κ opioid receptor

A depression drug candidate that’s a key part of Johnson & Johnson’s neuroscience strategy has failed a Phase 3 clinical trial, the latest dose of disappointing news for an emerging class of medicines addressing a novel target hoped to overcome limitations of currently available antidepressants. J&J is discontinuing the Phase 3 test of its drug, aticaprant, in major depressive disorder “due to insufficient efficacy in the target patient population,” the company said after Thursday’s market close. The pharmaceutical giant said this drug was safe and well-tolerated by patients, and no new safety signals were identified. No other details about the trial results were disclosed. The open-label clinical trial’s targeted enrollment was 840 adults ages 18 to 74. Participants received aticaprant once daily as an adjunct to depression drugs they were already taking. Efficacy goals for the 54-week study include measuring the percentage of patients with suicidal thoughts or behaviors and as well as the change in score over time according to a scale used to assess depression symptoms. presented by Artificial Intelligence What Keeps Healthcare CIOs Up at Night: Balancing Technology Investments with Consumer Expectations When it comes to managing inbound phone calls, underperformance has devastating cost implications. By Stephanie Baum The trial also measured for weight gain and sexual dysfunction, adverse effects that are common with currently available depression medications and lead many patients to stop taking them. Aticaprant was hoped to avoid or at least reduce these side effects. Better efficacy and improved safety and tolerability would be key advantages over the current slate of antidepressants. Analysts had projected aticaprant would become a blockbuster product. J&J said analysis of the failed study is underway and more details will be presented at a future medical meeting. But even though this Phase 3 trial is ending, J&J isn’t giving up on aticaprant. Based on the potential of the drug’s mechanism, the company said it will explore future development opportunities in other areas of high unmet need. Aticaprant is a small molecule designed to target and block kappa opioid receptors, an approach intended to modulate pathways that regulate mood and behavior. It’s the same target hit by Neumora Therapeutics’ lead drug candidate, navacaprant. In January, Neumora reported this daily pill did not beat a placebo on the main efficacy goal of a Phase 3 clinical trial. Earlier this week, Neumora said it will end the failed Phase 3 study, one of three late-stage tests for navacaprant. But the company also said it will apply learnings from the failed test to the two other Phase 3 studies, which have been paused for now. Changes include optimizing site selection and enhancing medical monitoring to ensure appropriate patients are enrolled. Neumora plans to resume the two studies later this month; preliminary data are expected in 2026. Neumora also stopped a Phase 2 test of navacaprant in bipolar depression in order to devote its resources to its major depressive disorder clinical research. Sponsored Post Tackling Messy Provider Data with an NPI-Forward Approach Mike Wirth of ProviderTrust shares insights about the company in this interview at the ViVE 2025 conference in Nashville last month. By ProviderTrust and MedCity News As for J&J, the company’s neuroscience portfolio includes the blockbuster schizophrenia drug Invega and the nasal spray depression drug Spravato. The pharma giant is bringing a depression drug prospect into the fold via the $14 billion acquisition of Intra-Cellular Therapies announced in January. Intra-Cellular’s main asset is Caplyta, which has approvals in schizophrenia and bipolar depression. The drug is currently under FDA review for major depressive disorder, an indication that could make the once-daily pill a blockbuster seller. J&J expects to complete the Intra-Cellular acquisition later this year.

iStock, BrasilNut1 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.

Tris Pharma said Thursday that its experimental pain drug delivered significant relief in another Phase III trial — this time in patients recovering from foot surgery. The results of ALLEVIATE-2 come weeks after a successful readout from ALLEVIATE-1, a late-stage study testing cebranopadol (TRN-228) in post-abdominoplasty surgery patients.Cebranopadol acts on both nociceptin/orphanin FQ peptide (NOP) and μ-opioid peptide (MOP) receptors, a mechanism Tris refers to as "dual-NMR agonism." By stimulating the NOP receptor, the company says its drug mitigates MOP-related side effects such as dependence, euphoria, respiratory depression and addiction, potentially reducing the risks associated with traditional opioid painkillers.Filing preparations"With our Phase III programme for cebranopadol… complete, we now have a comprehensive data package that will be submitted to the FDA as the basis for potential approval," said CEO Ketan Mehta. A US filing is planned for 2025.ALLEVIATE-2 tested cebranopadol against a placebo in about 240 patients with moderate-to-severe pain after bunionectomy, using an 11-point NRS pain scale.A daily 400 µg dose of oral cebranopadol reduced pain by 56.1 points compared to placebo. In a separate arm of the study, oxycodone IR 10 mg, given four times daily, provided more pain relief than placebo, but was less effective than cebranopadol based on NRS scores, according to a post-hoc analysis.Further, results over the course of the seven-day study period showed that 57.5% of cebranopadol patients did not require opioid rescue medication, compared to 28.4% in the placebo group. Tris said no serious adverse events were reported and nausea was the most common side effect.Filling a gapTodd Bertoch, lead investigator on ALLEVIATE-2, said "the biggest challenge in the search for new drugs for pain has been finding something safe that can treat more severe pain that today requires use of an opioid. The level of analgesia seen across both ALLEVIATE-1 and ALLEVIATE-2 as well as the safety data that has been generated suggest that cebranopadol could fulfill this urgent need."Full results from both studies will be presented at an upcoming medical congress. If approved, cebranopadol would provide another option in the quest for alternatives to traditional opioids. A few weeks ago, Vertex Pharmaceuticals won FDA approval for Journavx (suzetrigine), a non-opioid pain drug that blocks NaV1.8 sodium channels to reduce pain signaling (see – Spotlight on: The drugs that will shape 2025).Tris officials have said that while Journavx targets the gap between NSAIDs and opioids, cebranopadol is aimed at those "who can only be treated effectively with an opioid today."