AbbVie's Upadacitinib (RINVOQ®) Met Primary and Most Ranked Secondary Endpoints in Phase 3 Study for Non-Radiographic Axial Spondyloarthritis

- In Study 2 of the Phase 3 SELECT-AXIS 2 clinical trial, upadacitinib (RINVOQ®) met the primary endpoint of ASAS40 at week 14 versus placebo (45 percent compared to 23 percent)[1]

- The first 12 of 14 ranked secondary endpoints were met[1]

- Safety data were consistent with SELECT-AXIS 1, previous Phase 3 studies in other indications and the known safety profile of upadacitinib, with no new risks identified[1-6]

- Upadacitinib, a selective and reversible JAK inhibitor discovered and developed by AbbVie, is being studied as an oral therapy in several immune-mediated diseases[1,6-14]

NORTH CHICAGO, IL, USA I October 7, 2021 I AbbVie (NYSE: ABBV) today announced positive top-line results from Study 2 of the Phase 3 SELECT-AXIS 2 clinical trial in adults with active non-radiographic axial spondyloarthritis (nr-axSpA), showing upadacitinib (RINVOQ®; 15 mg, once daily) met the primary endpoint of Assessment in SpondyloArthritis International Society (ASAS) 40 response and the majority of ranked secondary endpoints at week 14.1 Significantly more upadacitinib-treated patients achieved ASAS40 response at week 14 compared to placebo (45 percent versus 23 percent; p<0.0001).1 

SELECT-AXIS 2 is the first trial to evaluate the efficacy and safety of upadacitinib in adult patients with non-radiographic axial spondyloarthritis.1 Earlier today, AbbVie announced positive results from Study 1 of SELECT-AXIS 2 in adults with active ankylosing spondylitis (AS) and inadequate response to biologic disease-modifying antirheumatic drugs (bDMARDs).1

"People living with active non-radiographic axial spondyloarthritis suffer from chronic inflammatory back pain and limited physical function that can be very debilitating," said Michael Severino, M.D., vice chairman and president, AbbVie. "These patients need treatments that help them improve their physical function and quality of life. We are encouraged by the potential of upadacitinib in helping to provide relief of these signs and symptoms through meaningful disease control."

Treatment with upadacitinib resulted in reductions in signs and symptoms of non-radiographic axial spondyloarthritis, including back pain and inflammation, as well as improvements in physical function and disease activity at week 14.1 Significantly more patients treated with upadacitinib achieved Ankylosing Spondylitis Disease Activity Score (ASDAS) Low Disease Activity compared to those treated with placebo (42 percent versus 18 percent; p<0.0001).1 A statistically significantly improvement in Magnetic Resonance Imaging (MRI) Spondyloarthritis Research Consortium of Canada (SPARCC) Score (SI Joints) as measured by mean change from baseline was reported in the upadacitinib group versus the placebo group (-2.49 versus 0.57; p<0.0001).1 Patients on upadacitinib experienced significantly greater decrease from baseline in Patient's Assessment of Total Back Pain at week 14 than those on placebo (-2.91 versus -2.00; p=0.0004).1 Additionally, patients treated with upadacitinib 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 (-2.61 versus -1.47; p<0.0001).1

SELECT-AXIS 2 (Study 2) Efficacy Results at Week 14*,1
 

Upadacitinib 15 mg,
once daily

(n=156)

Placebo

(n=157)

 
Percent of Patients achieving ASAS40a 45% 23%  
Percent of Patients achieving ASDAS Low Disease Activityb 42% 18%  
Mean Change from Baseline in Magnetic Resonance Imaging (MRI) SPARCC Score (SI Joints)c -2.49 0.57  
Mean Change from Baseline in Patient's Assessment of Total Back Paind -2.91 -2.00  
Mean Change from Baseline in BASFIe -2.61 -1.47  
*Primary and ranked secondary endpoints at week 14. Not all ranked secondary endpoints are shown. All endpoints shown with the exception of total back pain (p=0.0004) 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 SI-Joints are calculated by adding up the dichotomous outcomes from evaluations of the presence, depth, and intensity of bone marrow edema lesions of the SI-joints.  
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 axial SpA 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 axial SpA patients such as dressing, bending, reaching, turning, and climbing steps. The total scores range from 0 to 10.  

"Non-radiographic axial spondyloarthritis affects a younger adult patient population which can have a significant impact during prime years of those dealing with the disease," said Atul Deodhar, M.D., professor of medicine and medical director of the Rheumatology Clinics for the Division of Arthritis and Rheumatic Diseases at Oregon Health & Science University. "These data show that upadacitinib has the potential to improve non-radiographic axial spondyloarthritis symptoms and help patients take control of their disease."

Safety data were consistent with SELECT-AXIS 1, previous Phase 3 studies in other indications, and the known safety profile of upadacitinib, with no new risks identified.1-6 Through week 14, the most common adverse events (≥ 3 percent of patients) with upadacitinib were headache, COVID-19, nasopharyngitis and nausea.1 The proportion of patients with adverse events leading to discontinuation, serious adverse events and serious infections were 2.6 percent/2.6 percent/1.3 percent for upadacitinib and 1.3 percent/1.3 percent/0.6 percent for placebo, respectively.1 Serious infections included COVID-19 induced pneumonia and pyelonephritis in two patients on upadacitinib and hemorrhagic fever with renal syndrome in one patient on placebo.1 Two patients treated with upadacitinib and one treated with placebo developed non-serious, mild or moderate herpes zoster limited to one dermatome.1 One patient treated with placebo developed a malignancy (basal cell carcinoma).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. Use of upadacitinib in non-radiographic axial spondyloarthritis is not approved, and its safety and efficacy have not been evaluated by regulatory authorities.

About SELECT-AXIS 2 – Study 21,8
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 axial spondyloarthritis (axSpA) including biologic disease-modifying antirheumatic drug inadequate responders (bDMARD-IR) ankylosing spondylitis (Study 1) and non-radiographic axial spondyloarthritis (Study 2). Study 2 enrolled 314 participants who were randomized to receive upadacitinib for 104 weeks or placebo for 52 weeks followed by upadacitinib for 52 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.15 It consists of two subsets that have been clinically defined as ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA).15 In ankylosing spondylitis, patients have definitive structural damage of the sacroiliac joints visible on x-rays.15 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.15 

About upadacitinib (RINVOQ®)
Discovered and developed by AbbVie scientists, RINVOQ is a selective and reversible JAK inhibitor that is being studied in several immune-mediated inflammatory diseases.1-14 In human cellular assays, RINVOQ preferentially inhibits signaling by JAK1 or JAK1/3 with functional selectivity over cytokine receptors that signal via pairs of JAK2.5 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.7-14

EU Indications and Important Safety Information About RINVOQ® (upadacitinib)5

Rheumatoid arthritis
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.

Psoriatic arthritis
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.

Ankylosing spondylitis
RINVOQ is indicated for the treatment of active ankylosing spondylitis in adult patients who have responded inadequately to conventional therapy.

Atopic dermatitis
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.

ee 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.

About AbbVie

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 TwitterFacebookLinkedIn or Instagram.

References:

  1. AbbVie. Data on File: ABVRRTI73013
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. Pipeline – Our Science | AbbVie. AbbVie. 2021. Available at: https://www.abbvie.com/our-science/pipeline.html. Accessed on October 3, 2021.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. Deodhar AA, Understanding Axial Spondyloarthritis: A Primer for Managed Care. Am J Manag Care. 2019;25:S319-S330.

SOURCE: AbbVie

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