Pfizer Inc. announced that the European Commission (EC) has approved the 100 mg and 200 mg doses of Cibinqo (abrocitinib), an oral, once-daily, Janus kinase 1 (JAK1) inhibitor, for the treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy. Additionally, a 50 mg dose was approved to treat moderate-to-severe AD specifically in patients with moderate and severe renal impairment (kidney failure) or certain patients receiving treatment with inhibitors of cytochrome P450 (CYP) 2C19.

“For adults living with moderate-to-severe atopic dermatitis, Cibinqo could help provide relief from the hallmark symptom of intense itch and has demonstrated rapid improvements in skin clearance, extent, and severity of disease, versus placebo,” said Dr. Stephan Weidinger, Professor of Dermatology at Christian-Albrechts University Kiel and Vice Head of the Department of Dermatology at the University Hospital Schleswig-Holstein, Kiel, Germany. “The approval of Cibinqo in the European Union makes me hopeful for many patients who will have this additional option to help manage the often painful and disruptive symptoms of moderate-to-severe atopic dermatitis.”

The approval of Cibinqo was based on the results of five clinical studies of more than 2,800 patients including four phase 3 studies and an ongoing long-term open label extension study. Cibinqo demonstrated meaningful improvements across measures of symptom relief and disease control versus placebo. In one trial including an active control arm with dupilumab, which evaluated patients on background topical medicated therapy, Cibinqo 200 mg was associated with a greater improvement in itch relief after two weeks than dupilumab. Cibinqo also demonstrated a consistent safety profile across trials, including in a long-term extension study, showing a favorable benefit-risk profile.

“There have been few treatment innovations over the last decade for those in the European Union suffering with the daily discomfort, distress, and pain caused by moderate-to-severe atopic dermatitis,” said Mike Gladstone, global president of Pfizer Inflammation & Immunology. “The safety and efficacy established through a rigorous clinical trial program, designed to evaluate measures of symptom relief most important to patients, gives us great confidence in the positive impact Cibinqo could have on those living with this debilitating immuno-inflammatory condition.”

The most common adverse events reported with Cibinqo in =5% of patients were nausea (15.1%) and headache (7.9%). The most frequent serious adverse reactions were infections (0.3%).

Findings from the following five studies in the Cibinqo JAK1 Atopic Dermatitis Efficacy and Safety (JADE) global development program were included in the submission to support this approval. The trials evaluated measures of improvements for AD including the Investigator Global Assessment (IGA), Eczema Area and Severity Index (EASI), and Peak Pruritus Numerical Rating Scale (PP-NRS):

JADE MONO-1 and JADE MONO-2: A pair of randomized, double-blind, placebo-controlled studies designed to evaluate the efficacy and safety of two doses (100 mg and 200 mg once daily) of Cibinqo monotherapy in 778 patients 12 years of age and older with moderate-to-severe AD. The studies assessed the co-primary endpoints of IGA and EASI-75 responses at Week 12. Key secondary endpoints in MONO-1 and MONO-2 included improvement of =4 points in the severity of PP-NRS at Weeks 2, 4, and 12.

JADE COMPARE: A randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of two doses (100 mg and 200 mg once daily) of Cibinqo in 837 adult patients with moderate-to-severe AD on background topical medicated therapy. The study also included an active control arm with dupilumab, a biologic treatment administered by subcutaneous injection, compared with placebo. The study assessed the co-primary endpoints of IGA (0 or 1) and EASI-75 responses at Week 12. Key secondary endpoints in COMPARE were PP-NRS4 at Week 2, compared to patients in both the dupilumab and placebo groups, in addition to IGA (0 or 1) response and EASI-75 at Week 16, compared to patients in the placebo group only.

JADE REGIMEN: An induction, randomized withdrawal, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of two doses (100 mg and 200 mg once daily) of Cibinqo in patients 12 years of age and older with moderate-to-severe AD. Following response to 12-week, open label, induction treatment with abrocitinib 200 mg, 798 patients (64.7% of those enrolled in the study) were randomized into one of three arms: 100 mg, 200 mg, or placebo. The primary endpoint following response in the 12-week induction phase was the loss of response requiring rescue treatment, a protocol-defined “flare,” among groups during the blinded treatment period up to 40 weeks. During the blinded treatment period, subjects meeting the protocol definition of flare entered an open-label rescue period during which they receive a 12-week course of abrocitinib 200 mg once daily with topical therapy per local standard of care. The key secondary endpoint was the loss of IGA response.

JADE EXTEND: An ongoing, large, open-label, study designed to assess the long-term safety and efficacy of Cibinqo in a 92-week initial treatment period, followed by a variable length secondary treatment period during which subjects will receive treatment with open-label abrocitinib.

Select findings for Cibinqo 100 mg, 200 mg, and placebo follow. P-value differences versus placebo across endpoints in JADE MONO-1, JADE MONO-2, and JADE COMPARE were p<0.01 or p<0.001. Treatment effects in subgroups, such as age or weight, were consistent with the results in the overall study populations.

Cibinqo is an oral small molecule that selectively inhibits Janus kinase (JAK) 1. Inhibition of JAK1 is thought to modulate multiple cytokines involved in pathophysiology of atopic dermatitis, including interleukin IL-4, IL-13, IL-31, IL-22, and thymic stromal lymphopoietin (TSLP).

Cibinqo received marketing authorization from the UK Medicines and Healthcare products Regulatory Agency (MHRA), the Japanese Ministry of Health, Labour and Welfare (MHLW) and Korea’s Ministry of Food and Drug Safety (MFDS) earlier this year.