Regulation

Aduhelm: a tangled plot; plus INTREPID pandemic planning: a BioCentury podcast

A revised label and a request for an investigation by Acting FDA Commissioner Janet Woodcock are the latest tangles in the controversy over the approval of Alzheimer’s drug Aduhelm. In the latest BioCentury This Week podcast, BioCentury’s editors discuss the implications of the label change and what might come of any investigation into FDA’s interactions with Biogen. They also assess an industry-led initiative to prepare for the next pandemic and take a look at Novo’s ATTR deal with Prothena.

A month after FDA’s approval of Aduhelm aducanumab-avwa from  Biogen Inc. (NASDAQ:BIIB) and Eisai Co. Ltd. (Tokyo:4523), the agency narrowed the drug’s label to be consistent with clinical trial data. It’s also in accordance with statements from Biogen and Eisai.

But unlike clinical trials for the drug, and in contrast to recommendations from the drug’s manufacturers, the new label does not mandate or recommend diagnostic tests to confirm the presence of β-amyloid.

Washington Editor Steve Usdin says the lack of any requirement for a diagnostic to ensure that patients who receive the therapy have Alzheimer’s as defined by the presence of β-amyloid plaques puts people at risk because PET testing shows that about one third of those diagnosed with Alzheimer’s turn out not to have amyloid.

“This means that a third of the patients who get it could be exposed to the risk of brain swelling with no potential benefit,” says Usdin. “Or maybe FDA believes that it’s appropriate just to leave it to payers and the medical community to figure out who should get imaging and what to do with that imaging data, which is a pretty unusual and curious way for them to treat this.”

Executive Editor Selina Koch says, “PET imaging for amyloid has become standard practice and large Phase III trials for Alzheimer’s that test amyloid compounds for exactly the reasons Steve said: Many patients with suspected Alzheimer’s disease do not have amyloid buildup in their brain.”

Meanwhile, Woodcock has requested an independent investigation of FDA’s interactions with Biogen during the review of Aduhelm. Usdin says it’s an attempt to bolster public confidence in the agency’s integrity, and distance herself from a controversy that could derail her chances of being nominated as commissioner on a permanent basis.

Editor in Chief Simone Fishburn says there are several angles to unpack regarding Woodcock’s request.

“You could argue that’s smart because it was going to happen inevitably,” says Fishburn. “And she is at least showing FDA is more than cooperating. It’s showing transparency. It’s saying, ‘Come figure out if we did something right or wrong,’ and addressing that concern that people have had, that they’d been unduly influenced by the company and or deviated from what FDA procedures should be.”

A second angle, Fishburn says, is whether there’s a real danger that the outcome of the investigation that Woodcock is calling for could lead to clamp down on FDA’s interactions with biopharma companies.