Results from Upadacitinib Phase 3 SELECT-COMPARE Study Published in Arthritis and Rheumatology

• SELECT-COMPARE, the largest of the six studies in the robust SELECT programme, evaluates upadacitinib in patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to methotrexate (MTX), and remain on a stable background of MTX¹
  
• Both primary endpoints of the study were met, including the proportion of patients achieving ACR20 response and clinical remission (DAS28-CRP<2.6) at week 12 for upadacitinib versus placebo¹
• No new safety signals were reported compared to previously reported Phase 3 studies^1-5
• Upadacitinib, an oral agent engineered by AbbVie to selectively inhibit JAK1, is being studied as a once-daily therapy in rheumatoid arthritis

MAIDENHEAD, 11 July 2019 — AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced the publication of positive results from the pivotal Phase 3 SELECT-COMPARE clinical trial in Arthritis and Rheumatology. The study evaluates upadacitinib compared to placebo and adalimumab in patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to methotrexate (MTX), and remain on a stable background of MTX. Data show that at 12 weeks, patients receiving a once-daily dose of upadacitinib (15mg, n=651 met the primary endpoints with significantly higher rates of ACR20 response (71%) and clinical remission* (29%) versus patients receiving placebo (36% and 6% respectively, n=651, p≤0.001 for both endpoints).¹

All key secondary endpoints were also achieved, including significantly higher rates of ACR50 response, in patients receiving upadacitinib versus placebo or adalimumab [n=327] in combination with methotrexate at week 12 [p≤0.001].¹ Upadacitinib-treated patients showed significant improvements from baseline compared to patients receiving adalimumab in reduction of pain [-32.1 versus -25.6, p=≤0.001], as measured by the Visual Analog Scale (VAS), and improvements in physical function [0.60 versus -0.49, p≤0.01] , as measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI), at week 12.¹

Primary and secondary endpoints met at week 12 were maintained through 26 weeks, including significantly higher rates of low disease activity** and clinical remission* achieved in patients receiving upadacitinib plus MTX than those receiving adalimumab plus MTX and placebo plus MTX, respectively.¹

At week 12, an additional efficacy endpoint also demonstrated a significantly higher proportion of patients receiving upadacitinib plus MTX achieved low disease activity (45%) and remission (29%) versus adalimumab plus MTX (29% and 18% respectively, p≤0.001 for both endpoints)***.¹ This was maintained through week 26 when upadacitinib was also shown to significantly inhibit radiographic progression, as measured by a mean change from baseline in modified Sharp score (mTSS), versus placebo [p≤0.001].¹

The overall safety profile of upadacitinib was similar to adalimumab, except for higher rates of herpes zoster and CPK elevations with upadacitinib.¹ No new safety signals were reported compared to previously reported Phase 3 studies.^1-5 Upadacitinib is an investigational oral agent and has not been approved by any regulatory authorities.

“Over the past two decades important advances in the treatment of rheumatoid arthritis have been made, making clinical remission a possibility for more people living with rheumatoid arthritis,” said Alice Butler, UK Medical Director, AbbVie. “We are encouraged by the positive results of SELECT-COMPARE showing a significant impact on both signs and symptoms and radiographic progression compared to placebo, as well as improvements in important measures such as ACR response, remission and low disease activity compared to adalimumab."

Rheumatoid arthritis is a chronic and debilitating disease that affects an estimated 400,000 people in the UK.⁶ Despite current treatment recommendations underscoring the importance of clinical remission and low disease activity as treatment targets in the treatment of rheumatoid arthritis, many patients living with the disease do not achieve these results.^7-8 Achieving clinical remission can allow patients to return to living a more normal life and decreases the likelihood of severe joint damage.⁹

* Remission is defined as [DAS28-CRP]<2.6

** LDA is defined as Disease Activity Score 28 C-Reactive Protein [DAS28-CRP]≤3.2.

*** Multiplicity control was applied to comparisons for upadacitinib + MTX versus placebo + MTX, but not for upadacitinib + MTX versus adalimumab + MTX.

