New epilepsy drug cuts seizures by nearly 80% in mid-stage trial

Story: 2025 C.E.  |  Last updated: April 20, 2026

For the roughly one in three people with epilepsy whose seizures don’t respond to existing medications, the options have been limited and the waiting has been long. A new compound called RAP-219, developed by Boston-based Rapport Therapeutics, is now offering a reason for cautious optimism: in a mid-stage clinical trial, it reduced seizures by a median of 77.8% over eight weeks — and nearly a quarter of participants became seizure-free entirely.

At a glance

• Epilepsy drug: RAP-219 met its primary endpoint in an open-label proof-of-concept trial enrolling 30 adults with drug-resistant focal epilepsy, all implanted with responsive neurostimulation (RNS) devices for continuous, real-time brain activity recording.
• Seizure reduction: Participants experienced a median 77.8% drop in clinical seizures over eight weeks, with roughly one in four achieving complete seizure freedom — an outcome that is highly unusual in this population.
• Phase 3 trials: Rapport Therapeutics has announced plans to pursue two pivotal Phase 3 studies following FDA consultation, with initiation expected in the third quarter of 2026 C.E.

Why this epilepsy drug works differently

Most anti-seizure medications work by broadly suppressing electrical activity across the whole brain. That can reduce seizures, but it frequently brings sedation, memory problems, and motor side effects that push people off their medications entirely.

RAP-219 was built around a more precise idea. It modulates AMPA receptors — key drivers of excitatory brain signaling — through a regulatory protein called TARPγ8, which is concentrated in the neocortex and hippocampus. Those are exactly the regions where focal seizures most often begin. By targeting activity there specifically, the drug is designed to dial down abnormal electrical firing without affecting the rest of the brain.

Early results support that logic. Adverse events in the trial were mostly mild to moderate — dizziness, headache, fatigue — and no serious safety issues emerged, though three patients did discontinue due to side effects. The mechanism is novel enough that it represents a genuinely different category of therapeutic approach, not simply a variation on drugs that already exist.

The measurement approach is as notable as the results

One of the most significant things about this trial is how it was designed, not just what it found.

All 30 participants were already living with implanted responsive neurostimulation devices, which record brain electrical activity continuously and in real time. That gave researchers an objective, quantifiable biomarker — called “long episodes” — that doesn’t rely solely on patient recall. By the trial’s end, 85% of patients had at least a 30% drop in long episodes, and 72% had their clinical seizures cut in half or more.

Jacqueline French, MD, the study’s principal investigator and a professor of neurology at NYU Langone Health’s Comprehensive Epilepsy Center, described the trial as “the first time a novel anti-seizure medication was evaluated in focal seizure patients using the RNS system with an objective biomarker of seizure activity.” When a drug works — or doesn’t — real-time electrophysiology data makes the signal clearer earlier, which helps researchers move faster on genuine advances and abandon dead ends sooner.

What this means for people with drug-resistant epilepsy

Around 50 million people worldwide live with epilepsy, according to the World Health Organization. Roughly one in three of them do not achieve seizure control through available medications. For that group, the condition shapes nearly every part of life — whether someone can drive, hold a job, live independently, or simply feel safe at home.

A 77.8% median reduction in seizures is not a cure. But it can be the difference between a manageable life and one organized entirely around the fear of the next episode.

It is also worth being clear about where this research stands. Mid-stage trials are built to test whether a drug shows enough signal to pursue at larger scale — the harder test comes in randomized, controlled Phase 3 trials. Rapport has announced plans to initiate two such trials, a process that typically takes several years. And even if RAP-219 succeeds, precision medicines often carry high price tags. Drug-resistant epilepsy disproportionately affects people with fewer economic resources, and how broadly a therapy reaches patients will depend on pricing, insurance coverage, and health system infrastructure that trial data alone cannot guarantee.

Still, the combination here is notable: a precision molecular target, an objective measurement framework, and a collaboration between a focused biotech and leading academic epilepsy centers. That kind of alignment between molecular design and clinical rigor matters — and for a population that has been waiting a long time for something genuinely new, the signal is clear and the approach is sound.

The study is registered as NCT06377930 on ClinicalTrials.gov.

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For more on this story, see: Refractor

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