On its PDUFA date Thursday, the FDA cleared Xcopri (cenobamate) tablets from South Korea’s SK Biopharmaceuticals Co. Ltd. to treat partial-onset seizures in adults. The drug’s mechanism of action is not fully understood, but it's believed to work through two separate mechanisms: enhancing inhibitory currents through positive modulation of GABA-A receptors and decreasing excitatory currents by inhibiting the persistent sodium current.
The safety and efficacy of Xcopri was proved in two randomized, double-blind, placebo-controlled studies that enrolled 655 adults. In both experiments, patients had partial-onset seizures with or without secondary generalization for an average of about 24 years and median seizure frequency of eight and a half seizures per 28 days during an eight-week baseline period. Doses of 100 mg, 200 mg and 400 mg daily of Xcopri knocked down the percentage of seizures every 28 days vs. placebo. The recommended maintenance dose, following titration, is 200 mg daily, though some patients may need 400 mg daily, the maximum recommended dose.
Partial or focal seizures – the kind Xcopri is intended to treat – afflict about 60% of people with epilepsy, according to the National Institute of Neurological Disorders and Stroke. They're located in one part of the brain and are often treated with single or multiple medications, usually generics. Xcopri adds to the arsenal.
SK, of Jongno-gu, South Korea, founded its Fair Lawn, N.J.-based SK Life Science Inc. subsidiary in 2017. The company is advancing a handful of compounds for neurological disorders, such as sleep problems and attention deficit hyperactivity disorder.
The FDA noted that antiepileptic drugs (AEDs) such as Xcopri increase the risk of suicidal thoughts or behavior in patients taking those drugs for any indication. All the usual caveats apply. Patients taking an AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Xcopri may cause neurological adverse reactions, including somnolence and fatigue, dizziness, trouble with walking and coordination, trouble with thinking, and visual changes, regulators pointed out.
Earlier this month, Zug, Switzerland-based Arvelle Therapeutics GmbH in-licensed cenobamate outside the U.S. and hopes for EMA approval in the first half of next year. The startup has raised $207.5 million, one of the largest series A rounds for a European biopharmaceutical company. Approval by the FDA paves the way for the drug in Arvelle’s territories.
Ahead of the approval, SK Life had been building a commercial organization to market the drug, actively recruiting for its sales organization, Sebby Borriello, the company's vice president and chief commercial officer, told BioWorld. Borriello said the medicine will be competitively priced with branded antiepileptic drugs
There are no formal guidelines for the treatment of epilepsy, Marc Kamin, SK Life's chief medical officer, told BioWorld. But pharmaceutical treatments for the condition typically start with a single product, often generic, then evolve with patient response. Sometimes a second antiepileptic drug is added if seizure control is incomplete. At other times, the first drug isn't tolerated and is dropped to be replaced with another one. That Xcopri's label allows it to be combined with other antiepileptic drugs or used alone as an alternative is a boon for SK Life, which could have been restrained to adjunctive treatment if the FDA had decided differently.