FDA Announces Availability of a Final Guidance, “Drugs for Treatment of Partial Onset Seizures: Full Extrapolation of Efficacy from Adults to Pediatric Patients 2 Years of Age and Older”

On September 6, 2019, the U.S. Food and Drug Administration (FDA) announced the availability of a final guidance for industry entitled “Drugs for Treatment of Partial Onset Seizures: Full Extrapolation of Efficacy from Adults to Pediatric Patients 2 Years of Age and Older”, which provides recommendations to sponsors on the clinical development of drugs for the treatment of partial onset seizures (POS) in pediatric patients. Specifically, this guidance addresses FDA’s current thinking regarding clinical development programs that can support extrapolation of the efficacy of drugs approved for the treatment of POS in adults to pediatric patients 2 years of age and older. This guidance does not address clinical development programs for the treatment of POS in pediatric patients younger than 2 years of age and does not address the development of drugs to treat other types of seizures.

Efficacy can be extrapolated from adults to pediatric patients when it is reasonable to assume that children, compared with adults, have a similar progression of disease, similar response of disease to treatment, and similar exposure-response relationship. Clinical studies of drugs for the treatment of POS in pediatric patients, some of which enrolled patients as young as 2 years of age, have shown a response to treatment (reduction in seizure frequency) similar to the response to treatment seen in adults. Systematic and quantitative analyses conducted by FDA, using data from clinical studies of drugs approved for the treatment of POS in both adults and pediatric patients, have shown that the relationship between exposure and response (reduction in seizure frequency) is similar in adults and pediatric patients 4 years of age and older. These analyses and observations have allowed FDA to conclude that the efficacy of drugs approved for the treatment of POS can be extrapolated from adults to pediatric patients 2 years of age and older.

Considerations for clinical development programs that can support extrapolation of the efficacy of drugs approved for the treatment of POS in adults to pediatric patients 2 years of age and older are outlined in this guidance, and address formulation development, efficacy, clinical pharmacology and dosing, and safety considerations:

  • Formulation Development: It is essential for sponsors to formulate pediatric drugs to best suit a child’s age, size, and physiologic condition. FDA encourages sponsors to explore innovative approaches to pediatric formulation development and testing.
  • Efficacy: As noted above, this guidance does not apply to the treatment of POS in pediatric patients younger than 2 years of age or other types of seizures.
  • Clinical Pharmacology and Dosing: To support extrapolation, an adequately designed pharmacokinetic and tolerability study in patients 2 to 16 years of age should be conducted and include an appropriate distribution of pediatric patients across this age range and over a range of doses that covers drug concentrations known to be effective in adults. Simulations should be performed to select doses expected to achieve exposures similar to those in adults. Pharmacokinetic data from this study should be used to determine pediatric dose and regimens that provide drug exposure similar to that known to be effective in adult patients with POS.
  • Safety: Safety data generally cannot be extrapolated from adults to children. Therefore, sponsors should conduct clinical studies to characterize adequately the safety of the drug in pediatric patients 2 years of age and older with POS, with all ages well-represented.

The “Drugs for Treatment of Partial Onset Seizures: Full Extrapolation of Efficacy from Adults to Pediatric Patients 2 Years of Age and Older” guidance is available at https://go.usa.gov/xVRxA. Please refer to the guidance for more details. Instructions for submitting either electronic or written comments on Agency guidances at any time may be found in the federal register notice for this guidance at https://go.usa.gov/xVRxf.

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This communication was prepared by Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDA.

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