Very Nice New Years gift from Dr. Santini, Dr. Zeidan, Dr. Fenaux , Dr. Raza, Dr. Feller et.al

[Ryan]

Published 12/31:::
https://www.nature.com/articles/s41408-025-01444-0

[rccola335]

nice find - nice to see that the cardiac substudy is required for new agents and there were not concerns

[Ryan]

In like a Lion.

[biopearl123]

Nice find Ryan and thanks for posting this. Some of the data has been presented in meetings but I don't think the entirety has, and emphasizes that patients who have failed multiple therapies still have a place to go. But unstated is the clear between the lines, that patients had to fail existing therapies before they got to Imetelstat. What we don't know and the glaring omission (thank you FDA), is what would have happened if these patients had been able to start therapy much earlier in the course of their disease. The FDA has made answering this so so difficult by requiring the sickest patients to be tested first (see the relapsed, refractory studies and the rejection of Dr. T's initial protocol of 10 years ago.). The march to the front of the line is glacial but apparent.

[biopearl123]

RC, re the cardiac substudy--I can tell you that hundreds of patients got Imetelstat (and ECGs that would help unmask any evidence of QT prolongation, tendency toward Torsades type of arrhythmia etc, further supported by preclinical work in lab animals which I checked out early in my investigations into Geron,) my view (just my opinion) is that the substudy was a back door way to enroll more patients and further straighten the study. Maybe the FDA required specific data re ion channel blocking effects and if you've ever seen cases of Torsades (I rescued many from the jaws of death, most med related) you would understand the requirement, but really there was never any specific issue in the past, the way there was with liver function etc.

[rccola335]

what I am saying is - when this arm to the study was released to the public, there was concern why it was necessary - many people on here were concerned that some adverse events may have occurred - seeing this article it says doing that arm is just normal requirement for a new entity - no red flags had occurred

[biopearl123]

RC the question of ion channel effects was asked and answered several times in several ways including monkey studies and close evaluation of potential cardiac effects clinically. The sub study may have been yet another FDA required hurdle which Geron passed but my point was that they had for all intents and purposes already passed it and were able to enroll more patients in the MDS study than originally called for in the protocol to put the matter to rest.

[Ryan]

Longer life from BAT (best available therapy) is a great thing. Patients are living longer. Also should be expected, considering the Phase III is entering its 6th year (mas o menos)…

Won’t change that the results from Imet, from the subgroup or the crossover group, will be undeniable.

Prepare to not be disappointed this year…

Goldman’s $1 call already hit a month or so ago, and Goldman bought a ton of shares during the past 6 months or so. Cause their analysts and trading floors are completely siloed.
RA Capital and the other heavyweights are in.
Seems the science and the market are finally going to row in the same direction.

[biopearl123]

Ryan, longer life in the BAT arm IS a good thing for those patients and if present, likely represents advances in non Imetelstat related therapies, or the general benefits of just being in a study. Just being in any study often shows control arm improvements in its own right, likely due to closer follow up, patient compliance in other areas etc.) And yes there hopefully will be an outstanding difference between the two arms regardless, but how big that delta is will be important. The bigger the better and for a study with OS as the primary end point, the longer the control arm patients live, the smaller the delta, the less impressive the hazard ratio, the less significant the p value.

[lacour_98]

Understood that advances in non-IMET related therapies, BAT, may be contributing to control arm OS improvement and the general benefits of just being in a study contribute to patient improvement, but how will the trial assessment account for improvement due to BAT as opposed to many trials where the control arm is placebo? How many LR-MDS patients out there don't get BAT, whatever BAT is? Since no other treatments appear to treat the underlying cause, only symptom relief, I remain convinced IMET is the best answer to LR-MDS and MF and will move up the treatment ladder.