Analysts do not believe the Phase III stumble for aticaprant will derail J&J’s broader neuroscience strategy, particularly given its recent $14.6 billion acquisition of Intra-Cellular Therapeutics and the success of Spravato for treatment-resistant depression.
Johnson & Johnson’s neuro pipeline suffered a late-stage setback on Thursday after the pharma announced that it would discontinue the Phase III VENTURA program for its kappa opioid receptor blocker aticaprant in major depressive disorder.
The decision follows a disappointing late-stage readout that showed “insufficient efficacy” in VENTURA, according to the pharma’s announcement. J&J did not reveal specific data on Thursday, though it did reveal that no new safety signals were detected. Full findings and analyses from VENTURA will be presented at an upcoming medical congress.
Nevertheless, despite the Phase III failure in this indication, the pharma will stand by aticaprant, pointing to the “potential for this mechanism” in other therapeutic areas, according to its Thursday release. J&J will continue to “explore future development opportunities” for aticaprant in other indications.
Designed to be taken orally, aticaprant is a small-molecule inhibitor of the kappa opioid receptor (KOR), which plays a central function in modulating the reward and mood processes in the brain. Several studies have established KORs as promising targets for both addiction and depression. According to J&J’s pipeline page, it was only developing the drug candidate as an adjunctive therapy for major depressive disorder with anhedonia.
In a note to investors on Thursday evening, analysts at Guggenheim Partners called aticaprant’s stumble “disappointing,” however noting that “this outcome is not entirely surprising,” especially given the difficulty of developing therapies for depression, particularly by targeting the kappa opioid receptor.
In January, for instance, Neumora Therapeutics’ own kappa opioid receptor antagonist navacaprant also failed in its Phase III KOASTAL-1 study in major depressive disorder.
Still, Guggenheim doesn’t think VENTURA’s failure will derail J&J’s neuro portfolio, which it says “remains intact.”
“We believe JNJ’s broader neuroscience strategy remains on track, bolstered by Spravato’s recent milestone of surpassing $1 billion in annual sales,” the analysts wrote. The pharma’s $14.6 billion acquisition of Intra-Cellular Therapeutics—announced in January 2025 and expected to close in the second quarter—will also help beef up its neuro pipeline.
Aside from its sales milestone, Spravato, an esketamine nasal spray, also recently notched a regulatory win in January when the FDA cleared it as the first-ever monotherapy for treatment-resistant depression. The treatment can now be used without an oral agent in patients who have failed to respond to at least two lines of oral therapies.
