AbbVie's Upadacitinib (ABT-494) Meets All Primary and Ranked Secondary Endpoints in Phase 3 Study in Rheumatoid Arthritis

- First Phase 3 clinical trial shows positive results for upadacitinib and a safety profile consistent with that observed in Phase 2 clinical trials (1)(2)(3)

- Both 15 mg and 30 mg doses achieved all primary and ranked secondary endpoints with high statistical significance (1*)

- Nearly half of the patients achieved low disease activity (LDA) at both doses, around 30 percent achieved clinical remission (1)

- Upadacitinib is an investigational agent being studied as a once-a-day oral therapy and was engineered by AbbVie to selectively inhibit JAK1, which plays an important role in the pathophysiology of rheumatoid arthritis(4)(5)

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AbbVie

Jun 07, 2017, 07:56 ET

NORTH CHICAGO, Ill., June 7, 2017 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced positive top-line results from the Phase 3 SELECT-NEXT clinical trial evaluating upadacitinib (ABT-494), an investigational oral JAK1-selective inhibitor, in patients with moderate to severe rheumatoid arthritis (RA) who did not adequately respond to treatment with conventional synthetic DMARDs (csDMARDs).¹ Results showed that after 12 weeks of treatment, both doses of upadacitinib (15 mg and 30 mg) met the study's primary endpoints of ACR20 and low disease activity.¹ Key secondary endpoints were also achieved and included ACR50, ACR70 and clinical remission.¹ Full results will be presented at an upcoming medical meeting and published in a peer-reviewed publication. Upadacitinib is an investigational oral agent and is not approved by regulatory authorities.

"We are excited by these promising results for upadacitinib. Selective inhibition of the JAK1 pathway may offer a novel treatment for rheumatoid arthritis patients who do not adequately respond to conventional therapies," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "We are especially encouraged by the results on the more stringent measures of efficacy, such as ACR70, low disease activity and clinical remission. We look forward to seeing the full results from our Phase 3 program. AbbVie's longstanding leadership in the treatment of immune-mediated diseases provides an opportunity to build upon our understanding and develop innovative therapies to address unmet patient needs."

Results at week 12 showed that of patients receiving a 15 mg or 30 mg oral, once-daily dose of upadacitinib, 64 percent and 66 percent achieved ACR20, respectively, compared to 36 percent of patients receiving placebo.¹ Patients receiving upadacitinib achieved ACR50 responses of 38 percent and 43 percent in the 15 mg and 30 mg groups, respectively, compared to 15 percent of patients receiving placebo. ACR70 responses were achieved by 21 percent and 27 percent of patients in the 15 mg and 30 mg groups, respectively, compared to 6 percent of patients receiving placebo.¹ Low disease activity was achieved by 48 percent of patients receiving either dose of upadacitinib, compared to 17 percent of patients receiving placebo.¹ Additionally, clinical remission was achieved by 31 percent and 28 percent of patients receiving 15 mg or 30 mg of upadacitinib, respectively, compared to 10 percent receiving placebo.¹ All primary and key secondary endpoints achieved p-values of <0.001 versus placebo for both doses.¹

Dose	ACR20**	ACR50**	ACR70**	LDA***	Clinical Remission****
upadacitinib 15 mg (n=221)	64%	38%	21%	48%	31%
upadacitinib 30 mg (n=219)	66%	43%	27%	48%	28%
Placebo (n=221)	36%	15%	6%	17%	10%

*All primary and key secondary endpoints achieved p-values of <0.001 vs. placebo for both doses. Not all ranked secondary endpoints shown.

**ACR20/50/70 is defined as American College of Rheumatology 20 percent/50 percent/70 percent improvements in tender and swollen joint counts, 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) response rate less than 2.6.

In this study, the safety profile was consistent with that observed in the upadacitinib Phase 2 clinical trials.¹^,²^,³ No new safety signals were detected.¹ Serious adverse events were 4 percent and 3 percent in the 15 mg and 30 mg dose arms, respectively, compared to 2 percent in placebo.¹ No deaths were reported.¹

"Achieving the target of low disease activity in nearly half of the patients by 12 weeks and doing so at both high and low dose levels is encouraging," said Prof. Gerd Burmester, professor of medicine, Department of Rheumatology and Clinical Immunology, Charité Berlin. "Current treatment recommendations recognize the importance of this clinical target for patients, as achieving low disease activity has remained an unmet need in rheumatoid arthritis."

