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

- SELECT-BEYOND, the second study in the robust SELECT program, demonstrated positive results with both doses (15 mg and 30 mg once-daily) meeting the primary endpoints in a difficult-to-treat patient population, over half of whom had previously been treated with two or more biologics(1)
- Both doses achieved low disease activity in over 40 percent of patients at week 12 and over 50 percent of patients at week 24(1)
- The safety profile of upadacitinib was consistent with previously reported studies, with no new safety signals detected(1-4)
- 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(5-12)

NORTH CHICAGO, IL, USA I September 11, 2017 I AbbVie (NYSE: ABBV), a global research and development based biopharmaceutical company, today announced positive top-line results from the Phase 3 SELECT-BEYOND 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 or were intolerant to treatment with biologic DMARDs (bDMARDs).1 Results showed that after 12 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)**.1 All ranked secondary endpoints were also achieved with both doses.1 Upadacitinib is not approved by regulatory authorities and safety and efficacy have not been established.

"We are very pleased with the positive results for upadacitinib in the SELECT-BEYOND trial. Particularly exciting is the proportion of patients who achieved clinical remission by week 12 and 24, despite having inadequate responses with previous biologic therapies," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "Together with previously reported results from SELECT-NEXT, these data further support the potential for upadacitinib to be a meaningful treatment option for rheumatoid arthritis patients. We continue to build upon our leadership in immunology as we advance the development program for upadacitinib across a broad range of immune-mediated diseases."

Rheumatoid arthritis is a chronic and debilitating disease that affects an estimated 23.7 million people worldwide.13 Despite progress in the treatment of RA, many patients still do not achieve remission or low disease activity targets.14

"This trial strengthens previous upadacitinib study results in patients who do not respond adequately to biologic therapies. For these patients, therapeutic options are limited, and the unmet medical need is high," said Mark Genovese, M.D., professor of immunology and rheumatology, Stanford University and an investigator in the study. "More than half of upadacitinib patients achieved low disease activity by week 24. These results in difficult-to-treat patients further demonstrate the potential of upadacitinib to be an important new treatment option in rheumatoid arthritis."

Results at week 12 showed that of patients receiving an oral once-daily dose of 15 mg or 30 mg upadacitinib, ACR20/50/70* response was achieved in 65/34/12 percent of patients with the 15 mg dose, respectively, and 56/36/23 percent with the 30 mg dose, respectively, compared to 28/12/7 percent in the placebo group.1 These results were statistically significant compared to placebo (p<0.001) for all comparisons except ACR70 for the 15 mg dose.1

Additionally, a significantly higher proportion of upadacitinib patients in both doses achieved LDA and clinical remission targets at week 12 compared to patients receiving placebo (p<0.001).1 Low disease activity was achieved by 43 percent and 42 percent of patients in the 15 mg and 30 mg groups, respectively, compared to 14 percent of patients receiving placebo.1 Clinical remission was achieved by 29 percent and 24 percent of patients in the 15 mg and 30 mg groups, respectively, compared to 10 percent of patients receiving placebo.1

Results continued to be encouraging through week 24.1 Of patients treated with upadacitinib from study entry, ACR20/50/70* response was achieved in 62/43/22 percent of patients with the 15 mg dose and 59/43/24 percent with the 30 mg dose at week 24.1 Low disease activity was achieved by 52 percent of patients receiving either dose of upadacitinib.1 Clinical remission was achieved by 32 percent and 35 percent of patients in the 15 mg and 30 mg groups, respectively.1 Comparisons to placebo cannot be made at week 24, since all placebo patients received either upadacitinib 15 mg or 30 mg beginning at week 12.1

    Week 12 Week 24
Placebo
(PBO)
(n=169)
Upadacitinib
15 mg (n=164)
Upadacitinib
30 mg (n=165)
Upadacitinib
15 mg (n=164)
Upadacitinib
30 mg (n=165)
ACR20* 28% 65% 56% 62% 59%
ACR50* 12% 34% 36% 43% 43%
ACR70* 7% 12% 23% 22% 24%
LDA** 14% 43% 42% 52% 52%
Clinical
Remission***
10% 29% 24% 32% 35%
 
All week 12 endpoints shown in the table achieved p-values of <0.001 versus placebo for both doses except for the 15 mg ACR70 value. ACR50 and ACR70 were not ranked secondary endpoints. Not all ranked and non-ranked secondary endpoints shown. Statistical comparisons to placebo were not conducted for week 24 values since no patients received placebo beyond week 12. Data for week 24 only shown for patients treated with upadacitinib from study entry.
*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) less than 2.6.

In this study, the safety profile of upadacitinib was consistent with previously reported Phase 2 trials and the Phase 3 SELECT-NEXT clinical trial.1-4 No new safety signals were detected.1 During the placebo-controlled period, serious adverse events occurred in 5/7/0 percent of patients in the 15 mg/30 mg/placebo groups, respectively.1 There were two deaths reported during the study.1 One was a patient in the 15 mg dose group with cause of death unknown.1 The second was a patient in the 30 mg dose group who presented with fever and diarrhea, subsequent heart failure and presumed pulmonary embolism (PE) during hospitalization.1 Inclusive of the case mentioned above, a total of two cases of PE and no deep vein thrombosis (DVT) were reported during the placebo-controlled period. In the previously reported Phase 3 SELECT-NEXT trial, no cases of DVT or PE occurred.15 Across the SELECT RA 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.1,4,15-16

Further results of SELECT-BEYOND, the second of six studies in the SELECT RA clinical trial program, will be presented at a future medical meeting and published in a peer-reviewed publication.

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, ankylosing spondylitis and atopic dermatitis.7-12

About SELECT-BEYOND1
SELECT-BEYOND is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of two once-daily doses (15 mg and 30 mg) of upadacitinib in adult patients with moderate to severe rheumatoid arthritis who are on a stable dose of conventional synthetic DMARDs (csDMARDs) and have had an inadequate response or intolerance to bDMARDs. The primary endpoints included the percentage of subjects achieving an ACR20 response and low disease activity (LDA) after 12 weeks of treatment. Secondary endpoints included proportion of patients achieving ACR50 and ACR70 response at week 12. More information on this trial can be found at www.clinicaltrials.gov (NCT02706847).

About the SELECT Study Program                                                                                                        
The robust SELECT Phase 3 RA 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 and inhibition of radiographic progression. More information on this trial 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.5,6 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.7-12

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.

1 AbbVie. Data on File, ABVRRTI64730.
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 AbbVie. Data on File, ABVRRTI64466.
5 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
6 Pipeline – Our Science | AbbVie. AbbVie. 2017. Available at: https://www.abbvie.com/our-science/pipeline.html. Accessed September 7, 2017.
7 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 July 11, 2017.
8 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 July 11, 2017.
9 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 July 11, 2017.
10 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 July 11, 2017.
11 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 on July 19, 2017.
12 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 July 11, 2017.
13 World 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 on July 24, 2017.
14 Curtis JR, Singh JA. The Use of Biologics in Rheumatoid Arthritis: Current and Emerging Paradigms of Care. Clin Ther. 2011 June ; 33(6): 679–707. doi:10.1016/j.clinthera.2011.05.044.
15 AbbVie. Data on File, ABVRRTI64959.
16 Kim SC. Risk of Venous Thromboembolism in Patients with Rheumatoid Arthritis. Arthritis Care & Research. Vol. 65, No. 10, October 2013, pp 1600–1607.

SOURCE: AbbVie

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