Five companies are advancing psychedelic-derived and serotonergic therapies through late-stage clinical development for treatment-resistant depression and anxiety disorders. Academic medicine is preparing for potential regulatory approval, with the U.S. National Network of Depression Centers publishing a consensus statement in The Lancet on integrating psychedelics into routine clinical practice.
Clinical Progress and Key Data
Helus Pharma’s SPL026 met its primary endpoint in a randomized Phase 2a trial involving 34 participants with moderate-to-severe major depressive disorder across three clinical sites in the United Kingdom. Participants receiving a single 21.5 mg dose showed a mean MADRS difference of -7.35 versus placebo (p=0.023), with effects appearing within one week (p=0.002). Response rates at two weeks reached 35% versus 12% for placebo, while remission rates were 29% versus 12%. No treatment-related serious adverse events were reported, with effects sustained for up to three months in some cases.
The company’s lead asset HLP003, an oral compound with FDA Breakthrough Therapy Designation, demonstrated 100% response rates and 71% remission at 12 months after two 16 mg doses in Phase 2, with an approximately 23-point reduction in MADRS scores. HLP003 is advancing through two pivotal Phase 3 studies for adjunctive treatment of major depressive disorder, with the APPROACH study expecting topline data in Q4 2026.
Industry Momentum
AtaiBeckley’s lead candidate BPL-003, a nasal spray for treatment-resistant depression, met its primary and secondary endpoints in Phase 2b, with Phase 3 guidance expected in the first quarter and trial initiation by mid-year. GH Research announced FDA clearance to resume U.S. enrollment for GH001, an inhaled mebufotenin formulation for treatment-resistant depression, following a Phase 2b trial that met its primary endpoint with a 15.5-point placebo-adjusted MADRS reduction on Day 8. Definium Therapeutics expects three Phase 3 readouts in 2026 for its lead candidate DT120, an LSD-derived orally disintegrating tablet for generalized anxiety disorder.
LB Pharmaceuticals initiated its Phase 2 ILLUMINATE-1 trial of LB-102, a once-daily oral antipsychotic, in bipolar depression, enrolling approximately 320 patients across 30 U.S. sites.
This article is an AI-assisted summary. All facts and figures are drawn from the original report: https://www.prnewswire.com/news-releases/psychedelic-biotechs-push-toward-phase-3-five-companies-advancing-cns-treatments-302699781.html