Aticaprant

Johnson & Johnson once tipped aticaprant to generate peak sales of up to $5 billion a year.\n Johnson & Johnson has added to the opioid kappa blues. Months after Neumora reported a phase 3 flop, J&J has stopped development of its rival drug candidate aticaprant as an adjunctive treatment for major depressive disorder (MDD).Aticaprant and Neumora’s navacaprant are oral opioid kappa receptor antagonists. Navacaprant failed a phase 3 MDD trial in January. Earlier this week, Neumora halted one trial of the candidate and paused two late-stage studies after assessing a data set that was even worse than analysts feared based on the top-line failure.Neumora has cited phase 2 aticaprant data as evidence that its mechanism works and that its failed trial may be an anomaly. That argument took a hit after the stock market closed Thursday, when J&J said it is stopping a phase 3 aticaprant program because of insufficient efficacy in the target patient population.J&J is yet to give up on aticaprant. Noting that the molecule was safe and well tolerated, the Big Pharma said it will “explore future development opportunities for aticaprant in other areas of high unmet need.” The abandoned indication was the big near-term sales opportunity, though. J&J tipped (PDF) aticaprant to generate peak sales of $1 billion to $5 billion a year in the setting late in 2023. The Big Pharma made the forecast as it laid out its vision for becoming the No. 1 neuroscience company by 2030. J&J took a shortcut toward that goal in January by inking a deal to buy Intra-Cellular Therapies for $14.6 billion. Buying Intra-Cellular will give J&J control of Caplyta, a drug that has delivered phase 3 wins in MDD.Having seen J&J bolster its MDD portfolio, Wolfe Research analyst Alexandria Hammond, Ph.D., asked (PDF) the company on an earnings call in January whether people should “expect a deprioritization of seltorexant and aticaprant.” John Reed, M.D., Ph.D., executive vice president, innovative medicine, R&D at J&J, said “absolutely not,” because “J&J needs unique mechanisms that can play in different subpopulations.”

Previously highlighted by Johnson & Johnson as one of a number of assets that could generate between $1 billion and $5 billion in peak sales, the KOR antagonist aticaprant has come up short in its first pivotal test. J&J is ending the Phase III VENTURA programme for aticaprant as an adjunctive treatment for major depressive disorder (MDD), citing "insufficient efficacy in the target patient population." The programme consisted of a number of studies, including VENTURA-1, which investigated the drug in adults with MDD with moderate-to-severe anhedonia (ANH+) who have had an inadequate response to a selective serotonin reuptake inhibitor or a serotonin-norepinephrine reuptake inhibitor.Other trials in the programme included VENTURA-2 in adults with MDD with ANH+ and an inadequate response to current antidepressant therapy, and VENTURA-5 in those who experience a loss of interest and pleasure.Development to continueThe pharma did not disclose further results, noting only that aticaprant was safe and well tolerated in the trials, with full analyses under way. However, J&J indicated that it will continue to explore the drug in other areas of high unmet need. Along with aticaprant, the company's neuroscience pipeline is soon to benefit from the addition of the antipsychotic Caplyta (lumateperone), currently under review by the FDA as an adjunctive treatment for adults with MDD. Developed by Intra-Cellular Therapies — which J&J agreed to acquire in January for approximately $14.6 billion — the once-daily oral therapy is already approved for schizophrenia and bipolar depression.Impact on Neumora?Earlier this year, Neumora Therapeutics' oral KOR antagonist navacaprant failed to meet the primary endpoint of the Phase III KOASTAL-1 trial, performing no better than placebo in adults with moderate-to-severe MDD. Two other late-stage studies of the drug are ongoing, although the company recently paused the trials in order to implement protocol changes.Neumora hopes the amendments to the KOASTAL-2 and -3 studies — based on learnings from KOASTAL-1 — will salvage navacaprant in MDD. Top-line data from KOASTAL-3 are now due in the first quarter of 2026, with KOASTAL-2 set to read out in the second quarter of next year, both pushed back from their original timeline of the first half of 2025.