Analysts at Jefferies see blockbuster potential in zorevunersen in Dravet syndrome, with sales potentially reaching $1 billion to $4 billion.
Stoke Therapeutics and Biogen are building the case for their investigational antisense oligonucleotide zorevunersen, with new long-term data showing durable reductions in seizure burden in patients with Dravet syndrome.
Zorevunersen “could be a $1-4B+ blockbuster in Dravet,” largely attributable to its “disease-modifying potential” analysts at Jefferies wrote in a Sunday afternoon note, reacting to data presented at the 2025 annual meeting of the American Epilepsy Society. The firm expects more regulatory activity around the drug next year.
In a news release on Friday, the partners presented the findings of a propensity score-weighted analysis of zorevunersen, comparing patients treated with the drug across its clinical development program versus natural history controls. The companies adjusted their comparison by baseline differences between these two patient groups in an effort to “mimic randomization.”
Results showed that patients taking zorevunersen saw a “statistically significant” decrease in the frequency of major motor seizures at six months versus external controls—though the partners did not provide specific data in their announcement.
Jefferies provided more detail in its Sunday note, revealing an 82% drop in major motor seizures among five patients who were treated with two 70-mg loading doses of zorevunersen. Natural history comparators, meanwhile, experienced a 20% reduction over the same period.
The group also demonstrated that the treatment benefit was durable through 24 months, with those on zorevunersen showing a 76% drop in seizures versus 25% among the external comparators.
Stoke and Biogen also reported that zorevunersen treatment improved five key cognitive and behavioral measures, noting that “several” of these changes hit statistical significance. The partners also did not provide specific data for this evaluation.
“By ensuring both groups have similar baselines, [the companies] can present efficacy that more closely mimics potential Phase III outcomes,” which compare zorevunersen against placebo treatment, according to Jefferies. In this context, these new Dravet data are “partially de-risking” for zorevunersen’s ongoing Phase III EMPEROR trial.
Afflicting one person in every 15,700 people, Dravet syndrome is a rare and medication-resistant form of epilepsy that starts in infancy and persists throughout a patient’s life. Patients suffer from frequent and prolonged seizures, as well as behavioral and developmental problems, movement and balance difficulties and speech delays.
Most Dravet patients harbor a mutation in the SCN1A gene, which encodes for sodium channels that facilitate proper communication between nerve cells. Zorevunersen works by binding to a certain part of the SCN1A mRNA, in turn preventing certain mutations from producing a dysfunctional protein. This mechanism, Stoke claims, addresses the underlying cause of Dravet.
Stoke and Biogen are testing zorevunersen in the Phase III EMPEROR study, for which enrollment is ongoing. In its third quarter earnings report last month, Stoke revealed that it will meet with the FDA before year end to discuss “potential expedited regulatory pathways” for zorevunersen.