About SELECT-COMPARE¹

SELECT-COMPARE is a Phase 3, multicenter, randomized, double-blind, study designed to evaluate the safety and efficacy of upadacitinib compared to placebo and adalimumab in adult patients with moderately to severely active rheumatoid arthritis who are on a stable background of methotrexate and who have an inadequate response to methotrexate. Patients received background methotrexate and were randomized 2:2:1 to receive upadacitinib (15 mg once-daily), placebo or adalimumab (given as a subcutaneous injection of 40 mg every other week).

The primary endpoints included the percentage of subjects achieving ACR20 response and clinical remission (based on DAS28-CRP) after 12 weeks of treatment compared to placebo. Ranked secondary endpoints included change in the mTSS compared to placebo at week 26 and a comparison versus adalimumab in percentage of subjects achieving ACR50 response, low disease activity, change from baseline in pain as measured by VAS and change from baseline in physical function, as measured by the HAQ-DI at week 12. The trial is ongoing and includes a 48 week randomized, double-blind treatment period followed by a long-term extension study of up to five years. More information on this trial can be found at www.clinicaltrials.gov (NCT02629159).

About the SELECT Study Programme^1-5

The robust SELECT Phase 3 rheumatoid arthritis programme evaluates more than 4,900 patients with moderately to severely active rheumatoid arthritis in six studies. The studies include assessments of efficacy, safety and tolerability across a broad range of rheumatoid arthritis patients. Key measures of efficacy evaluated include ACR responses, Disease Activity Score (DAS28-CRP) and inhibition of radiographic progression. More information on these trials can be found at www.clinicaltrials.gov (NCT02706847, NCT03086343, NCT02629159, NCT02706873, NCT02706951, NCT02675426).

About Upadacitinib

Discovered and developed by AbbVie, upadacitinib is an investigational, oral, small molecule JAK1-selective inhibitor being studied for moderately to severely active rheumatoid arthritis. Upadacitinib is not approved and its safety and efficacy have not been evaluated by regulatory authorities.

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.co.uk . Follow @abbvieuk on Twitter

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References

1. Fleischmann, R, et al. Upadacitinib versus Placebo or Adalimumab in Rheumatoid Arthritis: Results of a Phase 3, Double-Blind, Randomized Controlled Trial. Arthritis and Rheumatology. 2019.
2. Smolen, J.S., et al. A Phase 3 Randomised, Placebo-controlled, Double-Blind Study of Upadacitinib as Monotherapy in Patients with Active Rheumatoid Arthritis and Inadequate Response to Methotrexate: SELECT-MONOTHERAPY. The Lancet. 2019.
3. Burmester GR, 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.
4. Genovese MC, et al; Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease-modifying anti-rheumatic drugs (SELECT-BEYOND): a double-blind, randomised controlled phase 3. Lancet. 2018 Jun 23;391(10139):2503-2512. doi: 10.1016/S0140-6736(18)31115-2. Epub 2018 Jun 18.
5. van Vollenhoven, et al. A Phase 3, Randomized, Controlled Trial Comparing Upadacitinib Monotherapy to MTX Monotherapy in MTX-Naïve Patients with Active Rheumatoid Arthritis. 2018 ACR/ARHP Annual Meeting; 891
6. NICE. Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept for rheumatoid arthritis not previously treated with DMARDs or after conventional DMARDs only have failed (TA375). January 2016.
7. Nagy G, van Vollenhoven RF. Sustained biologic-free and drug-free remission in rheumatoid arthritis, where are we now? Arthritis Res Ther 2015; 17:181
8. Smolen JS, Landewé R, Bijlsma J, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 2017.Jun;76(6):960-97
9. Ajeganova S. and Huizinga T. Sustained remission in rheumatoid arthritis: latest evidence and clinical considerations. Ther Adv Musculoskelet Dis. 2017 Oct;9(10):249-262. doi: 10.1177/1759720X17720366

July 2019

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