Re the early Mayo data, my response to a question on YMB

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Re the early Mayo data, my response to a question on YMB

Post by biopearl123 » Tue Jul 02, 2019 4:38 am

We have talked a lot about the Mayo data in the past and lamented its apparent burial. I think we just have to accept that we will never get a final reckoning. This is a response I posted earlier today in this regard on the YMB:

Cathy, The Mayo Clinic data was the first to show actual CRs and PRs. This data was published in the New England Journal, the most prestigious medical journal in the world. There were also CIs (clinical improvement patients) but the FDA required all patients who were not CR and PRs to be dropped due to the nutso hold due to elevated liver enzymes none of which met Hy's criterion for liver toxicity as far as I know. Also the patient numbers were small and as Scarlett said were "all over the place" in other words multiple different DIPPs criterion, basically all comers even a few AML patients who apparently showed a response. A lot of the data was published (see Geron's web site) but lots of other sub rosa stuff happened including an apparent freezing out of Dr T and a subsequent Mayo patent filing which I suspect was not done with the company's blessing but that's just conjecture. The structure of the study would not have been a path to approval. Nonetheless, seeing some survival data would have been welcome and we really don't know how long responses lasted or what other therapies were brought to bear. Yes there is valid criticism but little to be gained by looking at this study which was a hodgepodge anyway. As Dr. Raza said companies design studies to lead to approval if they can and the Mayo study wasn't it. We should move away from chasing this lost and potentially uninterpretable data. Also, Dr. T gave some patients a weekly injection of Imetelstat which led to profound cytopenias (I am not sure if they reversed or not, does anyone remember?) and the doses. The current doses schedule for existing and future studies have been modified in a major way. While I would have been very interested in a final reckoning from the Mayo, I think we will never get it and should move on to look carefully and more modern study design and dosing schedules. Regards, bp

Secret Third Arm
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Re: Re the early Mayo data, my response to a question on YMB

Post by Secret Third Arm » Wed Jul 03, 2019 1:38 pm

Very well said BP. If you're willing to re-post your comments on my SA blog I would greatly appreciate it.

My reading between the lines of Dr. Scarlett's words indicate that Dr. Tefferi was more interested in helping the patients in his clinic than he was in running a controlled study. I think he threw everything he could at the disease (dose changes, regimen changes, etc.) in the hopes of finding some efficacy. Unfortunately, while he did demonstrate the drug worked he did it in such a way that the data itself was a jumbled mess.

I think he is a passionate patient advocate and that he wanted to run to the FDA and insist Imetelstat be provisionally approved based on the Phase 1 or even a limited Phase 2. Perhaps with his clout he could have accomplished that; after all he helped get the FDA hold lifted. But I don't think that Scarlett thought that was the right path. Also, behind the scenes he knew JNJ was ready to take over the development of the drug and given his choice between Dr. Tefferi's long shot approach and JNJ's more methodical dual Phase 2 plan he chose the safer bet and went with JNJ.

Those who point to Dr. Tefferi now and say that he no longer likes 'any drug' for MF are being disingenuous and glossing over the egos that are involved here. Dr. Tefferi wanted Imetelstat to be used almost immediately in patients he felt could be helped. This is what all of us should want in a doctor. He probably also felt that it was his work that paved the way forward for a drug that had failed in multiple solid tumor trials. When cooler heads prevailed and a more likely path to approval was charted he was naturally upset that his vision for the drug was put aside in favor of a much longer road to approval.

There are very few things that I know with certainty in this world but I will say this; when Imetelstat is approved Dr. Tefferi will welcome it into his arsenal of treatments with open arms. His feelings may have been hurt by what transpired but if nothing else he has demonstrated that he is passionate about helping his patients. I also expect that he will be one of the first doctors to use Imetelstat off-label and hopefully he will be willing to share those experiences with his colleagues and with scientific journals.

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