KOR antagonist(Medical University of Vienna)

J&J is now looking to trial the therapy in other indications but has not specified details. Image credit: Shutterstock / josefkubes. Johnson & Johnson (J&J) is dropping its Phase III major depressive disorder (MDD) programme for aticaprant due to ‘insufficient efficacy in the target population’. The VENTURA programme, evaluating the experimental drug as an adjunctive treatment for MDD, included five Phase III trials. The company said that despite the efficacy failure, aticaprant remained safe and well-tolerated in the programme. Full data from the VENTURA programme will be presented at a future medical meeting. J&J said it plans to “explore future development opportunities for aticaprant in other areas of high unmet need”. A statement accompanying the announcement read: “Johnson & Johnson continues to build on its leadership in neuroscience, as demonstrated by the company’s significant investments in its current pipeline and the planned acquisition of Intra-Cellular Therapies. The company remains focused on driving innovation in neuropsychiatric and neurodegenerative disorders.” There had been a lot of hope for aticaprant, with GlobalData previously touting it as the most promising pipeline product for MDD due to its novel MOA and focus on anhedonia, a hard-to-treat symptom. GlobalData analysis previously projected that aticaprant could generate global sales of approximately $670.63m in MDD by 2029 subject to approval. J&J’s high hopes for the drug were also reflected, with the company saying the therapy had the potential to make $1bn to $5bn. Reacting to J&J’s news, Phillipa Salter, neurology analyst at GlobalData said: “It is surprising to see the announcement from J&J. Aticaprant had been effective in Phase II trials and the company had only recently initiated further Phase III trials within the VENTURA programme. VENTURA-5 initiated in September 2024 and VENTURA-7 initiated in June 2024 so it is surprising that the VENTURA programme is being discontinued so soon after this. J&J were targeting adults with MDD with moderate-to-severe anhedonia which is a hard to treat symptom of severe MDD.” GlobalData is the parent company of Clinical Trials Arena . Neumora’s KOR antagonist also failed in Phase III trial Aticaprant is a kappa-type opioid receptor (KOR) antagonist that should modulate dopamine and reward processing pathways. This is the second drug with this mechanism of action (MOA) to take a hit in MDD after Neumora’s navacaprant failed to meet the the primary endpoint in the Phase III KOASTAL-1 (NCT06029426) study. Earlier this week, the US-based company announced it was halting two other studies of the drug to change the trial design of the KOASTAL-2 and KOASTAL-3 studies (NCT06058039 and NCT06058013). Neumora’s stock, listed on the Nasdaq exchange, dipped on J&J’s announcement, dropping by 13.15% from a market close of $1.52 yesterday (6 March) to a market open of $1.32 today. J&J’s stock, listed on the New York Stock Exchange (NYSE), has remained stable despite the announcement. “This news follows the recent news that Neumora Therapeutics’ navacaprant, a drug with the same mechanism of action as aticaprant, failed a Phase III trial in MDD so there was prior information that this mechanism of action may not be effective for MDD,” Salter added Last year, J&J had success in a Phase III trial of its therapy seltorexant , which helped MDD patients with insomnia, with the study meeting all its endpoints. The MDD market across the eight major markets (8MM: US, France, Germany, Italy, Spain, UK, Japan, and Canada) is poised to grow at a compound annual growth rate (CAGR) of 7.4% from $4.7bn in 2019 to $9.6bn in 2029.