An experimental pill from Boston-based Rapport Therapeutics narrowly succeeded in a mid-stage study focused on bipolar mania, an outcome that analysts described as unexpected and a potential stepping stone to a billion-dollar-plus market.
Rapport’s study enrolled around 250 adults with bipolar mania, who, once a day for three weeks, were given either a placebo or the company’s drug, “RAP-219.” Researchers then evaluated participants on several health measures, with the most important being how they fared on a 0 to 60-point clinical scale where higher scores reflect more severe bipolar symptoms. According to Rapport, those on its drug improved an average of 15.4 points by the third week, versus 12.3 points among the placebo group.
That 3.1-point difference was just enough for the results to be statistically significant. Rapport said that, compared to the control arm, drug-treated patients showed improvements across all 11 components of the scale, which evaluates things like mood, speech, irritability and aggression. RAP-219 also beat the placebo on a “secondary” measure that used a different mania severity scale.
The drug was well-tolerated, according to Rapport, with all so-called treatment-emergent adverse events being mild to moderate. The incidence of these events was similar between the two groups, with a little more than half of patients experiencing them. The most common in the RAP-219 arm was agitation, and it generally lasted about two days.
Rapport now plans to meet with the Food and Drug Administration sometime in the first three months of next year to discuss these results as well as the design elements needed for a trial that would allow it to submit RAP-219 for approval in bipolar mania. The company said two late-stage trials in acute bipolar mania should start in the back half of 2027, while additional data from the Phase 2 study will be presented at a future medical meeting.
“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,” Rapport CEO Abraham Ceesay said in a statement. “Side effects drive discontinuation, and discontinuation drives relapse. RAP-219 has the potential to break that cycle with the first new mechanism of action for bipolar mania in decades.”
In a note to clients, Jefferies analyst Andrew Tsai wrote that RAP-219 appears to have “clean” safety, while its efficacy looks in-line with the 2- to 6-point improvements offered by already approved bipolar medications. Continued success in this disease could add more than a billion dollars to the drug’s peak sales estimates, Tsai added, and “should embolden” Rapport’s management team to consider other central nervous system indications with blockbuster potential, such as bipolar depression.
Previously, Rapport’s drug showed enough promise in a mid-stage study of “focal onset” seizures that it was pushed into a pair of Phase 3 trials. It’s designed to dampen the activity of a certain protein found mostly in select brain regions where seizures often originate. This protein helps regulate receptors that respond to glutamate, a key signaling molecule that prompts brain cells to electrically fire. Too much glutamate signaling can lead to overactive neurons, which is a hallmark of epilepsy and observed in diseases like bipolar mania.
Developing new drugs for psychiatric conditions like bipolar mania is notoriously difficult. Expectations that Rapport’s trial would succeed were low, according to Stifel’s Paul Matteis. Its surprise win is therefore a “clear positive” that helps validate the drug broadly, the analyst wrote in his own note.
Matteis did acknowledge a few caveats. The efficacy data, for example, were close to not hitting statistical significance. They were also at “the lower-end of the range that's considered competitive with available drugs today.” Even so, RAP-219 scored positive data on every piece of that symptom severity scale, and did so against a strong placebo arm performance.
Matteis and others also noted that, in diseases like bipolar disorder, the best treatments are typically the ones that patients stay on. “A novel, better-tolerated treatment should become commercially relevant,” wrote analysts at Raymond James.
“[E]fficacy matters, but willingness to remain on treatment may ultimately determine how useful a medication is in this setting,” they added. “The new findings strengthen that thesis, particularly for patients who have struggled with sedation or movement symptoms on existing therapies.”
Estimates hold that nearly 3% of adults in the U.S. — or more than 7 million people — have bipolar disorder.