AbbVie is continuing to evaluate the potential of upadacitinib across several immune-mediated conditions. Phase 3 trials of upadacitinib in psoriatic arthritis are ongoing, and it is also being investigated to treat Crohn's disease, ulcerative colitis and atopic dermatitis.^6,7,8,9,10

About SELECT-NEXT¹¹SELECT-NEXT is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of two doses (15 mg and 30 mg) of upadacitinib in adult patients with moderate to severe rheumatoid arthritis who are on a stable dose of csDMARDs and have had an inadequate response to csDMARDs. The primary endpoints included the percentage of subjects achieving an ACR20 response and low disease activity (LDA) after 12 weeks of treatment. Key secondary endpoints included proportion of patients achieving ACR50 and ACR70 response and clinical remission at week 12. More information on this trial can be found at www.clinicaltrials.gov (NCT02675426).

About the SELECT Study Program^{11,12,13,14,15,16}The robust SELECT Phase 3 program evaluates more than 4,000 patients with moderate to severe RA in six studies. The studies include assessments of efficacy, safety and tolerability across multiple RA patient populations. Key measures of efficacy evaluated include ACR responses, disease activity and inhibition of radiographic progression.

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.^4,5 Phase 3 trials of upadacitinib in psoriatic arthritis are ongoing and it is also being investigated to treat Crohn's disease, ulcerative colitis and atopic dermatitis.⁶^,⁷^,⁸^,⁹^,¹⁰

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-driven 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.

¹ AbbVie. Data on File, ABVRRTI64466
² Kremer 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 aheadof print].
³ Genovese 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].
⁴ 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
⁵ O'Shea JJ, Plenge R. JAK and STAT signaling molecules in immunoregulation and immune-mediated disease. Immunity 2012;(36):542–550.
⁶ A 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 on June 1, 2017.
⁷ A Study Comparing 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). Clinicaltrialsgov. 2017. Available at: https://clinicaltrials.gov/ct2/show/NCT03104374?term=ABT-494&phase=2&rank=8. Accessed on June 1, 2017.
⁸ 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 - Full Text View - ClinicalTrials.gov. Clinicaltrialsgov. 2017. Available at: https://clinicaltrials.gov/ct2/show/NCT02365649. Accessed on June 1, 2017.
⁹ 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 on June 1, 2017.
¹⁰ A 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 on June 1, 2017.
¹¹ A 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 on June 1, 2017.
¹² A Study Comparing ABT-494 to Placebo and to Adalimumab in Subjects With Rheumatoid Arthritis Who Are on a Stable Dose of Methotrexate and Who Have an Inadequate Response to Methotrexate (SELECT-COMPARE) - Full Text View - ClinicalTrials.gov. Clinicaltrialsgov. 2017. Available at: https://clinicaltrials.gov/ct2/show/NCT02629159?term=select+compare&rank=1. Accessed on June 1, 2017.
¹³ A Study Comparing ABT-494 Monotherapy to Methotrexate (MTX) Monotherapy in Subjects With Rheumatoid Arthritis (RA) Who Have an Inadequate Response to MTX (SELECT-MONOTHERAPY) - Full Text View - ClinicalTrials.gov. Clinicaltrialsgov. 2017. Available at: https://clinicaltrials.gov/ct2/show/NCT02706951?term=select+monotherapy&rank=1. Accessed on June 1, 2017.
¹⁴ A Study to Compare ABT-494 to Placebo in Subjects With Rheumatoid Arthritis on Stable Dose of Conventional Synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs) Who Have an Inadequate Response or Intolerance to Biologic DMARDs (SELECT-BEYOND) - Full Text View - ClinicalTrials.gov. Clinicaltrialsgov. 2017. Available at: https://clinicaltrials.gov/ct2/show/NCT02706847?term=select-beyond&rank=1. Accessed on June 1, 2017.
¹⁵ A Phase 3 Study to Compare ABT-494 to Abatacept in Subjects With Rheumatoid Arthritis on Stable Dose of Conventional Synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs) Who Have an Inadequate Response or Intolerance to Biologic DMARDs (SELECT-CHOICE). Clinicaltrialsgov. 2017. Available at: https://clinicaltrials.gov/ct2/show/NCT03086343?term=ABT-494&phase=2&rank=5. Accessed on June 1, 2017.
¹⁶ A Study to Compare ABT-494 Monotherapy to Methotrexate Monotherapy in Subjects With Rheumatoid Arthritis (RA) Who Have Not Previously Taken Methotrexate (SELECT-EARLY) - Full Text View - ClinicalTrials.gov. 2017. Available at: https://clinicaltrials.gov/ct2/show/NCT02706873?term=select+early&rank=1. Accessed on June 1, 2017.