AbbVie's RINVOQ® (upadacitinib) Met Primary and All Ranked Secondary Endpoints in Phase 3 Study in Ankylosing Spondylitis
- Category: Small Molecules
- Published on Friday, 08 October 2021 18:34
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- In Study 1 of the Phase 3 SELECT-AXIS 2 clinical trial, RINVOQ® (upadacitinib) met the primary endpoint of ASAS40 at week 14 versus placebo (45 percent compared to 18 percent) in patients with ankylosing spondylitis and inadequate response to bDMARD therapy
- All ranked secondary endpoints were met
- Safety data were consistent with SELECT-AXIS 1, previous Phase 3 studies in other indications and the known safety profile of RINVOQ, with no new risks identified[1-6]
- RINVOQ, a selective and reversible JAK inhibitor discovered and developed by AbbVie, is an oral therapy approved in the EU for the treatment of active ankylosing spondylitis
NORTH CHICAGO, IL, USA I October 7, 2021 I AbbVie (NYSE: ABBV) today announced positive top-line results from the first of two studies of the Phase 3 SELECT-AXIS 2 clinical trial evaluating the efficacy and safety of RINVOQ® (upadacitinib; 15 mg, once daily) in patients with active ankylosing spondylitis (AS) who had an inadequate response to biologic DMARD therapy. In this study, RINVOQ met its primary endpoint of Assessment in SpondyloArthritis International Society (ASAS) 40 response and all ranked secondary endpoints at week 14.1 Significantly more RINVOQ-treated patients achieved ASAS40 response at week 14 compared to placebo (45 percent versus 18 percent; p<0.0001).1
The results of SELECT-AXIS 1, a Phase 2/3 study in adult patients with ankylosing spondylitis who were naïve to bDMARDs and had an inadequate response or intolerance to nonsteroidal anti-inflammatory drugs (NSAIDs), were used to support the European Commission approval of RINVOQ for the treatment of active ankylosing spondylitis in January 2021.6
AbbVie will also announce the positive results of the second study of SELECT-AXIS 2 in adults with non-radiographic axial spondyloarthritis (nr-axSpA) later today.1
"Ankylosing spondylitis is a debilitating disease that can cause severe pain, stiffness, restricted mobility and lasting structural damage impacting patients' everyday life," said Michael Severino, M.D., vice chairman and president, AbbVie. "AbbVie is committed to improving standards of care for patients with rheumatic diseases. We are encouraged by these results that show RINVOQ was able to provide significant improvements in signs and symptoms, as well as other measures of disease activity, for patients living with ankylosing spondylitis who have already failed treatment with a biologic."
Treatment with RINVOQ resulted in statistically significant reductions in signs and symptoms of AS, including back pain and inflammation, as well as improvements in physical function and disease activity at week 14.1 Significantly more patients treated with RINVOQ achieved Ankylosing Spondylitis Disease Activity Score (ASDAS) Low Disease Activity compared to those treated with placebo (44 percent versus 10 percent).1 A statistically significantly greater improvement in Magnetic Resonance Imaging (MRI) Spondyloarthritis Research Consortium of Canada (SPARCC) Score (Spine) as measured by mean change from baseline was reported in the RINVOQ group versus the placebo group (-3.95 versus -0.04).1 Patients on RINVOQ experienced a significantly greater mean decrease from baseline in Patient's Assessment of Total Back Pain at week 14 than those on placebo (-3.00 versus -1.47).1 Additionally, patients treated with RINVOQ experienced significantly greater improvement in physical function as assessed by mean change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) compared to patients on placebo (-2.26 versus -1.09).1 All ranked secondary endpoints achieved p-values of <0.0001 versus placebo.1
|SELECT-AXIS 2 (Study 1) Efficacy Results at Week 14*,1|
RINVOQ 15 mg, once daily
|Percent of Patients achieving ASAS40a||45%||18%|
|Percent of Patients achieving ASDAS Low Disease Activityb||44%||10%|
|Mean Change from Baseline in Magnetic Resonance Imaging (MRI) SPARCC Score (Spine)c||-3.95||-0.04|
|Mean Change from Baseline in Patient's Assessment of Total Back Paind||-3.00||-1.47|
|Mean Change from Baseline in BASFIe||-2.26||-1.09|
|*Primary and ranked secondary endpoints at Week 14. Not all ranked secondary endpoints are shown. All primary and ranked secondary endpoints achieved p-values of <0.0001 versus placebo.|
