Rapport Therapeutics, a clinical-stage biotechnology company dedicated to the discovery and development of small molecule precision medicines for patients with neurological and psychiatric disorders, has announced positive topline results from its phase 2 trial of RAP-219 in adults with acute bipolar mania.
The trial met its primary endpoint, with RAP-219 achieving a 3.1-point placebo-adjusted improvement in the Young Mania Rating Scale (YMRS) total score at week 3 (mean reduction from baseline of 15.4 points with RAP-219 versus 12.3 points with placebo (p=0.045).
RAP-219 was well-tolerated, with no severe treatment emergent adverse events (TEAEs) or serious adverse events (SAEs) observed over the treatment period. These results establish clinical proof-of-concept for RAP-219 and its novel TARPγ8-selective mechanism in bipolar mania, supporting progression to phase 3 trials which are expected to begin in the second half of 2027.
This randomised, double-blind, placebo-controlled phase 2 trial, conducted in the United States, enrolled 253 adults with bipolar I disorder (BD) experiencing an acute manic episode (YMRS≥25 at baseline). During the screening period, all treatments indicated for BD and all anxiolytics and hypnotics were discontinued.
Lorazepam was allowed as a rescue medication at protocol-defined doses, and its use required an AE to be recorded, regardless of whether the symptom(s) were judged to be due to a pre-existing condition.
Eligible patients received 0.75 mg of RAP-219 once daily (following a two- or four- day titration) or placebo for three weeks in an inpatient setting. Mean baseline YMRS total score was 36.9 in the RAP-219 arm and 35.8 in the placebo arm.
Topline efficacy and safety data reported are from the three-week treatment period. Safety data from the eight-week post-treatment period will be presented at a future medical conference.
