AbbVie's JAK1 Inhibitor Upadacitinib Receives Priority Review Designation in China for Moderate-to-Severe Atopic Dermatitis

Source | Medical Horizon

According to the latest public notice from the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration, AbbVie’s JAK inhibitor upadacitinib extended-release tablets have been proposed for inclusion in the priority review program for two marketing authorization applications. The proposed indications are for the treatment of adults and adolescents aged 12 years and older with moderate-to-severe atopic dermatitis who are candidates for systemic therapy. As indicated in the CDE notice, the two marketing authorization applications correspond to two different strengths: 30 mg and 15 mg.

Source: CDE Official Website

Upadacitinib, discovered and developed by AbbVie scientists, is a selective and reversible JAK1 inhibitor administered orally once daily. JAK1 plays a crucial role in the pathophysiology of immune-mediated diseases. In August 2019, it received approval from the U.S. FDA for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate. It was also granted Breakthrough Therapy Designation by the FDA in 2018 for adult patients with moderate-to-severe atopic dermatitis who are candidates for systemic therapy.

In June 2020, upadacitinib as monotherapy for the treatment of patients with moderate-to-severe atopic dermatitis met the co-primary endpoints in a pivotal Phase 3 clinical trial named Measure Up 1, significantly reducing skin symptoms. Specifically, patients receiving upadacitinib monotherapy at doses of 15 mg or 30 mg showed significant improvement in skin symptom clearance rates. At Week 16 of treatment, 70% and 80% of patients, respectively, achieved an EASI-75 response (at least 75% improvement in the Eczema Area and Severity Index), compared to 16% in the placebo group. Using the vIGA score, 48% and 62% of patients treated with upadacitinib (15 mg/30 mg) achieved scores of 0 (complete clearance of skin symptoms) or 1 (almost complete clearance of skin symptoms), respectively, compared to 8% in the placebo group.

In July 2020, upadacitinib in combination with topical corticosteroids (TCS) met both co-primary endpoints and all secondary endpoints in the AD Up pivotal Phase 3 clinical trial for the treatment of moderate-to-severe atopic dermatitis. The results demonstrated that, at Week 16, a greater proportion of patients in either upadacitinib plus TCS group achieved significant improvement in skin symptoms compared with the placebo plus TCS group. Among patients treated with upadacitinib (15/30 mg) plus TCS, 65% and 77%, respectively, achieved an EASI 75 response (vs. 26%). Based on the vIGA-AD score, 40% and 59% of patients receiving upadacitinib (15/30 mg) plus TCS, respectively, achieved a score of 0 or 1, compared with 11% in the placebo group.

▲ Primary Efficacy Results of Upadacitinib in This Trial (Image Source: Reference [2])

In December 2020, upadacitinib achieved positive results in the Phase 3 HEADS UP clinical trial for the treatment of atopic dermatitis: After 16 weeks of treatment with upadacitinib (30 mg orally once daily), 71% of adult patients with moderate-to-severe atopic dermatitis achieved an improvement of 75% or greater in the Eczema Area and Severity Index (EASI 75). This result was superior to that of the control group treated with dupilumab (61%), thereby meeting the primary endpoint of the trial. Furthermore, upadacitinib demonstrated superior efficacy compared to the control drug in secondary endpoints such as pruritus and skin clearance.

These Phase 3 clinical studies demonstrated the potential therapeutic efficacy of upadacitinib in patients with atopic dermatitis. Currently, the product is under regulatory review in the United States. Meanwhile, the New Drug Application (NDA) for this product in China was accepted by the Center for Drug Evaluation (CDE) on December 28, 2020.

Atopic dermatitis is a common, chronic, relapsing, inflammatory skin disease characterized by recurrent cycles of itching and scratching, leading to skin pain and fissuring. It is estimated that 25% of adolescents and 10% of adults are affected by this condition at some point in their lives. Between 20% and 46% of adult patients with atopic dermatitis have moderate-to-severe disease. The condition imposes significant physical, psychological, and economic burdens on affected individuals.

References:

[1] Center for Drug Evaluation (CDE), National Medical Products Administration of China. Retrieved Jan 22, 2021, from http://www.cde.org.cn/news.do?method=changePage&pageName=service&frameStr=21#

[2] RINVOQ™ (upadacitinib) Achieved Superiority Versus DUPIXENT® (dupilumab) For Primary and All Ranked Secondary Endpoints in Phase 3b Head-to-Head Study in Adults with Atopic Dermatitis, Retrieved December 10, 2020, from https://www.prnewswire.com/news-releases/rinvoq-upadacitinib-achieved-superiority-versus-dupixent-dupilumab-for-primary-and-all-ranked-secondary-endpoints-in-phase-3b-head-to-head-study-in-adults-with-atopic-dermatitis-301190344.html

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