Frontline Treatment and a Geron / J&J carbon copy? - Pt 1

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kmall
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Joined: Thu Mar 21, 2019 3:57 pm

Frontline Treatment and a Geron / J&J carbon copy? - Pt 1

Post by kmall » Mon Jun 08, 2020 1:09 am

Last week Andrew posed several questions to the Imetelchat board directed at what seems to be Geron’s strategic use of Imetelstat in the IMbark trials towards the latter portion of patient treatment after BAT have failed and prognosis is quite dire. It seems to be a fair assessment of Imetelstats role these clinical trials. Patients enrolled are R/R to Jakafi and who are in the late stages of the disease, making treatment with Imet that more challenging. Logic would dictate a frontline approach since a high rate of success in these cases with very high transfusion burdens has been proven given these hurdles. Once again, as I’ve stated on multiple occasions, I’m far from an expert on the science / medical side. Instead of regurgitating stats and results which have been made public, and most of you have pondered over at great lengths, I’ll stick to the basics of what I know and can evaluate as far as strategies are concerned.

For starters, with the recent global pandemic of Covid and its propensity to strain global blood supplies; Andrew had pointed out 2 months ago that using Imetelstat as frontline treatment in both indications could possibly alleviate this shortage since we are seeing transfusion independence in a vast majority of patients treated starting at 8 weeks. And mind you, as most of you know, both trials contain very sick patients. The IMbark trial patients have been treated with Jakafi for a year or so before turning to Imet. If I remember correctly Andrews bottom-line assessment was a savings of over 400,000 units of blood / year with an economic saving of somewhere in the $250 million - $500 million ballpark – in just the MDS patient population (Please correct me if I’m off on any of this Andrew). Again, I would assume that its slightly difficult to pinpoint since multiple variables involved. Regardless, it should be incentive enough for EMA approval, since most European countries subsidize healthcare. I won’t go into detail since I’ve gone over this before, but it’s my belief that EMA approval may be the primary focus of Gerons management as of now – perhaps that will change given last weeks revelation of NEA Partners not only having a 9.6% stake in Geron’s recent public offering, but also the addition of the former FDA Director – Dr. Scott Gottlieb** to their “Healthcare Team.”
https://www.nea.com/team?team=526&locat ... am-members

*There are two divisions in NEA’s HC division – Washington D.C.** and Menlo Park, CA

Both of these locations bode well for Geron – Washington D.C. for being where FDA Headquarters are and Menlo Park just happens to be where Geron’s base of operations is………are the planets finally starting to line up here?

Going over Andrews concern towards frontline treatment. From my perspective of submitting data to the FDA on P3, since the current pattern for the IMbark trial targets R/R Jakafi patients; will a new set of exposure / response relationships be required by the FDA for frontline consideration? If anyone here knows the chain of events / timeline for that scenario I would appreciate some clarification. I was able to find an FDA Guidance for Industry (2003)pdf -https://www.fda.gov/media/71277/download , however, no mention of “frontline,” and if that would trigger any modifications with regards to changes in data / result criteria?

That brings me to the question that seems to be on everyone’s mind. During the most recent CC it was posed by Chad Messer and that was - It seems as if Imet is being held to a higher standard then that of other drugs in the space already approved?

Chad Messer -
“wondering if there's one thing you can maybe share your thoughts on with me with regards to MF. And that's -- all other drugs approved or late-stage development are kind of getting away with a sort of hybrid off their end point, and you guys are kind of being held to the sort of high bar of OS. But just wondering if you have any follow-ups on why that may be? And whether or not your really strong OS data from the Phase II, though smallish though it may be, is somehow ironically working against you”

John Scarlett
Well, let me take that, first of all, and then I'll invite Alex to make additional comments. I would actually look at it differently. I think that we view the ability -- the confidence we have in a potential OS benefit, which, as you commented on, came from both the real-world data analyses that we did and reported previously and also just the comparison in the IMbark study to the historical controls.
We always saw that as not a burden to bear, but actually an incredibly valuable finding and a deeply differentiating element to our drug, to imetelstat. So far from viewing it as something that we were going to be held to a higher standard than anyone else, it may be true that it's a higher standard. It takes a little bit longer and it takes substantial resources to do.
But on the other hand, coming out at the other end of this, I think we expect to have the only drug that will have been through -- the only drug in JAK refractory patients who make up a very substantial part of the market, the only drug that will have actually demonstrated a survival benefit in such patients and a survival benefit. In fact, JAK is a primary outcome measure.
So this is actually new ground. But with new ground also comes high barriers to entry potentially and also a great differentiation. I can tell you the investigators that we engaged in working through the details of this type of approach, we're just simply extremely excited about the possibility of getting a drug that would have this type of benefit demonstrated. So that was our real approach to it. And I think we feel pretty terrific about the opportunity to go there. Did I leave anything out, Alex?

Aleksandra Rizo
Yes. Maybe I can just reinforce, Chip. I mean, we love the fact that we have a drug that can improve overall survival in this relapsed/refractory setting as there's no other drug, as you mentioned, that has shown that. And as you know, right, other drugs are having primary end points that are addressing the symptom of the disease, whether that's a spleen or a symptom response or an anemia improvement or a combination of the above, right?
So what we have here is an overall survival. And I think that we have the possibility or the chance to have a paradigm shift in the thinking of how you approach treatment with myelofibrosis.

It looks like Dr. Scarlett and the team embrace the challenge and feel confident enough with the results and data as of now. As long term investors that should be reassuring……well, let’s hope so, but for the sake of the patients I have to admit my patience is stretched thin – I’m pounding my fists for frontline….NOW !!!!

.........cont...

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