Pfizer's JAK1 Inhibitor Abrocitinib Nears Priority Review in China for Atopic Dermatitis

On March 16, the CDE website indicated that Pfizer’s marketing application for abrocitinib tablets was proposed for inclusion in the priority review program and opened for public notice, on the grounds of being “a new pediatric drug product, dosage form, or strength aligned with children’s physiological characteristics.” The indicated use is for the treatment, including relief of pruritus, of patients aged 12 years and older with moderate-to-severe atopic dermatitis who have had an inadequate response to topical therapies or for whom such therapies are not advisable, used alone or in combination with topical therapies.

Atopic Dermatitis (AD) is a chronic, relapsing, inflammatory skin disease. Because patients often have comorbid atopic conditions such as allergic rhinitis and asthma, it is considered a systemic disease. Patients with AD frequently experience intense pruritus, which significantly impairs their quality of life.

Abrocitinib is an oral, small-molecule, selective Janus kinase (JAK) 1 inhibitor developed by Pfizer. JAK inhibitors exert their therapeutic effects by modulating multiple cytokines associated with atopic dermatitis, including interleukin (IL)-4, IL-13, IL-31, IL-22, and thymic stromal lymphopoietin (TSLP).

Structural Formula of Abrocitinib

In November 2020, Pfizer announced positive results from the Phase III JADE REGIMEN study (NCT03627767) evaluating abrocitinib for the treatment of moderate-to-severe atopic dermatitis in patients aged 12 years and older. The study results showed that during the induction period, 64.7% (798/1233) of patients treated with abrocitinib 200 mg achieved a clinical response. Furthermore, during the maintenance period, patients who continued on high-dose abrocitinib (200 mg) or switched to low-dose abrocitinib (100 mg) had a significantly higher probability of remaining free from acute flare events over 52 weeks compared with placebo, with rates of 81.1%, 57.4%, and 19.1%, respectively. Both abrocitinib dose groups demonstrated statistically significant differences compared with the placebo group (p<0.0001).

Safety results showed that the incidence of adverse events during the induction period was 66.5%, and the incidence of serious adverse events was 1.6%. After randomization, the proportion of patients experiencing adverse events in the abrocitinib 200 mg or 100 mg dose groups was higher than that in the placebo group, at 63.2%, 54%, and 45.3%, respectively. The incidence rates of serious adverse events were 4.9%, 1.5%, and 0.7%, respectively. A higher proportion of patients receiving abrocitinib discontinued the study due to adverse events (6%, 1.9%, and 1.5%, respectively).

The JADE REGIMEN study is a 52-week, randomized, double-blind, placebo-controlled Phase III clinical trial that enrolled a total of 1,233 participants globally. The study consisted of two phases. Participants first received a 12-week open-label monotherapy induction treatment with abrocitinib (200 mg once daily). Those who demonstrated a positive clinical response to abrocitinib induction therapy entered a 40-week double-blind maintenance phase, during which they were randomly assigned to one of three groups receiving either placebo, abrocitinib 100 mg, or abrocitinib 200 mg (once daily). During both the induction and maintenance phases, participants were not permitted to receive topical medications and/or standard systemic care treatments.

In February 2018, Abrocitinib received FDA Breakthrough Therapy Designation for the treatment of patients with moderate-to-severe atopic dermatitis (AD). Last October, the New Drug Application (NDA) for Abrocitinib in the treatment of patients aged 12 years and older with moderate-to-severe AD was granted Priority Review by the FDA, with approval expected in April 2021. The European Medicines Agency (EMA) has also accepted the Marketing Authorization Application (MAA) for Abrocitinib, with a regulatory decision anticipated in the second half of 2021.