NICE Expected to Approve New Treatment for Refractory Epilepsy

Dawn O'Shea

September 02, 2021

The National Institute for Health and Care Excellence (NICE) is set to approve cenobamate (Ontozry, Arvelle Therapeutics) as a treatment option for epilepsy, new draft guidance suggests.

The draft guidance recommends cenobamate as a third-line add-on treatment for focal-onset seizures with or without secondary generalised seizures in adults with epilepsy that has not been adequately controlled with at least two antiseizure medicines.

Because the risk-benefit balance with the treatment is unclear, NICE recommends that it should be started and managed in tertiary care.

The main evidence for cenobamate came from two multicentre, double-blind trials - C013 and C017, which compared the treatment with placebo in 659 adults aged 18-70 years with drug-resistant focal seizures despite treatment with at least one antiepileptic in the last 1 to 2 years and had one to three background therapies.

People with progressive central nervous system disease or psychiatric illness, psychological or behavioural problems were excluded.

C017 had a higher threshold for inclusion for seizure frequency at baseline (at least eight focal onset seizures over the 8-week phase before randomisation) compared with C013 (at least three seizures over 28 days).

C013 included one cenobamate arm (200 mg once daily), whereas C017 was a dose finding study and included three arms (100 mg, 200 mg and 400 mg, all once daily). Both trials had 6-week titration periods, but C013 also had a six-week maintenance phase, compared with 12 weeks in C017.

The primary end point of C013 was the percentage change from baseline in seizure frequency per 28 days in treatment period. In C017, it was at least a 50% reduction in seizures from baseline during the maintenance period.

The results showed that for this outcome, 25.5% of people had at least a 50 per cent reduction in seizure frequency compared with 40.2%, 56.1% and 64.2% in the 100 mg, 200 mg and 400 mg arms, respectively.

Two open-label extension, single-arm studies provided longer-term effectiveness and safety data. C017-OLE used 300 mg of cenobamate for 355 people who had completed the C017 trial. C021 is an ongoing phase 3, single-arm, open-label, multinational, multicentre study involving 1347 people with drug-resistant focal onset seizures. Cenobamate doses from 200 mg to 400 mg were titrated over 12 weeks followed by a 40-week maintenance period.

The results showed that 23.2% of people were seizure free for at least one year during the C017-OLE study; however, it was considered that the long-term evidence was at risk of bias because many people left the study during follow-up and there was no comparative evidence in the open-label extension arm.

NICE estimates that around 17,000 people will be eligible for treatment with cenobamate.

The draft guidance is now open for public consultation. Comments can be submitted here. The closing date for receipt of comments is 21 September 2021. The final guidance is expected to be published in December.

This article originally appeared on Univadis, part of the Medscape Professional Network.

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