Intra-Cellular Therapies, Inc.

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.”

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.

A depression drug candidate that’s a key part of Johnson & Johnson’s neuroscience strategy has failed a Phase 3 clinical trial, the latest dose of disappointing news for an emerging class of medicines addressing a novel target hoped to overcome limitations of currently available antidepressants. J&J is discontinuing the Phase 3 test of its drug, aticaprant, in major depressive disorder “due to insufficient efficacy in the target patient population,” the company said after Thursday’s market close. The pharmaceutical giant said this drug was safe and well-tolerated by patients, and no new safety signals were identified. No other details about the trial results were disclosed. The open-label clinical trial’s targeted enrollment was 840 adults ages 18 to 74. Participants received aticaprant once daily as an adjunct to depression drugs they were already taking. Efficacy goals for the 54-week study include measuring the percentage of patients with suicidal thoughts or behaviors and as well as the change in score over time according to a scale used to assess depression symptoms. presented by Artificial Intelligence What Keeps Healthcare CIOs Up at Night: Balancing Technology Investments with Consumer Expectations When it comes to managing inbound phone calls, underperformance has devastating cost implications. By Stephanie Baum The trial also measured for weight gain and sexual dysfunction, adverse effects that are common with currently available depression medications and lead many patients to stop taking them. Aticaprant was hoped to avoid or at least reduce these side effects. Better efficacy and improved safety and tolerability would be key advantages over the current slate of antidepressants. Analysts had projected aticaprant would become a blockbuster product. J&J said analysis of the failed study is underway and more details will be presented at a future medical meeting. But even though this Phase 3 trial is ending, J&J isn’t giving up on aticaprant. Based on the potential of the drug’s mechanism, the company said it will explore future development opportunities in other areas of high unmet need. Aticaprant is a small molecule designed to target and block kappa opioid receptors, an approach intended to modulate pathways that regulate mood and behavior. It’s the same target hit by Neumora Therapeutics’ lead drug candidate, navacaprant. In January, Neumora reported this daily pill did not beat a placebo on the main efficacy goal of a Phase 3 clinical trial. Earlier this week, Neumora said it will end the failed Phase 3 study, one of three late-stage tests for navacaprant. But the company also said it will apply learnings from the failed test to the two other Phase 3 studies, which have been paused for now. Changes include optimizing site selection and enhancing medical monitoring to ensure appropriate patients are enrolled. Neumora plans to resume the two studies later this month; preliminary data are expected in 2026. Neumora also stopped a Phase 2 test of navacaprant in bipolar depression in order to devote its resources to its major depressive disorder clinical research. Sponsored Post Tackling Messy Provider Data with an NPI-Forward Approach Mike Wirth of ProviderTrust shares insights about the company in this interview at the ViVE 2025 conference in Nashville last month. By ProviderTrust and MedCity News As for J&J, the company’s neuroscience portfolio includes the blockbuster schizophrenia drug Invega and the nasal spray depression drug Spravato. The pharma giant is bringing a depression drug prospect into the fold via the $14 billion acquisition of Intra-Cellular Therapies announced in January. Intra-Cellular’s main asset is Caplyta, which has approvals in schizophrenia and bipolar depression. The drug is currently under FDA review for major depressive disorder, an indication that could make the once-daily pill a blockbuster seller. J&J expects to complete the Intra-Cellular acquisition later this year.