Biogen & Stoke Aim to Remake Dravet Treatment with Zorevunersen Data

CAMBRIDGE, MA – December 05, 2025 – In the high-stakes world of biotechnology, the term “disease-modifying” is a coveted, often elusive, prize. For Biogen and its partner Stoke Therapeutics, that prize may be moving closer to reality. At the 2025 American Epilepsy Society (AES) Annual Meeting, the companies presented a compelling new slate of long-term data for zorevunersen, an investigational RNA-based medicine for Dravet syndrome, a catastrophic and rare form of childhood epilepsy.

The data goes beyond the standard metric of seizure reduction, suggesting the therapy could alter the fundamental course of the disease itself. For a condition that devastates neurodevelopment and carries a mortality rate of up to 20% before adulthood, this is a significant development. The presentations in Atlanta offer a deeper look into the strategic bet both companies have placed on zorevunersen, providing a critical update for investors tracking the next wave of innovation in neuroscience.

Beyond Symptom Control: The Science of Disease Modification

For decades, the standard of care for epilepsy has centered on managing symptoms—namely, reducing seizure frequency and severity. While crucial, this approach does little to address the underlying pathology that, in Dravet syndrome, leads to profound cognitive, behavioral, and motor impairments. Most cases are caused by a mutation in the SCN1A gene, which results in an insufficient supply of the critical NaV1.1 protein in the brain's neurons.

Zorevunersen, which utilizes Stoke’s proprietary TANGO antisense oligonucleotide (ASO) platform, is designed to tackle this root cause. Instead of merely suppressing seizures, it targets the healthy copy of the SCN1A gene to increase, or “upregulate,” the production of functional NaV1.1 protein. The hypothesis is that by restoring protein levels, the therapy can impact the full spectrum of the disease.

The latest open-label extension data appears to support this. Patients treated with zorevunersen on top of their standard anti-seizure medications showed not only durable seizure reductions but also notable increases in seizure-free days. More importantly, the data revealed improvements in cognition, behavior, and overall quality of life.

Perhaps the most compelling evidence for a disease-modifying effect comes from new electroencephalogram (EEG) analyses. These results demonstrated a dose-dependent decrease in the abnormal brain activity characteristic of Dravet syndrome. Critically, this reduction in abnormal EEG signals correlated with a higher probability of achieving a meaningful drop in seizure frequency. This finding provides a direct, physiological link between the drug's mechanism and its clinical effect, suggesting it is actively normalizing brain function rather than simply masking symptoms. As Dr. M. Scott Perry, a lead investigator, noted in the release, “Over the last four years we have gained an increasing appreciation for the potential to change the course of Dravet syndrome with new disease-modifying medicines.”

De-Risking Development with Advanced Analytics

For investors and analysts, open-label data can be difficult to interpret without a control group. To address this, Biogen and Stoke presented a new propensity score weighted analysis, a sophisticated statistical method designed to mimic randomization by comparing treated patients to a matched cohort from a natural history study. This provides a more rigorous context for the drug's performance.

The results were significant. Patients receiving two 70mg loading doses of zorevunersen showed statistically significant reductions in major motor seizure frequency at six months—a timeframe consistent with the primary endpoint of the ongoing Phase 3 trial. Furthermore, with continued dosing, patients showed improvements across five key assessments of cognition and behavior at 18 months, with effects holding durable through 24 months. This comparison to an untreated cohort strengthens the case that zorevunersen’s benefits go beyond what would be expected from the natural course of the disease.

“Data from this analysis, which allows us to match patients treated with zorevunersen directly to natural history, add to a growing body of information shaping our understanding of Dravet syndrome and the effects of zorevunersen over time,” stated Dr. Barry Ticho, Chief Medical Officer of Stoke Therapeutics.

Equally important from a risk-assessment perspective is the accumulating long-term safety data. With over 800 doses administered to 81 patients, some for over four years, the drug has been generally well tolerated. While elevations in cerebrospinal fluid (CSF) protein were common, they have not been associated with clinical symptoms, and only one patient discontinued due to the issue. This growing safety database is a crucial component for both regulatory review and future market adoption.

The Strategic Blueprint: A High-Stakes Partnership

The development of zorevunersen is underpinned by a strategic collaboration that leverages the strengths of both companies. Under the deal, Stoke retains commercial rights in North America, while Biogen, a giant in neuroscience, takes the helm for the rest of the world. This structure gives Stoke a significant infusion of capital and access to Biogen's global commercialization machine, while Biogen adds a high-potential, late-stage asset to its pipeline.

The market opportunity is substantial. An estimated 38,000 individuals live with Dravet syndrome across the U.S., Europe, and Japan. With no approved disease-modifying therapies and a high unmet need, a successful zorevunersen could command both significant market share and premium pricing. The recent failure of Takeda’s soticlestat in Phase 3 trials for Dravet and Lennox-Gastaut syndromes serves as a stark reminder of the challenges in this space, but it also clears the competitive field for a therapy that can demonstrate a superior profile.

By targeting the underlying genetic cause and showing potential benefits beyond seizure control, zorevunersen is positioned as a potential first-in-class therapy. Dr. Katherine Dawson, Head of the Therapeutics Development Unit at Biogen, emphasized this comprehensive potential, stating, “The totality of clinical data, in addition to the new EEG findings, demonstrates zorevunersen’s potential to restore protein function and address the underlying cause of Dravet syndrome to improve debilitating symptoms like seizures and cognitive impairment.”

The Road Ahead: Navigating the Phase 3 EMPEROR Study

While the latest data is highly encouraging, the ultimate fate of zorevunersen rests on the ongoing Phase 3 EMPEROR study. This global, double-blind, sham-controlled trial is the gold standard required for regulatory approval. It is enrolling approximately 150 patients aged 2 to 18 to evaluate the drug's efficacy and safety over 52 weeks.

The primary endpoint is the percentage change in major motor seizure frequency at week 28, directly testing the findings from the propensity score analysis in a controlled setting. However, all eyes will also be on the key secondary endpoints, including validated measures of cognition and behavior like the Vineland-3 scale. A positive outcome on these measures would be instrumental in cementing the drug’s disease-modifying label and differentiating it in the marketplace.

With pivotal data from EMPEROR expected in the second half of 2027, the path forward is clear, though not without risk. The FDA has already granted zorevunersen Breakthrough Therapy and Rare Pediatric Disease designations, signaling regulatory recognition of its potential and possibly expediting its review. For the thousands of families impacted by Dravet syndrome and the investors backing this novel approach, the results of the EMPEROR study will be a defining moment in the quest for a therapy that does more than count seizures—it aims to fundamentally improve lives.