Irfan Qureshi, MD, on Opakalim, Kv7 Activation, and the Future of Epilepsy Treatment

Despite the availability of numerous antiseizure medications (ASMs), many patients with epilepsy continue to experience uncontrolled seizures, treatment-limiting adverse events, or both. Central nervous system (CNS) adverse effects such as dizziness, somnolence, fatigue, and cognitive impairment remain among the most common reasons for medication discontinuation and can significantly affect quality of life, employment, and long-term adherence to therapy.

Opakalim (BHV-7000), an investigational selective Kv7.2/7.3 potassium channel activator being developed by Biohaven, is designed to provide seizure control while minimizing many of the CNS-related adverse effects commonly associated with existing ASMs. Recently reported data from the program demonstrated encouraging signals across multiple epilepsy populations, including focal epilepsy, idiopathic generalized epilepsy (IGE), and KCNQ2 developmental and epileptic encephalopathy (KCNQ2-DEE). In an ongoing open-label extension study involving more than 100 participants with focal epilepsy, 54% achieved at least a 50% reduction in seizure frequency over a consecutive six-month period of treatment.

With pivotal phase 2/3 focal epilepsy studies expected to read out later this year, NeurologyLive^® caught up with Irfan Qureshi, MD, chief medical officer at Biohaven, to discuss the durability of opakalim’s antiseizure effects, its differentiated tolerability profile, and the mechanistic rationale behind selective Kv7.2/7.3 activation. He also reflected on the broader implications of emerging efficacy signals across multiple epilepsy syndromes and what clinicians should watch for as the pivotal program advances.

What do the updated open-label extension data suggest about the durability of opakalim's antiseizure effects in refractory focal epilepsy?

Irfan Qureshi, MD: Opakalim offers potential for easy-to-use, once-daily treatment with no titration to control seizures without the burdensome side effects frequently reported with approved antiseizure medications (ASMs) and those in development.

The 50% responder rate we reported with opakalim in the focal epilepsy open-label expansion (OLE) provides an important signal of efficacy. This was observed over a clinically meaningful time frame, a consecutive 6-month window, with more than 100 participants, a relatively large number.

Importantly, the 50% responder rate of 54% is consistent with OLE and real-world data for approved ASMs and virtually identical to the 50% responder rate of 56% reported by Xenon for azetukalner in a similar OLE analysis.

These updated efficacy data from the OLE, coupled with the exceptional tolerability profile of opakalim, provide increasing confidence that opakalim will deliver a differentiated efficacy and tolerability profile in the ongoing pivotal studies in focal epilepsy. The first of these will be reading out in 2H 2026.

How clinically meaningful is opakalim's favorable CNS tolerability profile for patients living with epilepsy?

CNS tolerability is arguably the biggest unmet need for patients living with epilepsy. Dizziness, somnolence, and cognitive impairment aren't just a nuisance, they drive non-adherence and discontinuation, affect employment, and erode quality of life in patients already burdened by seizures. That’s why we developed opakalim.

Having low rates of these CNS adverse effects is highly clinically meaningful and very desirable, especially for patients who are often on one or more ASMs that already contribute to these burdensome side effects. A drug that is effective without high rates of CNS adverse events offers a genuinely differentiated value proposition.

What differentiates opakalim's selective Kv7.2/7.3 activation mechanism from earlier Kv7-targeting therapies?

What separates opakalim is the absence of off-target GABA potentiation seen with earlier Kv7 activators. Ezo-GABA-ine has GABAergic activity, which contributed to the CNS side effect burden; sedation, cognitive effects, and dizziness limited its clinical utility. Similar GABA activity is seen with ezogabine analogs, including Xenon’s investigational Kv7 activator, azetukalner. By contrast, opakalim is selective and does not have GABA effects. This precision explains the favorable CNS tolerability profile observed to date.

What do the emerging data across focal epilepsy, IGE, and KCNQ2-DEE suggest about opakalim's broader therapeutic potential?

We have seen convergent signals of efficacy across focal epilepsy, idiopathic generalized epilepsy (IGE), and KCNQ2-DEE. These are consistent with the genetically and clinically validated Kv7 activator mechanism of action. The M-current is a fundamental brake on neuronal excitability with broad spectrum activity in epilepsy, and potentially in other diseases.

As pivotal data approach, what key questions do you hope the upcoming readouts will answer about opakalim's role in epilepsy treatment?

The questions that matter most are randomized efficacy and safety. We believe that the responder rate from the OLE will translate to a placebo-controlled treatment difference similar in magnitude to that of azetukalner. That's the definitive test. Second, we believe the tolerability will be consistent with what we have seen to date, particularly the low rates of CNS AEs. A pivotal readout that confirms efficacy with differentiated tolerability would position opakalim as a genuinely new option in a field that needs one.

REFERENCE
Biohaven Ltd. Biohaven reports new data from selective Kv7.2/7.3 activator program and provides epilepsy pipeline update at 2026 R&D Day. News release. Biohaven. Accessed June 18, 2026. https://www.prnewswire.com/news-releases/biohaven-reports-new-clinical-data-in-epilepsy-with-opakalim-a-selective-kv7-27-3-activator-highlighting-seizure-control-and-markedly-differentiated-tolerability-profile-302781743.html