Pfizer's Oral JAK1 Inhibitor Cibinqo (abrocitinib) Receives First Global Approval in the UK for Moderate-to-Severe Atopic Dermatitis, Demonstrating Superior Efficacy Over Dupixent

September 9, 2021 News /BioonBIOON/ --Pfizer(Pfizer) recently announced, UK medicines andDietary SupplementsAdministration(MHRA) has approved Cibinqo (abrocitinib), a once-daily oral JAK1 inhibitor, for the treatment of moderate-to-severe atopic dermatitis (AD) in adolescent and adult patients aged 12 years and older who are candidates for systemic therapy.。In the UK, the recommended dose of Cibinqo is 100 mg or 200 mg。

It is worth mentioning that,This is the first global regulatory approval for abrocitinib.。Currently, marketing authorization applications for abrocitinib have been submitted to multiple countries and regions worldwide for review, including the United States, Australia, Japan, 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 Dupixent (Chinese trade name: Dabituo; generic name: dupilumab), abrocitinib demonstrated statistically superior efficacy across all evaluated endpoints.

In the UK, the MHRA granted abrocitinib the Promising Innovative Medicine (PIM) designation last year. In January this year, the MHRA issued a positive scientific opinion on abrocitinib, supporting its provision to patients with severe atopic dermatitis through the Early Access to Medicines Scheme (EAMS). This specifically applies to patients who require systemic therapy and have demonstrated an inadequate response to, or lost response to, approved systemic therapies, or who are unsuitable for or intolerant of marketed systemic therapies. This enables healthcare professionals to prescribe the treatment based on the clinical factors of patients with significant unmet medical needs prior to regulatory approval.

The regulatory approval of Cibinqo is based on data from the robust Phase 3 JADE global clinical development program. In this program, compared with placebo, abrocitinib demonstrated statistical superiority in skin clearance and the extent and severity of disease, with rapid improvement in pruritus (as early as Week 2). In AD clinical studies, a total of 3,128 patients were treated with Cibinqo, with 994 patients treated for at least 48 weeks. Data from 5 placebo-controlled studies were pooled (703 patients received 100 mg once daily, 684 patients received 200 mg once daily, and 438 patients received placebo) to evaluate the safety of Cibinqo compared with placebo for up to 16 weeks.

In placebo-controlled studies, the most common adverse reactions (incidence ≥2%) in patients treated with Cibinqo 200 mg included: nausea (15.1%), headache (7.9%), acne (4.8%), herpes simplex (4.2%), increased blood creatine phosphokinase (3.8%), vomiting (3.5%), dizziness (3.4%), and abdominal pain (2.2%). The most common seriousAdverse Reactionswas infection (0.3%).

Angela Hwang, President of the Pfizer Biopharmaceuticals Group, stated: “We are very pleased that the MHRA has approved abrocitinib for the treatment of patients with moderate-to-severe atopic dermatitis. This represents a significant development for patients in the UK living with moderate-to-severe disease who require innovative treatment options. Following approval, our immediate priority is to work with NICE and the Scottish Medicines Consortium (SMC) to ensure routine access to the medicine, so that patients with moderate-to-severe AD can benefit from this important therapy.”

Chemical 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, lichenification/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 pediatric skin diseases, affecting up to 10% of adults and up to 20% of children worldwide. Many patients with moderate-to-severe disease remain poorly controlled and require additional treatment options to alleviate the symptoms that matter most to them.

The 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 Authorisation 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 trial was conducted in adult patients with moderate-to-severe AD receiving background topical therapy and directly compared abrocitinib (200 mg, orally, once daily) with Dupixent (300 mg, subcutaneously, 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 loading dose; all patients received 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 a ≥4-point improvement from baseline in the Peak Pruritus Numerical Rating Scale (PP-NRS, score 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 (score 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 and key secondary efficacy endpoints: compared with Dupixent, abrocitinib demonstrated statistical 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 for the treatment of moderate-to-severe atopic dermatitis (AD), providing rapid, significant, and sustained improvement in skin lesion severity and pruritus in patients with AD.

Dupixent targets the key drivers of type 2 inflammation. This drug is a fully human monoclonal antibody that specifically inhibits the overactive signaling of two key proteins, IL-4 and IL-13. IL-4 and IL-13 are two inflammatory cytokines that serve as critical and central drivers of the underlying inflammation in type 2 inflammatory diseases. Type 2 inflammation in atopic dermatitis,`Asthma`, plays an important role in diseases such as chronic rhinosinusitis with nasal polyps (CRSwNP) and eosinophilic esophagitis.

Dupixent was launched in late March 2017 and is currently approved for the treatment of three diseases caused by type 2 inflammation: 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 June 2020, Dupixent (Dabita) was approved by China's 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 approved targeted biologic for the treatment of moderate-to-severe atopic dermatitis in adults, addressing an unmet clinical need in China. It can rapidly, significantly, and sustainably improve skin lesion severity and pruritus in patients with atopic dermatitis. Facilitated by drug regulatory reforms, Dupixent was approved in China two years ahead of schedule, providing a novel treatment option for Chinese patients. (Bioon.com)

Original Source:UK’s MHRA Grants Marketing Authorisation for Pfizer’s CIBINQO® (abrocitinib) for Adults and Adolescents With Moderate to Severe Atopic Dermatitis