J&J Halts Phase 3 Depression Trial Due to Low Efficacy

In recent developments in the pharmaceutical industry, Johnson & Johnson (J&J) has decided to halt the development of its drug candidate, aticaprant, as an adjunctive treatment for major depressive disorder (MDD). This decision follows a series of events that have cast doubt on the efficacy of opioid kappa receptor antagonists, a class of drugs to which aticaprant belongs. Aticaprant, along with a rival drug candidate, navacaprant from Neumora, aims to treat MDD by targeting the same opioid receptors in the brain.

Earlier this year, Neumora faced a setback when its drug navacaprant failed to demonstrate efficacy in a phase 3 clinical trial. This failure prompted Neumora to halt one trial and pause two other late-stage studies, as the data were even less promising than analysts had anticipated. Despite these challenges, Neumora had pointed to phase 2 data from aticaprant to argue that the drug mechanism could still be valid and that navacaprant's failure might be an exception rather than the rule.

However, J&J's recent announcement throws further doubt on this mechanism's viability. The company declared that it is discontinuing the phase 3 program for aticaprant due to insufficient efficacy observed in the target patient population. While the drug was deemed safe and well-tolerated, it failed to meet the necessary effectiveness benchmarks required for further development in treating MDD.

Despite this setback, Johnson & Johnson has not entirely abandoned aticaprant. The pharmaceutical giant stated that it would explore other potential applications for the drug in areas with significant unmet medical needs. This decision indicates that while the specific indication for MDD may not be viable, the company still sees potential value in aticaprant's underlying mechanism for other conditions.

This development represents a significant shift in J&J's strategy as the company had previously forecasted that aticaprant could achieve peak sales of $1 billion to $5 billion annually in its intended market. The drug was part of J&J’s broader ambition to become the leading neuroscience company by 2030, a goal they have pursued through strategic acquisitions and partnerships.

In January, J&J took a significant step towards this goal by acquiring Intra-Cellular Therapies for $14.6 billion. This acquisition gave J&J control over Caplyta, a drug that had shown success in phase 3 trials for MDD. With Caplyta, J&J strengthens its portfolio in the neuroscience sector, despite the setback with aticaprant.

The discontinuation of aticaprant's development does raise questions about the future focus of J&J's MDD treatment portfolio. However, John Reed, M.D., Ph.D., executive vice president of innovative medicine and R&D at J&J, has stated that the company remains committed to exploring unique mechanisms that can address different subpopulations. This commitment suggests that J&J will continue to innovate and invest in diverse approaches to MDD and other psychiatric disorders.

In conclusion, while the cessation of aticaprant’s phase 3 program marks a significant development in J&J’s MDD strategy, the company remains optimistic about exploring other therapeutic avenues. This adaptability reflects J&J’s broader strategic goals in the competitive field of neuroscience, maintaining its focus on innovation and addressing unmet medical needs.