1. Did the FDA give them any concrete idea on what should constitute proper grounds for an NDA for tirasemtiv? What set of endpoints? Any concern for TEAEs?
2. This one I could research, or just ask Mr Blum - cost of current SoC Riluzole? I am sure this has been discussed but they will anyway refuse to divulge - but probable pricing of tirasemtiv in ALS?
3. When will Amgen announce P3 for omecamtiv?
4. Was MTD achieved in oral/IV trials for omecamtiv? (Important because PD appears to be dose-dependent)
Here are the responses I received:
I was able to speak to Robert Blum on Thursday. FYI, he is not Dr. Blum- he is an MBA from Harvard...
Mr. Blum says he gets a lot of questions on what guidance the FDA has given regarding Tirasemtiv's potential approval. The Primary Endpoint related to SVC improvement will not be enough on its own,- some secondary endpoints in the trial will have to show improvement. However, he emphasized that there are secondary endpoints that should correlate with an improvement in SVC that meets the primary endpoint. Additionally, were the SVC improvement not only to meet the goal of the Primary Endpoint,but exceed it by a significant margin, he feels that would weigh in the FDA decision- it would still take progress on secondary endpoints to gain approval, but outperforming the goals of the Primary Endpoint could be a significant factor as the FDA weighs the totality of evidence from the trial. In addition to light-headedness, which has been reported by patients in many studies on Tirasemtiv, and which CK-2127107 is designed to avoid, weight loss is a potential AE that they are on the lookout for with VITALITY-ALS. Mr. Blum noted that weight loss is an issue for all ALS patients, but in VITALITY-ALS they are paying very close attention to it and any patients experiencing weight loss beyond the statistical norms will be given nutritional counseling. While not a definite answer to your question about TEAE's, I think it's clear that light-headedness and weight loss are two things that are having a lot of attention paid to them.
With regard to Riluzole,- going from memory he thought it was about $1,000 a month while it had patent protection, and he asked the investor relations chief to get back to me with the price now that it is generic. If they get back to me, I will follow up with you. As a side note, one thing I find extremely attractive about Tirasemtiv is that an ALS diagnosis automatically qualifies a patient in the USA for Medicare, so with regards to a potential Tirasemtiv approval the US very much has a single payer system.
I gave you the answer I'd recently heard on potential Omecamtiv Phase III in my last Email. They do expect to hear back from the FDA regarding the SPA soon. He reiterated in my conversation with him that he expects a decision this quarter. (Greg says: I can answer your third question right now! All they are willing to say is they believe Amgen will make a decision this quarter. Amgen said in its call Wednesday that they are waiting to hear back from FDA on the SPA they've submitted.
In Earnings call yesterday they stated they were beginning to look into pricing of Tirasemtiv with potential payers but did not give any range they were looking at. If I do get a chance to talk with Robert I will ask again- I will certainly share publicly any answers to your questions, or if I don't post them publicly because they aren't informative I will write you again to share whatever response I received...)
As for MTD in the IV Omecamtiv study, he stated they was not designed to reach MTD as they felt with Acute Heart Failure patients this would entail too much risk. They were looking for efficacy in a dosing range that they felt would be unlikely to produce AE's. With regards to the recent trial for Chronic Heart Failure, the dose titration strategy was specifically designed to keep patients within the therapeutic window of 300-400 ng/ml. Apparently, patients respond significantly disparately to Omecamtiv so that treatment needs to be customized to ensure no outlier patients do not go over 1000 ng/ml. The narrow therapeutic window of Omecamtiv is something that they feel they've learned a great deal about in the decade it's been under development- hopefully both you and I will get to see how they approach this in Phase III.
I hope these answers are helpful to you!
Analyst X was on my Geron panel when I was writing on SeekingAlpha.