Thoughts on this week's presentation
Posted: Thu Nov 16, 2017 3:28 pm
Thoughts on this week's presentation in no particular order or organization, in other words if you read this prepare yourself for some chaotic thinking, others are welcome to modify, criticize.
1. We can glean that the marker that allowed for the decision to drop the 4.7 arm was HI (hematologic improvement). This would have shown up early and would not require bone marrow studies or major spleen effect. We know that Dr. T has stated the effect in MF is deeper or more profound than in MDS and in MDS there was an impressive alteration in TI between 30 and 50%. HI should address the FDAs need for a surrogate marker for drug effect.
2. Even 10% improvement in spleen volume is associated with an improvement in survival. Its not about spleen effect for approval, that is a byproduct of targeting the malignant clone. Get over the pursuit of 35% spleen reduction in R/R population. But (implied) improvements in bone marrow in some patients has been seen (don't know if this applies also to R/R patients because we don't know if they have had BM bx). The marker however is HI and this is where the action is. If there is HI, one could assume symptom improvement and improvement in hematologic parameters and reduction in transfusion requirement. Scarlet said "it does happen" (re bone marrow clearing) not it "has happened"(which we know). Small tense issue but it suggests a more current view.
3. Lots of patients on Imetelstat for 3+ years. This can only apply to the pilot study (unless some patients from the old ET study are still on Rx and we don't know that.) If so more evidence for survival effect.
4. FDA has asked for MF info not because there is trouble but because they wish to consider BAT/accelerated approval.
5. If granted, drug approval in R/R could precede the anticipated "continuation agreement". In other words get over holding your breath for the Janssen agreement, this is likely to happen. Its really about FDA approval which may antedate action by Janssen.
6. All those disclaimer about how things can change are always (and usually are) thought about as negatives. In this case timing could change in favor of the drug and the timelines could be revised.
7.OS looks good and is the gold standard, especially in a population with a life expectancy so short. The antecedent bar for spleen reduction must be revised in light of new data in a heretofore unstudied population. FDA knows this.
8. Patients have remained in the 4.7 arm for reasons we don't know but presumably showed something, but not as profound as the 9.4 group which is the "right dose".
9. They are looking for survival effect in MDS as well and think they will find it.
10. Targeting the malignant clone is unique to Imetelstat and address a very primary etiology of the disease.
11. A disconnect between the "continuation" agreement which everyone is holding their breath for and FDA approval for R/R could be real in favor of an approval time line.
Best Regards, and good luck to all bp
1. We can glean that the marker that allowed for the decision to drop the 4.7 arm was HI (hematologic improvement). This would have shown up early and would not require bone marrow studies or major spleen effect. We know that Dr. T has stated the effect in MF is deeper or more profound than in MDS and in MDS there was an impressive alteration in TI between 30 and 50%. HI should address the FDAs need for a surrogate marker for drug effect.
2. Even 10% improvement in spleen volume is associated with an improvement in survival. Its not about spleen effect for approval, that is a byproduct of targeting the malignant clone. Get over the pursuit of 35% spleen reduction in R/R population. But (implied) improvements in bone marrow in some patients has been seen (don't know if this applies also to R/R patients because we don't know if they have had BM bx). The marker however is HI and this is where the action is. If there is HI, one could assume symptom improvement and improvement in hematologic parameters and reduction in transfusion requirement. Scarlet said "it does happen" (re bone marrow clearing) not it "has happened"(which we know). Small tense issue but it suggests a more current view.
3. Lots of patients on Imetelstat for 3+ years. This can only apply to the pilot study (unless some patients from the old ET study are still on Rx and we don't know that.) If so more evidence for survival effect.
4. FDA has asked for MF info not because there is trouble but because they wish to consider BAT/accelerated approval.
5. If granted, drug approval in R/R could precede the anticipated "continuation agreement". In other words get over holding your breath for the Janssen agreement, this is likely to happen. Its really about FDA approval which may antedate action by Janssen.
6. All those disclaimer about how things can change are always (and usually are) thought about as negatives. In this case timing could change in favor of the drug and the timelines could be revised.
7.OS looks good and is the gold standard, especially in a population with a life expectancy so short. The antecedent bar for spleen reduction must be revised in light of new data in a heretofore unstudied population. FDA knows this.
8. Patients have remained in the 4.7 arm for reasons we don't know but presumably showed something, but not as profound as the 9.4 group which is the "right dose".
9. They are looking for survival effect in MDS as well and think they will find it.
10. Targeting the malignant clone is unique to Imetelstat and address a very primary etiology of the disease.
11. A disconnect between the "continuation" agreement which everyone is holding their breath for and FDA approval for R/R could be real in favor of an approval time line.
Best Regards, and good luck to all bp