809/Kalydeco Final Results & Conference Annotated Summary
Key Take-Aways from 809/770 Final Results:
Homozygous Results: In sum, the results are very good, albeit in some ways weaker than the interim results; but while slightly weaker, still excellent results which bode well for Phase 3 trials and eventual approval. Initially, it is important to understand that Vertex presented the data differently for its final results. Vertex’s table for the final results shows the FEV absolute change (baseline and compared to placebo) and responders analysis for days 0 - 28 and day 28 - 56 for only the 600 dose. The interim results showed the absolute change and responder analysis from day 0 to day 56 and also did a pool result. As explained below, the FEV absolute change is lower than at the interim level and since only given for the 600 mg dosing, you can extrapolate that the lower-doses must have had some much more significant changes in FEV absolute change. Now, frankly, that the pooled results would be worse (if disclosed), I don’t care about because 600 is safe and had the most robust response. And 600 mg is the dose Vertex will move forward with for Phase 3 (with the possibility of higher dosing). Also, while Vertex used a table breaking down the improvement days 0 - 28 and 28 - 56, Vertex disclosed the total change from day 0 - 56 in the press release (and you can do the math from the chart.) The final results for 600 mg from Day 0 - 56 absolute improvement compared to baseline is 3.4% with a p of .03. And compared to placebo is 6.7% with a p of .002. The interim results were better with a 0 - 56 absolute improvement (for pooled results) compared to baseline of 4.0 with a p of .002 and compared to placebo of 8.5% with a p of .002. But remember part of the 8.5% improvement came from the -4.6% decrease in the placebo arm with a p of .04. Such a high decrease in the placebo arm seemed off and also seemed to skew the data. That issue, though, is not as significant now, though, as with the final data the placebo arm had a 3.4% total decrease from day 0 - 56, making the total change of 6.7% compared to placebo a little more solid looking. The p value for the placebo decrease though for day 0 - 28 is pretty weak–only .54. It is impossible to know from the released data if the responder analysis is stronger, the same, or weaker than the interim results because from the chart the information is provided day 0 - 28 and day 28 to 56 so you can’t figure out who had a 5%/10% improvement from day 0 to 56 (as the interim results provided), versus just a 5% or 10% increase after the initial decrease in lung from days 0 - 28.
So what does this mean: 1. The results are not as strong as the interim results, but are still very strong and strong enough to get to Phase 3 and if results stay similar there, then approved. 2. The breakdown of improvement from day 28 - 56 makes sense in some ways because prior to day 28, there was no “fix” to the CFTR. You need both drugs. So the improvement in the second part of the study when the individual is taking both drugs is key. 3. The increase from day 28 - 56 is striking and large. 6.1% compared to baseline and 8.6 compared to placebo. And both have very tight p values of less than .001. This bodes well for the fact that these drugs are working and working wonders.