The world's first Upadatinib extended-release tablets approved by FDA for non-radiological axial spondyloarthritis

On October 21, AbbVie announced that the FDA has approved upadatinib extended-release tablets (RINVOQ, 15 mg, once daily) for the treatment of adults with active nonradiographic axial spondyloarthritis (nr-axSpA), these patients had objective signs of inflammation and had an inadequate response to tumor necrosis factor (TNF) blockers. Upatinib is the first and only JAK inhibitor approved for the treatment of nr-axSpA patients, and the first JAK inhibitor approved for both nr-axSpA and ankylosing spondylitis.

Axial spondyloarthritis (axSpA) is a chronic, progressive, and disabling inflammatory disease that affects the spine, causing back pain, limited mobility, and structural damage after attacks. axSpA is mainly divided into radiological axial spondyloarthritis (r-axSpA) and non-radiological axial spondyloarthritis (nr-axSpA), of which r-axSpA is also known as ankylosing spondylitis (AS). About 5% of nr-axSpA patients progressed to AS after 5 years, and 19% developed AS after 10 years.

Upatinib is a JAK1 inhibitor independently developed by AbbVie and was first approved for marketing in August 2019 for moderate to severe rheumatoid arthritis. Since then, upatinib has become the first JAK1 inhibitor approved for marketing.

As of today, the global approved indications for Upatinib extended-release tablets include: (1) moderately to severe active rheumatoid arthritis; (2) active psoriatic arthritis; (3) moderate to severe atopic (4) active ankylosing spondylitis; (5) moderate to severe ulcerative colitis; (6) active non-radiological axial spondyloarthritis.

In addition, AbbVie submitted a marketing application for upatinib extended-release tablets to the FDA and EMA in July this year for the treatment of Crohn's disease, and its phase III trials in giant cell arteritis and Takayasu arteritis are ongoing middle.

The FDA approval is based on positive results from the Phase III SELECT-AXIS 2 study. The study is a multicenter, randomized, double-blind, placebo-controlled Phase III clinical trial involving a total of 314 patients to evaluate the efficacy, safety and tolerability of upatinib in patients with nr-axSpA.

The data showed that at week 14 of treatment, a significantly higher proportion of patients in the upatinib group achieved an International Spondyloarthritis Society 40 Response (ASAS40, a measure of a patient's physical activity) than in the placebo group (45% vs 23%; p<0.0001), and ASAS40 was observed within 2 weeks. In addition, the trial met multiple secondary endpoints: significant improvements in back pain, signs of inflammation, physical function, and disease activity. At week 14, adverse event rates were similar in the upatinib and placebo groups (48% vs 46%).