Regulatory Focus™ > News Articles > 2019 > 9 > FDA Offers Advice on Extrapolating Efficacy of Seizure Drugs from Adults to Children

FDA Offers Advice on Extrapolating Efficacy of Seizure Drugs from Adults to Children

Posted 05 September 2019 | By Michael Mezher 

FDA Offers Advice on Extrapolating Efficacy of Seizure Drugs from Adults to Children

The US Food and Drug Administration (FDA) on Thursday finalized guidance providing recommendations for developing drugs to treat pediatric patients with partial onset seizures (POS) by extrapolating efficacy data from drugs approved to treat adult patients with the condition.
 
The three-page guidance finalizes a draft version released for comment in February 2018. Most notably, the final guidance extends the age range of patients for whom efficacy data can be extrapolated to from four years and older to two years and older.
 
FDA notes that the guidance does not apply to the development of drugs to treat other types of seizures, nor does it apply to clinical development programs for treating POS in children less than two years of age.
 
“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. After excluding children with POS associated with epileptic encephalopathies, such as Lennox-Gastaut syndrome, the pathophysiology of POS appears similar in adults and pediatric patients 2 years of age and older,” FDA writes.
 
According to FDA, clinical studies involving patients as young as two years of age have shown that children have a similar response to treatment to adult patients with POS. However, FDA still acknowledges that its own analyses of clinical trial data show the relationship between exposure and response is similar between adults and children ages four years 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,” FDA writes.
 
The final guidance makes the same recommendations as the draft version regarding drug formulation, noting that sponsors should focus on the feasibility of the route of administration, drug-related toxicity and taste preferences when developing drugs to treat children with POS.
 
FDA also maintains its recommendation that sponsors should conduct pharmacokinetic and tolerability studies in patients with an appropriately distributed sample of patients ages two to 16. Dose selection should be based on simulations designed to identify doses that would achieve exposure levels similar to those in adults.
 
Sponsors are instructed to share data from those analyses with the agency before proceeding to open-label safety studies.
 
Because “safety data generally cannot be extrapolated from adults to children,” FDA says that sponsors should conduct open-label safety studies involving a minimum of 100 pediatric patients who should be exposed to the drug for at least six months, with doses “at or above those determined to be effective in the pediatric population.”
 
FDA says that sponsors should quantify the blood concentrations of the drug and its active major metabolites if serious or severe adverse events occur during the safety study.
 
FDA

 

© 2021 Regulatory Affairs Professionals Society.

Regulatory Focus newsletters

All the biggest regulatory news and happenings.

Subscribe