3. Was the sweat chloride change at 200 mg and 400 mg statistically significant?
A. The late June PR states, I am quoting:
[A statistically significant reduction in sweat chloride was observed from Day 0 to 28 in homozygous patients treated with VX-809 (200mg, 400mg) alone compared to placebo. Additional reductions in sweat chloride were observed between Day 28 and 56, but were not statistically significant.].
This result is qualitatively similar to the change in the 600 mg arm.
4. Why did VX-809 as a monotherapy do worse than placebo? What activity does VX-809 have in the first place?
A. Feuerstein thought that this highlights one of [weirder] data points of the study. This question is rather meaningless and I disagree with Adam's response. The Placebo arm scored -0.9 (p=0.54), the 600 mg arm scored -2.9 (p=0.07) after 28 days. Both numbers have high p-values. This means that the difference between their decreases is also NOT statistically significant.
But it is significant that both decreased. I have been saying that it is important to know the first 28 day course of 200 mg and 400 mg arms. The reason is that if FEV1 for both arms decreased like the placebo and 600 mg arms, we know why all of them decreased. I predict that all arms show a decreasing lung function in the first half (28 days) of the trial.
5. What were the baseline values for the patients in the study?
A. This is an excellent question. The lung function had to be determined before the dosing in order to measure the effect of the drugs. Since antibiotics dosing was withdrawn for all participants at the beginning of 809 dosing, its effect on the lung function has to be estimated with a good data collected from the placebo arm before and after the withdrawal. In Ph. III, 50% of the placebo arm should receive antibiotics to isolate its effect.