Well, I don't find his arguments all that compelling. His problems...
(1) 35% response rate.
To be a response, a patient must walk faster on-drug 3 out of 4 times vs. best time while off drug (out of 5 tries?? I forget). If he/she misses one of the on-drug walks, that is counted as a strike. That is pretty tough endpoint as people with walking issues with MS have good days and bad days. In the 203 trial, the ITT group had a stat. advantage over the placebo group in improved walking time.
(2) .51ft/sec of improved walking speed for responders.
That is .35 miles/hr. A normal person walks normally at like 3 miles/hr. These patients walk at a max speed of 1.5 miles/hr. If you are a normal walker than an extra .35 miles/hr is not much since you have the leg strength to speed up or even run. But with maximum speed at half the normal walking speed, a 25% improve of .35 mph is real. And this is supported by measures of leg strength and global impressions and the MS walking scale. I put this in the category of people who never get headaches think headaches are no big deal.
(3) What about the other 65% who didn't respond?
He doesn't understand that the drug provides other benefits beyond just walking faster. Even if we just look at walking, common sense tells us that a group of the non-responders will get some benefits from this drug. In other words, the walking improvement curve does not drop to zero for everyone else/non-responders. There also will be maybe decent off-label use. But even if I give him the 35%, this is still a large enough market as unfortunately many people have/will need such a drug. Patients who need such a drug will try this drug because of the hope it provides re: a more normal life. This drug will let the patient know pretty quickly when it is doing something. I predict that after an initial sorting of benefits, patients will stay on this drug for a decent duration.
(4) The FDA will not approve, safety vs. benefit.
Anyone can see the side effect profile of the drug in the 2 phase 3 trials. At 10mg BID, it is I think within the acceptable range for risks of such a drug. The drug has a dose response and also a side effect profile that goes up with the dose. One shouldn't mix up this drug (a sustained release version) with the side effect profile of other similar drugs. Or confuse the issues re: dose and side effects. I think the writer of this article is very lucky that he doesn't have MS and don't have to understand what it means to need such a drug.
(5) Male/Female ratio.
The male/female ratio is an issue. MS is a more female disease. And the drug arm has more females. Other than that, ACOR did some stat work on this issue and found the ratio did not change the primary answer. |
