FDA Approves AbbVie’s JAK1 Selective Inhibitor Rinvoq (Upadacitinib) for Moderate to Severe Active Rheumatoid Arthritis

On August 16, 2019, VCBeat (WeChat ID: vcbeat) learned from foreign media reports that the biopharmaceutical company AbbVie announced that the U.S. Food and Drug Administration (FDA) had approved its JAK1-selective inhibitor Rinvoq (upadacitinib) for marketing. It is indicated for the treatment of adult patients with moderate to severe active rheumatoid arthritis (active RA) who have had an inadequate response or intolerance to methotrexate. Rinvoq is the first approved JAK1-selective inhibitor and is expected to be launched in the United States by the end of August 2019.

This FDA approval was supported by data from the Phase III SELECT program, which evaluated treatment outcomes in approximately 4,400 patients with rheumatoid arthritis (RA) across five studies. The Phase III SELECT program demonstrated that Rinvoq achieved higher ACR20 response rates and clinical remission rates compared with placebo.

Rinvoq is an oral small-molecule selective JAK inhibitor indicated for the treatment of moderate-to-severe active rheumatoid arthritis and other immune-mediated diseases. Rinvoq is under review by the European Medicines Agency (EMA) as well as regulatory authorities in Canada and Japan for the treatment of adult patients with moderate-to-severe active RA.

Currently, Phase III clinical trials of Rinvoq for the treatment of psoriatic arthritis (PsA), Crohn’s disease (CD), atopic dermatitis (AD), and ulcerative colitis (UC) are ongoing. In addition, Rinvoq is also being evaluated for the treatment of ankylosing spondylitis.

The Janus kinase (JAK) family is a group of tyrosine kinases composed of JAK1, JAK2, JAK3, and TYK2. They play crucial roles in the signaling cascades of various type I and type II cytokine receptors. Given the significant involvement of JAK-mediated cytokine signaling pathways in immune-mediated and neoplastic diseases, the JAK kinase family has emerged as an important therapeutic target for these conditions. JAK1 plays a key role in the pathophysiology of various inflammatory diseases.

Rheumatoid arthritis (RA) is a chronic systemic disease of unknown etiology, characterized primarily by inflammatory synovitis. It is marked by polyarticular, symmetric, and erosive inflammation of the small joints in the hands and feet, often accompanied by extra-articular organ involvement and positive serum rheumatoid factor, which can lead to joint deformity and loss of function. The pathogenesis of RA may be associated with genetic factors, infections, and sex hormones. The main pathological features of RA include hyperplasia of synovial lining cells, extensive infiltration of inflammatory cells in the interstitium, neovascularization, formation of pannus, and destruction of cartilage and bone tissue.

“Although there are currently multiple therapies for treating rheumatoid arthritis, many patients still fail to achieve the goals of entering clinical remission or maintaining low disease activity,” said Dr. Roy M. Fleischmann, Clinical Professor at UT Southwestern Medical Center and principal investigator of the SELECT-COMPARE clinical trial. “Based on this FDA approval, Rinvoq may help patients with rheumatoid arthritis who have not yet achieved these goals reach clinical remission.”

AbbVie is a global research-based biopharmaceutical company that was officially spun off from Abbott Laboratories and listed on the New York Stock Exchange on January 2, 2013. AbbVie is dedicated to developing innovative advanced therapies for some of the world’s most complex and serious diseases. The company’s mission is to leverage its expertise, dedicated workforce, and unique approach to innovation to significantly improve outcomes in four key therapeutic areas: immunology, oncology, virology, and neuroscience. AbbVie employs nearly 29,000 people worldwide and markets its products in more than 170 countries and regions.

(Compiled by Cheng Tao)