AbbVie's Upadacitinib Shows Positive Results as Monotherapy in Phase 3 Rheumatoid Arthritis Study, Meeting All Primary and Key Secondary Endpoints

- SELECT-MONOTHERAPY, the third study in the robust SELECT program, showed positive results, with both doses (15 mg and 30 mg once-daily) meeting the primary endpoints in patients with an inadequate response to methotrexate(1)

- Upadacitinib monotherapy resulted in low disease activity by week 14 in 45 percent of patients in the 15 mg group and 53 percent in the 30 mg group(1*)

- A response of ACR20/50/70 was achieved by 68/42/23 percent of patients receiving 15 mg upadacitinib and 71/52/33 percent of patients receiving 30 mg of upadacitinib(1*)

- The safety profile of upadacitinib was consistent with previously reported Phase 3 studies, with no new safety signals detected(1-5)

- 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(6-13)

News provided by

AbbVie

Dec 20, 2017, 07:00 ET

NORTH CHICAGO, Ill., Dec. 20, 2017 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global research and development-based biopharmaceutical company, today announced positive top-line results from the Phase 3 SELECT-MONOTHERAPY clinical trial. This ongoing study evaluated upadacitinib (ABT-494), an investigational oral JAK1-selective inhibitor, as a monotherapy treatment in patients with moderate to severe rheumatoid arthritis (RA) who did not adequately respond to treatment with methotrexate. Results showed that after 14 weeks of treatment, both once-daily doses of upadacitinib (15 mg and 30 mg) met the study's primary endpoints of ACR20** and low disease activity (LDA)*** versus continuing prior stable methotrexate therapy.¹ Both doses also achieved all ranked and all key secondary endpoints.¹ Upadacitinib is not approved by regulatory authorities and its safety and efficacy have not been established.

"The positive results from the SELECT-MONOTHERAPY study are encouraging, as they are the first evidence to support the potential of upadacitinib as a therapy without the need for background methotrexate," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "These findings add to the growing body of data showing the potential for upadacitinib as a meaningful treatment option for patients suffering from rheumatoid arthritis. We look forward to sharing additional data from the upadacitinib Phase 3 rheumatoid arthritis program with the scientific community in 2018."

Rheumatoid arthritis, which affects an estimated 23.7 million people worldwide, is a chronic and debilitating disease.¹⁴ Methotrexate is commonly used as a first-line therapy in rheumatoid arthritis, but many patients do not respond to or cannot tolerate methotrexate, which puts them at risk for disease progression.^15-17

"This trial addresses the clinical impact of switching from methotrexate to upadacitinib as monotherapy in patients with an inadequate response to methotrexate. Results suggested that both doses of upadacitinib can provide clinically meaningful responses," said Josef S. Smolen, M.D., Department of Medicine, Division of Rheumatology, Medical University of Vienna, Austria, and an investigator in the study. "These findings support the potential for upadacitinib monotherapy as a treatment option for patients with rheumatoid arthritis."

The study showed that at week 14, 68/42/23 percent of patients switched to 15 mg once-daily upadacitinib and 71/52/33 percent of patients switched to 30 mg once-daily upadacitinib achieved an ACR20/50/70** response, compared to 41/15/3 percent of patients continuing on methotrexate.¹ These results were statistically significant (p<0.001 for all comparisons) compared to patients who continued on their baseline methotrexate dose.¹

Additionally, a significantly higher proportion of upadacitinib patients in both dose groups achieved LDA and clinical remission targets at week 14 compared to patients continuing on methotrexate (p<0.001).¹ Low disease activity was achieved by 45 percent and 53 percent of patients in the 15 mg and 30 mg groups, respectively, compared to 19 percent of patients continuing on methotrexate.¹ Clinical remission was achieved by 28 percent and 41 percent of patients in the 15 mg and 30 mg groups, respectively, compared to 8 percent of patients continuing on methotrexate.¹

	SELECT-MONOTHERAPY Efficacy Results at Week 14*
	Methotrexate (n=216)	Upadacitinib 15 mg (n=217)	Upadacitinib 30 mg (n=215)
ACR20**	41%	68%	71%
ACR50**	15%	42%	52%
ACR70**	3%	23%	33%
LDA***	19%	45%	53%
Clinical Remission****	8%	28%	41%

*All week 14 endpoints shown in the table achieved p-values of <0.001 versus methotrexate for both doses. Not all ranked secondary endpoints shown. ACR50 and ACR70 were not ranked secondary endpoints. Methotrexate patients shown are patients who continued on their baseline methotrexate dose in a blinded manner.

**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.

*** LDA 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.

**** Clinical remission was based on DAS28 (CRP) less than 2.6.

In this study, the safety profile of upadacitinib was consistent with previously reported Phase 3 SELECT clinical trials and Phase 2 studies.^1-5 No new safety signals were detected.¹ Serious adverse events occurred in 5/3 percent of patients in the 15 mg/30 mg upadacitinib groups, respectively, compared to 3 percent in the methotrexate group.¹ One patient, with pre-existing cardiovascular risk factors, had a fatal event of hemorrhagic stroke caused by a ruptured aneurysm, while receiving upadacitinib 15 mg.¹ There was one event of pulmonary embolism (PE) in the study, which occurred in the 15 mg dose group in a patient with pre-existing risk factors for PE.¹ Across the SELECT rheumatoid arthritis program, including both the placebo-controlled and extension periods, the rate of deep vein thrombosis and PE remains consistent with the background rate for the RA patient population.^1-3,18,19

Further results of SELECT-MONOTHERAPY, the third of six studies in the SELECT rheumatoid arthritis clinical trial program, will be presented at a future medical meeting and published in a peer-reviewed publication.

