Rapport Therapeutics reports positive Phase 2 data for RAP-219 in bipolar mania

Rapport Therapeutics (Nasdaq: RAPP) announced positive topline results from its Phase 2 trial of RAP-219 for the treatment of acute bipolar mania, meeting both primary and secondary endpoints with statistically significant placebo-adjusted improvements at Week 3. The company disclosed that RAP-219 achieved a 3.1-point improvement in the Young Mania Rating Scale (YMRS) total score and a 0.4-point improvement in the Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Mania score compared to placebo.

The randomized, double-blind, placebo-controlled trial enrolled 253 adults with bipolar I disorder experiencing an acute manic episode in the United States. Patients received either 0.75 mg of RAP-219 once daily or placebo for three weeks in an inpatient setting. The primary endpoint was met with a p-value of 0.045 for the YMRS total score, while the pre-specified secondary endpoint for mania severity was met with a p-value of 0.024. All 11 items measured by the YMRS improved numerically on RAP-219 compared to placebo, with irritability, thought content, disruptive-aggressive behavior, and sexual interest reaching nominal significance.

Safety data indicated that RAP-219 was well tolerated during the three-week treatment period, with no serious adverse events or severe treatment-emergent adverse events observed. The incidence of treatment-emergent adverse events was similar between the RAP-219 and placebo groups at 51.6% and 52.8%, respectively. Agitation was the most common adverse event in the RAP-219 group, occurring in 16.7% of participants, though it was generally considered unrelated to treatment in more than 80% of cases. Adverse effects commonly associated with current bipolar medications, such as orthostatic hypotension and akathisia, were not reported.

Abraham N. Ceesay, chief executive officer of Rapport, stated that the results establish clinical proof-of-concept for RAP-219 and its novel TARP gamma 8-selective mechanism. The company plans to initiate Phase 3 trials in the second half of 2027, following a meeting with the U.S. Food and Drug Administration in the first quarter of 2027 to discuss registrational trial design.