AbbVie Presents Data Showing RINVOQ™ (upadacitinib) Meets Primary and Key Secondary Endpoints in Phase 3 Head-to-Head Study Versus ORENCIA (abatacept) in Rheumatoid Arthritis Patients

– In SELECT-CHOICE, RINVOQ™ (upadacitinib, 15 mg, once daily) met both the primary (non-inferiority) and key secondary (superiority) endpoints compared to ORENCIA® (abatacept) on change from baseline in DAS28-CRP at week 12 in patients with rheumatoid arthritis and inadequate response to biologic DMARDs[1]

– The safety profile of RINVOQ was consistent with previously reported results in rheumatoid arthritis, with no new risks identified[1,2]

– SELECT-CHOICE is the sixth and final Phase 3 study from the robust SELECT rheumatoid arthritis clinical trial program[1,2]

– Results presented at the Annual European E-Congress of Rheumatology

NORTH CHICAGO, IL, USA I June 6, 2020 I AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced new Phase 3 data from the SELECT-CHOICE clinical trial, showing that RINVOQ™ (upadacitinib, 15 mg, once daily) met the primary endpoint of non-inferiority versus ORENCIA^® (abatacept) on change from baseline in Disease Activity Score 28 C-Reactive Protein (DAS28-CRP) at week 12.¹ In addition, RINVOQ met the key secondary endpoints of superiority versus ORENCIA on change from baseline in DAS28-CRP at week 12 and proportion of patients achieving clinical remission at week 12 as measured by DAS28-CRP<2.6.¹ The study evaluated RINVOQ in adult patients with moderate to severe active rheumatoid arthritis and prior inadequate response or intolerance to biologic disease-modifying anti-rheumatic drugs (DMARDs). Full results were presented today at the 2020 Annual European E-Congress of Rheumatology (EULAR).

SELECT-CHOICE is the sixth and final Phase 3 study from the robust SELECT rheumatoid arthritis clinical trial program.^1,2 RINVOQ, a selective and reversible JAK inhibitor discovered and developed by AbbVie, is approved 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 DMARDs.²

“Despite tremendous progress in the treatment of rheumatoid arthritis, about 70 percent of patients are still not achieving clinical remission with established therapies,” said Michael Severino, M.D., vice chairman and president, AbbVie. “We are pleased with the results as they add to our growing body of evidence that RINVOQ may offer more adult patients with rheumatoid arthritis a better chance at achieving clinical remission, including those who have already failed a prior biologic.”

“These data show that upadacitinib was superior to abatacept with regard to the proportion of patients achieving remission,” said Professor Andrea Rubbert-Roth, M.D., deputy director, Division of Rheumatology, Cantonal Hospital St. Gallen, Switzerland. “SELECT-CHOICE represents the first head-to-head study in rheumatoid arthritis patients who have failed biologic DMARDs and compares upadacitinib to a different biologic DMARD. Studies like this are important for daily decision-making in practice.”

In this study, RINVOQ met both the primary (non-inferiority) and secondary (superiority) endpoints, with a change from baseline in DAS28-CRP at week 12 of -2.52 compared to -2.00 in patients treated with ORENCIA.¹ In addition, 30 percent of patients receiving RINVOQ achieved clinical remission at week 12 (DAS28-CRP<2.6) compared to 13 percent of patients receiving ORENCIA (p<0.001).¹

ACR20/50/70 responses were also higher in the RINVOQ group compared to the ORENCIA group (76/46/22 percent versus 66/34/14 percent, respectively, nominal p<0.05) at week 12.¹ Improvements in disease activity and remission rates were maintained through 24 weeks.¹

SELECT-CHOICE Efficacy Results1,†
	Week 12		Week 24
	RINVOQ 15 mg (n=303)	ORENCIA (n=309)	RINVOQ 15 mg (n=303)	ORENCIA (n=309)
Δ DAS28-CRP, (Δ 95% CI)	-2.52***### (-2.66, -2.37)	-2.00 (-2.14, -1.85)	-2.91*** (-3.06,-2.76)	-2.57 (-2.72,-2.42)
Clinical Remission (DAS28-CRP)a	30%***###	13.3%	45.9%***	31.4%
ACR20b,‡	75.6%*	66.3%	78.9%	73.8%
ACR50b,‡	46.2%**	34.3%	59.4%*	49.5%
ACR70b,‡	21.5%**	13.6%	37.3%**	26.5%
† Primary endpoint was non-inferiority versus ORENCIA as measured by change from baseline in DAS28-CRP at week 12 against a margin of 0.6. Ranked secondary endpoints were superiority as measured by change from baseline in DAS28-CRP versus ORENCIA and proportion of patients achieving clinical remission, as measured by DAS28-CRP<2.6 at week 12. Not all additional endpoints shown.
*, **, *** p≤0.05, 0.01 and 0.001, respectively for RINVOQ vs. ORENCIA.
### p<0.001 for RINVOQ vs. ORENCIA, non-inferiority/superiority.
‡ ACR20/50/70 were prespecified, unranked endpoints, P values are nominal. ACR20 response was not statistically significant between RINVOQ and ORENCIA at 24 weeks.
a Clinical remission is defined as Disease Activity Score with 28 joint counts (C-reactive protein) (DAS28-CRP) less than 2.6.
b ACR20/50/70 is defined as at least a 20 percent/50 percent/70 percent reduction from baseline in the number of both tender and swollen joint counts and equivalent improvement in three or more of the five remaining American College of Rheumatology core set measures: patient assessments of pain, global disease activity, physical function, physician global assessment of disease activity and acute phase reactant.

