Dupilumab Achieves Positive Results in Pivotal Trial for Atopic Dermatitis

A long-term clinical trial of dupilumab (Dupixent) with topical corticosteroids (TCS) significantly improved measures of overall disease severity compared with TCS alone in patients with moderate-to-severe atopic dermatitis (AD).

In the phase 3 CHRONOS study, patients were randomized to receive either dupilumab 300 mg weekly with TCS, dupilumab 300 mg every 2 weeks with TCS, or placebo with TCS, according to a press release.

The results of the study showed that dupilumab with TCS significantly improved measures of overall disease severity at weeks 16 and 52 compared with placebo plus TCS.

“These new results build upon positive phase 3 monotherapy data,” principal investigator Andrew Blauvelt, MD, president of Oregon Medical Research Center, said in a release. “In the CHRONOS study, [dupilumab] used with topical corticosteroids showed significantly greater clearance of skin lesions and overall disease severity compared to topical corticosteroids alone, which are commonly prescribed for moderate-to-severe atopic dermatitis. This study provides positive long-term data for [dupilumab], which is important given atopic dermatitis is a chronic inflammatory disease. Additionally, the presentation highlights the critical role of IL-4 and IL-13 as drivers of this atopic condition.”

Regeneron Pharmaceuticals and Sanofi previously announced in June 2016 the primary endpoint results at week 16, and the secondary endpoint results at week 52.

At week sixteen, 39% of patients administered either dupilumab 300 mg weekly with TCS or dupilumab 300 mg every 2 weeks with TCS achieved clear or almost clear skin compared with 12% of patients who received placebo with TCS.

Also, at 16 weeks, 64% of patients in the dupilumab 300 mg weekly with TCS arm and 69% in the dupilumab 300 mg every 2 weeks with TCS achieved EASI-75 compared with 23% of patients in the placebo with TCS arm. This is a 75% reduction on an index measuring eczema severity.

At 52 weeks, 40% of patients in the dupilumab 300 mg weekly with TCS arm and 36% in the dupilumab 300 mg every 2 weeks with TCS achieved clear or almost clear skin compared with 12.5% of patients in the placebo with TCS arm. Furthermore, 64% of patients in the dupilumab 300 mg weekly with TCS arm and 65% of patients in the dupilumab 300 mg every 2 weeks with TCS arm achieved EASI-75, compared with 22% of patients who received placebo with TCS.

The latest data presented as a late-breaking oral abstract at the American Academy of Dermatology annual meeting were the following:

The mean improvement in EASI form baseline was 77% for patients who received dupilumab weekly with TCS and dupilumab every 2 weeks with TCS, compared with 42% of patients receiving placebo with TCS at 16 weeks.

The mean improvement from baseline in the intensity of patient-reported itch­­—–measures by the Pruritus Numerical Rating Scale––was 55% in the dupilumab weekly with TCS group and 58% in the dupilumab every 2 weeks with TCS group, compared with 29% in the placebo with TCS arm at week 16.

At 16 weeks, 77% of patients administered dupilumab weekly with TCS or dupilumab every 2 weeks with TCS achieved a ≥4-point improvement in the severity of their AD, compared with 37% of patients administered placebo with TCS. Additionally, 74% of patients in the dupilumab weekly with TCS arm and 81% in the dupilumab every 2 weeks with TCS arm achieved a ≥4-point improvement in aspects of quality of life, compared with 43% in the placebo with TCS arm.

The following results at week 52 were also presented:

The mean improvement in EASI from baseline was 80% for patients administered dupilumab weekly with TCS and 78% for patients administered dupilumab every 2 weeks with TCS, compared with 46% for patients who received placebo with TCS.

The mean improvement from baseline in the intensity of patient-reported itch was 54% for patients in the dupilumab weekly with TCS arm and 56% for patients in the dupilumab every 2 weeks with TCS arm, compared with 27% in the placebo with TCS arm.

Sixty-five percent administered dupilumab weekly with TCS and 76% administered dupilumab every 2 weeks with TCS achieved a ≥4-point improvement in the severity of AD, compared with 26% of patients who received placebo with TCS. Additionally, 63% of patients in the dupilumab weekly with TCS arm and 80% in the dupilumab every 2 weeks with TCS arms achieved a ≥4-point improvement in quality of life, compared with 30% in the placebo with TCS arm.

The dupilumab Biologics License Application was accepted for Priority Review with a target action date of March 29, 2017.