Use of Newer Antiepileptic Drugs in Children
Newer, efficacious antiepileptic drugs (AEDs) with improved side-effect profiles are becoming available for the treatment of pediatric patients with focal onset epilepsy faster than in the past, thanks to US Food and Drug Administration (FDA) policies allowing data extrapolation. Physicians, children, and families are benefitting as a result.
Professor and Chief of Pediatric Neurology
“Once adult studies are completed, pediatric AED studies can now be completed in as quickly as 1 year, whereas in the past they could take up to 5 years or longer.”
Newer, efficacious AEDs for children are making it to the market much faster than in the past, owing to an FDA decision in 2017. That decision permits the extrapolation of AED efficacy data from adults to children ages 4 years and older for identical seizure types that have the same pathophysiology in each population (ie, partial onset or focal seizures). This is a promising development for both physicians and patients that has resulted in faster approvals of newer medications that may have fewer side effects on cognition and learning, fewer interactions with other medicines, and simple, once-daily administration. Agents approved by the FDA in this manner for the treatment of focal onset seizures (FOS) in children after being approved for the same indication in adults include eslicarbazepine, lacosamide, brivaracetam, and perampanel.
Prior to its 2017 decision, the FDA required AEDs to undergo the same safety and efficacy testing in children that had already been performed in adults. This resulted in lengthy delays, sometimes lasting many years, before AEDs that were previously approved for use in adults could be approved for the treatment of children. The efficacy requirement, however, was eliminated after the Pediatric Epilepsy Academic Consortium for Extrapolation (PEACE) found that children with FOS have similar disease progression and response to intervention, including side-effect profiles, as adults with FOS. As a result, the actual AED—instead of potentially a placebo—can now be used to treat pediatric on-trial patients while concurrently being evaluated for safety.
With respect to proper pediatric dosing, a scientific understanding of how AEDs are metabolized in the adult body permits approximate dosage determinations for children, which can then be verified using a small number of children (usually 20-30) in a pharmacokinetic open-label trial by measuring blood levels and then adjusting the dose when required (also known as a pharmacokinetic bridging approach). Real-world studies can help to further characterize our experience with these agents in practice (eg, without the forced titration of a clinical trial). For example, real-world studies with perampanel in adolescents suggest that some patients may experience sustained efficacy with good tolerability and retention at the lower dosages referenced in the original labeling.
The FDA’s new practice has proven to be a boon to physicians, the FDA, and children. Pediatric AED studies can now be completed in as quickly as 1 year, whereas in the past they could take up to 5 years or longer. An AED approval process that used to be horrendous for families and children has evolved to become much faster and friendlier to both physicians and patients. This has the added benefit of providing the clinician with pediatric dosing and safety guidance soon after the drug comes to market, rather than waiting several years (as was the case in the past).
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