Pfizer’s Oral JAK1 Inhibitor Cibinqo (abrocitinib) Approved in Japan for Moderate-to-Severe Atopic Dermatitis, Demonstrating Superior Efficacy Over Dupixent

Atopic Dermatitis (Image source: icresearch.net)

October 16, 2021 /BioonBIOON/ ---Pfizer(Pfizer) recently announced that Japan's Ministry of Health, Labour and Welfare (MHLW) has approvedCibinqo（abrocitinib）, this drug is aOnce-daily oral JAK1 inhibitor, for the treatment of patients aged 12 years and older who are eligible for systemic therapy and have had an inadequate response to existing therapiesAdolescent and adult patients with moderate-to-severe atopic dermatitis (AD). In early September this year, Cibinqo received the world's first approval in the UK, with indications identical to those mentioned above. In Japan and the UK, Cibinqo is dosed at 100 mg or 200 mg.

The approval of Cibinqo in Japan is based on data from the robust Phase 3 JADE global clinical development program, including four Phase 3 studies (treatment duration: 12 to 16 weeks) and one long-term extension study.

Currently, marketing authorization applications for abrocitinib have been submitted for regulatory review in multiple countries and regions worldwide, including the United States, Australia, and the European Union. In multipleClinical TrialIn,Abrocitinib demonstrates robust efficacy in alleviating the symptoms and signs of AD, including rapid relief of pruritus and clearance of skin lesions.。Specifically, in the head-to-head Phase 3 JADE DARE (B7451050) study,Compared with the subcutaneous injection formulation Dupixent (Chinese brand name: Dabito, generic name: dupilumab), abrocitinib demonstrated statistically significant superiority across every evaluated efficacy endpoint.

Angela Hwang, President of Pfizer Biopharmaceuticals Group, stated: “Treatment options for patients with moderate-to-severe atopic dermatitis are limited. The approval of Cibinqo for market launch is expected to have a positive impact on the lives of patients in Japan. We thank Japan’s Ministry of Health, Labour and Welfare (MHLW) and all those who participated in our extensive”Clinical Trialpatients and their families in the program. Now, our primary goal is to ensure that as many patients as possible can routinely access Cibinqo and benefit from this important therapy.”

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

Atopic dermatitis (AD) is a chronic skin disease characterized by cutaneous inflammation and skin barrier dysfunction, presenting with erythema, pruritus, induration/papule formation, and exudation/crusting. It is a severe, unpredictable, and often debilitating skin condition that significantly impacts the daily lives of patients and their families. AD is one of the most common chronic, relapsing skin diseases in children, affecting up to 10% of adults and up to 20% of children worldwide. Disease control remains inadequate for many patients with moderate-to-severe AD, necessitating additional treatment options to alleviate the symptoms that matter most to them.

Active pharmaceutical ingredient of Cibinqo 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, IL-22, and thymic stromal lymphopoietin (TSLP).。In the United States, the FDA granted abrocitinib Breakthrough Therapy Designation (BTD) for the treatment of moderate-to-severe AD in February 2018. Currently, the New Drug Application (NDA) for abrocitinib (100 mg, 200 mg) for the treatment of patients aged ≥12 years with moderate-to-severe AD is under review by the U.S.FDAreview. In addition, the Marketing Authorization Application (MAA) for abrocitinib in the same patient population is also under review by the European Medicines Agency (EMA), with a decision expected in the second half of 2021.

In August this year, Pfizer announced positive results from the head-to-head Phase 3 JADE DARE (B7451050) study. The study was conducted in adult patients with moderate-to-severe AD receiving background topical therapy, and directly compared abrocitinib (200 mg, oral, once daily) with Dupixent (300 mg, subcutaneous injection, once every 2 weeks). In the study, abrocitinib was administered as a 200 mg oral tablet once daily, while Dupixent was administered as a 300 mg subcutaneous injection every other week following a 600 mg induction dose, with all patients receiving background topical therapy.

The co-primary efficacy endpoints of the study are: (1) the proportion of patients achieving a pruritus response at Week 2 of treatment, defined as an improvement of ≥4 points from baseline in the Peak Pruritus Numerical Rating Scale (PP-NRS, scoring range: 0–10) score; (2) the proportion of patients achieving an Eczema Area and Severity Index-90 (EASI-90) response at Week 4 of treatment, defined as a ≥90% improvement from baseline in the EASI (scoring range: 0–72) score. The key secondary endpoint is the proportion of patients achieving an EASI-90 response at Week 16 of treatment. The study will allow for the evaluation of any efficacy differences that may persist at Month 6 of treatment.

The results showed that the study met its co-primary efficacy endpoints and key secondary efficacy endpoints: compared with Dupixent, abrocitinib demonstrated statistically significant superiority across all evaluated efficacy measures, and its safety profile was consistent with previous studies.

Dupixent（达必妥®）, co-developed by Sanofi and Regeneron, is the world's first and only approved targeted biologic therapy for moderate-to-severe atopic dermatitis (AD), which rapidly, significantly, and sustainably improves the severity of skin lesions and pruritus in patients with atopic dermatitis.

Dupixent Targets the Key Drivers of Type 2 Inflammation, this drug is a fully humanized monoclonal antibody that specifically inhibits the overactive signaling of two key proteins, IL-4 and IL-13. IL-4/IL-13 are two inflammatory cytokines that serve as key and central drivers of the underlying inflammation in type 2 inflammatory diseases. Type 2 inflammation is involved in atopic dermatitis,Asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), eosinophilic esophagitis, and other diseases.

Dupixent was launched in late March 2017 and is currently approved for the treatment of three type 2 inflammatory diseases: moderate-to-severe atopic dermatitis (in patients aged ≥6 years), moderate-to-severeAsthma(patients aged ≥12 years), chronic rhinosinusitis with nasal polyps (CRSwNP, adult patients).

In China, in June 2020, Dupixent (dupilumab) was approved by the National Medical Products Administration (NMPA) for the treatment of moderate-to-severe atopic dermatitis (AD) in adults.. Dupixent is the world's first and only targeted biologic approved for the treatment of moderate-to-severe atopic dermatitis in adults, addressing unmet clinical needs in China. It can rapidly, significantly, and sustainably improve the severity of skin lesions and pruritus symptoms in patients with atopic dermatitis. Driven by pharmaceutical regulatory reforms, Dupixent was approved in China two years ahead of schedule, providing Chinese patients with a novel treatment option. (Bioon.com)

Original Source:Japan’s MHLW Approves Pfizer’s CIBINQO (abrocitinib) for Adults and Adolescents with Moderate to Severe Atopic Dermatitis