Things to look for in the New Year

Perhaps the biggest Alzheimer’s news in 2021 was the controversial FDA approval of the anti-amyloid monoclonal antibody Aduhelm (aducanumab).  Controversy surrounds the mixed results of two parallel phase 3 trials.  Both trials showed efficacy at removing beta-amyloid from the brain.  One trial showed a modest slowing of cognitive decline while the other trial did not. The FDA advisory panel recommended against approval without further study, but the FDA granted approval, requiring a post-approval trial to address the mixed results. On December 16, the European Medicines Agency rejected Biogen’s marketing application for Aduhelm stating “the Agency’s opinion was that the benefits of Aduhelm did not outweigh its risks.” Biogen is appealing the rejection.  Perhaps in response, today Biogen lowered the cost of Aduhelm in the US from $56,000 to $28,200 per year and has announced plans to start enrolling for a third, placebo-controlled clinical trial in May 2022. Results are expected in 2026. Meanwhile, the Centers for Medicare and Medicaid Services (CMS) are deliberating on whether to approve Medicare coverage for Aduhelm.  A decision is expected on or about January 12.

When the controversy about the FDA approval of Aduhelm erupted, I was concerned that there would be an impact on further research into possible treatments for Alzheimer’s disease. I was afraid that it would be difficult to find volunteers for new studies. Everyone would want to be on Aduhelm.  That has not turned out to be an issue. When I searched clinicaltrials.gov today, I found 407 Alzheimer’s trials recruiting subjects or ongoing but no longer recruiting. My understanding is that recruitment for studies is still going well. I am particularly interested in trials involving donanemab, an anti-amyloid monoclonal antibody similar to Aduhelm that appears to be more effective in removing beta-amyloid and may not need to be given after the amyloid has been cleared. Like Aduhelm, it can cause side effects including brain swelling and bleeding, and it is unclear if it is any better in slowing cognitive decline. To that end, Lilly is recruiting for a head-to-head trial of donanemab vs Aduhelm in subjects with mild Alzheimer’s.  As I described in a previous post, donanemab is also being tested in cognitively normal subjects who have a positive blood test for an Alzheimer’s biomarker. I am particularly excited to see the results of that trial because I believe that early treatment for Alzheimer’s disease, even before cognitive decline begins, is likely to be our most effective strategy.