FDA Officials Discuss Extrapolation & Confusion Around Pediatric Therapies

WASHINGTON, D.C.—Officials with the U.S. Food & Drug Administration (FDA) described the agency’s extrapolation approach for approving drugs in pediatric rheumatology and reviewed several recent approvals in a session at ACR Convergence 2024. They also described similarities and differences in how biosimilar therapies and interchangeables are approved.

The speakers fielded an array of questions on the lack of availability of biosimilar medications for some pediatric conditions and in some formulations, and on lingering confusion from clinicians about biosimilar products that can affect how they may prescribe therapies for their patients.

Recent Drug Approvals in Pediatric Rheumatology

Ozlem Belen, MD, MPH

Ozlem Belen, MD, MPH, deputy director of the FDA’s Division of Rheumatology and Transplant Medicine, reviewed the approvals over the past year of sarilumab, certolizumab pegol and upadacitinib for pediatric juvenile idiopathic arthritis (pJIA), all of which werebased on the extrapolation approach. This strategy relies on pharmacokinetic matching and extrapolation from established efficacy data from the relevant adult population to provide evidence of effective and safe use in the pediatric population.

“In this approach, we have to assume that the course of disease and expected response to drug product would be sufficiently similar in pediatric and adult populations,” said Dr. Belen.

Pharmacokinetic extrapolation was supplemented with data from open-label studies of 93 patients for sarilumab, 193 for certolizumab and 83 for upadacitinib.

The FDA also recently approved upadacitinib for pediatric psoriatic arthritis (PsA), even though this indication was not directly studied. Instead, Dr. Belen said, the decision was based on an extrapolation of efficacy from adults with PsA and on safety data from patients with JIA who had active polyarthritis.

Dr. Belen also described a recent update to safety labeling for tocilizumab, anakinra and canakinumab, Interleukin (IL) 1/IL-6 inhibitors. The data indicate the drugs can cause drug reaction with eosinophilia and systemic symptoms (DRESS)—a severe, life-threatening, delayed-onset reaction characterized by skin manifestations, fever, lymphadenopathy, hematologic abnormalities and internal organ involvement. After drug withdrawal, the symptoms generally resolve gradually, she said.

“The DRESS cases considered relevant for the labeling changes were serious, including one with a fatal outcome, and had reasonable evidence of causal association between DRESS and these products,” she said.

Biosimilars & Interchangeable Products

Suzette Peng, MD, a medical officer in the Division of Rheumatology and Transplant Medicine, reviewed the FDA’s program for developing biosimilars, saying they’ve had a big impact on healthcare.