Biogen’s aducanumab is inching closer to an FDA decision. The Big Biotech, along with partner Eisai, announced on Friday that the FDA accepted its regulatory submission for aducanumab, its once-failed Alzheimer’s drug—with priority review to boot.
The agency expects to decide the fate of the treatment by March 7. Along the way, it will hold an advisory committee meeting. It has not set a date for the meeting, but Jefferies analyst Michael Yee expects it sometime in the first quarter of 2021.
How the FDA rules on aducanumab will show how far the FDA and its commissioner, Stephen Hahn, M.D., are willing to diverge from its established approval standards. Under U.S. law, companies need to show “substantial” evidence of effectiveness to win approval.
Aducanumab has had a bumpy ride, failing a futility analysis in March 2019, which led Biogen to axe its phase 3 program. Eight months later, the company resurrected the drug saying the analysis was “incorrect," arguing that it was based on a smaller dataset that featured fewer patients who received high-dose aducanumab. Adding in the additional data showed aducanumab reduced clinical decline, the company said.
Biogen believes that, if approved, aducanumab would become the first treatment to slow decline in people with Alzheimer’s disease, a neurodegenerative disorder whose treatments focus on controlling symptoms. The data, however, are not so clear. In Yee’s words, “the phase 3 data was largely mixed and still inconclusive.”
The data underpinning the filing come from a phase 1b study, as well as a pair of phase 3 studies that tested aducanumab in patients with early-stage and mild Alzheimer’s. The phase 3 results were mixed, with one study suggesting that aducanumab is no better than placebo, while the other linked the drug to improved scores on a dementia scale.
Patients who received the highest dose of aducanumab in a phase 3 trial dubbed EMERGE showed statistically significant improvement on a clinical dementia scale. But the same patient group in the ENGAGE phase 3 study did worse than patients taking placebo on that same measure, as well as on a test of cognitive function.
Biogen did not use a priority review voucher to snag a speedy review, “suggesting FDA sees this as an unmet need and willing to review this under an accelerated window,” Yee wrote in an investor note.
Optimists argue that the speedy review suggests the agency is “comfortable with the totality of the data, recognizes high unmet need, and really wants to get an Alzheimer’s drug approved,” Yee wrote. Others might read less into the priority review, as the FDA could still ask Biogen for more data or extend their review period.
Some analysts have been cautiously optimistic. Cantor Fitzgerald’s Alethia Young wrote earlier this year that she was “reasonably confident” the FDA would accept aducanumab’s application, adding the caveat that she and her colleagues “don’t view this approval as certain,” given “the complicated issues around the statistical analysis and the inconsistent outcomes from both pivotal trials.” Brian Abrahams of RBC Capital Markets estimated a 30% chance the FDA would approve the drug “despite the mixed ph.III data.”
But Baird analyst Brian Skorney has dismissed aducanumab’s chances, saying the bulk of the data shows aducanumab doesn’t provide a clinical benefit.
“If Biogen said based on this data it was running another study, the stock would be down because the data doesn’t justify investing in another study. The regulatory threshold is higher than that,” Skorney wrote in December. “The bottom line is, the FDA standard of approval is substantial evidence of efficacy and the cumulative data for aducanumab falls really far of this standard.”