The U.S. Food and Drug Administration (FDA)’s accelerated approval of ADUHELM™ (aducanumab) for the treatment of early Alzheimer’s disease in 2021 met with controversy, and uptake was curtailed by a lack of clinician support and Medicare coverage. Now, supported by landmark clinical data from a phase 3 trial, next-in-class anti-Aβ monoclonal antibody (MAb) lecanemab has been granted accelerated approval by FDA and appears poised for ex-U.S. launches, marketed under the brand name LEQEMBI™. Donanemab, and others in the class (e.g., Roche’s gantenerumab), may follow suit pending the results of ongoing trials. If approved, differentiation in the areas of adverse events (AEs), convenience and clinical and biomarker efficacy will be key determinants of future uptake.
The U.S. FDA’s accelerated approval of ADUHELM based on biomarker endpoints (i.e., decreased amyloid levels in the brain) opened the gate for U.S. regulatory submission based on similar data from other disease-modifying therapies (DMTs). The phase 3 trial readout for lecanemab validates the clinical efficacy of agents in this class, positions the drug for global regulatory approvals and bodes well for the phase 3 trial results for donanemab, which are still pending.
• 2023: United States
• 2025: Japan and Europe
Patents estimated to expire beginning in 2031
How will donanemab impact the market for Alzheimer’s disease?
What gaps in treatment does donanemab fill?
The most critical need for patients with Alzheimer’s disease has long been safe, effective DMTs that slow cognitive and functional decline. Uptake of ADUHELM is minimal for a multitude of reasons, limiting the patient benefit. Lecanemab and donanemab appear to offer improved risk/benefit profiles over ADUHELM, while additional therapies could eventually provide greater patient choice and the potential for synergistic combinations to maximize outcomes.
What hurdles might it need to overcome to reach blockbuster status?
Backed by positive phase 3 outcomes, blockbuster sales for lecenamab (and other putative DMTs) should easily be within reach based on population size, market demand and pricing. That said, the entry of ADUHELM accomplished little to prime health system preparedness, and questions and challenges remain regarding access, reimbursement and affordability; early patient detection and presentation; seamless specialist referral and diagnosis pathways; infusion infrastructure; and healthcare provider perceptions about the risk/benefit of drugs in the class and their willingness to prescribe. Upcoming regulatory and payer decisions on lecanemab will likely set the precedent for others in the class, and uptake is expected to be slow until reimbursement terms are set.
“I think it’s going to be better than aducanumab (due to the short treatment duration) because we can expect improvement in a shorter time. We can even compromise with the patients who would be not waiting so much to see if the drug works. We can take only maybe six months, and, if it doesn’t, we can stop the treatment.”