Been swamped and yahoo’s finance kept losing stuff so just never tried, but here it goes.
I’m thrilled. Not so much re the 809/770 combos presentation–as I said to DH, there wasn’t anything really “new” there, but it was very good to see anyway for several reasons: 1) there wasn’t anything hidden–the partial release made lots of folks nervous that there was a shoe to drop that wasn’t good; 2) the individual responses (they showed everyone), shows that the combo does really work; 3) the graphics really make it clear that the combo really does work. 4) I'm not longer as nervous re SC b/c I have several anecodotes of those on Kalydeco having continued (6 months later) even better SC reductions.
But what had me crying was the “future” that Vertex spoke of in its investort conference (and do listen--it was amazing): they already have discovered correctors that when used in combination can fix CFTR function in vitro to the extent of Kalydeco. At the CF conference, according to my sources, Vertex said Kalydeco in vitro fixed CFTR function to 50%; by tweeking with the levels of 809/770 Vertex got CFTR function to 30%–that they said in investor conference and is the level needed to get a clinical benefit, they think; but using several correctors to fix the misfolding, sequencing etc. at several levels, Vertex got CFTR function to 70-80%!!!! You might remember that last year at the CF conference Vertex and others were discussing the need for a third corrector–the presentations this year were in much more depth . . . they have learned A LOT in one year about how to fix the ddf508 at several points in the process and as noted, already have several other correctors that get to the 70-80, although not sure if they are ones “fit for humans.” I wish someone had asked what about 661? What level of CFTR function improvement. Also, very happy re the Phase 2 which is the n of 1 study Vertex confirmed. This will really open the door for many more Cfers to get Kalydeco. I am curious as to how the labeling will work on that. Anyone want to take a stab? The only sadness for me was that Vertex is having more trouble with the df508 heteros–they think the new drug combos will do it, but they are obviously even further behind and my heart aches for those Cfers and there families who doesn’t see their miracle quite as bright yet as the double deltas.
Finally, Third’s post below (I’ll respond there later too if I can), has me excited about 661. Third: Thoughts on what your comments mean re 661's potential given its better tissue absorption? Can Vertex get even better responses b/c they can go even higher so it won’t matter b/c they can get to that “dose response” easier than with 809??
I still haven't had a chance to look at all the documents from the conference or listen more closely to the investor conference, but this is one happy mamma! Please pray for us, though, and the other CFers to stay healthy until our miracle is ready. And a donation to the CFF can make that happen even quicker!!
Verity, this weekend was a good time for me to review the data and digest what was said during the investor conf. call.
The phase II trial data for 809/770 were not great, but good enough to reward the share price rather than punish it as if the trial had been a complete failure. The market is often very irrational.
Mueller was induced to say a more about 661 in the Q&A session. As you said 661 has higher tissue distribution/absorption properties, less metabolism induction problems, third advantage I couldn't catch, and all of the above can make it to be potentially more efficacious and safer than 809. But he said that its potential launch time will be 2 years behind the potential launch time of 809, which makes the potential market launch date for 661 to be in 2016. Until 2016 809 can maintain the health of CFers and can even reverse the CF progression in 508 homozygous population. 2 years will pass fast.
That 661 is more effective implies that threshold dose will go down and the dose at which the FEV1 is at the half of the maximal FEV1 will go up. This and safety mean that the therapeutic window will be wider, and even heterozygous 508 group may benefit from 661.
Van Goor and his slides stated in the CC that many residual CF genotypes fall on the category of pancreatic sufficiency, and CFTR does benefit in vitro from Kalydeco. So, should this N of 1 clinical trial for the pancreatic sufficient CFer lead to success, a natural expansion of the label for Kaly would include Pancreas Sufficient CFers.
Vertiy... Thanks for your response. The second corrector invitro data certainly seems very hopeful. At the end of the Q&A part of the investor conference Yaron Werber from Citi asked why 661 and 809 were being developed in parallel, when 661 might turn out to be even more effective due to it's properties of better penetration into target cells and perhaps better drug pk pd properties with it's interactions with Kalydeco. Peter Mueller's response was implying that because 809 would get to market two years ahead of 661, it was going to be expedited to help the homozygotes 508 group ASAP while 661 would be developed in parallel with studies yet to be announced that would include the heterogygotes. I'm not sure when the current 661 study results treating homozygotes will be released, but it appears hopeful that Mueller's statement about expanding 661 trials to include heterozygotes means hope for this subset of CF population as well, and sooner rather than later.