Lumateperone Tosylate

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.

Johnson & Johnson scrapped its Phase 3 program for aticaprant, an experimental and new type of major depressive disorder drug, following “insufficient efficacy,” the pharma giant disclosed late Thursday evening. The drugmaker was trying to bring to market a type of drug called a kappa opioid receptor (KOR) antagonist, which is meant to hit upon the reward processing and dopamine pathways. It follows a major setback from its main KOR competitor, Neumora, which flunked the first of its three Phase 3 trials in January and last week said it paused the other two studies to adjust them for a shot at better outcomes. AbbVie also has a KOR antagonist (by way of its Cerevel acquisition ) named icalcaprant. A Phase 2 study of the drug, for forms of bipolar disorder, is listed as “not yet recruiting” in the US clinical trials registry. “[T]his is a big blow to the thesis for KORAs, in our view,” Stifel analyst Paul Matteis wrote in a Thursday evening note to clients. Matteis said the decision came as a surprise since J&J was running a “very conservative” Phase 3 program with “large over-powered studies,” including an additional Phase 3 that was initiated in the fall. Two months ago, J&J doubled down in neuroscience with its proposed $14.6 billion acquisition of Intra-Cellular Therapies, which makes the marketed brain health treatment called Caplyta. A few weeks later, J&J’s global head of pharma R&D, John Reed, said the pharmaceutical and medical device conglomerate would not deprioritize its clinical-stage depression medicines, including aticaprant and seltorexant, as a result of the megadeal. “On the other hand, in retrospect,” Matteis wrote in the note, “there was JNJ’s recent decision to acquire ITCI, which may have been executed by JNJ to further their leadership in CNS under the concern that aticaprant could fail.” The setback could mark a slight dent in J&J’s future neuro prospects. The company has previously projected $1 billion to $5 billion in peak annual sales for aticaprant. In neuro, the drugmaker also markets the esketamine depression treatment called Spravato, which eclipsed $1 billion in sales for the first time last year. In a Thursday evening note, Leerink Partners analyst David Risinger said his firm had been modeling 2032 sales of aticaprant at $1.1 billion, or less than 1% of the healthcare company’s total revenue estimates for that year. Despite the setback in the Phase 3 program for the adjunctive treatment for major depressive disorder, J&J said it “will explore future development opportunities” for the late-stage asset in “other areas of high unmet need.” J&J said aticaprant was “safe and well-tolerated, and no new safety signals were identified.” The company plans to present a more complete look at the so-called VENTURA program at an undisclosed medical meeting.