Rapport Therapeutics' RAP-219 Meets Phase 2 Goals in Bipolar Mania Trial

Rapport Therapeutics, Inc.'s experimental drug RAP-219 met the primary and prespecified secondary goals in a U.S. Phase 2 trial for acute bipolar I mania, though treatment discontinuation was higher than with placebo.

After three weeks, the modeled decline on the Young Mania Rating Scale was 15.4 points for RAP-219 and 12.3 points for placebo. The 3.1-point difference favored RAP-219 (p=0.045). A separate clinician-rated measure of mania severity also favored the drug, with a 0.4-point difference (p=0.024).

The randomized, double-blind study enrolled 253 adults, who received treatment during a 21-day inpatient period. RAP-219 participants took 0.75 mg once daily after a two- or four-day dose increase. Rapport is also developing the drug for seizure disorders.

Of the 126 people assigned RAP-219, 95 completed treatment. In the placebo group, 112 of 127 completed it. Treatment ended early for 31 RAP-219 recipients, or 24.6%, and 15 placebo recipients, or 11.8%. Withdrawal of consent was the most common reason in both groups, accounting for 21 departures from the drug group and six from the placebo group.

Adverse events during treatment affected 51.6% of RAP-219 recipients and 52.8% of placebo recipients. All recorded events were mild or moderate, with no severe or serious events. Four people in the RAP-219 group and one in the placebo group stopped treatment because of an adverse event. Those safety figures reflect an interim database lock on Sept. 16.

All 11 individual items on the mania scale improved numerically relative to placebo. Four showed nominally significant results in exploratory analyses, but those comparisons were not adjusted for multiple testing.

“For people with bipolar disorder, the challenge isn’t just finding a treatment that’s efficacious. It’s finding one they can tolerate and stay on,” said Rapport Chief Executive Officer Abraham N. Ceesay.

Rapport changed the trial’s statistical analysis plan and raised its enrollment target so the study could potentially serve as confirmatory evidence of effectiveness. The company expects to meet with the U.S. Food and Drug Administration (FDA) in the first quarter of 2027 and begin two Phase 3 trials in the second half of that year. It plans to present additional Phase 2 findings, including eight-week safety follow-up after treatment, at a future medical meeting.