PARIS & TARRYTOWN, N.Y.—Mid-September saw Sanofi report results from its pivotal Phase 3 trial of Dupixent monotherapy in adolescent patients with moderate-to-severe atopic dermatitis whose disease was inadequately controlled with topical therapies or for whom topical treatment was medically inadvisable. Dupixent is currently approved for those indications for adults in the United States, and in the European Union for adults with moderate-to-severe AD who are candidates for systemic therapy, among other countries. The drug received Breakthrough Therapy designation for moderate-to-severe (12 to 17 years of age) and severe (6 months to 11 years of age) AD in 2016. Dupixent inhibits interleukin-4 and interleukin-13 (IL-4 and IL-13), both of which contribute to Type 2 inflammation, which is known to be a factor in moderate-to-severe AD.
“Limited treatment options leave adolescents with uncontrolled moderate-to-severe atopic dermatitis to cope with intense, unrelenting itch and skin lesions,” said Dr. Amy S. Paller, director of the Northwestern University Skin Disease Research Center and principal investigator of the trial. “The results we are presenting today show the potential for Dupixent in adolescents to not only help clear the skin and reduce itching, but also improve certain aspects of quality of life in adolescents who may be dealing with these unbearable symptoms.”
The trial consisted of 251 adolescents ages 12 to 17, who were randomized into one of three treatment groups—subcutaneous injection of 200 or 300 mg of Dupixent every two weeks (based on weight), 300 mg of Dupixent every four weeks or placebo. The co-primary endpoint for the trial—outside of the United States—was 75-percent improvement in Eczema Area and Severity Index (EASI-75) at 16 weeks. Within the United States, the primary endpoint consisted of the proportion of patients that achieved an Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 (almost clear).
In the trial, 41.5 percent of patients who were treated with Dupixent every two weeks and 38 percent of patients who were treated every four weeks saw 75 percent or greater skin improvement, versus 8 percent on placebo. Of the group that took Dupixent every two weeks, there was a 66-percent improvement in average percent change from baseline in score, while the group that took Dupixent every four weeks saw an improvement of 65 percent. The placebo group posted an improvement of 24 percent. The Dupixent every two weeks cohort saw a 48-percent improvement in average percent change from baseline in the pruritus numerical rating scale, compared to 45.5 percent in the four weeks group and 19 percent in the placebo cohort.
Within the cohort that received either 200 or 300 mg of Dupixent every two weeks, 24 percent achieved the primary endpoint of an IGA score of 0 or 1, while 18 percent of patients who received 300 mg every four weeks achieved the same endpoint. Only 2 percent of patients in the placebo cohort reached the primary endpoint.
Positive data was recorded for secondary endpoints as well, with improvements in in EASI and SCORAD scores from baseline, as well as improvements in itch, quality of life and patient-reported symptoms.
Adverse events were seen at a rate of 72 percent for the two weeks group, 64 percent for the four weeks group and 69 percent for placebo. The most common adverse events were injection site reactions and conjunctivitis.
Sanofi first shared details from this trial in May, noting at the time that it planned to submit its regulatory submission for Dupixent treatment in this patient population in the third quarter of the year.
“Current treatment options for these adolescent patients such as topical steroids, oral steroids, and non-steroidal immunosuppressants can have significant side effects,” remarked Dr. Elias Zerhouni, president of Global R&D at Sanofi, in a May press release. “We continue to explore Dupixent’s role in targeting Type 2 inflammation as an underlying cause of atopic dermatitis to potentially provide adolescents, some of whom have lived with this disease their entire lives, a therapy that treats more than just their symptoms.”
May also featured news from Sanofi regarding the results of two Phase 3 trials—QUEST and VENTURE—of Dupixent in moderate-to-severe asthma, results that were published in the New England Journal of Medicine. The drug was found to significantly reduce the risk of severe asthma attacks, improve lung function and reduce the need for oral corticosteroids. Improvements were seen in the key primary and secondary endpoints across overall populations in both studies.