AbbVie announced that it has submitted applications seeking approvals for upadacitinib (Rinvoq, 15 mg once daily) to the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of adults with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation who have responded inadequately to nonsteroidal anti-inflammatory drugs (NSAIDs). The applications are supported by the phase 3 SELECT-AXIS 2 (Study 2) clinical trial.

In the SELECT-AXIS 2 trial (Study 2), evaluating the efficacy and safety of upadacitinib in adult patients with nr-axSpA, upadacitinib met its primary and most ranked secondary endpoints. Treatment with upadacitinib 15 mg once daily resulted in reductions in signs and symptoms of nr-axSpA, including back pain and inflammation, as well as improvements in physical function and disease activity at week 14 versus placebo.1

"Axial spondyloarthritis is a chronic inflammatory disease affecting the spine and can cause patients, who tend to be younger adults living active lives, to suffer from debilitating pain and significantly decrease their quality of life," said Thomas Hudson, M.D., senior vice president of research and development, chief scientific officer, AbbVie. "AbbVie is committed to working with the FDA and EMA to make upadacitinib available as a treatment option for patients living with this disease."

In addition, AbbVie has requested label enhancements for upadacitinib in the European Union (EU) to include adult patients with active ankylosing spondylitis (AS) who had an inadequate response to biologic disease-modifying anti-rheumatic drugs (bDMARDs), based on the results of the phase 3 SELECT-AXIS 2 clinical trial (Study 1), as well as two-year results of the phase 2/3 SELECT-AXIS 1 clinical trial. AbbVie also provided these data to the FDA in support of the agency's ongoing review of the supplemental New Drug Application (sNDA) for upadacitinib in AS.

The safety data observed in these patients with AS or nr-axSpA were generally consistent with the known safety profile of upadacitinib. No new safety risks were identified.

Axial spondyloarthritis is a chronic inflammatory disease that affects the spine, causing back pain, limited mobility, and structural damage. It consists of two subsets that have been clinically defined as ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA).6 In ankylosing spondylitis, patients have definitive structural damage of the sacroiliac joints visible on x-rays. Non-radiographic axial spondyloarthritis is clinically defined by the absence of definitive x-ray evidence of structural damage to the sacroiliac (SI) joint by plain x-ray.

SELECT-AXIS 1 is a phase 2/3, multicenter, randomized, double-blind, parallel-group, placebo-controlled study designed to evaluate the safety and efficacy of Rinvoq in adult patients with active ankylosing spondylitis who are bDMARD-naïve and had inadequate response to at least two NSAIDs or intolerance to/contraindication for NSAIDs. Period 2 is an open-label extension period to evaluate the long-term safety, tolerability and efficacy of Rinvoq in subjects who completed Period 1. Primary results from SELECT-AXIS 1 were previously announced in November 2019 with 2-year results presented in November 2021. More information on this trial can be found at www.clinicaltrials.gov (NCT03178487).

SELECT-AXIS 2 was conducted as a master study protocol that contains two standalone studies with randomization, data collection, analysis and reporting conducted independently. The phase 3, randomized, placebo-controlled, double-blind studies are evaluating the efficacy and safety of upadacitinib compared with placebo on reduction of signs and symptoms in adult participants with active axSpA including bDMARD-IR AS (Study 1) and nr-axSpA (Study 2).

Discovered and developed by AbbVie scientists, Rinvoq is a selective JAK inhibitor that is being studied in several immune-mediated inflammatory diseases. Based on enzymatic and cellular assays, Rinvoq demonstrated greater inhibitory potency for JAK-1 vs JAK-2, JAK-3, and TYK-2.8 The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness and safety is not currently known. Rinvoq 15 mg is approved by the US Food and Drug Administration (FDA) for adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more TNF blockers and adults with active psoriatic arthritis who have had an inadequate response or intolerance to one or more TNF blockers. Rinvoq 15 mg is approved by the European Commission for adults with moderate to severe active rheumatoid arthritis, adults with active psoriatic arthritis and adults with active ankylosing spondylitis. Rinvoq is approved by the European Commission for adults (15 mg and 30 mg) and adolescents (15 mg) with moderate to severe atopic dermatitis. Phase 3 trials of Rinvoq in rheumatoid arthritis, atopic dermatitis, psoriatic arthritis, axial spondyloarthritis, Crohn's disease, ulcerative colitis, giant cell arteritis and Takayasu arteritis are ongoing.9-16 Use of Rinvoq in AS is not approved by FDA and its safety and efficacy remain under review. Use of Rinvoq in nr-axSpA is not approved and its safety and efficacy have not been evaluated by regulatory authorities.