J&J's Alzheimer's Ambitions Suffer Setback as Anti-Tau Antibody Fails Phase 2 Trial

Johnson & Johnson's aspirations to develop a blockbuster Alzheimer's disease treatment have been dealt a significant blow following the failure of its anti-tau antibody, posdinemab, in a phase 2 clinical trial. The company announced that the drug failed to significantly slow clinical decline in patients with early Alzheimer's, leading to the termination of the study.

Trial Details and Outcomes

The Autonomy trial, which enrolled over 500 participants with early Alzheimer's disease, randomized patients to receive one of two doses of posdinemab or a placebo. The primary endpoint was the change in the integrated Alzheimer's Disease Rating Scale (iADRS), a measure of cognition and function, at 104 weeks. Despite high hopes, a scheduled data review revealed that the drug did not achieve statistical significance in slowing clinical decline.

J&J's executive vice president for innovative medicine R&D, John Reed, M.D., Ph.D., had previously expressed confidence in the drug's potential, citing its unique targeting of a specific tau epitope. The company had projected peak sales exceeding $5 billion for posdinemab, with a potential market entry as early as 2028.

Implications for Tau-Targeting Approaches

The failure of posdinemab adds to growing skepticism about the efficacy of monoclonal antibodies targeting tau in Alzheimer's treatment. This setback follows similar disappointments in the field, including UCB's bepranemab, which failed to improve cognition and function in early Alzheimer's patients a year ago.

Both posdinemab and bepranemab target tau's mid-domain, a strategy that was thought to differentiate them from other anti-tau antibodies and potentially lead to success. However, the consistent failures in this approach raise questions about the viability of tau as a therapeutic target in Alzheimer's disease.

J&J's Ongoing Alzheimer's Research

Despite this setback, J&J continues to pursue other avenues in Alzheimer's research. The company is collaborating with AC Immune on JNJ-2056, a tau active immunotherapy currently in phase 2 trials. This approach aims to stimulate patients' immune systems to produce antibodies against tau.

Additionally, J&J has indicated that it has other tau-focused programs nearing clinical stages. The pharmaceutical giant remains committed to exploring tau as a target, with Reed describing it as "the best target out there right now" for Alzheimer's treatment.