Key Takeaways:
Biohaven's opakalim tripled the median time to a second generalized seizure to 141 days from 47 days in a placebo-controlled proof-of-concept study in idiopathic generalized epilepsy.
"What stands out is not just that opakalim controls seizures — it's that it does so without the burdensome side effects that compromise quality of life and adherence for people with epilepsy," Jason Lerner, medical director of research and development and epilepsy development lead at Biohaven, said.
In the 27-subject trial, 33% of patients on opakalim completed the 24-week double-blind phase without a second generalized tonic-clonic seizure, compared with zero on placebo. Twenty percent were seizure-free for the full period. The drug also showed a 54% responder rate — patients achieving at least a 50% reduction in seizure frequency — over any consecutive six months in an open-label extension study of more than 100 patients with refractory focal epilepsy.
Opakalim's tolerability profile may give it a commercial edge. The IGE study reported zero cases of somnolence, dizziness, fatigue or memory impairment — side effects that occur in more than one-third of patients on a competitor's Kv7 activator in long-term studies. Biohaven is on track to report top-line results in the second half of 2026 from the first of two registrational Phase 2/3 studies in refractory focal epilepsy needed to support approval.
Differentiated Safety Profile
In the focal epilepsy open-label study, dizziness occurred in 5% of opakalim patients, compared with 25% in a competitor's Kv7 activator extension study, according to Biohaven's presentation. Rates of somnolence, fatigue and memory impairment were each 5% or less. The company attributes the profile to opakalim's selectivity for Kv7.2/7.3 heteromeric channels with minimal activity at GABA receptors.
KCNQ2-DEE Compassionate Use
A 9-year-old boy with KCNQ2-developmental and epileptic encephalopathy who was transitioned to opakalim under a single-patient FDA-authorized compassionate use protocol remained clinically stable at six months. Overnight EEG showed a 50% reduction in seizure counts relative to baseline. The patient had a history of daily tonic seizures despite three concurrent antiseizure medicines, including a first-generation Kv7 activator.
Market Opportunity
Opakalim has been studied in more than 1,000 subjects across multiple trials. The drug is administered once daily without requiring titration, a potential advantage over existing therapies. Biohaven is conducting two Phase 2/3 randomized, double-blind, placebo-controlled studies of opakalim as adjunctive therapy for refractory focal onset epilepsy.
The differentiated safety data position opakalim to capture share in the epilepsy market if approved. Investors will watch for the Phase 2/3 top-line readout in the second half of 2026, which will determine whether the clean tolerability profile translates to registrational efficacy.
This article is for informational purposes only and does not constitute investment advice.
