AbbVie Announces Positive Phase 3 Results for Upadacitinib in Rheumatoid Arthritis with Superior Long-Term Efficacy Over Standard Therapies

Today, AbbVie announced at the European Alliance of Associations for Rheumatology (EULAR) Annual Congress held in Madrid, Spain, that its JAK1 inhibitor upadacitinib demonstrated superior long-term efficacy compared with conventional therapies in a Phase 3 trial for the treatment of moderate-to-severe rheumatoid arthritis.

Rheumatoid arthritis, a chronic and debilitating disease, affects approximately 23.7 million people worldwide. The potential cause of this disease is the body’s immune system attacking joint tissues, thereby triggering the condition. Methotrexate is a commonly used first-line therapy for rheumatoid arthritis; however, many patients do not respond to it or cannot tolerate it. Effective early intervention in rheumatoid arthritis is crucial for controlling disease progression and preventing permanent joint damage. Despite the availability of various treatment options, many patients with rheumatoid arthritis still fail to achieve the goals of clinical remission or low disease activity (LDA).

Upadacitinib, developed by AbbVie, is an investigational oral selective inhibitor of Janus kinase 1 (JAK1). JAKs belong to the cytoplasmic tyrosine kinase family and function to mediate signaling pathways of cytokines such as interferons. There are four JAK subtypes, with overlapping binding partners among them. Inhibitors of this kinase family have demonstrated efficacy in treating certain inflammatory and autoimmune diseases, such as rheumatoid arthritis and Crohn’s disease.

Upadacitinib is a second-generation JAK inhibitor with high selectivity for the JAK1 subtype. Upadacitinib is undergoing clinical studies for multiple indications, including rheumatoid arthritis, psoriatic arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis, and atopic dermatitis. The New Drug Application (NDA) for upadacitinib in the treatment of rheumatoid arthritis was accepted by the FDA this February and has been granted Priority Review status.

▲Molecular structure of upadacitinib and schematic diagram of its interaction with JAK1 (Image source: Reference [5])

The SELECT-EARLY trial aimed to evaluate the efficacy and safety of upadacitinib monotherapy versus methotrexate in adult patients with moderate-to-severe rheumatoid arthritis who were naïve to methotrexate. The SELECT-COMPARE trial aimed to evaluate the efficacy and safety of upadacitinib versus placebo or conventional therapy (adalimumab) in adult patients with moderate-to-severe rheumatoid arthritis who were receiving background methotrexate therapy.

The results of two trials showed that after 48 weeks of continuous treatment, the proportion of patients achieving clinical remission in the upadacitinib-treated group was significantly higher than that in the active control group. Furthermore, upadacitinib demonstrated a favorable safety profile.

Dr. Ronald van Vollenhoven, Director of the Amsterdam Rheumatology and Immunology Center, stated, “These trial results continue to support the sustained and consistent efficacy of upadacitinib in moderate-to-severe rheumatoid arthritis. Although clinical remission is the primary treatment target recommended by both the American and European rheumatology associations, unfortunately, most patients fail to achieve this goal with current therapeutic options.”

Dr. Marek Honczarenko, Vice President of Immunology Development at AbbVie, stated, “Over the past decade, our understanding of how to treat and manage rheumatoid arthritis has deepened, particularly in achieving symptom remission. As data from the SELECT trials continue to emerge, AbbVie looks forward to gaining further insights into the efficacy and safety of JAK inhibition for treating moderate to severe active rheumatoid arthritis across diverse patient populations.”

References:

[1] New Long-Term Data from Upadacitinib Phase 3 Studies in Rheumatoid Arthritis Including Results on Clinical Remission at 48 Weeks Presented at EULAR. Retrieved June 13, 2019, from https://news.abbvie.com/news/press-releases/new-long-term-data-from-upadacitinib-phase-3-studies-in-rheumatoid-arthritis-including-results-on-clinical-remission-at-48-weeks-presented-at-eular.htm

[2] Flash Update | New Arthritis Drug Surpasses Humira in Efficacy, Reaches Phase 3 Endpoint. Retrieved June 13, 2019, from https://mp.weixin.qq.com/s/ojdXWuuVXe-hnL1jQN9FUQ

[3] Express | AbbVie’s Blockbuster New Drug Achieves Positive Phase 3 Progress in Treating Arthritis. Retrieved June 13, 2019, from https://mp.weixin.qq.com/s/ZV2rL-pxegsJiu-CP5j5Yw

[4] These 7 New Drugs Launched This Year Are Poised to Become Blockbusters Within 5 Years. Retrieved June 13, 2019, from https://mp.weixin.qq.com/s/45CK1xeed2psAz8xNETFiw

[5] In vitro and in vivo characterization of the JAK1 selectivity of upadacitinib (ABT-494). Retrieved June 13, 2019, from https://bmcrheumatol.biomedcentral.com/articles/10.1186/s41927-018-0031-x

Original Title: Flash Update | Long-term Efficacy Superior to Common Therapies, AbbVie’s New Rheumatoid Arthritis Drug Shows Positive Phase 3 Results

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