Top researchers who advised the U.S. Food and Drug Administration on Biogen Inc.’s Alzheimer’s drug blasted the agency for approving it, calling the decision a “regulatory failure” that is “at odds with the evidence.”
The New England Journal of Medicine opinion piece, signed by seven members of an advisory panel that opposed clearing Biogen’s Aduhelm, is another sign of persistent furor over the agency’s decision … The new commentary is signed by them and four other panel members, including doctors from Harvard Medical School, the Mayo Clinic, and the University of California, San Francisco.
An investigation of Aduhelm’s approval “should be expeditiously performed, so as to learn how this regulatory failure occurred and to ensure that it doesn’t occur again,” the researchers wrote.
Revisiting FDA Approval of Aducanumab (oped at The New England Journal of Medicine)
The committee was never consulted about beta-amyloid’s suitability as a surrogate. Indeed, the lead FDA scientist told us, “We’re not using the amyloid as a surrogate for efficacy.” Moreover, the data did not support this use. An effective surrogate should strongly correlate with a clinical end point in clinical studies, but an FDA statistical review of Studies 301 and 302 found no evidence that amyloid changes correlated with cognitive or functional changes, concluding that “it is not clear that there is any linkage between reduction in plaque and long term clinical change” …
The FDA’s decision is at odds with the evidence and with the agency’s biostatistical review. The overwhelming unmet need in this common and devastating disease should drive research investments, not lowering of regulatory standards that Americans rely on for safe and effective medicines. The FDA has released key internal reviews, but they neither provide a persuasive scientific basis for declaring beta-amyloid a reasonable surrogate nor justify the failure to seek advisory-committee input on this important question. The interim FDA Commissioner’s decision to call for an Office of the Inspector General investigation is appropriate, and we believe such an investigation should be expeditiously performed, so as to learn how this regulatory failure occurred and to ensure that it doesn’t occur again. Though the decision will reverberate for years, early signs of its gravity are already reflected in announcements by two other manufacturers that they will seek accelerated approval for Alzheimer’s treatments on the basis of amyloid as a surrogate.
News in Context:
- Growing backlash against the FDA approval of unproven Alzheimer’s treatment Aduhelm, by Biogen
- First, do no harm? Six reasons to approach anti-amyloid drug Aduhelm cautiously, if at all
- Can the controversial FDA approval of Aduhelm backfire and delay the discovery of actual Alzheimer’s treatments? (Yes, it can)
- US Senator Joe Manchin calls for a new FDA Commissioner to replace current (acting) one who “has repeatedly ignored public health concerns and shown a dereliction of duty” over opioids and aducanumab
- Health payers–including Medicare and Point32Health–to question Aduhelm pricing and its “reasonable and necessary” use