Biogen gives up on aducanumab (Aduhelm)
On January 31, Biogen put out a press release indicating that it “plans to reprioritize its resources in Alzheimer’s disease” by halting development and marketing of the anti-amyloid monoclonal antibody aducanumab (Aduhelm). Patients currently taking aducanumab will be able to continue receiving the drug until November 1, 2024. The confirmatory Envision trial will end in May. Biogen reports that it recorded a one-time $60 million dollar charge during the fourth quarter of 2023 related to close-out costs associated with the aducanumab program. Rights to aducanumab will revert to the original developer, the Swiss company Neurimmune, that has reported plans to pursue a subcutaneous formulation for use in early-intervention trials.
Recall that aducanumab was the first anti-amyloid monoclonal antibody approved by the FDA for treatment of Alzheimer’s disease. The approval was based solely on efficacy in reducing the amount of beta-amyloid in the brain. Effects on cognition were mixed. Only one of two identical trials showed a modest slowing of cognitive decline. The other trial did not show slowing of cognitive decline, despite reducing the amyloid burden in the brain.
Two anti-amyloid monoclonal antibodies are still in the game, lecanumab (Leqembi) and donanemab. Lecanumab, also developed by Biogen, is already FDA approved. It is very effective at removing brain beta-amyloid, and it significantly slows the rate of cognitive decline. Demand for this drug has been enormous. Donanemab, developed by Eli Lilly, appears to be even more effective than lecanumab, and it is currently awaiting FDA approval. Both of these drugs are promising, especially when used very early in the disease, but both share the risk of fatal swelling in the brain (ARIA-e) and/or bleeding (ARIA-h) when used in subjects who have two copies of the APOE-4 allele. I speak from experience as one of those APOE-4 homozygotes in the aducanumab trial who suffered life-threatening swelling and micro-hemorrhages that resulted in two days of ICU care and several months of recovery.
What are the statistics for ARIA occurring in patients with one ApoE-4 allele?
Great question Lisa. I have responded to you by email so that I could include a relevant paper. If I can get my wits together, I will try to also respond in a blog post soon.
Dan
Dan, I attended your presentation at yesterday’s Pomona College Book club , regarding ‘A Tattoo on my Brain’. I thank you and Lois for a fine discussion. I have a few questions, one relevant to the drugs focused on decreasing amyloid plaques-
1. is the FDA rushing approval of these drugs given the higher incidence of ARIA?
2.as in Oregon, California has the Death with Dignity Act. but for Alzheimer’s patients and caregivers, the best option for end of life care is to address it on the Advanced Directives. Do you think that there will ever be an opportunity for an Alzheimer’s patient who still has intact cognitive function to make an declaration, with the support of a caregiver, for death with dignity?
3.the National Institute of Aging-Alzheimer’s Assoc. Revised Criteria for Diagnosing and Staging Alzheimer’s Disease has now proposed classifying anyone with elevated p-Tau level though no cognitive abnormality as Stage 1 Alzheimer’s Disease. I find this recommendation unfortunate. I’d appreciate your comments.
Thank you
Tom Mahrer MD, ( Internal medicine, pulmonary medicine, now retired), Pomona class of ’75
Hi Tom, thanks for your thoughtful comments. I feel that the approval of aducanumab was wrong. There was minimal evidence for benefit, and there was a significant incidence of ARIA. I personally experienced life-threatening ARIA. Aducanumab has recently been withdrawn from the market. Lecanemab and donanemab appear to be somewhat more effective than aducanumab in slowing cognitive decline, but severe ARIA are possible, especially in APOE-4 homozygotes. At least two deaths have been reported. In my opinion, APOE-4 carriers should not take these drugs. The risk-benefit ratio is not favorable. Still, I am keeping my fingers crossed that these or similar drugs may turn out to be more effective in presymptomatic AD. Several trials are underway. Regarding assisted suicide in AD, this needs to looked at closely. Currently in Oregon, Alzheimer’s patients are not eligible for assisted suicide under the Death With Dignity Act because they must be cognitively intact and have less than 6 months to live. I think this needs to change. Finally, I feel that the presymptomatic stage of AD may turn out to be our best target for successfully treating this disease.