New pivotal phase 3 findings support an upcoming sBLA for the IL4 and IL13-targeting agent.
Amy S. Paller, MD
New data for add-on dupilumab (Dupixent) in pediatric patients with severe atopic dermatitis show one-third of patients treated with it plus topical corticosteroid (TCS) achieved clear or almost clear skin within 16 weeks.
The findings from the phase 3 LIBERTY AD PEDS trial, presented at the Revolutionizing Atopic Dermatitis virtual conference this weekend, provide pivotal evidence for the interleukin 4 and 13 (IL4; IL13)-targeting therapy’s efficacy and safety in the younger, severe patient population—just 7 weeks before the anticipated supplemental Biologics License Application (sBLA) decision date for such an indication under the US Food and Drug Administration (FDA).
The data, presented by principal investigator Amy S. Paller, MD, Walter J. Hamlin Professor and Chair of Dermatology and Professor of Pediatrics at Northwestern University Feinberg School of Medicine, showed nearly three-fold children with severe eczema achieved Investigator’s Global Assessment (IGA) scores of 0-1 with dupilumab plus TCS than those treated with lone TCS by week 16.
Paller and colleagues conducted the randomized, double-blind, placebo-controlled trial with 367 children with severe atopic dermatitis that covered a mean 60% of patient’s skin. As is common in younger patients with severe allergic conditions, nearly all (≥90%) of the participating children had at least 1 atopic comorbidity.
Investigators sought a primary endpoint of IGA 0 or 1 in dupilumab plus TCS patients, versus those treated with lone TCS. At 16 weeks, 33% of patients treated with 300 mg dupilumab every 4 weeks, and 30% treated with 100-200 mg (dependent on weight) dupilumab every 2 weeks achieved either IGA 0 or 1—versus just 11% of those treated with lone TCS (P <.0001, P = .0004, respectively).
An even greater rate of patients treated with dupilumab every 4 weeks (70%) and every 2 weeks (67%) achieved Eczema Area and Severity Index 75% clearance (EASI-75) by week 16 (P <.0001). Only one-quarter of lone TCS patients (27%) achieved the outcome.
Mean EASI score improved 82% from baseline in patients receiving dupilumab every 4 weeks, and 78% in patients who received it every 2 weeks (P <.0001).
Adverse events were observed in about two-thirds of patients dosed different for dupilumab (65%; 67%), and nearly three-fourths of lone TCS patients (73%). Common adverse events among dupilumab-treated patients included conjunctivitis, nasopharyngitis, and injection site reactions.
Supplementary benefits—including improved symptoms, itching, and metrics of patient quality of life—were observed and reported by Paller and colleagues.
The monoclonal antibody therapy from Regeneron Pharmaceuticals-Sanofi is currently approved by the FDA for approved for moderate-to-severe atopic dermatitis and asthma in patients aged 12 years and older, and severe chronic rhinosinusitis with nasal polyposis (CRSwNP) in adults. Upon receiving Breakthrough Therapy designation for it a potential indication to treat pediatric moderate-to-severe, inadequately-controlled eczema patients aged 6-11, its sBLA was set for May 26.
In a DocTalk podcast interview with HCPLive®, Paller expressed confidence in dupilumab’s chances of receiving approval for this patient population. Paller said the 16-week results showed “absolutely no red flags,” and cited dupilumab’s unprecedented benefit with skin clearance for these younger patients.
“This is a patient group that needs it so much, that I’m sure our FDA will help these families out,” she explained.
An open-label extension of the pivotal trial is ongoing, as Paller and colleagues continue to assess long-term safety and efficacy of the add-on agent. She expressed equal-parts concern and interest in learning how a stronger biologic agent affects younger patients beyond the trial’s end.
The study, "Dupilumab Significantly Improves Atopic Dermatitis in Children Aged ≥6 to <12 Years: Results from a Phase 3 Trial (LIBERTY AD PEDS), was presented virtually at RAD.