The Food and Drug Administration’s (FDA) historic, and controversial, decision to approve Biogen and partner Eisai’s Alzheimer’s drug will likely have ripple effects across the industry for years.
Analysts are already trying to game out what it might mean for the future of Alzheimer’s drug-focused companies using similar therapeutic approaches in brain disorders. Others believe the reverberations could lead to a change in how the FDA approaches diseases for which there’s no therapy available, such as for amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease).
“When I speak with regulatory professionals, the people inside of companies who are charged with getting a product to approval by the FDA, the thing that they constantly ask me is, what precedent is there?” says Alec Gaffney, senior director of research at AgencyIQ, an independent regulatory intelligence arm of the news site Politico. “What examples are there of companies that have successfully obtained FDA approval? And is the process…they went through [for] that approval able to be emulated by me?”
Given the massive scope of the Alzheimer’s treatment market and the landmark nature of the approval of Biogen’s aducanumab (to be marketed as Aduhelm), companies developing dementia drugs like Eli Lilly and Denali Therapeutics may rush into the breach.
About a week before Biogen’s regulatory green light, analysts like RBC Capital Markets’ Brian Abrahams noted the sea change it could portend. “If approved, [aducanumab] would set multiple precedents…essentially creating a framework for future [Alzheimer’s disease drug] development,” he wrote in a research note.
One area to keep an eye on is companies that focus on the so-called amyloid hypothesis of Alzheimer’s treatment. This centers on a strange biological entity called beta-amyloid that has proven to be controversial in Alzheimer’s drug development (until Biogen’s surprise FDA victory).
Technically a protein, it doesn’t fold in the way proteins should. It’s kind of like having tar-like plaques clinging to parts of your brain and messing with your neurons. The presence of these plaques is extremely common in dementia and Alzheimer’s patients, and the theory goes that chopping away at these brain plaques in patients can eventually slow cognitive decline.
That’s a hypothesis that has historically failed after some promising starts. Some in the medical community had ditched the amyloid hypothesis altogether. Even aducanumab has fairly shaky evidence of slowing cognitive decline, and the FDA admitted in its own approval statement that further clinical trials are necessary to see if reducing these plaques has any tangible effects on Alzheimer’s patients. Those follow-up trials could take nine years to complete.
In the meantime, companies like Eli Lilly have experimental products such as solanezumab and donanemab, both of which target different kinds of amyloid, that it may feel more confident in pushing for approval. Denali has a sprawling drug pipeline meant to treat Alzheimer’s, ALS, and other central nervous system disorders that could also hypothetically benefit from an accelerated market approval.
Other drugmakers and patient groups may push for their own early approvals despite little efficacy data as well. “You’ve seen the ALS community in particular take a look at what happened with aducanumab and say, ‘Well, there are other experimental products for our disease, which is also a serious condition without adequately approved therapies for treatment,’” says Gaffney. “Can you make an approval on an accelerated basis? What do we have to do to benefit from this in the same way?”
President Joe Biden has yet to appoint a permanent FDA commissioner, and aducanumab’s future isn’t set in stone. It could theoretically be pulled from the market should it prove a failure over the next decade. But the agency’s signal could very well reshuffle companies’ boldness in seeking drug approvals.
