AbbVie announced that the EC has approved Rinvoq (upadacitinib, 15 mg), an oral, once daily selective and reversible JAK inhibitor for the treatment of active psoriatic arthritis (PsA) in adult patients who have responded inadequately to, or who are intolerant to one or more DMARDs. Rinvoq may be used as monotherapy or in combination with methotrexate. Rinvoq is also indicated for the treatment of active ankylosing spondylitis (AS) in adult patients who have responded inadequately to conventional therapy. The EC approval is supported by data from the three pivotal clinical trials SELECT-PsA 1, SELECT-PsA 2 and SELECT-AXIS 1, demonstrating Rinvoq’s efficacy across multiple measures of disease activity.
“Psoriatic arthritis and ankylosing spondylitis have a significant impact on many aspects of life for those living with these conditions,” said Tom Hudson, MD, senior vice president, R&D, chief scientific officer, AbbVie. “We are proud to provide Rinvoq as a new treatment option to patients with PsA and a first-in-class treatment option to those living with AS. These approvals are important milestones in our commitment to develop a portfolio of solutions that advance standards of care for people living with rheumatic diseases.”
“Psoriatic arthritis and ankylosing spondylitis are multi-faceted diseases that can cause severe pain, restricted mobility, and lasting structural damage,” said Iain McInnes, Professor of Medicine and Versus Arthritis Professor of Rheumatology at University of Glasgow, UK. “In clinical trials, Rinvoq demonstrated improvements across multiple manifestations of these diseases. The approvals of Rinvoq for the treatment of PsA and AS offer physicians in the European Union an important new therapeutic option and for their patients a new opportunity to find meaningful relief from their debilitating symptoms.”
In both phase 3 clinical trials, SELECT-PsA 1 and SELECT-PsA 2, Rinvoq met the primary endpoint of ACR20 response at week 12 versus placebo in adults with active PsA who had an inadequate response to non-biologic disease-modifying antirheumatic drugs (DMARDs) or biologic DMARDs, respectively. Rinvoq also achieved non-inferiority to adalimumab (40mg, every other week) for ACR 20 at week 12. Patients receiving Rinvoq experienced greater improvements in physical function (as measured by HAQ-DI at week 12) and skin symptoms (as measured by PASI-75 at week 16), and a greater proportion achieved minimal disease activity (MDA) compared to those receiving placebo at week 24.
Rinvoq also met the primary endpoint of Assessment of Spondyloarthritis International Society (ASAS) 40 response at week 14 versus placebo in SELECT-AXIS 1, a phase 2/3 study in adult patients with AS who were naïve to biologic DMARDs and had an inadequate response or intolerance to nonsteroidal anti-inflammatory drugs (NSAIDs). Additionally, Rinvoq achieved statistical significance across several multiplicity adjusted key secondary endpoints versus placebo, including ASAS partial remission (PR) at week 14 and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 at week 14.
Safety results from SELECT-PsA 1, SELECT-PsA 2 and SELECT-AXIS 1 have been previously reported and were consistent with those observed in rheumatoid arthritis, with no new significant safety risks identified. Integrated safety data for SELECT-PsA 1 and SELECT-PsA 2 through week 24 show that Serious Adverse Events occurred in 4.1% of the patients in the Rinvoq 15 mg group compared to 3.7% in the adalimumab group and 2.7% in the placebo group. The most common adverse events reported with Rinvoq 15 mg were upper respiratory tract infection, nasopharyngitis, increased blood CPK, ALT increase and AST increase. In SELECT-AXIS 1, Serious Adverse Events were reported in 1% of the patients in both the Rinvoq 15 mg and placebo group. The most common adverse events reported with Rinvoq 15 mg included blood CPK increase, diarrhea, nasopharyngitis, headache and nausea.
The Marketing Authorization means that Rinvoq is approved in all member states of the European Union, as well as Iceland, Liechtenstein and Norway. Rinvoq is already approved for the treatment of adults with moderate to severe active rheumatoid arthritis.
SELECT-PsA 1 is a phase 3, multicenter, randomized, double-blind, parallel-group, active and placebo-controlled study designed to evaluate the safety and efficacy of Rinvoq compared to placebo and adalimumab in adult patients with active psoriatic arthritis who have a history of inadequate response to at least one non-biologic DMARD. Patients were randomized to Rinvoq 15 mg, Rinvoq 30 mg, adalimumab 40 mg EOW or placebo at baseline. At week 24, placebo patients were switched to either Rinvoq 15 mg or Rinvoq 30 mg.
The primary endpoint was the percentage of subjects receiving Rinvoq 15 mg or Rinvoq 30 mg who achieved an ACR20 response at 12 weeks of treatment versus placebo. Key secondary endpoints included change from baseline in HAQ-DI, proportion of patients achieving ACR50 and ACR70 at week 12, proportion of patients achieving PASI 75 at week 16 and proportion of patients achieving minimal disease activity (MDA) at week 24. These are not all of the secondary endpoints. The trial is ongoing and the long-term extension will provide data on the long-term safety, tolerability and efficacy of Rinvoq in patients who have completed the placebo-controlled period.
SELECT-PsA 2 is a phase 3, multicenter, randomized, double-blind, parallel-group, placebo-controlled study designed to evaluate the safety and efficacy of Rinvoq in adult patients with active psoriatic arthritis who have a history of inadequate response to at least one biologic (bDMARD). Patients were randomized to Rinvoq 15 mg, Rinvoq 30 mg or placebo followed by either RINVOQ 15 mg or Rinvoq 30 mg at week 24.
The primary endpoint was the percentage of subjects achieving an ACR20 response after 12 weeks of treatment. Key secondary endpoints included change from baseline in HAQ-DI, proportion of patients achieving ACR50 and ACR70 at week 12, proportion of patients achieving PASI 75 at week 16, as well as proportion of patients achieving MDA at week 24. These are not all of the secondary endpoints. The trial is ongoing and the long-term extension will provide data on the long-term safety, tolerability and efficacy of Rinvoq in patients who have completed the placebo-controlled period.
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.
Key ranked secondary endpoints included proportion of subjects achieving Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 and ASAS partial remission (PR) at week 14, as well as change from baseline in Ankylosing Spondylitis Disease Activity Scores (ASDAS), MRI Spondyloarthritis Research Consortium of Canada (SPARCC) score (spine) and Bath Ankylosing Spondylitis Functional Index (BASFI) at week 14. 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.
Discovered and developed by AbbVie scientists, Rinvoq is a JAK inhibitor that is being studied in several immune-mediated inflammatory diseases.3,17-27 In August 2019, Rinvoq received US FDA approval for adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate. In December 2019, Rinvoq was approved by the European Commission for the treatment of adult patients with moderate to severe active rheumatoid arthritis who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs. The approved dose for Rinvoq in rheumatoid arthritis is 15 mg. 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.
