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 as well as the change in score over time according to a scale used to assess depression symptoms.
The Top Surgical Instruments Needed for Extractions
Discover what tools are essential for efficient, safe surgical extractions in today’s health care landscape, from elevators to forceps and beyond.
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.
5 Major Trends Emerging in Healthcare Benefits in 2025
Employees who enjoy their benefits are more inclined to stay with their company. A 2025 Marsh McLennan Agency report said 73% of employees would remain if plan options were better.
[Paragraph added with analyst comments.] In a note sent to investors Friday, William Blair analyst Myles Minter acknowledged Neumora’s explanations for the trial failure and the planned adjustments to the two other Phase 3 tests. But he added that the back-to-back Phase 3 misses for Neumora and J&J against the kappa opioid receptor diminishes confidence in this target as a mechanism for treating major depressive disorder. The firm has reduced the Neumora study’s probability of success to 5% and also downgraded the biotech’s shares.
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.
Photo: Mario Tama, Getty Images