AbbVie's Upadacitinib Meets Primary and Key Efficacy Endpoints in Phase 2b/3 Rheumatoid Arthritis Study in Japanese Patients

- In SELECT-SUNRISE, upadacitinib met the primary endpoint of ACR20 across all doses (7.5 mg, 15 mg, 30 mg, once-daily) at week 12, with a significant difference in ACR20 compared to placebo observed as early as week one(1)

- Significantly more patients receiving upadacitinib achieved ACR50, ACR70 and clinical remission at week 12 compared to placebo(1)

- The safety profile of upadacitinib was consistent with previously reported results, with no new safety signals detected(1-7)

- Upadacitinib, an oral agent engineered by AbbVie to selectively inhibit JAK1, is being studied as a once-daily therapy in rheumatoid arthritis in the SELECT program and across multiple immune-mediated diseases(8-15)

News provided by

AbbVie

Apr 25, 2018, 08:30 ET

NORTH CHICAGO, Ill., April 25, 2018 /PRNewswire/ -- AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced positive results from the ongoing Phase 2b/3 SELECT-SUNRISE clinical trial, showing that at 12 weeks, all doses of upadacitinib (7.5 mg, 15 mg and 30 mg, once-daily) met the study's primary endpoint of ACR20^a versus placebo.¹ Certain key efficacy endpoints were also achieved versus placebo.¹ The study, conducted in Japan, evaluates upadacitinib, an investigational oral JAK1-selective inhibitor, in adult Japanese patients with moderate to severe rheumatoid arthritis who are on a stable dose of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and have had an inadequate response to csDMARDs.¹ These data will be presented during an oral presentation at the Japan College of Rheumatology (JCR) 2018 Annual Scientific Meeting in Tokyo on Saturday, April 28, 2018. Upadacitinib is not approved by regulatory authorities and its safety and efficacy have not been established.

SELECT-SUNRISE is a local dose-ranging study in Japanese patients and is part of AbbVie's robust global upadacitinib SELECT clinical trial program, which is evaluating more than 4,000 patients with moderate to severe rheumatoid arthritis.

"We are encouraged by these data, which show that upadacitinib provides improvements in important measures such as achieving ACR response and clinical remission, in people living with rheumatoid arthritis in Japan," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "SELECT-SUNRISE reflects our continued commitment to offering innovative solutions with the potential to improve the lives of Japanese patients living with this serious, debilitating condition."

Rheumatoid arthritis, which affects an estimated 1 million people in Japan, is a chronic and debilitating disease.^16, 17 Despite increasing availability of a range of treatments in Japan, some patients with rheumatoid arthritis still do not achieve clinical remission or tight control of their disease.¹⁶

Results at week 12 showed that of patients receiving an oral once-daily dose of upadacitinib 7.5/15/30 mg, 76/84/80 percent achieved ACR20, respectively, compared to 43 percent of patients receiving placebo (p<0.001).¹ As early as week one, significantly more patients on upadacitinib achieved ACR20 compared to placebo (31/25/34 percent in the 7.5/15/30 mg upadacitinib groups, respectively, compared to 8 percent in the placebo group, p<0.01/0.05/0.01).¹ Additionally, significantly more patients receiving upadacitinib also achieved ACR50^a and ACR70^a responses compared to placebo.¹ Among upadacitinib patients receiving the 7.5/15/30 mg doses, ACR50 was achieved by 41/65/58 percent, respectively, compared to 16 percent with placebo (p<0.01/0.001/0.001), and ACR70 was achieved by 20/35/28 percent, respectively, compared to 2 percent with placebo (p<0.01/0.001/0.001).¹

The study also showed that a significantly higher proportion of upadacitinib patients across all doses achieved low disease activity^cand clinical remission^b at week 12 compared to patients receiving placebo.¹ Low disease activity was achieved by 53/69/72 percent of upadacitinib patients in the 7.5/15/30 mg groups, respectively, compared to 18 percent in the placebo group (p<0.001).¹ Clinical remission was achieved by 37/57/50 percent of upadacitinib patients in the 7.5/15/30 mg groups, respectively, compared to 6 percent in the placebo group (p<0.001).¹ Patients receiving upadacitinib also had greater improvements in physical function, as measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI), and decreased severity of morning stiffness.¹