|a ASAS 40 is defined as a ≥40 percent improvement and an absolute improvement of ≥2 units (on a scale of 0 to 10) from Baseline in at least 3 of the 4 domains (patient's global assessment, back pain, function, and inflammation) with no worsening at all in the remaining domain.|
|b ASDAS Low Disease Activity is defined as ASDAS score <2.1.|
|c SPARCC scores for spine are calculated by adding up the dichotomous outcomes from evaluations of the presence, depth, and intensity of bone marrow edema lesions of the spine.|
|d Back Pain is measured using 0 - 10 numerical rating scale (NRS) for Total Back Pain (0 = no pain and 10 = severe pain).|
|e BASFI is a validated patient-reported outcome (PRO) instrument for use in the AS patient population. It consists of 10 items measured on a 0 to 10 NRS, which assesses the ability to perform activities known to be problematic to AS patients such as dressing, bending, reaching, turning, and climbing steps. The total scores range from 0 to 10.|
"Ankylosing spondylitis can have a profound impact on patients and severely limit their ability to perform daily tasks," said Filip Van den Bosch, SELECT-AXIS 2 investigator and professor in the Department of Rheumatology at the University Hospital of Ghent University. "There is a great need for effective treatment options for patients with an inadequate response to biologic DMARDs. These encouraging study results further demonstrate RINVOQ has the potential to impact the existing treatment paradigm for patients with ankylosing spondylitis."
Safety data were consistent with SELECT-AXIS 1, previous Phase 3 studies in other indications, and the known safety profile of RINVOQ, with no new risks identified.1-6 Through week 14, the most common adverse events (≥3 percent of patients) for RINVOQ were COVID-19 and headache.1 The proportion of patients with adverse events leading to discontinuation, serious adverse events and serious infections were 0 percent/2.8 percent/2.4 percent for RINVOQ and 1.4 percent/0.5 percent/0 percent for placebo, respectively.1 Serious infections included four events of COVID-19 and one of uveitis with RINVOQ; two patients on RINVOQ developed non-serious, mild or moderate herpes zoster limited to one dermatome.1 One patient treated with placebo developed a malignancy (tonsil cancer).1 No adjudicated major adverse cardiovascular events, venous thromboembolic events or deaths were reported in either group through week 14.1
Full results from the SELECT-AXIS-2 trial will be presented at a future medical meeting and submitted for publication in a peer-reviewed journal.
About SELECT-AXIS 2 – Study 11,7
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 RINVOQ 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). Study 1 enrolled 420 who were randomized to receive RINVOQ for 104 weeks or placebo for 14 weeks followed by RINVOQ for 90 weeks. More information on this trial can be found at www.clinicaltrials.gov (NCT04169373).
About Axial Spondyloarthritis (axSpA)
Axial spondyloarthritis is a chronic inflammatory disease that affects the spine, causing back pain, limited mobility, and structural damage.8 It consists of two subsets that have been clinically defined as ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA).8 In ankylosing spondylitis, patients have definitive structural damage of the sacroiliac joints visible on x-rays.8 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.8
About RINVOQ® (upadacitinib)
Discovered and developed by AbbVie scientists, RINVOQ is a selective and reversible JAK inhibitor that is being studied in several immune-mediated inflammatory diseases.1,6,7,9-15 In human cellular assays, RINVOQ preferentially inhibits signaling by JAK1 or JAK1/3 with functional selectivity over cytokine receptors that signal via pairs of JAK2.6 RINVOQ is approved by the European Commission for adults (15 mg and 30 mg) and adolescents (15 mg) with moderate to severe atopic dermatitis. 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 15 mg is also approved by the U.S. Food and Drug Administration (FDA) for adults with moderately to severely active rheumatoid arthritis. 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.9-15 Use of RINVOQ in non-radiographic axial spondyloarthritis is not approved and its safety and efficacy have not been established by regulatory authorities.
