Pfizer's Next-Gen Oral JAK1 Inhibitor Abrocitinib Succeeds in Four Phase III Trials for Atopic Dermatitis

June 11, 2020 News /BioValleyBIOON/ --PfizerPfizer recently announced that the Phase III JADE TEEN study (NCT03796676), evaluating once-daily oral JAK1 inhibitor abrocitinib (PF-04965842) in adolescents aged 12–18 years with moderate-to-severe atopic dermatitis (AD) who were also receiving background topical therapy, achieved positive results. Data showed that both doses of abrocitinib met the co-primary endpoints, demonstrating improvements in skin clearance, disease extent and severity, and pruritus, with good overall tolerability.

Abrocitinib is an oral small molecule that selectively inhibits Janus kinase 1 (JAK1). Inhibition of JAK1 is believed to modulate multiple cytokines involved in the pathophysiology of atopic dermatitis (AD), including interleukin (IL)-4, IL-13, IL-31, and interferon-gamma. In the United States,FDABreakthrough Therapy Designation (BTD) for abrocitinib in the treatment of moderate-to-severe AD was granted in February 2018.

It is worth noting that the JADE TEEN study is the fourth successfully completed study in Pfizer’s global development program, JADE, which evaluates abrocitinib for the treatment of moderate-to-severe atopic dermatitis (AD). The three previously completed Phase III studies in this program (JADE MONO-1, JADE MONO-2, and JADE COMPARE) also achieved success, demonstrating attainment of the co-primary endpoints and key secondary endpoints related to skin clearance and itch relief. Most recently, Pfizer announced the full results from the second Phase III study, JADE MONO-2. The company will release detailed data from other studies in the JADE program later this year.

Data from the JADE COMPARE study, together with results from the JADE MONO-1 and JADE MONO-2 studies, will support the submission of marketing authorization applications to regulatory authorities. Pfizer plans to initiate submissions to the U.S. Food and Drug Administration (FDA) Submitting a New Drug Application (NDA) for abrocitinib in the treatment of moderate-to-severe atopic dermatitis (AD).

Pfizer Global Product Development, Inflammation andImmunologyDr. Michael Corbo, Chief Development Officer, stated, “Up to 20% of children are affected by atopic dermatitis (AD), and there remains an unmet need for new treatment options that may improve care. For children and adolescents, these findings from the JADE TEEN study build upon the positive results of our previously reported Phase 3 monotherapy study, which included patients aged 12 years and older.”

Molecular structure of abrocitinib (Image source: medchemexpress.cn)

JADE TEEN is a randomized, double-blind, placebo-controlled, parallel-group study that enrolled 285 adolescent patients aged 12 to less than 18 years with moderate-to-severe atopic dermatitis (AD). In this study, patients were randomly assigned to receive once-daily abrocitinib 200 mg, abrocitinib 100 mg, or placebo for 12 weeks, along with background topical therapy. Patients who completed the 12-week treatment period and met eligibility criteria could opt to enter a long-term extension (LTE) study, B7451015. Patients who discontinued treatment early or did not qualify for the LTE study entered a 4-week follow-up period.

The co-primary endpoints of the study were: the proportion of patients achieving an Investigator’s Global Assessment (IGA) score of clear (0) or almost clear (1), with a reduction of ≥2 points from baseline, at Week 12 of treatment; and the proportion of patients achieving at least a 75% improvement in the Eczema Area and Severity Index (EASI) score from baseline at Week 12 of treatment. Key secondary endpoints included: the proportion of patients achieving a reduction of ≥4 points from baseline in itch severity, as measured by the Peak Pruritus Numerical Rating Scale (PP-NRS), at Weeks 2, 4, and 12 of treatment; and the magnitude of reduction in the Atopic Dermatitis Itch and Symptoms Assessment (PSAAD) score at Week 12 of treatment. The PSAAD is a patient-reported outcome measure developed by Pfizer.

The results showed that the study met its co-primary endpoints at Week 12: the proportions of patients achieving each primary efficacy endpoint were significantly higher in both abrocitinib dose groups than in the placebo group. Regarding key secondary endpoints, the proportions of patients with clinically significant reductions in pruritus were statistically significantly higher in the placebo group than in the 200-mg abrocitinib group at Weeks 2, 4, and 12, and in the 100-mg abrocitinib group at Week 2. Although a significant difference was observed in the 100-mg abrocitinib group at Week 2, no further testing of the key secondary endpoints was conducted due to the lack of significance at Week 4. Consequently, improvements in other key secondary endpoints, including PSAAD, could not be inferred.

In the study, the safety profile of abrocitinib was consistent with previous studies. Safety results showed that the proportion of patients experiencing adverse events was higher in those treated with 100 mg or 200 mg of abrocitinib compared to the placebo group (56.8%, 62.8%, and 52.1%, respectively). The proportions of patients experiencing serious adverse events or adverse events leading to discontinuation of the study were similar across groups: placebo group (2.1% for each), 100 mg abrocitinib group (0% and 1.1%, respectively), and 200 mg abrocitinib group (1.1% and 2.1%, respectively). The full results of this study will be presented at future medicalMeetingpublished on Bioon.com.

Original Source: Pfizer Announces Positive Top-Line Results from JADE TEEN Trial of Abrocitinib in Adolescents with Moderate-to-Severe Atopic Dermatitis