SELECT-SUNRISE Efficacy Results at Week 12^†
	Placebo (n=49)	Upadacitinib 7.5 mg (n=49)	Upadacitinib 15 mg (n=49)	Upadacitinib 30 mg (n=50)
ACR20^a	43%	76%	84%	80%
ACR50^a	16%	41%	65%	58%
ACR70^a	2%	20%	35%	28%
Clinical Remission (DAS28-CRP)^b	6%	37%	57%	50%
Low Disease Activity (DAS28-CRP)^c	18%	53%	69%	72%

^†All week 12 endpoints shown in the table achieved p-values of <0.001 except ACR50/70 responses with 7.5 mg upadacitinib which achieved p-values of <0.01. Not all secondary endpoints shown.

^a ACR20/50/70 is defined as American College of Rheumatology 20 percent/50 percent/70 percent improvements in both tender and swollen joint counts, plus 3 of the following: patient assessments of pain, global disease activity and physical function, physician global assessment of disease activity and acute phase reactant.

^b Clinical remission was based on Disease Activity Score with 28 joint counts (C-reactive protein) (DAS28 [CRP]) less than less than 2.6.

^c Low disease activity was defined by a clinical response Disease Activity Score with 28 joint counts (C-reactive protein) (DAS28 [CRP]) less than or equal to 3.2.

The safety profile of upadacitinib during the 12-week reporting period was consistent with previously reported results.^1-7 No new safety signals were detected.¹ Serious adverse events occurred in 2/2/10 percent of the 7.5/15/30 mg upadacitinib groups, respectively, compared to 0 percent in the placebo group.¹ Serious infection occurred in 0/2/6 percent of the upadacitinib 7.5/15/30 mg groups, compared to 0 percent in the placebo group.¹ There were no major adverse cardiovascular events reported in the trial.¹ There were no deaths, no events of pulmonary embolism (PE) or deep vein thrombosis (DVT) reported.¹Across the SELECT rheumatoid arthritis program, including both the placebo-controlled and extension periods, the rate of DVT and PE remains consistent with the background rate for the RA patient population.^{1-5, 18-20}

About SELECT-SUNRISE¹

SELECT-SUNRISE is an ongoing Phase 2b/3 study designed to evaluate the safety and efficacy of upadacitinib compared to placebo in adult Japanese patients with moderate to severe rheumatoid arthritis who are on a stable dose of csDMARDs and have an inadequate response to csDMARDs. In addition, the study is also intended to confirm dose response in the efficacy of upadacitinib 7.5 mg, 15 mg and 30 mg in the Japanese population. The study includes two periods. The first period of the study is a 12 week randomized, placebo-controlled, double-blind period designed to compare the safety and efficacy of a once-daily dose of upadacitinib (7.5 mg, 15 mg or 30 mg) versus placebo. Period 2 is a blinded long-term extension period to evaluate the long-term safety, tolerability and efficacy of upadacitinib 30 mg, 15 mg, 7.5 mg in subjects who have completed Period 1. At week 12, patients on placebo, were equally switched (pre-assigned at baseline) to receive a once-daily dose of upadacitinib 7.5 mg, 15 mg or 30 mg. The primary endpoint of the study is the proportion of patients achieving an ACR20 response at week 12. Other key efficacy endpoints include the proportion of patients achieving ACR50, ACR70, clinical remission and low disease activity at week 12 as well as the change from baseline to week 12 in Health Assessment Questionnaire-Disability Index (HAQ-DI) and severity of morning stiffness. More information on this trial can be found at www.clinicaltrials.gov (NCT02720523).

About the SELECT Study Program

The robust SELECT Phase 3 rheumatoid arthritis program evaluates more than 4,000 patients with moderate to severe rheumatoid arthritis in six studies. The studies include assessments of efficacy, safety and tolerability across multiple rheumatoid arthritis patient populations. 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). SELECT-SUNRISE is a Phase 2b/3 clinical trial program that is evaluating 197 patients with moderate to severe rheumatoid arthritis in Japan. More information on SELECT-SUNRISE trial can be found at www.clinicaltrials.gov (NCT02720523).

