Alto Neuroscience Initiates Phase 2b Trial of ALTO-207
Alto Neuroscience announced the initiation of a Phase 2b randomized, placebo-controlled trial of ALTO-207 in treatment-resistant depression, a program designed to replicate the strongly positive PAX-D study results and support a streamlined path to registration. The Phase 2b trial design is informed by the PAX-D study, a randomized, placebo-controlled trial published in The Lancet Psychiatry, which demonstrated a Cohen's d effect size of 0.87 for pramipexole augmentation in TRD - substantially exceeding the effect sizes observed with currently approved therapies. ALTO-207, a fixed-dose combination of pramipexole and ondansetron, with a novel, modified-release formulation, is designed to mitigate pramipexole-associated nausea, thus enabling improved tolerability, more rapid titration, and higher dosing. The combination is further supported by results from a prior Phase 2a trial of ALTO-207, which demonstrated statistically significant improvement on MADRS with a favorable tolerability profile at a higher mean dose of pramipexole. The Phase 2b trial will enroll approximately 178 adults with treatment-resistant depression who have experienced two to five prior treatment failures during their current episode of depression and remain on a stable background antidepressant. Participants will be randomized 1:1 to receive ALTO-207 or placebo over an eight-week treatment period. ALTO-207 will be titrated up to a target dose of 3.2 mg pramipexole and 15 mg ondansetron per day. The trial will be conducted at sites in the United States and United Kingdom, including National Health Service sites that participated in the PAX-D study. The primary endpoint is change from baseline in MADRS, consistent with FDA guidance for depression trials. Topline data are expected in the second half of 2027.
