The FDA has accepted Eisai’s supplemental New Drug Application (sNDA) for Priority Review for its antiepileptic drug Fycompa (perampanel) CIII for monotherapy and adjunctive use for the treatment of partial-onset seizures (POS) with or without secondarily generalized seizures in pediatric patients (ages two to less than 12 years).
The submission also proposes a pediatric indication for adjunctive use for primary generalized tonic-clonic (PGTC) seizures in patients with epilepsy (ages two to less than 12 years). The sNDA application includes both the Fycompa tablet and oral suspension formulations.
“The incidence of seizures in the pediatric age group has been steadily increasing in the U.S. where an estimated 470,000 children are living with epilepsy today. Approximately 30 percent of all patients have uncontrolled seizures, and it is crucial that we do whatever we can to help these patients achieve the ultimate goal of seizure freedom,” said Trevor Resnick, MD, pediatric neurologist at Nicklaus Children’s Hospital. “Approximately 71 percent of all people living with epilepsy miss at least one dose of their medication per month, and 45 percent of those missed doses result in a subsequent breakthrough seizure. Fycompa’s long, 105 hour half-life may play an important role for patients who miss doses.”
Fycompa is currently approved as therapy (adjunctive and monotherapy uses) for POS with or without secondarily generalized seizures in patients with epilepsy 12 years of age and older, and as adjunctive therapy for PGTC seizures in patients with epilepsy 12 years of age and older. To date, more than 100,000 patients have been treated with Fycompa worldwide across all indications.
“The FDA’s Priority Review designation for this sNDA underscores the urgent need for more treatment options like Fycompa in the pediatric population,” said Lynn Kramer, MD, chief clinical officer and chief medical officer, Neurology Business Group, Eisai. “We are committed to working with the FDA to bring forward more treatments for young patients to help physicians achieve seizure freedom, a critical goal in epilepsy care.”
Eisai is seeking approval to expand the pediatric use for Fycompa based on a 2018 Draft Guidance noting the FDA’s current thinking regarding clinical development programs that can support extrapolation of the effectiveness of drugs approved for the treatment of POS in adults to pediatric patients 4 years of age and older.
This determination was based on the similarity of POS in adults and in pediatric patients four years of age and older, and on an analysis of multiple antiepileptic drugs, conducted by the FDA, that demonstrated a similar exposure-response relationship in pediatric and adult patients with POS.
In support of the extrapolation approach, the sNDA includes data from an ongoing global open-label, multicenter study (Study 311) with an extension phase that evaluated the safety, tolerability, and exposure-efficacy relationship of perampanel oral suspension when administered as an adjunctive therapy in children, ages four through 11, with inadequately controlled POS or PGTC seizures. The study enrolled 180 patients –149 with POS and 31 with PGTC seizures – with an overall mean daily dose of 6 mg.
The primary objective of Study 311 was safety and tolerability, evaluated based on incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), laboratory parameters, vital signs, and ECG parameters. Secondary endpoints included the efficacy of perampanel as measured by the median percent change per 28 days in seizure frequency, by the proportion of responders (≥25 percent , ≥50 percent, and ≥75 percent), and by the proportion of subjects who are seizure-free for POS, PGTC, and secondarily generalized tonic-clonic (SGTC) seizures as well as the effects of perampanel on cognition, behavior, visuomotor skills, and growth and development in children during short-term (23 weeks) and long-term (up to 52 weeks) treatment.
The sNDA also includes data from an open-label pilot study (Study 232) with an extension phase to evaluate the pharmacokinetics, and to generate preliminary data on safety, tolerability, and efficacy of Fycompa oral suspension when given as an adjunctive therapy in pediatric subjects from two to less than 12 years of age with epilepsy.
Fycompa, the first and only seizure medication that targets the AMPA receptor, was initially approved for adjunctive use in POS in 2012 and has treated over 100,000 patients worldwide in 55 countries across all indications. Fycompa was approved for adjunctive use in patients with PGTC seizures in 2015 and as monotherapy use for the treatment of POS in 2017. An oral suspension formulation was also approved in 2016.
(Source: Eisai Inc.)
Filed Under: Drug Discovery