Dupilumab Achieves Primary Endpoint in Phase 3 Trial

George D. Yancopoulos, MD, PhD

In a recent phase 3 trial evaluating it for efficacy and safety as a monotherapy, dupilumab (Dupixent, Sanofi) reportedly met its primary endpoints as well as some key secondary endpoints.

Of the 251 patients enrolled, 24% of those receiving a weight-based dose (either 200 or 300 mg) of the moderate-to-severe atopic dermatitis therapy were shown to achieve clear or almost-clear skin, as measured by the Investigator’s Global Assessment (IGA) score of 0 to 1, compared with only 2% of those receiving placebo (P <.0001). Additionally, 18% patients that received dupilumab in a fixed, 300-mg dose every 4 weeks achieved an IGA score of 0 to 1 (P = .0007).

"Moderate-to-severe atopic dermatitis can place a particularly significant burden on adolescents, who have to deal with oozing skin lesions with unrelenting, intense itching during their formative years," George D. Yancopoulos, MD, PhD, the president and chief scientific officer of Regeneron, said in a statement. "Dupixent blocks the IL-4/IL-13 pathway, which is emerging as a central driver of Type 2 allergic inflammation. We are committed to investigating the potential for Dupixent across Type 2 inflammatory diseases with high unmet need including atopic dermatitis, asthma, eosinophilic esophagitis, nasal polyps, chronic obstructive pulmonary disease, and food allergy."

The trial evaluated dupilumab with patients aged 12 to 17 years, who had uncontrolled or difficult-to-treat, moderate-to-severe atopic dermatitis for 16 weeks. Ultimately, 92% of those enrolled had at least one concurrent allergic condition such as allergic rhinitis, asthma or food allergy. Patients were randomized to 1 of 3 groups, to receive either a weight-based dose every 2 weeks, a fixed dose monthly (with an initial 600-mg dose), or placebo.

The therapy also showed marked improvement in Eczema Area and Severity Index (EASI-75) scores at 16 weeks. All told, 41.5% of those receiving dupilumab every 2 weeks and 38% of those receiving it every 4 weeks achieved a ≥75% score, compared with 8% of those receiving placebo (P <.0001).

In comparison with placebo for changes from baseline EASI scores, the 4-week group and 2-week groups experienced 65% and 66% improvements, respectively, compared with 24% with placebo (P <.0001). The mean percent change from baseline in pruritus numerical rating scale scores was 19% with placebo compared with 48% and 45.5% for the 2-week and 4-week groups, respectively (P <.0001).

"Current treatment options for these adolescent patients such as topical steroids, oral steroids, and non-steroidal immunosuppressants can have significant side effects," Elias Zerhouni, MD, the president of Global R&D at Sanofi, said in a statement. "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."

The safety profile of dupilumab was shown to be consistent with what has been shown in adult patients, with the overall rate of adverse events (AEs) being 72% for the 2-week group, 64% for the 4-week group, and 69% for the placebo group. None were considered serious, nor did any lead to treatment discontinuation.

In total, injection site reactions (8.5% for 2 weeks; 6% for 4 weeks; 3.5% for placebo) and conjunctivitis (10% for 2 weeks; 11 for 4 weeks; 5% for placebo) were the only AEs that occurred at a higher rate with dupilumab.

Sanofi expects further data from the trial will be presented at a future medical meeting, and the data is expected to be submitted to the FDA and other regulatory authorities later this year, the company noted.

The US Food and Drug Administration (FDA) granted it a Breakthrough Therapy Designation in 2016. On March 2, 2018, the FDA accepted the supplemental Biologics License Application of dupilumab as an add-on maintenance therapy for adults and adolescents aged 12 years or older with moderate-to-severe asthma. The therapy was also discussed at the American Academy of Asthma, Allergy, and Immunology and World Allergy Organization’s 2018 Joint Congress, in Orlando, Florida, as an effective therapy for nasal polyps.