of sample UHP Box of 2” x 2” Pouches indicates the material begins to dissolve in water within one minute. The sample is completely dissolved within 24 hours. Not enough material remains for analysis at the 24 hour time point.
If HemoStyp dissolves too soon, the surgical wound would start bleeding again, and this would be a very serious safety issue.
Imagine a major disaster when bleeding re-occurs after the surgeon has already closed the outmost patient skin layer! The outcomes 2-4 directly address this key safety concern, describing in quantitative terms how well the initially achieved hemostasis is maintained during the surgery. Outcome 4 is about the failure of initial hemostasis, as measured in reoperations, during the one month after surgery. It seems to us that a hemostatic agent that is quick to achieve initial hemostasis, but rapidly dissolves and may frequently fail later resulting in recurrence of bleeding, is a major health hazard. Why would the FDA approve HemoStyp, if it indeed fails to maintain hemostasis, knowing that Surgicel is already a reasonably effective and safe FDA approved product?
From all these observations, we conclude that the clinical study of HemoStyp versus Surgicel was likely a failure. However, if and when its PMA application" gets rejected, we doubt that shareholders will hear about it. We expect it will be just like when UEEC applied for PMA approval for Class III in late 2017, there will just not be any updates, like it never happened."
