J&J Halts Phase 3 Depression Program, Citing Insufficient Efficacy

Johnson & Johnson (J&J) has announced the discontinuation of its phase 3 program for aticaprant, an oral opioid kappa receptor antagonist, as an adjunctive treatment for major depressive disorder (MDD). The pharmaceutical giant cited "insufficient efficacy in the target patient population" as the reason for halting the development in this indication.

Setback for Opioid Kappa Receptor Antagonists in MDD

The decision comes on the heels of a similar setback in the field of opioid kappa receptor antagonists. Earlier this year, Neumora Therapeutics reported a phase 3 failure for its candidate navacaprant in MDD. Following this initial setback, Neumora took further action by halting one trial and pausing two late-stage studies of navacaprant after assessing additional data that proved to be even more disappointing than initially anticipated.

These developments cast a shadow over the potential of this drug class in treating depression. Neumora had previously pointed to phase 2 data from J&J's aticaprant as evidence supporting the mechanism of action. However, J&J's recent announcement weakens this argument and raises questions about the viability of opioid kappa receptor antagonists in MDD treatment.

J&J's Future Plans for Aticaprant

Despite the setback in MDD, J&J has not completely abandoned aticaprant. The company noted that the molecule demonstrated a favorable safety and tolerability profile. As a result, J&J plans to "explore future development opportunities for aticaprant in other areas of high unmet need."

This pivot comes as a significant blow to J&J's neuroscience ambitions. The company had previously forecasted peak annual sales of $1 billion to $5 billion for aticaprant in the MDD indication. This projection was part of J&J's broader strategy to become the leading neuroscience company by 2030.

Strategic Shifts in J&J's Neuroscience Portfolio

In light of the aticaprant setback, J&J's recent acquisition of Intra-Cellular Therapies for $14.6 billion takes on added significance. This purchase gives J&J control of Caplyta, a drug that has shown success in phase 3 trials for MDD.

During a January earnings call, J&J's executive vice president of innovative medicine R&D, John Reed, M.D., Ph.D., emphasized the company's commitment to pursuing "unique mechanisms that can play in different subpopulations" of MDD patients. This strategy underscores J&J's recognition of the complex nature of depression and the need for diverse therapeutic approaches.