Remember back when AstraZeneca was fighting off Pfizer’s ardent, tax-issue-resolving embrace a year ago? One of their weapons was a pitch to their own shareholders about what potential their own pipeline had, and how much of that would presumably go to waste should the deal go through. Even at the time, people thought that their estimates of what was to come might be a bit optimistic. But I can’t really fault them, because if someone were trying to buy me, I’d probably be willing to say all kinds of things to keep it from happening, too.
Well, one of those pipeline assets has just taken a major hit. Brodulamab, targeted against the IL-17 receptor, was part of a 2012 deal between AstraZeneca and Amgen to develop inflammation therapies. Late last November, the companies announced some good clinical results in psoriasis.
But now Amgen has dropped the project, and hard.
The decision was based on events of suicidal ideation and behavior in the brodalumab program, which Amgen believes likely would necessitate restrictive labeling.
“During our preparation process for regulatory submissions, we came to believe that labeling requirements likely would limit the appropriate patient population for brodalumab,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen.
That really would be a show-stopper – psoriasis is a cruel disease, but suicide is worse. It’s surprising, though, that an antibody would have this as a side effect (I’ll bet it was surprising to Amgen and AZ, for sure). That’s certainly a real side effect of some drugs (it was one of the big factors that scuppered rimonabant, and its competitor taranabant back when). But those were CNS agents, and that’s the sort of thing you always look out for in a new CNS drug. What’s an antibody to an interleukin receptor doing causing the same problem?
Well, IL-17 certainly has roles in the brain (those recent papers will lead you to others). And given how painfully little we know about what’s going on up there, it’s certainly possible that these pathways could lead to such a side effect – I mean, how do suicidal thoughts form, mechanistically? Right, it’s a black box like all those questions are. But wouldn’t brodulamab have to cross the blood-brain barrier for that to happen?
That’s very unlikely for an antibody, but (as the various efforts targeting beta-amyloid show), not impossible, either. But if that’s what’s going on, what it is is hideous bad luck, because no one is looking for a CNS effect to stop a peripheral antibody target. And if it’s somehow a peripheral mechanism, feeding back to the brain via who-knows-how, that’s hideous bad luck, too. I hope that at some point we find out more about what’s going on here, out of sheer scientific curiosity.