Here all are the comments from the REAL doctors who voted at the Advisory Committee Meeting , the one dissenting doctor was adamant re the requirement to conduct an RCT , which is DocMcStuffins position as well, just in case you've missed it.
DR. GARCIA: Thank you, Dr. Hoffman. Jorge Garcia. I voted yes. I do believe the question perhaps to me was a bit too narrow
and simple, but based upon the available data, I do believe this agent has efficacy in the disease in question. Do I believe it's better than any other
existing agents? I don't know. Do I believe it's a safe agent? I do. Do I believe with 15 years of experience, no overlapping side effects,
in a diseased setting where there is clearly an unmet need -- I think that agent has shown some efficacy.DR. HALABI: Yes. Susan Halabi. I voted yes, and I believe that the drug has activity. Even though I was 51 percent for voting yes versus
49, it was really a struggle to make a decision,
but I was persuaded by the clinical experts who made the argument that it may not be possible to do
a randomized trial. I'm also hopeful that the sponsor will try to address some of the concerns that we have made in the next randomized trial.
DR. SUNG: My name is Anthony Sung, and I voted yes. While I agree with Dr. Hinrichs of the importance of rigorous studies, including
randomized clinical trials, I think back to Dr. Baird's slide on single-trial requirements and demonstration of a clinically meaningful effect on
a potentially serious outcome. With respect to Dr. Przepiorka's earlier comments,
I still cannot help but think that ruxolitinib received FDA approval with a single-arm trial, and I believe this study shows actually better data for the same indication. Although the landscape is a little different in that ruxolitinib is FDA approved for patients 12 and older, there's still a gap for patients younger than 12, and I believe that this fills that gap for patients in that age range.
Now, for patients who are 12 and older,
I do think randomized clinical trials are needed to provide further evidence, and it sounds like the sponsor's already planning such a trial with ruxolitinib as a control, which in my mind would be appropriate.DR. BUNIN: Hi. Nancy Bunin. I voted yes. I do think there are additional studies that need to be done on this drug. GVHD studies -- and I've
participated in more than a few -- are extremely messy and not as clear-cut as looking at a cancer drug for a variety of reasons. I do think this may
fill a gap. We use many drugs for GVHD which are not approved. For example, we use rux for many kids less than 12 for chronic GVHD.
Much of the experience I think is anecdotal, but I do think it may fill a hole and additional studies will be needed.
But what strikes me most
is the safety profile of this drug, which is much safer than the many other immunosuppressives we use to treat graft-versus-host disease.DR. FINESTONE: Sandra Finestone. I voted
yes, based on a need and compelling efficacy.
DR. KAMANI: Hi. This is Naynesh Kamani. I voted yes, and my reasons are similar to those expressed by other members.
Clearly, this is not a
randomized trial demonstrating efficacy over placebo or efficacy over best available treatment, but a 65 to 70 percent complete remission or
overall response at day 28 is impressive in a subset of patients who have a fairly dismal prognosis. There's also an unmet need for approved
drugs for this indication. Just to reiterate what Dr. Bunin said, the dozen or more than a dozen drugs that are often used to treat these patients all have toxicity profiles, which are probably much worse than the ones with remestemcel, so I voted yes.
DR. WALTERS: Yes. Mark Walters. I voted yes. I was also on the fence for all the reasons stated, and in the end,
I was persuaded by the
public voice and the patient efficacy arguments, and my own clinical practice facing those situations with families as well.
DR. HOFFMAN: Okay. This is Dr. Hoffman. I voted yes, and I don't think I have additional reasons beyond what many of my colleagues have
already voiced and what I said toward the end of the question discussion, that
I find the clinical evidence compelling. Even though it is not
randomized, it's a product that's hard to characterize. And because there were no significant safety signals that were new or different or worse, on balance, I felt that I would vote yes.
The Doctor's voted on this question.
Do the available data support the efficacy of remestemcel-L in pediatric patients with steroid refractory acute GVHD?The FDA had issues with earlier trials using Prochymal vs a later trial using the improved product Ryoncil. They also had concerns with chemistry, manufacturing and control items. In particular adequate potency assays and batch consistency from multiple donors. This is the stuff that Whytee has been banging on about for the last few years, ad nauseam.
Whytee refuses to acknowledge that any progress has been made in addressing the FDA concerns since August 2020. Indeed he has recently said it would take a miracle to be approved.
DocMcStuffins holds fast to his line that only an RCT trial results would see Ryoncil approved. Then even if approved he wouldn't use it, nor would it sell . That an approval is already baked into the share price, top dollar is $1.50 and is wondering why the company has not announced patient survival improvement numbers despite multiple company announcements and presentations to the contrary.
You know what they say about doctor's, get a second opinion. See above for multiple second opinions.
Finally , one more opinion or should I say point- from the top dog, numero uno , the Big Kahuna, the person who Whytee would need to call a Saint if a miracle occurs- Saint Silviu of Collins Place
John Hester
And is there any confusion now as to the level of potency that the product that’s been manufactured in recent years will deliver? Because this analysis indicates there was a significant difference between the earlier Prochymal product and the – products…
Silviu Itescu
That’s precisely the point. That’s exactly the point. The clarification has come through the analysis that demonstrates that improvement in manufacturing, changes in manufacturing, which were implemented in, at a particular point in time in the development history of the product, delineates a more potent product currently in use in our studies from the less potent product that was called Prochymal that failed in other earlier studies. And so we believe that the, the reason that we’re seeing greater clinical outcomes with our newly improved product is because of its greater potency as measured by our validated potency assay. And that is very encouraging both in terms of the pediatric data and the data that we expect to generate in adults.
John Hester
So to what extent has that – new data on the potency been available in over the last two years since the complete response letter? Or has that always been available?
Silviu Itescu
No, these are data that are newly generated as part of the BLA resubmission in alignment with optimization of the potency assay. But the assay itself has been in place and was in place when products were being used in both the EAP and the Phase 3 trial. And so what this provides us now is an understanding of how changes in manufacturing have resulted in a more potent product, which correlates with better survival.
Was that the turning point, scientific proof of Ryoncil efficacy without the need for an RCT?
We are about to find out
Reg
(20min delay)