J&J Discontinues Late-Stage Depression Trial, Reaffirms Commitment to Neuroscience

Johnson & Johnson (J&J) has announced the discontinuation of its Phase III VENTURA program for aticaprant, a kappa opioid receptor blocker, in major depressive disorder (MDD) due to insufficient efficacy. This setback comes amid a series of developments in the pharmaceutical giant's neuroscience portfolio, including a recent major acquisition and success with another depression treatment.

Aticaprant Trial Termination and Industry Implications

J&J's decision to halt the VENTURA program follows disappointing late-stage results that failed to demonstrate adequate efficacy in treating MDD. The company did not disclose specific data but confirmed that no new safety signals were detected during the trial. Full findings and analyses from VENTURA are expected to be presented at an upcoming medical congress.

This development adds to the challenges faced by pharmaceutical companies targeting the kappa opioid receptor for depression treatment. In January, Neumora Therapeutics' kappa opioid receptor antagonist navacaprant also failed in its Phase III KOASTAL-1 study for MDD. These setbacks highlight the difficulties in developing effective therapies for depression, particularly those targeting this specific receptor.

Despite the trial's failure, J&J remains optimistic about aticaprant's potential in other therapeutic areas. The company plans to explore future development opportunities for the drug candidate, citing the "potential for this mechanism" in addressing other unmet medical needs.

J&J's Neuroscience Strategy and Recent Acquisitions

Analysts believe that the Phase III stumble for aticaprant is unlikely to derail J&J's broader neuroscience strategy. The company's recent $14.6 billion acquisition of Intra-Cellular Therapeutics, announced in January 2025 and expected to close in the second quarter, is seen as a significant boost to its neuroscience pipeline.

J&J's commitment to becoming a leader in neuroscience is further evidenced by the success of Spravato, its esketamine nasal spray for treatment-resistant depression. Spravato recently surpassed $1 billion in annual sales and received FDA approval as the first monotherapy for treatment-resistant depression, allowing its use without an oral agent in patients who have failed to respond to at least two lines of oral therapies.

Industry Outlook and Future Directions

The pharmaceutical industry continues to face challenges in developing effective treatments for depression and other neurological disorders. While the setbacks in kappa opioid receptor antagonists have been disappointing, companies like J&J are diversifying their approaches and strengthening their portfolios through strategic acquisitions and ongoing research.

As the landscape of neuroscience drug development evolves, the industry remains focused on exploring novel mechanisms and combination therapies to address the complex needs of patients with depression and other mental health conditions. The coming months and years will likely see continued investment and innovation in this critical area of medicine.