Opakalim

In focal epilepsy, a small group of brain cells starts firing electrical signals too fast and all at the same time, which triggers a seizure. Nerve cells have tiny channels called Kv7 that act like a natural 'off switch', when they open, they calm the cell down and make it harder to fire. Opakalim turns on these Kv7 switches, specifically the Kv7.2 and Kv7.3 types, so overactive nerve cells get quieted before a seizure can start.

An older drug called ezogabine (Potiga) worked on the same switches but was pulled from the market in 2017 because it caused eye and skin discoloration from effects outside the brain. Opakalim is a different molecule designed to avoid those problems and also to avoid the sleepiness and foggy thinking common with many seizure medicines, because it doesn't act strongly on the brain pathway (GABA-A) that causes those side effects^[11][9].

So far, opakalim has been well tolerated in patients. No serious side effects have forced patients to stop the drug, and there have been no signs of the eye or skin discoloration that caused the older drug ezogabine to be pulled from the market^[9].

In September 2026, the FDA paused enrollment of new patients while it reviews a finding from animal testing. Rodent studies turned up a metabolite, a substance the body creates as it breaks the drug down, and the agency said it did not yet have enough information to judge what risk, if any, that metabolite poses to people. This came from animal data, not from a problem seen in patients, and everyone already enrolled continues to be dosed^[1].

Biohaven has also reported that patients are not experiencing the sleepiness, dizziness, or slowed thinking that are common on many existing seizure medicines, if the Phase 3 results confirm this, it would be a meaningful advantage. The full safety picture will come from the Phase 3 results expected in 2026.

Opakalim's pivotal focal-epilepsy program consists of 2 Phase 2/3 studies, RISE 2 (NCT06132893) and RISE 3 (NCT06309966), in adults whose focal seizures are not well controlled on 1 to 3 current medications. Patients take opakalim (tested at 25 mg, 50 mg, or 75 mg once daily) or a placebo, added on top of their existing seizure medicine.

Neither patients nor doctors know who is getting which until the study ends^[2][3]. Biohaven completed enrollment in RISE 3 at the end of June 2026, with high double-blind completion and open-label rollover rates (both about 95%), while RISE 2 was still enrolling at that point, and topline results from the first pivotal study are now expected in the second half of 2026^[4].

Important for anyone looking to join: the FDA's partial clinical hold of September 4, 2026 pauses enrollment of new patients across the opakalim program, so RISE 2 is not currently taking new participants. As of September 30, 2026, ClinicalTrials.gov lists RISE 2 as active, not recruiting, with primary completion expected in December 2026; the record does not give a reason for the status change^[2]. RISE 3 was already fully enrolled, dosing continues there, and Biohaven says the topline readout remains on schedule^[1]. In May 2026, Biohaven reported additional data highlighting seizure control and a markedly differentiated tolerability profile^[7]. An earlier brain-wave (EEG) study showed that opakalim was doing what it was designed to do inside the brain^[10].

Biohaven also started a trial in a different type of epilepsy called generalized epilepsy, but ClinicalTrials.gov lists it as terminated on March 12, 2026 by sponsor decision after 27 people enrolled^[13]. Biohaven tried opakalim for depression and bipolar disorder too, and it did not work in those conditions, so the company is now focused on epilepsy^[12].

Opakalim did not start at Biohaven. It was the lead drug of Channel Biosciences, a subsidiary of Pittsburgh-based Knopp Biosciences, and Biohaven bought that Kv7 program in February 2022 for $35 million in cash and $65 million in stock, as MedCity News reported on February 25, 2022, renaming the drug BHV-7000^[14]. Early studies in healthy volunteers showed it was safe and could be given just once a day.

In 2023, a brain-wave study confirmed it was working the way Biohaven hoped, which allowed the company to move it into the large Phase 3 trial^[10]. A 2025 trial in bipolar disorder didn't work, so Biohaven narrowed its focus to epilepsy, where the 2026 results will determine whether the drug can be submitted to the FDA for approval^[12].

In August 2026, Biohaven licensed opakalim and its entire Kv7 platform worldwide to SK Biopharmaceuticals, the maker of Xcopri (cenobamate), in a deal worth $350 million at closing, another $50 million in 2027 and up to $795 million in total, which still needs antitrust clearance before it closes. SK will lead the drug through FDA submission^[6]. Fierce Biotech reported in August 2026 that SK hopes to launch it in the U.S. as soon as 2029 through its subsidiary SK Life Science, the same organization that sells Xcopri^[15].

Adjunctive therapy for treatment-resistant focal epilepsy is a crowded space with more than a dozen approved anti-seizure medications including lamotrigine, levetiracetam (Keppra), lacosamide (Vimpat), perampanel (Fycompa), brivaracetam (Briviact), and cenobamate (Xcopri). Most work through sodium-channel blockade, GABA-A enhancement, or SV2A modulation, mechanisms that often cause dose-limiting sedation, cognitive slowing, or mood changes.

The Kv7 channel is a validated but largely untapped target: ezogabine (Potiga) proved the mechanism works in epilepsy but was withdrawn from the market in 2017 due to off-target retinal and skin pigmentation^[16]. Opakalim aims to be the first selective, tolerable Kv7 activator to reach approval, positioning it for patients not adequately controlled on existing mechanisms.

Cenobamate (Xcopri, SK Biopharmaceuticals, 2019) is the most recent high-efficacy approval and the closest commercial comparator. It has set a high seizure-freedom bar that opakalim will need to approach to differentiate. In a notable twist, SK Biopharmaceuticals licensed opakalim itself in August 2026, putting the benchmark drug and this challenger under the same roof^[6].