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

Story: 2025 C.E.  |  Last updated: September 17, 2025

A new drug for hard-to-treat epilepsy is producing results that researchers rarely see in this patient population. RAP-219, developed by Boston-based Rapport Therapeutics, reduced clinical seizures by a median of 77.8% over eight weeks in adults whose epilepsy had not responded to previous medications — and nearly a quarter of participants became seizure-free entirely.

At a glance

• Epilepsy drug: RAP-219 met its primary endpoint in a mid-stage, open-label proof-of-concept trial involving 30 adults with drug-resistant focal epilepsy, all implanted with responsive neurostimulation (RNS) devices for continuous 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 unusual in this population.
• Phase 3 trials: Rapport Therapeutics has announced plans to pursue two pivotal Phase 3 studies following regulatory consultation, the standard pathway toward potential approval.

Why this drug works differently

Most anti-seizure medications work by broadly suppressing neuronal activity across the entire brain. That approach can reduce seizures, but it often brings sedation, memory problems, or motor side effects that make daily life harder. RAP-219 was designed around a more targeted idea. It modulates AMPA receptors through a regulatory subunit called TARPγ8, which is concentrated in the neocortex and hippocampus — exactly the brain regions where focal seizures most often begin. The logic: if you can dampen abnormal electrical activity in those specific areas without touching the whole brain, you might get strong seizure control with fewer of the side effects that drive people off their medications. Early results support that reasoning. The drug reduced so-called “long episodes” — objective markers of pathological brain activity captured by the implanted RNS devices — while clinical seizures fell sharply. Adverse events reported by the sponsor were mostly mild to moderate.

The measurement approach matters as much as the drug

One of the most significant things about this trial is not just what it found, but how it found it. The study enrolled adults already living with implanted responsive neurostimulation devices, which record electrical activity in the brain continuously and in real time. That gave investigators an objective, quantifiable biomarker of seizure activity that does not depend solely on patient recall — a meaningful step forward in a field where endpoint measurement has historically been complicated. Jacqueline French, MD, an epilepsy specialist at NYU Langone Health, has emphasized the trial’s novel use of continuous electrophysiology data to anchor its endpoints. When a drug works — or doesn’t — this kind of real-time data makes the signal clearer and earlier, which can help researchers fail fast on dead ends and move faster on genuine advances. The study is registered as NCT06377930 and was designed as a multicenter, open-label proof-of-concept trial. Results and the overall trial design have been covered by NeurologyLive, which noted both the scale of the seizure reductions and the significance of the objective biomarker framework.

What this means for people with drug-resistant epilepsy

About one in three people with epilepsy do not achieve seizure control through currently 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 sustained 77.8% 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 promising by design — they are built to test whether a drug shows enough signal to pursue at scale. The harder test comes in randomized, controlled Phase 3 trials with larger populations. Rapport Therapeutics has announced plans to meet with regulators and initiate two such trials, a process that typically takes several years. Still, the combination here is notable: a precision mechanism, an objective measurement approach, and a collaboration between a focused biotech and leading academic epilepsy centers including NYU Langone Health. That kind of alignment between molecular design and clinical rigor is not always present in drug development, and it matters. Research like this shares a spirit of methodological ambition with work such as the landmark Alzheimer’s prevention trial that cut risk in half — trials that use sharper tools to ask sharper questions.

A broader shift in how neurological drugs get built

RAP-219 reflects something larger happening in neuroscience: a move away from blunt instruments and toward medicines designed around specific molecular targets in specific brain circuits. The Epilepsy Foundation estimates that 3.4 million people in the U.S. live with epilepsy, and globally the number exceeds 50 million. A meaningful share of those people have already tried multiple medications without success. For them, precision approaches like TARPγ8 modulation represent a genuinely different direction — not a variation on what already exists, but a new category of therapeutic logic. The question of access will matter too. Precision medicines often carry high price tags, and drug-resistant epilepsy disproportionately affects people with fewer economic resources and less access to the specialized care required to qualify for trials like this one. How broadly a therapy like RAP-219 reaches patients — if it succeeds — will depend on pricing, insurance coverage, and health system infrastructure in ways that trial data alone cannot answer. For now, though, the signal is clear and the approach is sound. That is genuinely good news for a population that has been waiting a long time for something new.

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