So given enough time, all your questions will be answered. It turns out the question of before or after the event (briefing papers) was to be pretty important after all. :) I was hoping for $15/share but it never got there (And interesting action in the options). Still it got close to $16. I will take it. I mentioned the word complex before and it is a complex decision and the FDA is not immune to it. This drug is a pretty good example for why we should have an advisory pathway. If something were a silver bullet, the FDA would not need help to make the decision. But somewhere between the two extremes of Zero to Hero, we have drugs like this that need expert opinions. And so this is the way it is suppose to work.
The FDA is not out to get this drug as far as I can tell from reading the briefing documents. The FDA is asking why they should approve a bird poison for human use if they can’t figure out the worth of the benefits. And they won’t unless they get strong support from the committee. That is the way it should be. Something happened within the FDA re: the SPA and the cost/benefit equation for the ACOR drug. What happened? I don’t know and I don’t think at the end it would be the key question. Bottomline, the FDA is not the expert and the neuro experts on the panel will have to agree on the positive nature of this drug and convince the other members to vote yes or the drug will not pass go. This is the way it should be. If your own experts won’t fight for a drug than maybe the drug is not worthy. I think it is worthy. But it won’t be the first time I am wrong.
If I look beyond the basic FDA thinking of “We can’t figure out why we should approve a bird poison, etc. etc.” to the actual technical arguments, the FDA is saying they don’t know if the Responder Endpoint is indicative so therefore they want to look at how the drug did in the ITT population. And within ITT, the drug didn’t do great. And the FDA knows this is a bird poison, and the FDA knows dose is one of the safety keys and since the FDA doesn’t understand the benefit of the drug, the FDA should put safety first.
The questions to the panel are clear and reasonable and as far as I can tell fairly unbiased.
The questions are:
1. Has the sponsor demonstrated substantial evidence of effectiveness of fampridine as a treatment to improve walking in patients with multiple sclerosis (MS)? YES/NO/ABSTAIN If yes, has the sponsor demonstrated that this effect is clinically meaningful, either in the group of fampridine-treated patients as a whole, or in a specific subset? DISCUSSION
2. If yes to question #1, should the sponsor be required to evaluate the effects of doses lower than 10 mg twice daily (BID)? YES/NO/ABSTAIN If yes, should this be required prior to approval? YES/NO/ABSTAIN
3. If substantial evidence of a clinically meaningful effect has been demonstrated, do you conclude that there are conditions under which fampridine SR could be considered safe in use for this indication? YES/NO/ABSTAIN If yes, what are those conditions (e.g., specific enrollment criteria, specific monitoring, etc.)? DISCUSSION
The focus is on risk/benefit and NOT on the overall safety of the drug. If I take apart the FDA’s safety concern, I find the FDA understands that this is seizure and that Neuros are use to dealing with seizure issues. In other words, the targeted population is distinct and is treated by one type of specialists. This is not heart damage or liver damage, which would be purely a safety issue. On the plus side of the safety issue is the known nature of this drug and the good behavior of the drug during the phase trials. The safety data from the phase trials point to a drug that is pretty “clean” and are not different than expectation. We should not forget that there are really no other safety concerns but seizure and the actual seizure data were VERY clean including the long term extension data. One side thought on safety is the fact that patients are already using the “less safe” compounded product with less control and higher doses today so what maybe the counter safety issue with blocking the “more safe” version of the same drug?
Risk/benefit is the key decision. If the benefit is very low, then there is no need to take any risks. If the benefit is concrete, then the seizure risks should be acceptable. Rightly the focus is on efficacy.
The committee is made up of 14 people. If the committee were made up of only practicing MS docs, I would be much more comfortable of the outcome. But the majority of them are not MS docs. It takes a treating doc to appreciate the benefit of this drug. There is one doc that focuses on ALS/cord injury and one on Epilepsy. Because of the nature of these other diseases, these two docs should be receptive to a good argument from ACOR. In order for ACOR to receive a positive vote from the committee, other members of the committee must be won over. This will require firm support from the REAL experts of the committee. AND ACOR has to bring their A game and give a good supporting presentation. Never hurts if the public shows real support of the candidate drug. I am guessing that the vote will be something like 12-2, either way. Either strong support or strong rejection, depending on the delivery by ACOR and the Experts on the panel.
We should remember that the phase 3 trials were successful and that the actual safety data were pretty clean. This is not a subset or some version of a failed effort. If you go to the link below and check out the charts in the Errata link which outlines the ITT data for the 2 phase 3 trials, you will find that even in the ITT data, you have pretty strong evidence that the drug is doing something positive. It is not the case where the ITT data has no evidence of activity. No one has argued that this drug should work in all MS patients. The argument has always been that this drug will help an unknown sub-group of MS patients.
fda.gov
The risks are that ACOR does less than a great job and the experts on the panel don’t believe in the benefit of this drug. The FDA I don’t believe will stand in the way of the experts here but the FDA has to get a clear answer from this panel to approve this drug.
I am still traveling and Friday was crazy for me with the briefing paper and all other stuff going on. Good luck to all. Don't gamble unless you have a good feel about the real benefit of this drug. |
