Ken,
You are plenty smart. A couple of comments:
<<Darapladib is a high risk/high return project. It is pretty early given the indication. They have yet to start the 2nd phase 3 and the first won't get data till 2012. This is a n=15k per phase 3 for a good reason. The important stuff comes at the end of the trial>>
In the P2s they were not looking for clinical outcomes and remembering the data, they didn't see anything in those relatively small trials. The P3s are huge (as you point out) to show differences to first MACE. Also, (as you point out) the trial has started relatively recently. GSK will stop the trial after 1,500 pts unfortunately have a first MACE. They estimate the time it will take the trial to get that many is around 3 years. I conceptualize Lp-PLA2 as a plaque stabilizer. I don't know how long it would take the drug to stabilize the plaque (? weeks or months?), but after that, GSK is looking for MACE to be less in the Lp-PLA2 group vs. SOC. Thus, this situation may be similar to what HGSI saw in the first LSB P3 in regard to the PGA score graph -- the divergence between LSB+SOC vs SOC began at 4 weeks and continued to widen throughout the 52 weeks. With Lp-PLA2, there may already (or may not) be divergence. I don't know when (if at all) the divergence will start, but I doubt that if there is no divergence after 1.5 years, that it will start to diverge after that time. Importantly, GSK gets to look at the data from time to time, so they will be the first to know whether it is likely to be successful or not.
<<We can walk around the elephant, but it still means the elephant is the most important thing in the room. BENLYSTA.>>
If Benlysta is the elephant in the room (and I agree with you), then Lp-PLA2 is the elephant down the hall.
-- Steve |
