J&J halts depression drug development after poor trial results

USA – Johnson & Johnson (J&J) has stopped developing aticaprant, a selective kappa opioid receptor (KOR) antagonist, as a treatment for major depressive disorder (MDD) due to disappointing phase 3 trial results.

The drug was once considered a potential blockbuster, with projected annual sales of up to US $5 billion.

Aticaprant was being tested as an add-on therapy for patients with MDD, particularly those struggling with anhedonia—the inability to find pleasure in life.

However, J&J revealed that the phase 3 VENTURA trials, which involved five studies, showed “insufficient efficacy” in improving depressive symptoms.

Despite these results, J&J found the drug to be safe and well-tolerated, leading them to consider exploring its potential in other medical conditions with high unmet needs.

“We remain committed to identifying effective treatments for depression and will evaluate aticaprant’s future development in other areas,” the company stated.

Impact on other KOR antagonist drugs

J&J’s decision has raised concerns about the effectiveness of KOR antagonists in treating depression.

Neumora Therapeutics, another company developing a similar drug, navacaprant, is now under scrutiny.

Analysts at Stifel downgraded Neumora’s stock from buy to hold, citing J&J’s trial results as a major setback for the KOR antagonist approach in MDD treatment.

Earlier this year, Neumora reported that navacaprant failed its phase 3 KOASTAL-1 study, which tested its ability to improve depressive symptoms.

The company responded by pausing two other studies, KOASTAL-2 and KOASTAL-3, to adjust their protocols. New results are expected in 2026.

J&J’s focus on other depression treatments

Although aticaprant’s failure is a setback, J&J is still making progress in the depression treatment market.

Its Spravato (esketamine), a drug for treatment-resistant depression (TRD) and MDD, is performing well, generating over US $1 billion in sales last year.

Recently, Spravato gained approval as a standalone treatment, expanding its potential market.

Additionally, J&J has another promising depression drug, seltorexant, an orexin-2 receptor antagonist.

It showed positive results in treating MDD with insomnia in a phase 3 trial and remains on J&J’s list of potential blockbuster drugs.

Depression remains one of the most pressing global health issues, affecting 260 million people worldwide.

More than 30% of patients do not find relief with existing treatments, highlighting the need for new, effective therapies.