Pfizer Inc. edged closer to Dermira Inc. in the rush for an approved treatment for atopic dermatitis (AD), a field dominated by Regeneron Pharmaceutical Inc.'s FDA-approved blockbuster, Dupixent (dupilumab), as Pfizer reported positive top-line results from a phase III trial evaluating the efficacy and safety of its oral JAK1 inhibitor, abrocitinib.
The data are from the second of two monotherapy trials in Pfizer's JAK1 Atopic Dermatitis Efficacy and Safety (JADE) global development program. The randomized, double-blind, placebo-controlled, parallel-group study was designed to evaluate the efficacy and safety of two doses (100 mg and 200 mg once daily) of abrocitinib monotherapy over 12 weeks. At week 12, the percentage of patients, ages 12 and older, with moderate to severe AD hit each co-primary efficacy endpoint and each key secondary endpoint with either dose of abrocitinib, performing statistically significantly higher than placebo. Also, a statistically significant number of patients achieved a reduction in pruritus by week two, as measured by a four-point or larger reduction in itch severity measured with the pruritus numerical rating scale (NRS).
The co-primary study endpoints were the proportion of patients who achieved an Investigator Global Assessment score of clear (0) or almost clear (1) skin and two-point or greater improvement; and the proportion of patients who achieved at least a 75% or greater change from baseline in their Eczema Area and Severity Index score. The key secondary endpoints were the proportion of patients achieving a four-point or larger reduction in itch severity measured with the pruritus NRS and the magnitude of decrease in the Pruritus and Symptoms Assessment for Atopic Dermatitis.
Results from Pfizer's first JADE monotherapy trial, a randomized, double-blind, placebo-controlled, parallel-group study, also designed to evaluate the efficacy and safety of two doses (100 mg and 200 mg once daily) of abrocitinib monotherapy over 12 weeks, were released in May. Top-line results showed that by week 12, the percentage of patients achieving each co-primary efficacy endpoint and each key secondary endpoint with either dose of abrocitinib was statistically significantly higher than placebo. In addition, the results demonstrated response to treatment for a statistically significant number of patients during the first two to four weeks following first dose.
Regeneron won FDA approval for the Sanofi SA-partnered biologic more than three years ago as a treatment for adults with moderate to severe AD who are either not helped by topical drugs or for whom those therapies aren't advised, a group then estimated to encompass about 300,000 patients in the U.S. By the end of 2016, the partners had invested a cumulative €5.1 billion (US$5.5 billion) to advance programs covered by the alliance, with the majority spent by Sanofi. (See BioWorld, March 29, 2017.)
In October 2018, Regeneron received FDA approval for Dupixent in asthma and in March of this year, it was approved for adolescents with AD. In 2018, Dupixent brought Regeneron $922 million in revenue.
Dupixent's availability created new competition for Pfizer's topical PDE4 inhibitor, Eucrisa (crisaborole), approved in December 2016 for patients, 2 and older, with mild to moderate AD. Still, both therapies are likely to find opportunity in meeting needs in AD, which until Eucrisa's approval hadn't seen a significant new treatment for more than a decade. (See BioWorld Today, Dec. 15, 2016.)
Earlier this year, data from Dermira's midstage study revealed its anti-IL-13 candidate, lebrikizumab (lebri), in AD showed a monthly dose performing roughly in line with Dupixent. Though no head-to-head test with Dupixent was included in Dermira's phase IIb study, three different doses of lebri outperformed a placebo on a standard measure of eczema severity, showing efficacy that analysts said nearly matched Regeneron's drug. (See BioWorld, March 19, 2019.)
AD, often called eczema, is common and affects about 5% to 20% of children worldwide and about 11% of children in the U.S. It's also estimated to affect about 3% to 7% of adults in the U.S., according to a draft evidence report assessing the comparative clinical effectiveness and value of Eucrisa and Dupixent for the treatment of AD published by the Institute for Clinical and Economic Review.