Several pharmaceutical companies have recently discontinued programs targeting Alzheimer's and Parkinson's diseases, marking a period of attrition in the pipelines for these challenging neurodegenerative conditions. Despite recent approvals like Eisai and Biogen’s Leqembi and Eli Lilly’s Kisunla, which generated momentum in the Alzheimer’s treatment space, companies are re-evaluating their strategies based on clinical data and commercial viability.
Roche's Alzheimer's Pipeline Adjustments
Roche has been particularly active in pruning its Alzheimer's assets. The company recently terminated its collaboration with UCB, relinquishing rights to bepranemab (UCB0107), an anti-tau antibody treatment. This follows Roche's earlier decision to end its long-term collaboration with AC Immune, returning two Alzheimer's assets: anti-amyloid beta antibody crenezumab and anti-tau antibody semorinemab. Semorinemab had previously failed to meet its primary and secondary endpoints in a Phase II trial, while crenezumab also faltered in Phase II and III clinical trials.
Roche's struggles in the Alzheimer's space are further highlighted by the failure of gantenerumab in two Phase III studies in November 2022. However, Roche is not entirely abandoning Alzheimer's research, with RG6289 and trontinemab currently in Phase II studies. Promising data from a Phase Ib/IIa study of trontinemab showed "rapid and robust" amyloid plaque reduction.
Johnson & Johnson Cuts Neurology Programs
Johnson & Johnson also scaled back its neurology and psychiatry pipeline, discontinuing seltorexant for Alzheimer's disease and JNJ-0376 for Parkinson's disease. Seltorexant, an orexin-2 receptor blocker intended for agitation or aggression in Alzheimer’s, was in Phase II development. J&J will continue to evaluate seltorexant as a treatment for major depressive disorder with insomnia symptoms. JNJ-0376, a Phase I Parkinson’s candidate touted as having “novel mechanisms to modify, treat and/or prevent neurodegenerative disorders,” was also dropped.
Sage Therapeutics' Dalzanemdor Discontinued
Sage Therapeutics faced setbacks with dalzanemdor, an oral drug candidate targeting cognitive disorders associated with NMDA receptor dysfunction. After failing a mid-stage trial in Parkinson's disease, where it showed no meaningful differences over placebo in exploratory endpoints, including a cognition test (PRECEDENT study, n=86), Sage discontinued its development for this indication. Dalzanemdor also missed the primary endpoint in the Phase II LIGHTWAVE study in Alzheimer's disease, showing no statistically significant difference from baseline compared to placebo on a cognition test. Sage has halted further development of dalzanemdor in Alzheimer’s. A Phase II study of dalzanemdor is ongoing in Huntington’s disease.
Otsuka Pharmaceutical Halts AVP-786 Development
Otsuka Pharmaceutical discontinued the development of AVP-786 after it failed to improve agitation associated with dementia due to Alzheimer's disease in a Phase III trial. Topline results showed no improvement over placebo. Otsuka is still developing brexpiprazole for agitation associated with dementia due to Alzheimer’s, which has been filed with regulatory authorities in Japan.
Market Outlook and Expert Commentary
Despite these program discontinuations, Graig Suvannevejh, senior biopharmaceuticals and biotechnology equity research analyst at Mizuho Americas, suggests that this is not indicative of major shifts in the R&D landscape but rather a “coincidence” driven by data and competitive pressures. He noted that anti-amyloid antibody programs face market traction challenges despite recent approvals. The Alzheimer’s treatment space is projected to be worth $15.5 billion by 2031, according to iHealthcareAnalyst. The global market for Parkinson’s disease drugs is currently valued at $5.56 billion and is expected to reach $6.63 billion by 2029.
