J&J's Alzheimer's Antibody Fails in Phase II Trial, Dealing Another Blow to Tau-Targeting Approach

Johnson & Johnson has announced the discontinuation of its Phase II Au𝜏onomy study evaluating posdinemab, an anti-tau antibody, in patients with early Alzheimer's disease. The decision comes after a scheduled review revealed the drug's failure to significantly slow clinical decline, marking another setback in the pursuit of effective Alzheimer's treatments.

Study Details and Outcome

The Au𝜏onomy study, which began in January 2021, enrolled over 500 patients with early Alzheimer's disease. Participants were randomized to receive either posdinemab or a placebo, with the primary endpoint assessing the drug's effect on clinical decline using the iADRS scale, which measures cognition and function, at 104 weeks.

Despite being hailed as a "first-of-its-kind precision approach" by Johnson & Johnson, the study failed to achieve statistical significance in its primary objective. The company plans to share full data from the trial at a later date, emphasizing that the findings underscore the "deep complexity" of Alzheimer's disease.

Implications for Tau-Targeting Therapies

This failure adds to a growing list of disappointments for anti-tau antibodies in Alzheimer's treatment. In November of the previous year, UCB's bepranemab also failed to improve cognition and function in a Phase II trial, leading to Roche's withdrawal from their collaboration a month prior.

These setbacks raise questions about the efficacy of targeting tau proteins in Alzheimer's disease, a approach that has garnered significant attention in recent years. However, the field remains active, with Eisai set to present data on its anti-tau antibody etalanetug at the upcoming Clinical Trials on Alzheimer's Disease (CTAD) conference in San Diego.

Industry Response and Future Directions

The announcement from Johnson & Johnson comes just days before the CTAD conference, where researchers and pharmaceutical companies will gather to discuss the latest developments in Alzheimer's research. Eisai's presentation on etalanetug, scheduled for December 1, will include data on the antibody's impact on a novel plasma tau biomarker in patients with dominantly inherited Alzheimer's disease (DIAD).

As the Alzheimer's research community grapples with these recent setbacks, attention may shift towards alternative approaches and combination therapies. The complex nature of Alzheimer's disease continues to challenge researchers, highlighting the need for innovative strategies and continued investment in understanding the underlying biology of the condition.