One of J&J's blockbuster depression hopes has flamed out

Johnson & Johnson has decided to halt the development of selective kappa opioid receptor (KOR) antagonist aticaprant as a treatment for major depressive disorder (MDD), blowing a hole in its late-stage CNS pipeline.

Last year, the company listed aticaprant among 15 late-stage programmes that could generate $1 billion to $5 billion in peak annual sales, pointing it its potential as an adjunctive treatment for MDD patients who have anhedonia – an inability to generate interest, enjoyment, or pleasure from life experiences.

The company now says that it saw "insufficient efficacy" with aticaprant in the phase 3 VENTURA programme, which spanned five separate studies looking at the drug's potential as an add-on to current MDD therapy, including patients with an inadequate response to current therapy alone and to prevent the return of anhedonia symptoms.

It's not necessarily the end of the programme, however. Buoyed by data from VENTURA showing that aticaprant was safe and well-tolerated, and the potential for its mechanism of action, J&J said it will "explore future development opportunities for aticaprant in other areas of high unmet need."

Now, one question is whether the fortunes of aticaprant in MDD have any implications for another company developing a KOR antagonist for this indication - Neumora Therapeutics - whose navacaprant candidate is also in phase 3 testing.

Analysts at Stifel downgraded their rating on Neumora from buy to hold on the back of J&J's announcement, saying they had looked to the VENTURA trials to validate the KOR antagonist mechanism in MDD with anhedonia.

Meanwhile, in January, Neumora said navacaprant had failed the phase 3 KOASTAL-1 study in MDD, looking at depression symptoms, but had taken the learnings from the study to pause two other studies – KOASTAL-2 and KOASTAL-3 – in order to tweak the protocols. It is now expecting topline data from the two studies in the first and second quarters of 2026, respectively.

J&J is already seeing strong sales growth for its treatment-resistant depression (TRD) and MDD therapy Spravato (esketamine), which made more than $1 billion in sales last year, and recently scored an important new approval as a standalone therapy.

The company also has another shot on goal in depression with seltorexant, an orexin-2 receptor antagonist that has been shown to be effective in MDD with insomnia in a phase 3 trial.

J&J also listed seltorexant among its 15 potential blockbuster candidates in its R&D update (PDF) last year.

The company estimates that there are 260 million people worldwide who suffer from chronic depression, which is a leading cause of disability, and more than 30% of them do not get relief from their current medicines.