The safety profile of RINVOQ (15 mg) was consistent with that observed in previously reported studies in rheumatoid arthritis, with no new safety risks detected.¹ Through week 24, serious adverse events occurred in 3.3 percent of patients in the RINVOQ group, compared to 1.6 percent of patients in the ORENCIA group.¹ There were three cases of serious infection reported in the RINVOQ group and one in the ORENCIA group.¹ There were also 23 cases of hepatic disorder (primarily liver enzyme elevations) in the RINVOQ group compared to five cases of hepatic disorder in the ORENCIA group.¹ All hepatic disorder events were non-serious.³ Most of the events were transient ALT/AST elevations and considered mild to moderate in severity.³ None led to study drug interruption.³ Four cases of herpes zoster were reported in the RINVOQ group and four cases in the ORENCIA group.¹ Across both groups, there were no malignancies reported.¹ One major adverse cardiovascular event (MACE) and two adjudicated cases of venous thromboembolic events (VTE) were reported in the RINVOQ group, and both patients had at least one risk factor for VTE.¹ There were no MACE and VTE reported in the ORENCIA group.¹ There were two deaths in the RINVOQ group, one of which was non-treatment emergent, as well as one non-treatment emergent death in the ORENCIA group.¹

About SELECT-CHOICE¹

SELECT-CHOICE is a Phase 3, multicenter, randomized, double-blind, active-controlled study designed to evaluate the safety and efficacy of RINVOQ in combination with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) compared to ORENCIA (abatacept) in combination with csDMARDs in adult patients with moderate to severe active rheumatoid arthritis who have an inadequate response to or intolerance to biologic DMARDs. Patients were randomized to once daily RINVOQ (15 mg) or intravenous ORENCIA (at day 1, weeks 2, 4, 8, 12, 16 and 20 [<60 kg: 500 mg; 60-100 kg: 750 mg; >100 kg: 1,000 mg]), with all patients continuing background stable csDMARDs.

The primary endpoint was change from baseline in DAS28-CRP at week 12 showing non-inferiority in patients receiving RINVOQ (15 mg) compared to those receiving ORENCIA. Ranked secondary endpoints included superiority to ORENCIA in terms of change from baseline in DAS28-CRP at week 12 and proportion of patients achieving clinical remission, as defined by DAS28-CRP<2.6 at week 12. More information on this trial can be found at www.clinicaltrials.gov (NCT03086343).

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, 2, 4-12} In August 2019, RINVOQ received U.S. 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, psoriatic arthritis, axial spondyloarthritis, Crohn’s disease, atopic dermatitis, ulcerative colitis and giant cell arteritis are ongoing.^{1, 4-12} 

About AbbVie in Rheumatology

For more than 20 years, AbbVie has been dedicated to improving care for people living with rheumatic diseases. Our longstanding commitment to discovering and delivering transformative therapies is underscored by our pursuit of cutting-edge science that improves our understanding of promising new pathways and targets in order to help more people living with rheumatic diseases reach their treatment goals. For more information on AbbVie in rheumatology, visit https://www.abbvie.com/our-science/therapeutic-focus-areas/immunology/immunology-focus-areas/rheumatology.html.

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 Twitter, Facebook, Instagram, YouTube and LinkedIn.

References:

1. Efficacy and Safety of Upadacitinib Versus Abatacept in Patients With Active Rheumatoid Arthritis and Prior Inadequate Response or Intolerance to Biologic Disease-modifying Anti-rheumatic Drugs (SELECT-CHOICE): A Double-Blind, Randomized Controlled Phase 3 Trial. 2020 EULAR E-Congress; SAT0151.
2. RINVOQ [Summary of Product Characteristics]. AbbVie Deutschland GmbH & Co. KG; March 2020. Available at: https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf.
3. AbbVie Data on File. ABVRRTI70664.
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6. 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. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT02365649. Accessed on May 18, 2020.
7. Evaluation of Upadacitinib in Adolescent and Adult Patients With Moderate to Severe Atopic Dermatitis (Eczema)- Measure Up 1. ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT03569293. Accessed on May 18, 2020.
8. 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. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT02819635. Accessed on May 18, 2020.
9. A Study Evaluating the Safety and Efficacy of Upadacitinib in Subjects With Active Ankylosing Spondylitis (SELECT Axis 1). ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/study/NCT03178487. Accessed on May 18, 2020.
10. A Study to Evaluate the Safety and Efficacy of Upadacitinib in Participants With Giant Cell Arteritis (SELECT-GCA). ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT03725202. Accessed on May 18, 2020.
11. A Study Comparing Upadacitinib (ABT-494) to Placebo in Participants With Active Psoriatic Arthritis Who Have a History of Inadequate Response to at Least One Biologic Disease Modifying Anti-Rheumatic Drug (SELECT – PsA 2). ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT03104374. Accessed on May 18, 2020.
12. A Study to Evaluate Efficacy and Safety of Upadacitinib in Adult Participants With Axial Spondyloarthritis (SELECT AXIS 2). ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT04169373. Accessed on May 18, 2020.

SOURCE: AbbVie