AbbVie's Upadacitinib (ABT-494) Meets Primary Endpoint in Phase 2b Study in Atopic Dermatitis

NORTH CHICAGO, Ill., Sept. 7, 2017 /PRNewswire/ -- AbbVie ABBV, a global research and development based biopharmaceutical company, today announced positive top-line results from the Phase 2b randomized, placebo-controlled, dose-ranging study of upadacitinib (ABT-494), an investigational, once-daily oral JAK1-selective inhibitor, in adult patients with moderate to severe atopic dermatitis not adequately controlled by topical treatments, or for whom topical treatments were not medically advisable.¹ In this study, all upadacitinib dose groups (30/15/7.5 mg once-daily) met the primary endpoint (mean percent change in EASI at week 16 versus placebo).¹ Upadacitinib is not approved by regulatory authorities and safety and efficacy have not been established.

"We are excited by the results of this study, which show that upadacitinib has the potential to be an important treatment option for patients with atopic dermatitis," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "We look forward to advancing upadacitinib to Phase 3 studies in 2018. AbbVie's continued progress across our upadacitinib clinical development program further demonstrates that selective inhibition of the JAK1 pathway may be a novel therapeutic approach across a broad range of immune-mediated diseases."

Results at week 16 showed that across all doses, the primary and all skin and itch-specific secondary endpoints, patients treated with upadacitinib achieved improvements that were statistically significant compared to placebo (p<0.05).¹ Additionally, reduction in itch was observed within the first week and improvement in skin within the first two weeks (p<0.001 across all doses).¹

"Atopic dermatitis is a serious, chronic skin disease that can have a negative impact on patients' lives," said Emma Guttman-Yassky, M.D., Ph.D., Professor of Dermatology and Immunology, Icahn School of Medicine at Mount Sinai Medical Center and lead study investigator. "I am very encouraged that itch reduction was achieved within the first week and that up to half of patients achieved a 90 percent or more improvement in skin lesions (EASI 90) by week 16. These are both major concerns for patients with atopic dermatitis. With these results upadacitinib has the potential to be an important treatment option for patients."

The primary endpoint of mean percentage change from baseline in the EASI score, a measure of the extent and severity of atopic dermatitis, was achieved by 74/62/39 percent of patients receiving the 30/15/7.5 mg doses of upadacitinib, respectively, compared to 23 percent for patients receiving placebo (p<0.001/0.001/0.05, respectively).¹ A 75 percent improvement in disease (EASI 75) was achieved by 69/52/29 percent of patients receiving the 30/15/7.5 mg doses of upadacitinib respectively, compared to 10 percent for patients receiving placebo (p<0.001/0.001/0.05, respectively).¹ Disease improvement of 90 percent or more (EASI 90) was achieved by 50/26/14 percent of patients receiving the 30/15/7.5 mg doses of upadacitinib, respectively, compared to 2 percent for patients receiving placebo (p<0.001/0.01/0.05, respectively).¹ Correspondingly, clear or almost clear skin was achieved by 50/31/14 percent of patients receiving the 30/15/7.5 mg doses of upadacitinib, as measured by the Investigator's Global Assessment scale (IGA 0 or 1), compared to 2 percent of patients receiving placebo (p<0.001/0.001/0.05, respectively).¹ 

In addition, significant improvement was observed with respect to pruritus (itch). Patients treated with upadacitinib experienced 69/48/40 percent improvement in itch across the 30/15/7.5 mg upadacitinib doses, as measured by the pruritus numerical rating scale (NRS), compared to 10 percent for patients receiving placebo (p<0.001/0.001/0.01, respectively).¹

In this study, no new safety signals were detected.¹ The most common adverse events were upper respiratory tract infection, atopic dermatitis and acne.¹ Serious adverse events across treatment groups occurred in 2/1/0 patients in the 7.5/15/30 mg groups compared to 1 patient on placebo.¹ No herpes zoster, malignancies, deaths or cases of pulmonary embolism (PE) or deep vein thrombosis (DVT) occurred in this Phase 2b study.¹ The safety profile of upadacitinib in this patient population will be further evaluated in the Phase 3 program.

Additional data 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.

AbbVie is continuing to evaluate the potential of upadacitinib across several immune-mediated conditions. Phase 3 trials of upadacitinib in rheumatoid arthritis and psoriatic arthritis are ongoing and it is also being investigated to treat Crohn's disease, ulcerative colitis and ankylosing spondylitis.^4-9

About the Phase 2b Upadacitinib Study¹
This study is an ongoing 88-week Phase 2b, randomized, double-blind, parallel-group, placebo-controlled multicenter study designed to evaluate the safety and efficacy of upadacitinib in adult patients with moderate to severe atopic dermatitis. In Period 1, subjects were randomized in a 1:1:1:1 ratio to one of four treatment groups (three dosing groups and one placebo group) for 16 weeks. The primary endpoint of the study was mean percentage change in Eczema Area and Severity Index (EASI) score at 16 weeks in comparison with placebo. Key secondary endpoints included proportion of patients achieving EASI 90, EASI 75, an Investigator Global Assessment (IGA) of 0 or 1 and percent change in pruritus/itch numerical rating scale from day 1 (baseline) to week 16 in comparison with placebo. More information on this trial can be found at www.clinicaltrials.gov (NCT02925117).

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 inflammatory disorders.^2,3 Phase 3 trials of upadacitinib in rheumatoid arthritis and psoriatic arthritis are ongoing and it is also being investigated to treat Crohn's disease, ulcerative colitis and ankylosing spondylitis.^4-9

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. Upadacitinib AD Phase 2b Press Release 05SEPT2017
[2] 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
[3] O'Shea JJ, Plenge R. JAK and STAT signaling molecules in immunoregulation and immune-mediated disease. Immunity 2012;(36):542–550.
[4] 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 August 11, 2017.
[5] 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 August 11, 2017.
[6] 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 August 11, 2017.
[7] A Study to Evaluate the Safety and Ecacy 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 August 11, 2017.
[8] A Study Evaluating the Safety and Ecacy 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 August 11, 2017.
[9] 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 August 11, 2017.

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