About Upadacitinib

Discovered and developed by AbbVie, upadacitinib is an investigational oral agent engineered to selectively inhibit JAK1, which plays an important role in the pathophysiology of immune-mediated disorders.^8,9 Phase 3 trials of upadacitinib in rheumatoid arthritis, psoriatic arthritis and Crohn's disease are ongoing and it is also being investigated to treat ulcerative colitis, ankylosing spondylitis, atopic dermatitis and giant cell arteritis.^10-15,21

Upadacitinib is an investigational oral agent and is not approved by regulatory authorities. Safety and efficacy have not been established.

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 or LinkedIn.

Forward-Looking Statements

Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2017 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

¹AbbVie. Data on File, ABVRRTI66173.
² AbbVie. Data on File, ABVRRTI66053.
³AbbVie. Data on File, ABVRRTI65458.
⁴AbbVie. Data on File, ABVRRTI64730.
⁵AbbVie. Data on File, ABVRRTI64466.
⁶ Kremer JM, et al. A Phase 2b study of ABT-494, a selective JAK1 inhibitor, in patients with rheumatoid arthritis and an inadequate response to anti-TNF therapy. Arthritis Rheumatol 2016; (doi:10.1002/art.39801): July 7 [Epub ahead of print].
⁷Genovese MC, et al. A randomized Phase 2b study of ABT-494, a selective JAK1 inhibitor in patients with rheumatoid arthritis and an inadequate response to methotrexate. Arthritis Rheumatol 2016;(doi: 10.1002/art.39808): July 7 [Epub ahead of print].
⁸ Voss, J, et al; Pharmacodynamics Of a Novel Jak1 Selective Inhibitor In Rat Arthritis and Anemia Models and In Healthy Human Subjects. [abstract]. Arthritis Rheum 2013;65 Suppl 10 :2374. DOI: 10.1002/art.2013.65.issue-s10
⁹Pipeline – Our Science | AbbVie. AbbVie. 2017. Available at: https://www.abbvie.com/our-science/pipeline.html. Accessed on April 18, 2018.
¹⁰A Study Comparing ABT494 to Placebo in Subjects With Rheumatoid Arthritis on a Stable Dose of Conventional Synthetic Disease Modifying Antirheumatic Drugs (csDMARDs) Who Have an Inadequate Response to csDMARDs Alone (SELECT-NEXT). ClinicalTrials.gov. 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT02675426. Accessed on April 18, 2018.
¹¹A 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. 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT03104400. Accessed on April 18, 2018.
¹² A Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Subjects With Moderately to Severely Active Crohn's Disease Who Have Inadequately Responded to or Are Intolerant to Biologic Therapy. Clinicaltrialsgov. 2018. Available at: https://www.clinicaltrials.gov/ct2/show/NCT03345836. Accessed on April 18, 2018.
¹³ A Study Evaluating the Safety and Efficacy of Upadacitinib in Subjects With Active Ankylosing Spondylitis (SELECT Axis 1). 2018. Available at: https://clinicaltrials.gov/ct2/show/study/NCT03178487. Accessed on April 18, 2018.
¹⁴A 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. 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT02819635. Accessed on April 18, 2018.
¹⁵ A Study to Evaluate ABT-494 in Adult Subjects With Moderate to Severe Atopic Dermatitis. ClinicalTrials.gov. 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT02925117. Accessed on April 18, 2018.
¹⁶Yamanaka H, et al. Estimates of the prevalence of and current treatment practices for rheumatoid arthritis in Japan using reimbursement data from health insurance societies and the IORRA cohort (I). Mod Rheumatol 2013. DOI 10.1007/s10165-013-0863-6. Available at https://link.springer.com/article/10.1007/s10165-013-0863-6. Accessed on April 18, 2018.
¹⁷ McInnes I, Schett G. The Pathogenesis of Rheumatoid Arthritis. New England Journal of Medicine. 2011;365(23):2205-2219. doi:10.1056/nejmra1004965.
¹⁸ Kim SC, et al. Risk of Venous Thromboembolism in Patients with Rheumatoid Arthritis. Arthritis Care & Research. Vol. 65, No. 10, October 2013, pp 1600–1607.
¹⁹ AbbVie. Data on File, ABVRRTI64959.
²⁰AbbVie. Data on File, ABVRRTI66056.
²¹ AbbVie's (ABBV) CEO Richard Gonzalez on Q4 2017 Results - Earnings Call Transcript. Available at: https://seekingalpha.com/article/4140615-abbvies-abbv-ceo-richard-gonzalez-q4-2017-results-earnings-call-transcript. Accessed on April 18, 2018.