Abrocitinib Improves Moderate-to-Severe Atopic Dermatitis in Phase 3 Study

March 23, 2020

Phase 3 clinical data demonstrate abrocitinib’s efficacy and safety in treating moderate-to-severe atopic dermatitis in adults.

Abrocitinib, an investigational oral once-daily Janus kinase 1 (JAK1) inhibitor for atopic dermatitis (AD), demonstrated disease improvement in adults, according to a phase 3 study.

Abrocitinib (Pfizer), which received Breakthrough Therapy designation from the FDA in 2018, is under investigation for the treatment of adults with moderate-to-severe AD.

The phase 3 JADE COMPARE trial evaluated the safety and efficacy of abrocitinib in adults with moderate-to-severe AD who were also on background topical therapy. The study also included an active control arm, dupilumab, compared with placebo.

A total of 837 patients were randomized to 5 treatments arms in the study:

  • Abrocitinib (100 mg) with dupilumab matching placebo administered by subcutaneous injection every other week from day 1 to week 16, followed by abrocitinib (100 mg) until week 20.

  • Abrocitinib (200 mg) with dupilumab matching placebo administered every other week with abrocitinib matching orally administered placebo once-daily from day 1 to week 16, followed by abrocitinib matching orally administered placebo once-daily until week 20.

  • Dupilumab (300 mg; with a 600 mg loading dose at baseline) administered every other week with abrocitinib matching orally administered placebo once-daily from day 1 to week 16, followed by abrocitinib matching orally administered placebo once-daily until week 20.

  • Abrocitinib matching orally administered placebo once-daily with dupilumab matching subcutaneously injected placebo administered every other week from day 1 to week 16, followed by abrocitinib (100 mg) until week 20.

  • Abrocitinib matching orally administered placebo once-daily with dupilumab matching subcutaneously injected placebo administered every other week from day 1 to week 16, followed by abrocitinib (200 mg) until week 20.

Study participants used non-medicated emollients at least twice per day and medicated topical therapy such as corticosteroids, calcineurin inhibitors, or PDE4 inhibitors. Treatment duration was 20 weeks.

The co-primary endpoints were the proportion of patients who achieved an Investigator’s Global Assessment (IGA) of clear or almost clear and a 2-point or greater reduction from baseline at week 12; and the proportion of patients who achieved at least a 75% or greater change from baseline in their Eczema Area and Severity Index (EASI) score at week 12.

Overall, the results showed that the percentage of patients achieving each co-primary efficacy endpoint at week 12 was statistically superior with both doses of abrocitinib than with placebo. Superiority to placebo with both doses was maintained at week 16. Dupilumab, the active control, demonstrated superiority to placebo at week 12 and week 16.

Additionally, patients met a key secondary endpoint with clinically significant reductions in itch by week 2 of treatment that was statistically superior for the 200 mg abrocitinib dose compared with dupilumab and numerically higher, but not statistically significantly higher, for the 10 mg abrocitinib dose compared with dupilumab.

Regarding safety, the data showed that a larger percentage of patients receiving abrocitinib 200 mg experienced adverse events (AEs) (61.9%) than in other treatment arms. The percentages of patients experiencing AEs were similar for placebo (53.4%), abrocitinib 100 mg (50.8%), and dupilumab (50%). The percentage of patients experiencing serious AEs and AEs leading to study discontinuation were similar across the placebo (3.8% each), abrocitinib 100 mg (2.5%), abrocitinib 200 mg (0.9% and 4.4%, respectively), and dupilumab (0.8% and 3.3%), respectively) treatment arms.

“It was helpful to study abrocitinib in combination with topical therapies to provide data relevant to the real-world setting,” Michael Corbo, PhD, chief development officer, Inflammation & Immunology, Pfizer Global Product Development, said in a statement. “The addition of an active control was also important to better understand the significance of this potential new medicine and we’re encouraged by the positive data from this trial.”

The data from this study, along with results from other trials MONO-1 and MONO-2, will support filings with regulatory bodies, including the FDA, planned for later this year, according to Pfizer.