AbbVie is evaluating the potential of upadacitinib across several immune-mediated conditions. Phase 3 trials in psoriatic arthritis are ongoing, and it is also being investigated to treat Crohn's disease, ulcerative colitis, ankylosing spondylitis and atopic dermatitis.^8-13

About SELECT-MONOTHERAPY¹SELECT-MONOTHERAPY is a Phase 3, multicenter, randomized, double-blind, parallel-group study designed to evaluate the safety and efficacy of upadacitinib monotherapy in adult patients with moderate to severe rheumatoid arthritis and an inadequate response to a stable dose of methotrexate. Patients were randomized to switch from methotrexate to upadacitinib monotherapy (15 mg or 30 mg once-daily) or continue on their prior stable dose of methotrexate in a blinded manner.

The primary endpoints of the first phase included the percentage of subjects achieving an ACR20 response and low disease activity (LDA) after 14 weeks of treatment. Secondary endpoints included proportion of patients achieving ACR50, ACR70 and clinical remission at week 14. The trial is ongoing and the second phase is a blinded long-term extension period to evaluate the long-term safety, tolerability, and efficacy of the two once-daily doses (15 mg and 30 mg) of upadacitinib monotherapy in patients who have completed the first phase. More information on this trial can be found at www.clinicaltrials.gov (NCT02706951).

About the SELECT Study ProgramThe 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).

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 rheumatoid arthritis and other immune-mediated inflammatory disorders.^6-7 Phase 3 trials of upadacitinib in psoriatic arthritis are ongoing and it is also being investigated to treat Crohn's disease, ulcerative colitis, ankylosing spondylitis and atopic dermatitis.^8-13

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 may be 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," in AbbVie's 2016 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, ABVRRTI65458.
²AbbVie. Data on File, ABVRRTI64730.
³ AbbVie. Data on File, ABVRRTI64466.
⁴Kremer JM, Emery P, Camp HS, 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].
⁵Genovese MC, Smolen JS, Weinblatt ME, 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].
⁶Voss, 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
⁷Pipeline – Our Science | AbbVie. AbbVie. 2017. Available at: https://www.abbvie.com/our-science/pipeline.html. Accessed December 19, 2017.
⁸A Study Comparing ABT-494 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) - Full Text View - ClinicalTrials.gov. Clinicaltrialsgov. 2017. Available at: https://clinicaltrials.gov/ct2/show/NCT02675426?term=select+next&rank=1. Accessed December 19, 2017.
⁹A Study Comparing 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). Clinicaltrialsgov. 2017. Available at: https://clinicaltrials.gov/ct2/show/NCT03104400?term=ABT-494&phase=2&rank=10. Accessed December 19, 2017.
¹⁰A 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 - Full Text View - ClinicalTrials.gov. Clinicaltrialsgov. 2017. Available at: https://clinicaltrials.gov/ct2/show/NCT02365649. Accessed December 19, 2017.
¹¹ 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. Clinicaltrialsgov. 2017. Available at: https://clinicaltrials.gov/ct2/show/NCT02819635. Accessed December 19, 2017.
¹² A Study Evaluating the Safety and Efficacy of Upadacitinib in Subjects With Active Ankylosing Spondylitis (SELECT Axis 1). 2017. Available at: https://clinicaltrials.gov/ct2/show/study/NCT03178487?term=ABT-494&cond=ankylosing+spondylitis&rank=1. Accessed December 19, 2017.
¹³A Study to Evaluate ABT-494 in Adult Subjects With Moderate to Severe Atopic Dermatitis. Clinicaltrialsgov. 2017. Available at: https://clinicaltrials.gov/ct2/show/NCT02925117. Accessed December 19, 2017.
¹⁴World Health Organization. The Global Burden of Disease, 2004 Update. Available at: http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_full.pdf. Accessed December 19, 2017.
¹⁵Shinde, CG, Venkatesh, MP, Pramod Kumar, TM, Shivakumar, HG. J Pain Palliat Care Pharmacother. 2014 Dec;28(4):351-8. doi: 10.3109/15360288.2014.959238. Epub 2014 Oct 16.
¹⁶ Swierkot J and Szechinski J. Methotrexate in rheumatoid arthritis. Pharmacol Rep. 20116 Jul-Aug;58(4)473-92.
¹⁷Fautrel B, Nab HW, et al. Identifying patients with rheumatoid arthritis with moderate disease activity at risk of significant radiographic progression despite methotrexate treatment. RMD Open. 2015; 1(1). DOI: 10.1136/rmdopen-2014-000018.
¹⁸ AbbVie. Data on File, ABVRRTI64959.
¹⁹ Kim SC. Risk of Venous Thromboembolism in Patients with Rheumatoid Arthritis. Arthritis Care & Research. Vol. 65, No. 10, October 2013, pp 1600–1607.