Seeking Alpha has a transcript of the earnings call, so I won’t be summarizing, but a few comments:
First, for the Cfers and their families: Read the transcript (especially Q&A) or listen to the call. Very exciting. Specifically in my mind two things: 1) The number of times in response to a question about the FDA discussing the pivotal trial for 809/770 which Vertex said it couldn’t answer, they said "Breakthrough Therapy." In other words, this is going to turn out great for the design of the pivotal trial: I predict 99% confidence of a 400 bid dosing arm and with 70% confidence 6 month trial length, with conditional approval. 2) In discussing the 400 bid, Vertex said it is not just that it is higher dosing but that it will give better cmax/cmin and distribution so this could be doubly good, i.e., much improvement over 600 daily dose because a higher dose and better distribution!!
Second, for the regular investors who helped me learn so much in those dark early days. I don’t think many (i.e., the market investors) have quite gotten a grip on the Breakthrough Therapy designation and what the means for the future of Vertex. Investment should not be based on today but tomorrow and what this designation means for the CF Pipeline at Vertex is HUGE. Not just for the 809/770 combo, but for 661 and for the second generation correctors which will be fixing the CFTR for all 100% of the Cfers. It will mean not just quicker trials and faster approvals, but also the use of surrogate markers for approval, both validated and potentially unvalidated. Those who follow this know that there is a lot of research on other (non SC/non FEV markers) and Vertex I believed participated in one of those studies presented in the last two years at the CF convention. Together this is going to mean that 809/770; 661/770; and second generations are going to be to market soooo much quicker. I’m not thinking DS will have the 809 combo in 1.5 years as oppose to 2.5 years.
Verity, it is good to see your post.
It is not always perfectly clear what Peter Mueller says in a Q&A session, but it has been perfectly clear because he stated more than once, that the preferred objective is to develope VX-661, not merely as a better alternative to VX-809, but as a component of a truly second generation drug candidate to repair all F508del CFTR. If you compare VX-809 as a single hit in baseball, 661 belongs to a class of triple-base hit that brings in a runner, not because 661 is so good by itself, but because it can be combined with other correctors which may debut in the near future.
A single CFTR protein has at least two NBDs (nucleotide binding domains), but the 508 mutation is defective in the first two NBDs. So, to repair 508 CFTR fully it may take more than one corrector. This is the insight of van Goor. It is much much harder to find a right molecular pair to repair 508 than to screen for a single molecule. There are millions of drug candidates one can screen to find singles, but it takes screening of multiple trillion molecular pairs to find right duo combo drugs.(because if you had 10 single candidates, there would be 10x9/2 pairs to test)
Thanks third. That makes a lot of sense. I was surprised because this was first time they seemed to say 661 is the corrector for combo correctors...I assumed it would also be 809 and others. But that to me is hopeful because that must mean they have some other correctors that they know in vitro will work with 661. They mentioned having in vitro multiple correctors working as well as 770 does for 551, but knowing it is with 661 is exciting because that's seems to me that they have a theory for perfecting the corrector combos close in hand. Al always appreciate you insights!
Sorry, what I was referring to was the timeframe for a new combined drug (661 + Kalydeco + additional correctors) which would have a dramatic effect on the health of DD508 CF patients, to come to market.
Sentiment: Strong Buy
Verity....Thanks for your valuable insights on the 4th quarter conference call, Your comments regarding the future of the CF pipeline are most exciting and encouraging. 809, 661 and 770 will turn the treatment of CF into a disease that has normal life expectancy, with a more normal quality of life being restored to 70,000 young people. Breakthrough drug status has net yet been defined by the FDA or Vertex in terms of how quickly these drugs will be released, but the CFcommunity needs to keep the FDA true to honoring the committment to facilitate expediting postive clinical trials and translating positive interim results into early provisional approval of these drugs at six months of testing to allow the sickest CF patients a shot at salvaging their pulmonary function and stabliizing their condition. Best wishes to you and your CF child and all the families with CF who share your hope and optimism. Those of us investing in this most worthwhile of projects may succeed finiancially on this breakthrough, but the greatest success will be in hearing that your child and the others like him or her will be reporting their improved health and quality of life in the coming year.
Sentiment: Strong Buy
Thanks. Tears in my eyes from your compassionate note. And I can't wait to report back in a few years that ds is no longer doing two hours of treatments and tenish meds each day. And that we no longer own stock in Purell!
I think that 661 results will be stronger based upon feedback through the CF community. The next generation correctors are the key for everyone with CF but I think it will be 6 years from market. Hopefully good phase 3 results for 809/770 will make the road easier for the next drugs to follow.
Sentiment: Strong Buy