Replies to post #41634 on Biotech Values

[iwfal]

Everyone says how wonderful alexion trial was. They had an 18 percent reduction of events with a p value of .08 in a 3 or 4 thousand patient trial

In the primary pre-pivotal trial in CABG (PRIMO-CABG):

a) It was about a 24% reduction in MI/Death

b) The 30 day p value was 0.01


Now for the poser - if you had two trials, one of 1500 per arm with a p value of 0.01 and the other with two treatment arms of 300 (two arms allows some cherry picking) and p value of 0.028, which would you say was more likely to be repeatable (p value under 0.05 when trial is duplicated). Answer is, I believe, a. It is the p value that matters and Alexion had the better p value and yet failed utterly to repeat. This is the point of the warning - it would, IMO, be wise to understand why the Alexion trial failed. Change in SoC? Change in endpoint definition? And then know that MCU isn't going to have the same failings.

[fid]

This is a trial destined to fail, as I stated before the endpoint is so far to the right that it renders this trial pretty much useless.


Everyone says how wonderful alexion trial was.

The only person saying the Alexion trial was wonderful is yourself as they met your non fatal mi and no reduction in death criteria.


The drug doesn't have to reduce death in 30 days to have a meaningful benefit. Reducing non fatal mi is all it needs to do. As long as it doesn't increase death, which it shouldn't.

To repeat the results, the Alexion trial was in fact statistically significant in reducing non fatal mi and did not reduce death in 30 days which you said it doesnt have to do.

http://www.biospace.com/news_story.aspx?StoryID=14315320&full=1

<<Day 30 in the overall Intent to Treat population (18% relative
reduction; placebo 12.0%, pexelizumab 9.8%; p=0.042)>>


The Alexion trial failed and basically showed that reducing the 100ng/ml endpt has no effect on mortality. Even the MPH Phase II results showed no efficacy on mortality and in fact there was higher mortality in each treatment arm as compared to placebo.

To repeat myself, lets say for example that the Phase III MPH trial was successful and the results were the same as the Phase II. They were able to reduce CK-MB from 100ng/ml to 90ng/ml in a small number of patients. This would really have no outcome on mortality 30, 90 day or even longer time frames.


My thoughts FWTW

fid