RINVOQ™ (upadacitinib) Meets Primary and Key Secondary Endpoints in Phase 3 Study in Psoriatic Arthritis

– In this large Phase 3 study, RINVOQ™ (upadacitinib; 15 mg and 30 mg, once daily) met the primary endpoint of ACR20 response at week 12 versus placebo in adult patients with active psoriatic arthritis[1]

– The 30 mg dose of RINVOQ achieved superiority to adalimumab in terms of ACR20 response at week 12, whereas both doses achieved non-inferiority versus adalimumab[1]

– Both doses of RINVOQ also significantly inhibited radiographic progression at week 24 compared to placebo[1]

– Significantly more patients receiving either dose of RINVOQ achieved PASI 75 at week 16 compared to placebo[1]

– The safety profile of RINVOQ was consistent with previously reported results across indications, with no new safety risks detected[1,2]

NORTH CHICAGO, IL, USA I February 5, 2020 I AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced positive top-line results from the Phase 3 SELECT-PsA 1 clinical trial. In this study, both doses of RINVOQ^TM (upadacitinib; 15 mg and 30 mg, once daily) met the primary endpoint of ACR20 response at week 12 versus placebo in adult patients with active psoriatic arthritis who have responded inadequately or are intolerant to one or more non-biologic disease modifying anti-rheumatic drugs (DMARDs).¹ RINVOQ also demonstrated significant improvements in signs and symptoms of the disease across a variety of endpoints compared to placebo.¹ RINVOQ, a selective and reversible JAK inhibitor discovered and developed by AbbVie, is being studied as a once-daily therapy in psoriatic arthritis and multiple immune-mediated inflammatory diseases.^1,3-10

“Patients living with psoriatic arthritis often suffer from joint pain, stiffness and fatigue, impacting their ability to work and lead a physically active life,” said Michael Severino, M.D., vice chairman and president, AbbVie. “The results of this large Phase 3 study further support the potential of RINVOQ to help these patients. We look forward to sharing these data with regulatory bodies around the world to support our application for label expansion for RINVOQ to include adult patients with active psoriatic arthritis.”

Results show that at week 12, 71 percent and 79 percent of patients receiving 15 mg and 30 mg of RINVOQ achieved ACR20, respectively, compared to 36 percent of patients receiving placebo (p<0.0001).¹ In terms of ACR20 response at week 12 versus adalimumab, both RINVOQ doses achieved non-inferiority and only the 30 mg dose showed superiority.¹ ACR50 at week 12 was achieved by 38 percent and 52 percent of patients receiving 15 mg and 30 mg of RINVOQ, respectively, compared to 13 percent of patients receiving placebo (nominal p<0.0001).¹ In addition, 16 percent and 25 percent of patients receiving 15 mg and 30 mg of RINVOQ achieved ACR70, respectively, at week 12 compared to 2 percent of the placebo group (nominal p<0.0001).¹

Patients receiving RINVOQ also had greater improvements in physical function at week 12, as measured by the Health Assessment Questionnaire Disability Index (HAQ-DI).¹ Patients in the 15 mg and 30 mg RINVOQ groups reported a -0.42 and -0.47 change from baseline in HAQ-DI score, respectively, compared to -0.14 on placebo (p<0.0001).¹ RINVOQ also showed improvement in skin symptoms at week 16, with 63 percent and 62 percent of patients receiving 15 mg and 30 mg of RINVOQ achieving a 75 percent improvement in the Psoriasis Area Severity Index (PASI 75), respectively, compared to 21 percent on placebo (p<0.0001).¹ Minimal disease activity (MDA) at week 24 was achieved in 37 percent and 45 percent of 15 mg and 30 mg RINVOQ-treated patients, respectively, versus 12 percent of the placebo group (p<0.0001).¹

“The results of SELECT-PsA 1 showed that both doses of upadacitinib demonstrated significantly greater efficacy in joint and skin symptoms, as well as inhibition of radiographic progression, compared to placebo,” said Professor Iain McInnes, F.R.C.P., Ph.D., University of Glasgow Institute of Infection, Immunity & Inflammation. “These data are encouraging and add to the growing body of evidence that upadacitinib has the potential to improve outcomes for people living with psoriatic arthritis.”

SELECT-PsA 1 Efficacy Results1,†
	RINVOQ 15 mg (n=429)	RINVOQ 30 mg (n=423)	Placebo (n=423)
ACR20a at week 12	71%	79%	36%
ACR50a at week 12	38%	52%	13%
ACR70a at week 12	16%	25%	2%
HAQ-DIb at week 12	-0.42	-0.47	-0.14
PASI 75c at week 16	63%	62%	21%
MDAd at week 24	37%	45%	12%
† Primary endpoint was ACR20 at week 12 versus placebo. Ranked secondary endpoints included change in HAQ-DI from baseline at week 12 versus placebo, proportion of patients achieving PASI 75 at week 16 versus placebo and proportion of patients achieving MDA at week 24 versus placebo. All comparisons as defined above achieved p-values of <0.0001. Not all ranked secondary endpoints shown.
a 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.
b HAQ-DI is defined as change in baseline in the Health Assessment Questionnaire Disability Index, which is a is a patient-reported questionnaire including categories of dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. It asks patients about the amount of difficulty they experience in these activities as well as the use of aids and/or devices.
c PASI 75 is defined as a 75 percent improvement in the Psoriasis Area Severity Index. It was assessed in patients with ≥3 percent body surface area (BSA) psoriasis at baseline.
d MDA is defined as the fulfillment of 5 of 7 outcome measures: TJC≤1; SJC≤1; PASI≤1 or BSA-Ps≤3 percent; Patient’s Assessment of Pain NRS≤1.5; PtGA-Disease Activity NRS ≤2.0; HAQ-DI score ≤0.5; and LEI (Leeds Enthesitis Index) ≤1.

