Biotech Values

[iwfal]

XOMA

If SOC involves trigger happy physicians, they would have to be careful here in striking the right balance in that they don't loosen the criteria so much they end up losing power. I think it's a tough call, but still worth a discussion to share with the FDA what they've learned.

FWIW I think the phrase "it's a tough call" is the key one. For just about everything involved in this at this point - including the physicians call on the scene to start treatment or not (without a method for central adjudication or very routine reinforcement of the importance of the protocol... it would be hard to resist the desire to treat. Especially when you know the patient's steroids have been reduced.)

BTW - the thing I found most disturbing about the call was that:

A) the company is fooling themselves (or defending Servier - who is actually running the trial) when they say that the problem was that the protocol should allow for steroid use even when protocol exacerbation didn't happen. Almost certainly that is not what the physicians were doing since if that is what they had been doing there would be few events requiring reversing.

B) the company may not understand that this problem is hardly unique to them or this trial. It is why centralized adjudication/assistance is used in some trials (especially where there is much subjectivity or diverse opinion about SOC or where the trial has defined a SOC that is clearly at odds with normal SOC)

Both of the above mean it is less likely the company is applying lessons learned to their other uveitis trials. Finally, I suspect that most of this is actually Serviers fault so it is unfair to blame XOMA. (I used to think big Pharma didn't make such mistakes, but I have seen more and more strong evidence that there are at least areas within Big Pharma that are as bad or worse than small biotech.). Nonetheless they clearly don't have the best teacher - I seriously hope they hire a consultant like Master or Flemming. May not be a pleasant experience. But it would be valuable to them.

General background comment for anyone else reading the thread:

a) Behcets does have a myriad of non-uveitis symptoms that are treated by steroids. But probably less so by immune modulation like Gev. So there does need to be an escape clause that allows a physician to treat with steroids the patients having these events. The problem is the large fraction of reversals implies that this is probably not what the physicians were doing.

b) uveitis and scleritis are both diseases where there has been considerable disorganization about SOC. There are guidelines, but they are routinely not obeyed. E.g. There was a paper in the last few years that lamented the fact that a large fraction of people with anterior uveitis (or scleritis? Don't remember which) were getting systemic steroids despite the fact that the treatment guidelines call for topical because it works just as well with much less toxicity.