Rapport Therapeutics said its experimental drug RAP-219 met the primary and secondary endpoints in a Phase 2 trial of adults with acute bipolar mania, supporting plans for two Phase 3 studies in 2027.
The randomized, double-blind, placebo-controlled U.S. trial enrolled 253 adults with bipolar I disorder experiencing an acute manic episode. Participants received 0.75 milligrams of RAP-219 daily, following dose titration, or placebo for three weeks in an inpatient setting.
At Week 3, patients receiving RAP-219 had a 15.4-point reduction from baseline on the Young Mania Rating Scale, compared with 12.3 points for placebo. The placebo-adjusted difference of 3.1 points was statistically significant, with a p-value of 0.045.
The drug also met the prespecified secondary endpoint, improving the Clinical Global Impression–Bipolar mania severity score by 0.4 points versus placebo, with a p-value of 0.024.
All 11 mania rating scale items improved numerically compared with placebo, although only four individual items reached nominal statistical significance.
Treatment-emergent adverse events occurred in 51.6% of RAP-219 recipients and 52.8% of placebo recipients. All were mild or moderate, and no serious adverse events occurred during treatment.
Adverse events led 3.2% of RAP-219 patients to discontinue, compared with 0.8% receiving placebo. Common events included agitation, insomnia, restlessness, anxiety, headache and nausea.
Rapport plans to meet with the FDA in the first quarter of 2027 to discuss the findings and trial design, with Phase 3 studies expected to start in the second half.
Safety findings from an eight-week post-treatment period will be presented at a future medical conference.
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