What if Kalydeco was dosed together with VX-809 from the beginning
The clinical data presented on the last 11th confirm the data reported in June, and displays a robust synergy between 809 at 600 mg qd and Kalydeco. However, because the FEV1 decreased during the 809 monotherapy phase of first 28 days, its overall increase from Day 1 thru Day 56 was modest when its final outcome is measured wrt the Day 1 (and averaged over all individuals). I think that the FEV1 decrease in the monotherapy phase is real because all of different dose arms including the placebo arm show 0-3% decrease (I think that this decrease is partly a placebo effect and partly due to individuals coming off from inhaled antibiotics). Therefore, the increase of FEV1 over the period of Day 28 to 56 displays not only the synergy btw 809 and 770 , but also exhibits the efficacy of the combo drugs. So, if you dosed the combo from the beginning (that is, if the monotherapy phase is removed), the FEV1 increase at Day 28 would be at least 6.1%, certainly not 3.4%. The good responders had much higher value than 6.1%.
Third, I agree that dosing VX-770 and VX-809 from the beginning ought to result in better FEV1 results compared to the phase II trial. At the Vertex webcast from North American Cystic Fibrosis Conference 10/11/12, an analyst asked about dosing both drugs from the start during the upcoming phase III trial and the response from Vertex management seemed to be that they planned to do this.
Dr. White, the Phase III should last long enough to contain more than one antibiotic cycle, so that it is possible to isolate and to determine the effects of removing antibiotics. I expect that the antibiotics 'on' cycle corresponds to a higher FEV1 level and the 'off' cycle corresponds to a lower level.
In a few months from now the Phase II data from 661 trial will be reported, and I am confident that there will be another 25+ point jump from here because the bears have to wake up from the current complacency. Good earnings and revenue from Kalydeco tomorrow, positive news for VX-787 trial, and the final relapse data from GS-7977 (unlike last year there is no Plenary or late-breaker abstracts for this molecule) are other potential wild cards.
It is difficult to understand why there is not more enthusiasm for Vertex stock given the phase II data for VX-770 (Kalydeco)/VX-809 in F508del patients showing significant improvement in FEV1 that is not dependent on a few super responding patients. There were no serious safety concerns with either medication. The upcoming phase III pivotal trials should show even better FEV1 numbers when all patients are dosed at the higher 600 mg VX-809 or, possibly, 800 mg VX-809 levels and the when both VX-770 and VX-809 are given together starting on day 1 of the trial. And this combination therapy for F508del patients has FDA fast track status which should allow Vertex to bring it to the market that much sooner. There are more than 30,000 patients in the U.S. and europe that can be treated with this regimen and it is their best hope to extend their lifespan by treating the underlying cause of this disease.