Following 24 weeks of treatment, RINVOQ at 15 mg and 30 mg significantly inhibited radiographic progression, as measured by the change from baseline in modified PsA Sharp/van der Heijde Score, compared to placebo (p<0.01).¹ The inhibition of joint damage is important for psoriatic arthritis patients as this can impact physical function and disability.¹¹

The safety profile of RINVOQ was consistent with that observed in previously reported studies, with no new safety risks detected.¹ Through week 24, serious infections occurred in 1.2 percent and 2.6 percent of patients in the 15 mg and 30 mg RINVOQ groups, respectively, compared to 0.9 percent in the placebo group and 0.7 percent in the adalimumab group.¹ There was one case of adjudicated venous thromboembolic events (VTE) in the RINVOQ 30 mg group (0.2 percent), no cases in the RINVOQ 15 mg group, two cases in the adalimumab group (0.5 percent) and one case in the placebo group (0.2 percent).¹ No major adverse cardiovascular events (MACE) were reported in either RINVOQ group.¹ There was one MACE reported in the placebo group and two MACE reported in the adalimumab group.¹ There were no deaths in either RINVOQ group, one death in the placebo group (0.2 percent) and no deaths in the adalimumab group.¹

Psoriatic arthritis is a heterogeneous systemic inflammatory disease with hallmark manifestations in joints and skin, affecting more than 50 million people worldwide.^12,13 In psoriatic arthritis, the immune system creates inflammation that can lead to pain, fatigue and stiffness in the joints.¹²

Results from the SELECT-PsA 1 study will be presented at a future medical meeting and published in a peer-reviewed publication.

About SELECT-PsA 1^1,14

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 followed by either RINVOQ 15 mg or RINVOQ 30 mg at week 24.

The primary endpoint was the percentage of subjects receiving RINVOQ 15 mg or 30 mg who achieved an ACR20 response after 12 weeks of treatment versus placebo. Ranked secondary endpoints included change from baseline in HAQ-DI at week 12, proportion of patients achieving PASI 75 at week 16 and proportion of patients achieving MDA at week 24. The trial is ongoing, and the long-term extension remains blinded to evaluate the long-term safety, tolerability and efficacy of the two once-daily doses (15 mg and 30 mg) of RINVOQ in patients who have completed the placebo-controlled period. More information on this trial can be found at www.clinicaltrials.gov (NCT03104400).

About RINVOQ (upadacitinib)

Discovered and developed by AbbVie, RINVOQ is a selective and reversible JAK inhibitor studied in several immune-mediated inflammatory diseases.^1-10 In August 2019, RINVOQ received U.S. Food and Drug Administration 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 also received approval 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. 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.^1,6-10

About AbbVie

AbbVie is a global, research and development-based biopharmaceutical company committed to developing innovative advanced therapies for some of the world’s most complex and critical conditions. The company’s mission is to use its expertise, dedicated people and unique approach to innovation to markedly improve treatments across four primary therapeutic areas: immunology, oncology, virology and neuroscience. In more than 75 countries, AbbVie employees are working every day to advance health solutions for people around the world. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook, LinkedIn or Instagram.

References:

1. AbbVie Data on File. ABVRRTI69835.
2. Cohen S., et al. Safety profile of upadacitinib in Rheumatoid Arthritis: Integrated analysis from the SELECT Phase 3 Clinical Program. EULAR 2019; THU0167.
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4. Pipeline – Our Science | AbbVie. AbbVie. 2020. Available at: https://www.abbvie.com/our-science/pipeline.html. Accessed on January 28, 2020.
5. Burmester G.R., et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018 Jun 23;391(10139):2503-2512. doi: 10.1016/S0140-6736(18)31115-2. Epub 2018 Jun 18.
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 January 28, 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 January 28, 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 January 28, 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 January 28, 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 January 28, 2020.
11. Tucker L., et al. Novel Concepts in Psoriatic Arthritis Management: Can We Treat to Target? Curr Rheumatol Rep. 2018;20(11):71.
12. Duarte G.V., et al. Psoriatic arthritis. Best Pract Res Clin Rheumatol. 2012 Feb;26(1):147-56. doi: 10.1016/j.berh.2012.01.003.
13. International Federation of Psoriasis Associations. Psoriasis is a Serious Disease Deserving Global Attention. Available at: https://ifpa-pso.com/wp-content/uploads/2017/01/Brochure-Psoriasis-is-a-serious-disease-deserving-global-attention.pdf. Accessed January 28, 2020.
14. A Study Comparing Upadacitinib (ABT-494) to Placebo and to Adalimumab in Participants With Psoriatic Arthritis Who Have an Inadequate Response to at Least One Non-Biologic Disease Modifying Anti-Rheumatic Drug (SELECT – PsA 1). ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT03104400. Accessed January 28, 2020.

SOURCE: AbbVie