In case Sdraw reads this board--repost from SA

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biopearl
Posts: 367
Joined: Wed Dec 09, 2015 12:12 am

In case Sdraw reads this board--repost from SA

Post by biopearl » Wed Mar 21, 2018 9:27 pm

Jay, I read every one of Sdraw's posts carefully and slowly. He has really helped me think about the data and structure of the various studies. I hope he reads this board because this question is for him (or anyone else who might be able to respond). I have always been sensitive to the ethics of how studies are structured and have sat on hospital IRBs that review studies. I just don't see how "closing P2 and moving quickly to P3" happens. I agree they want to close P2 but first off if they haven't reached median OS, the longer the wait the higher the impact but at some point as suggested by others after 24 months further OS determinations could take place after the study closes and the amendment allow for remaining patients to continue treatment and follow up. My issue is this. How does one structure a P3 in a terminal patient population? It implies a control arm. I think the ethics of this are apparent and hence the depth of foresight J and J had in hoping the FDA would allow a "historical control arm"--granted this is not pure. Sdraw, with all due respect (and you are due much) I don't see how they can do a P3 in R/R. Perhaps you were thinking a P3 for front-line? That would make good sense. If so please respond. Even if FDA allows a P3 for frontline we should see the drug approved for R/R patients (soon) and therefore on the market and maybe available for off label use earlier in the disease, (I have gotten some harsh responses for this suggestion) before but I still think it has validity and might make doing a front line study harder. Your points need no emphasis: 1. OS now in territory never before seen 2. Study closed early because a large sized group not required to prove statistical significance. That's a big one. Regards, bp
21 Mar 2018

Dogonenuts
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Re: In case Sdraw reads this board--repost from SA

Post by Dogonenuts » Wed Mar 21, 2018 10:04 pm

In regards to skipping a P3 with imetelstat, one only has to look back at SRPT. They got a drug approved that really is questionable whether it works at all. This drug passed on anecdotal performance in 12 patients with no controls. Truly this is a friendlier FDA, and I will not be surprised to see IMET approved fairly soon. There is no ethical way to do a double blinded study on r/r pts with no other choice.

jpheis
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Joined: Thu Jul 27, 2017 2:55 pm

Re: In case Sdraw reads this board--repost from SA

Post by jpheis » Thu Mar 22, 2018 2:25 am

sdrawkcabeman via Yahoo Finance
The story of Azacitidine parallels Imetelstat
In 2004, Pharmion’s hypomethylating agent, Azacitidine, was the first drug approved by the FDA for all subtypes of MDS. Celgene bought Pharmion for $2.9 billion in 2008. Meanwhile, Celgene had gotten approval by the FDA for lenalidomide in 2005. The idea was to build a portfolio of blood treatments, a strategy on which they’ve recently expanded with their $7 billion purchase of Impact Biomedicines to acquire Fedtratinib.

In 2008, Azacitidine received an expanded label by the FDA to include overall survival for treatment of higher risk MDS based on median OS advantage of 24 months to the conventional care of 15 months.

In 2015, Azacitidine received approval by the EMA for treatment of AML in elderly pts over 65y.o. based on a medial OS advantage of 10.4 months to 6.5 months for conventional care.

We know blood is a primary focus of Janssen, and Imet is a strategic property in that regard; it has already been positively demonstrated to work across all the myeloid malignancies. That is an astounding, I repeat, ASTOUNDING breadth of efficacy, especially considering the depth of response in those indications. And so it has more value to Janssen b/c of this blood focus. Also, Janssen will have sponsored preclinicals we haven’t even seen yet, no doubt a revisitation of the lymphocytic malignancies, if not also solid tumors.

The expanded label to include the 24 month to 15 month median OS advantage of Azacitidine in MDS reflects the FDA’s acknowledgement that it is indeed a significant result! We can say it’s an even more significant duration for an R/R pop in MF!

And again we see the critical unmet need in AML with an approval to treat pts based on a very modest 4-month median OS advantage with Azacitidine. Imet in preclinicals has shown much more promise. We know Imet in AML will be a combo study, and, within all reason, considering Imet’s global efficacy in the myleoid group, that study is very likely to be groundbreaking.

The data have shown again and again that Imet’s target is, in fact, progenitor cells. This is so critical! We continually see that patients become harder and harder to treat in correlation to genomic instability. Might we even say that disease progression correlates to genomic instability? Targeting the cancer stem cells is a surgical way to nip genomic instability in the bud by preventing that proliferation in the first place. And this really is the excitement surrounding the development of Imet. JAK inhibitors simply have a ceiling, and you can put them ALL under that ceiling. To beat the drums again, yes, those drums, targeting telomerase isn’t specific to any particular cancer; and that’s been outlined in that wonderful Yale study. So in that regard we can say the parallel to Azacitidine’s story ends, b/c Imet will continue beyond the myeloid group, and the more daring among us will say beyond blood soon enough.

http://theoncologist.alphamedpress.org/ ... 3/176.full

http://www.bloodjournal.org/content/126 ... ecked=true

http://www.pnas.org/content/pnas/111/30/E3062.full.pdf

The Oncologist is a journal devoted to medical and practice issues for surgical, radiation, and medical oncologists.
theoncologist.alphamedpress.org

Fishermangents
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Re: In case Sdraw reads this board--repost from SA

Post by Fishermangents » Thu Mar 22, 2018 10:23 am

the Gupta PNAS article is great. Will add it to imetelstat.info soon.

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