Johnson & Johnson announced Thursday it will discontinue development of aticaprant as an adjunctive therapy for major depressive disorder (MDD) following disappointing efficacy results from its Phase III VENTURA clinical program.
The pharmaceutical giant had previously projected the kappa opioid receptor antagonist could generate between $1 billion and $5 billion in peak annual sales. However, despite demonstrating a favorable safety profile, the drug showed "insufficient efficacy in the target patient population," according to the company's statement.
Clinical Program Details
The VENTURA trials evaluated aticaprant in adults with treatment-resistant major depressive disorder who exhibited moderate-to-severe anhedonia—a core symptom characterized by loss of interest or inability to experience joy. While J&J did not disclose specific data points in its announcement, the company confirmed no new safety signals were detected during the trials.
Complete findings and analyses from the VENTURA program are expected to be presented at an upcoming medical congress, providing the scientific community with more detailed insights into the drug's performance.
Future Development Pathways
Despite this setback, J&J indicated it has not abandoned aticaprant entirely. The company plans to "explore future development opportunities" for the compound in other "areas of high unmet need," suggesting potential applications beyond depression.
"We believe in the potential for this mechanism," J&J stated in its release, indicating continued confidence in the kappa opioid receptor as a therapeutic target, despite the disappointing results in MDD.
Impact on J&J's Neuroscience Strategy
The termination represents a significant blow to J&J's neuroscience pipeline, potentially complicating the company's ambitious goal of becoming the leading neuroscience company by 2030. However, J&J emphasized its ongoing commitment to the neuroscience space, pointing to its recent $14.6 billion acquisition of Intra-Cellular Therapies, maker of the antipsychotic medication Caplyta.
J&J also reaffirmed its financial guidance, stating it still expects its medicines division to achieve a compound annual growth rate of 5% to 7%. The division recorded $57 billion in sales last year, representing a 4% increase from 2023.
David Risinger, an analyst at Leerink Partners, noted that Wall Street had been projecting approximately $1 billion in annual sales from aticaprant by 2032, significantly below J&J's more optimistic forecast.
Broader Implications for Kappa Opioid Receptor Antagonists
The failure of aticaprant raises broader questions about the viability of kappa opioid receptor antagonists as treatments for depression. These receptors, which regulate various aspects of the nervous system including mood, stress, and pain perception, have been considered promising targets for both depression and addiction therapies.
Notably, J&J's announcement comes just months after Neumora Therapeutics reported that its own kappa opioid receptor antagonist, navacaprant, failed to outperform placebo in a Phase III study for moderate-to-severe MDD.
Brian Abrahams, an analyst at RBC Capital Markets, suggested the discontinued J&J trials could erode "any residual hope" that these drugs might prove useful in depression. Similarly, Stifel analyst Paul Matteis described the news as a "big blow" to the thesis surrounding kappa opioid receptor drugs in this indication.
Market Response
The market reaction to J&J's announcement was relatively muted, with the company's stock rising more than 1% following the news. This limited impact likely reflects the diversified nature of J&J's pipeline, which includes nearly 20 other novel drug programs with blockbuster potential.
In contrast, shares of Neumora Therapeutics fell approximately 5% on the news, extending the biotech's struggles since its IPO. Neumora's stock has declined more than 90% since going public in summer 2023, trading at approximately $1.45 per share as of Friday.
Current Depression Treatment Landscape
The development setback highlights the persistent challenges in addressing treatment-resistant depression, a condition affecting millions worldwide. Despite numerous approaches and mechanisms being investigated, finding effective therapies for patients who don't respond to existing treatments remains difficult.
J&J's neuroscience portfolio continues to include Spravato (esketamine), which recently surpassed $1 billion in annual sales as a treatment for treatment-resistant depression and major depressive disorder with suicidal thoughts. The upcoming acquisition of Intra-Cellular Therapies is expected to further strengthen J&J's position in the CNS space when it closes in the second quarter of 2024.
Analysts at Guggenheim Partners noted that while aticaprant's failure is "disappointing," it is "not entirely surprising" given the historical difficulties in developing effective therapies for depression, particularly those targeting the kappa opioid receptor pathway.
