less competition

[jayfish101]

Novartis noted that its Phase 3 STIMULUS of Sabatolimab (MBG453) to treat Myelodysplastic syndromes (MDS) did not meet its primary endpoint,

[Ryan]

Click the link to see the reaction from Dr. Steensma.
(Don’t need to login to see…)

https://twitter.com/DavidSteensma/statu ... 7171474463

“Discouraging news today: #MDSsm sabatolimab+azacitidine STIMULUS-MDS2 trial was negative (no OS benefit vs aza alone.) It has been so long since there was good news in HR MDS. If venetoclax+HMA trial is negative will Pharma give up on HR-MDS as too hard?”

This is High Risk (HR) whereas Imetelstat is currently going after Low Risk.

[biopearl123]

Interesting. This from the primary author of the PII study in L/R MDS, one so intimately familiar with Imetelstat and of course a world authority on myelodysplastic syndromes. He correctly laments the inability of current treatments to prolong life in HR MDS. Those of us who as non oncologists try to understand this universe of diseases have seen the classification and understanding of both AML and HR MDS conflate. The Novartis study failed to show an improvement in OS. The Geron HR MDS/AML study is ongoing with a short trial period and with an endpoint of overall improvement (not OS which would be hard to prove with such a short study) but this current study sets the stage for a future combination study that will likely be longer and enroll more patients, no doubt looking for an end point of OS. So why, oh why, does Dr. Steensma not shed a glimmer of optimism on Imetelstat as providing the highly sought after agent (alone or in combination) that could deliver this improvement in OS in this terrible disease?? Dr. Lane’s lab did provide that glimmer. Dr. Steensma of course left Novartis after a short stay. Why? We do not know. Now he comments on the terrible outlook for any effective therapy on the horizon for the treatment of HR/MDS. Is he setting the stage for Geron’s day in the sun? Or is he damning the drug by totally ignoring its existence. Thoughts? bp

[LWS]

Imetelstat--safe, unique, effective

My thought is that the data is convincing and the EAP (JS said---could be considered a phase 4) is ongoing. The trials (with minimal safety concerns) have shown positive results in transfusion independence, survival time, disease modification, and quality of life (fatigue). I think all is well, but one never knows. The March 14 (ODAC meeting) seems to be a big step in the right direction. The conferences and publications that I have seen all appear to be very positive,
==================

Now he comments on the terrible outlook for any effective therapy on the horizon for the treatment of HR/MDS. Is he setting the stage for Geron’s day in the sun? Or is he damning the drug by totally ignoring its existence. Thoughts? bp

[Ryan]

My take on your question about Dr. Steensma's intent, which of course is an uneducated guess:

I think High Risk and Low Risk MDS are just different diseases. You know that, and I think in that is the reason. This expert is focusing on the High Risk designation, and is not considering imet yet without defined trial results.

His quote: "It has been so long since there was good news in HR MDS."

I think if asked about LR MDS, it would be a different statement. Prior pronouncements on social media, before entering Novartis, were congratulatory praising the "good news".... when *he* presented the data at the major conference.

I would expect to hear from Dr. Steensma, whether directly or indirectly, at the March meeting.

Interesting. This from the primary author of the PII study in L/R MDS, one so intimately familiar with Imetelstat and of course a world authority on myelodysplastic syndromes. He correctly laments the inability of current treatments to prolong life in HR MDS. Those of us who as non oncologists try to understand this universe of diseases have seen the classification and understanding of both AML and HR MDS conflate. The Novartis study failed to show an improvement in OS. The Geron HR MDS/AML study is ongoing with a short trial period and with an endpoint of overall improvement (not OS which would be hard to prove with such a short study) but this current study sets the stage for a future combination study that will likely be longer and enroll more patients, no doubt looking for an end point of OS. So why, oh why, does Dr. Steensma not shed a glimmer of optimism on Imetelstat as providing the highly sought after agent (alone or in combination) that could deliver this improvement in OS in this terrible disease?? Dr. Lane’s lab did provide that glimmer. Dr. Steensma of course left Novartis after a short stay. Why? We do not know. Now he comments on the terrible outlook for any effective therapy on the horizon for the treatment of HR/MDS. Is he setting the stage for Geron’s day in the sun? Or is he damning the drug by totally ignoring its existence. Thoughts? bp

[biopearl123]

Hi Ryan, thanks for sharing your thoughts. I also would certainly hope Dr. Steensma would weigh in, in March. He clearly has been pleased with the LR results and was lead author on the JCO article. We have reviewed articles on this board that suggest that LR and HR/MDS are not necessarily different diseases. For example buried somewhere here is an article that suggests that even "de novo" AML starts somewhere with LR disease that may not be picked up. It is also established that LR MDS can "transform" to HR/AML (or it may never do that or just smolder while requiring continued blood transfusions.). In any case you are right there is limited data for HR/MDS and AML re Imetelstat but there is some. Recall the preclinical work in mice the used the word "cure". Also we await further data from the likes of Dr. Lane et. al. I do doubt that any of this will be presented to the FDA in March and the focus will surely be limited to the LR/MDS data which now seems firmly established and demonstrated the unique properties of Imetelstat particularly with reference to disease modification. bp