Quote:Fallout continues from the Food and Drug Administration’s contentious decision this week to approve Biogen’s Alzheimer’s drug Aduhelm (aducanumab) despite a lack of efficacy data.

Three experts who sat on an advisory committee for the FDA have now resigned over the decision.

The advisory committee reviewed the data behind Aduhelm last November and voted overwhelmingly against approval. Of the 11 advisers on the committee, 10 voted “no” on the question of whether Biogen had collected enough evidence to indicate that the drug is effective. The remaining adviser voted “uncertain.”

Nevertheless, the FDA approved the drug on Monday. Though the regulator acknowledged that there are “residual uncertainties regarding [the] clinical benefit” of Aduhelm, the FDA said it decided to lower the requirements for approval after the advisory committee voted. Instead of basing the approval on the drug’s demonstrated efficacy, the agency relied on a “surrogate endpoint.” In this case, the surrogate is the ability of the drug to reduce amyloid beta plaques in the brains of some Alzheimer’s patients.

“This reduction in plaques is reasonably likely to result in clinical benefit,” Patrizia Cavazzoni, director of the FDA’s Center for Drug Evaluation and Research, wrote in a statement this week.

The approval and explanation riled advisory committee member Aaron Kesselheim, a professor at Harvard Medical School who is also director of the Program on Regulation, Therapeutics, and Law at Brigham and Women's Hospital. In a searing resignation letter sent to acting FDA Commissioner Janet Woodcock on Thursday, Kesselheim called the FDA’s decision "probably the worst drug approval decision in recent US history."

He noted that the surrogate endpoint was not discussed by the advisory committee—in fact, he notes, the FDA told the committee specifically that it would not use amyloid beta plaque clearing as a surrogate for efficacy.