On March 4, 2016, late-breaking research on Regeneron/Sanofi’s Dupixent (dupilumab) in patients with moderate-to-severe atopic dermatitis (AD) was presented at the 75th Annual American Academy of Dermatology (AAD) meeting. Dupixent is a human monoclonal antibody that specifically binds to interleukin 4 receptor alpha (IL-4RA), which is involved in both IL-4- and IL-13-mediated effects that play a central role in chronic allergic inflammation. The AD disease space lacks novel systemic therapies, marking a substantial unmet need in this indication. FDA approval of Dupixent is expected to occur within the next month and would be the first biologic to target IL-4RA in the AD space, offering the drug first-to-market advantage—a significant opportunity for Regeneron and Sanofi.
In a long-term Phase III, randomized, placebo-controlled trial, adults patients with moderate-to-severe AD and an inadequate response to topical corticosteroids were randomized 3:1:3 to receive 300mg of Dupixent once-weekly or once every two weeks, or placebo—all with concomitant topical corticosteroids for 52 weeks. At Week 16, more of the Dupixent-treated patients achieved Investigator’s Global Assessment (IGA) score of zero or one (Dupixent once weekly/every two weeks: 39.2%/38.7%, placebo: 12.4%, p<0.001), Eczema Area and Severity Index (EASI) 75 improvement (63.9%/68.9%%, 23.2%, p<0.001), and peak pruritus numerical rating scale improvement of at least four (PRN≥4) (50.8%/58.8%, 19.7%, p<0.001). In addition, at Week 52, more of the Dupixent-treated patients achieved IGA score of zero or one (39.2%/38.7%, 12.4%, p<0.001), EASI 75 improvement (63.9%/68.9%%, 23.2%, p<0.001), and peak pruritus NRS≥4 (50.8%/58.8%, 19.7%, p<0.001).
Further, results from an open-label Phase IIa trial assessing the safety, efficacy, and pharmacokinetics of Dupixent in children (6–11 years) and adolescents (12–17 years) with moderate-to-severe AD were presented. AD patients (30 children and 40 adolescents) uncontrolled by topical medications were administered 2mg/kg or 4mg/kg of subcutaneous Dupixent. and after an eight week follow-up and they then received four once-weekly injections of Dupixent, 2mg/kg or 4mg/kg accordingly. At Week 12, adolescents treated with 2mg/kg and 4mg/kg demonstrated baseline EASI improvements of 66.4% and 69.7%, respectively, and peak pruritus NRS improvements of 30.8% and 37.6%, respectively. Children treated with 2mg/kg and 4mg/kg of Dupixent demonstrated baseline EASI improvements of 76.2% and 63.4%, respectively, and peak pruritus NRS improvements of 41.6% and 39.6%, respectively, at Week 12. In addition, in adolescents and children treated with 2mg/kg and 4mg/kg of Dupixent, 10%, 35%, 16.7%, and 21.1% achieved IGA0-1, respectively.
Dupixent shows a similar safety and efficacy profile in children compared with adults, marking an opportunity for Regeneron and Sanofi to expand the use of Dupixent to an underserved pediatric population.