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July 26, 2011
Alzheimer's: The News Is Not Getting Better
Is there something going on with patients in Alzheimer's trials that we didn't expect? There have been reports of an unexpected side effect (vasogenic edema) in several trials, for drugs that work through completely different mechanisms.
It makes some sense in the case of antibody-based therapies like bapineuzumab (where this problem first got attention) and solanezumab. After all, the immune system is pretty powerful stuff, and you could certainly imagine these sorts of side effects (either directly or from some effect of clearing out amyloid debris). As those reports indicate, the problem may lessen with time, and may be more severe in patients with the APOE4 allele, a known (but not understood) risk factor for Alzheimer's.
But this latest report is for the Bristol-Myers Squibb gamma-secretase inhibitor avagacestat (BMS-708163). That shouldn't be involved with any inflammatory/immune mechanisms, nor, really, with amyloid clearance. A secretase inhibitor should just keep new amyloid from being formed and deposited, which should be beneficial if the beta-amyloid theory of Alzheimer's is correct, which is what we're all still in the middle of deciding these days. Expensively and excruciatingly deciding.
Meanwhile, the most recent big clinical failure in this area continues to reverberate. Lilly's gamma-secretase inhibitor semagacestat, the first that went deep into the clinic, imploded when the company found that patients in the treatment group were deteriorating faster than those in the control group. Seven months on, they're still worse. What does this mean for the BMS compound targeting the same mechanism? That is the big, important, unanswerable question - well, unanswerable except by taking the thing deep into big clinical trials, which is what BMS is still committed to doing.
For more on Alzheimer's drug development - and it hasn't been pretty - scroll back in this category.
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