Parsing the obnubulate Scarlett
Posted: Sun Dec 22, 2019 9:06 pm
What to make of the last press release re the EOP2 meeting with the Feds? Here we have this:"Based on feedback from the meeting, over the coming months Geron plans to submit several Phase 3 trial design proposals in relapsed/refractory MF and to have further discussions with the FDA regarding potential regulatory approval pathways. The Phase 3 trial proposals will be designed to fully characterize the efficacy, safety, and benefit-risk profile of imetelstat treatment for these patients, as well as to confirm the clinical benefit and disease-modifying potential of imetelstat in this indication."
So several is "more than two but not many". So at least three different proposals for continued study in R/R phase III. Why not just one incorporating the guidance from the FDA? Seems a little odd. What is Scarlett trying to say that he just as usual does not come out and just say? One can only speculate. First off it is clear that they do not as yet plan to pursue front line, something we all wanted to see. Each proposal is for R/R indication not front line. Why? I think it's the same problem of front line requiring a longer study time. Well that would be true if mortality were a primary end point but in this day of molecular markers and objective bone marrow findings as well as objective spleen and symptom assessment and I would think a much shorter front line study could be designed. Yet they choose R/R probably because there is no competition here. Possibly a good business decision. Now why "several" study designs? Please add your voices to this speculation but here are my thoughts. A post market P 4 would probably be large and long but allow for easy approval and allow actual sales of the drug. Thats one possibility. If the FDA did not allow a P4 study then a smaller faster PIII study design would be a fall back. But since there is no income associated with this and Geron is pouring a lot of resources into the MDS study they might not proceed. This is the "implied Scarlett threat"--if you don't give us a shot at early approval we won't develop the drug. Scarlett has made that abundantly clear and if the FDA does not support an early to market strategy, it is on them and a patient revolt would be warranted. Scarlett's iron fist in the velvet glove approach. So that's two studies. What's the third (to complete the definition of several?). This would likely be a combination study with Rux in cooperation with Incyte (my speculation only), but this makes some sense based on the recent presentation at ASH. Each of these study designs ironically would compete with each other for patient enrollment and could slow a companion study down unless it was one study with several arms perhaps including a RWD arm. In theory a RWD arm already exists and is there for the taking as long as proper statistical rules are followed. Geron has strong leadership courtesy of Janssen in this regard. To keep the studies short a surrogate end point will be needed that is acceptable to the agency. We should know more soon. Clearly the best route to market is a provisional approval and a P4 study, I hope the FDA sees it that way, but the better treatment for patients could end up being the proposed Rux/Imet combo. Not sure how Geron would get around that but we should know more soon. Best wishes to all for a happy holiday season and a prosperous New Year. The latter would certainly be a pleasant surprise. bp
So several is "more than two but not many". So at least three different proposals for continued study in R/R phase III. Why not just one incorporating the guidance from the FDA? Seems a little odd. What is Scarlett trying to say that he just as usual does not come out and just say? One can only speculate. First off it is clear that they do not as yet plan to pursue front line, something we all wanted to see. Each proposal is for R/R indication not front line. Why? I think it's the same problem of front line requiring a longer study time. Well that would be true if mortality were a primary end point but in this day of molecular markers and objective bone marrow findings as well as objective spleen and symptom assessment and I would think a much shorter front line study could be designed. Yet they choose R/R probably because there is no competition here. Possibly a good business decision. Now why "several" study designs? Please add your voices to this speculation but here are my thoughts. A post market P 4 would probably be large and long but allow for easy approval and allow actual sales of the drug. Thats one possibility. If the FDA did not allow a P4 study then a smaller faster PIII study design would be a fall back. But since there is no income associated with this and Geron is pouring a lot of resources into the MDS study they might not proceed. This is the "implied Scarlett threat"--if you don't give us a shot at early approval we won't develop the drug. Scarlett has made that abundantly clear and if the FDA does not support an early to market strategy, it is on them and a patient revolt would be warranted. Scarlett's iron fist in the velvet glove approach. So that's two studies. What's the third (to complete the definition of several?). This would likely be a combination study with Rux in cooperation with Incyte (my speculation only), but this makes some sense based on the recent presentation at ASH. Each of these study designs ironically would compete with each other for patient enrollment and could slow a companion study down unless it was one study with several arms perhaps including a RWD arm. In theory a RWD arm already exists and is there for the taking as long as proper statistical rules are followed. Geron has strong leadership courtesy of Janssen in this regard. To keep the studies short a surrogate end point will be needed that is acceptable to the agency. We should know more soon. Clearly the best route to market is a provisional approval and a P4 study, I hope the FDA sees it that way, but the better treatment for patients could end up being the proposed Rux/Imet combo. Not sure how Geron would get around that but we should know more soon. Best wishes to all for a happy holiday season and a prosperous New Year. The latter would certainly be a pleasant surprise. bp