EU Indications and Important Safety Information About RINVOQ® (upadacitinib)6
RINVOQ is indicated for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs). RINVOQ may be used as monotherapy or in combination with methotrexate.
RINVOQ is indicated for the treatment of active psoriatic arthritis 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 indicated for the treatment of active ankylosing spondylitis in adult patients who have responded inadequately to conventional therapy.
RINVOQ is indicated for the treatment of moderate to severe atopic dermatitis in adults and adolescents 12 years and older who are candidates for systemic therapy.
RINVOQ is contraindicated in patients hypersensitive to the active substance or to any of the excipients, in patients with active tuberculosis (TB) or active serious infections, in patients with severe hepatic impairment, and during pregnancy.
See RINVOQ full summary of product characteristics (SmPC) at www.ema.europa.eu. Globally, prescribing information varies; refer to the individual country product label for complete information.
AbbVie's mission is to discover and deliver innovative medicines that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas: immunology, oncology, neuroscience, eye care, virology, women's health and gastroenterology, in addition to products and services across its Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook, LinkedIn or Instagram.
- AbbVie. Data on File: ABVRRTI73012
- Cohen S., et al. Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELECT phase III clinical programme. Ann Rheum Dis. 2020 Oct 28;80(3):304-11.
- Mease, P.J., et al. Upadacitinib in Patients with Psoriatic Arthritis and Inadequate Response to Biologics: 56-Week Data from the Randomized Controlled Phase 3 SELECT-PsA 2 Study. Rheumatol Ther. 2021 Apr 28. doi: 10.1007/s40744-021-00305-z. Online ahead of print.
- Guttman-Yassky E., et al. Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from two replicate, double-blind, randomized controlled phase 3 studies. Lancet. doi:10.1016/s0140-6736(21)00588-2.
- Van der Heijde, D., et al. Efficacy and safety of upadacitinib in patients with active ankylosing spondylitis (SELECT-AXIS 1): a multicentre, randomised, double-blind, placebo-controlled, phase 2/3 trial. Lancet. 2019 Dec 7;394(10214):2108-2117. doi: 10.1016/S0140-6736(19)32534-6. Epub 2019 Nov 12.
- RINVOQ [Summary of Product Characteristics]. AbbVie Deutschland GmbH & Co. KG; September 2021. Available at: https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf.
- A Study to Evaluate Efficacy and Safety of Upadacitinib in Adult Participants With Axial Spondyloarthritis (SELECT AXIS 2). ClinicalTrials.gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT04169373. Accessed on October 3, 2021.
- Deodhar AA, Understanding Axial Spondyloarthritis: A Primer for Managed Care. Am J Manag Care. 2019;25:S319-S330.
- Pipeline – Our Science | AbbVie. AbbVie. 2021. Available at: https://www.abbvie.com/our-science/pipeline.html. Accessed on October 3, 2021.
- A Study to Evaluate the Safety and Efficacy of ABT-494 for Induction and Maintenance Therapy in Subjects With Moderately to Severely Active Ulcerative Colitis. ClinicalTrials.gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT02819635. Accessed on October 3, 2021.
- A Study to Compare Safety and Efficacy of Upadacitinib to Dupilumab in Adult Participants With Moderate to Severe Atopic Dermatitis (Heads Up). ClinicalTrials.gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT03738397. Accessed on October 3, 2021.
- A Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Participants With Moderately to Severely Active Ulcerative Colitis (U-ACCOMPLISH). ClinicalTrials.gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT03653026. Accessed on October 3, 2021.
- A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of ABT-494 for the Induction of Symptomatic and Endoscopic Remission in Subjects With Moderately to Severely Active Crohn's Disease Who Have Inadequately Responded to or Are Intolerant to Immunomodulators or Anti-TNF Therapy. ClinicalTrials.gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT02365649. Accessed on October 3, 2021.
- A Study to Evaluate the Safety and Efficacy of Upadacitinib in Participants With Giant Cell Arteritis (SELECT-GCA). ClinicalTrials.gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT03725202. Accessed on October 3, 2021.
- A Study to Evaluate the Efficacy and Safety of Upadacitinib in Subjects With Takayasu Arteritis (TAK) (SELECT-TAK). ClinicalTrials.gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT04161898. Accessed on October 3, 2021.