May 9, 2017

AbbVie Announces Positive Phase 2 Study Results for Upadacitinib (ABT-494), an Investigational JAK1-Selective Inhibitor, in Crohn's Disease

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- Phase 2 study showed positive results in a moderately to severely active Crohn's disease patient population, the majority of whom had previously failed two or more biologics
- Promising Phase 2 dose-ranging study supports advancement to Phase 3
- Safety profile of upadacitinib in this Crohn's disease study was consistent with that observed in the upadacitinib investigational rheumatoid arthritis clinical trials

NORTH CHICAGO, Ill., May 9, 2017 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced promising results from CELEST, a Phase 2, randomized, double-blind, placebo-controlled study evaluating upadacitinib (ABT-494), an investigational oral JAK1-selective inhibitor, in adult patients with moderately to severely active Crohn's disease. These data are being presented today during the Clinical Science: Late-Breaking Abstract Plenary Session (Presentation #874h) at Digestive Disease Week® 2017.

"Crohn's disease is a serious, chronic disease with symptoms and complications that can have a major impact on patients' daily lives, and additional treatments are needed to improve the prognosis for many living with the disease," said William Sandborn, M.D., study investigator and director, Inflammatory Bowel Disease Center chief, Division of Gastroenterology and Professor of Medicine at the University of California, San Diego. "The CELEST study included patients with difficult-to-treat Crohn's disease who failed two or more biologics. These positive results support advancement into Phase 3 to further explore a potential new treatment option that may address the unmet needs of patients living with this challenging disease."

The Phase 2 study evaluated the safety and efficacy of multiple dosing regimens of upadacitinib after 16 weeks of treatment. The positive results support advancement of the program into Phase 3. Results showed that more patients achieved endoscopic remission with upadacitinib compared to placebo, specifically within the 24 mg twice daily treatment group 22 percent of patients (n=8/36) achieved endoscopic remission with upadacitinib compared to 0 percent of patients (n=0/37, P≤0.01) taking placebo. Additionally, significantly more patients receiving upadacitinib 6 mg twice daily achieved clinical remission (27 percent, n=10/37) compared to placebo (11 percent, n=4/37, P≤0.1). Secondary endpoint results included the finding that nearly twice as many patients achieved clinical response with upadacitinib (61 percent, n=22/36 and 57 percent, n=21/37 in the 24 mg and 6 mg twice daily groups, respectively) compared with the placebo group (32 percent, n=12/37, P≤0.05 for both comparisons). Significantly more patients receiving upadacitinib doses greater than or equal to 6 mg twice daily achieved endoscopic response compared to placebo (P≤0.01 for all comparisons).1

"Results from CELEST are encouraging and provide new information to the gastroenterology community on the potential for upadacitinib as an oral treatment option for patients with Crohn's disease," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "For nearly two decades, AbbVie has pioneered research in immune-mediated diseases, and these findings demonstrate our commitment to meaningful scientific innovation with the potential to improve patient lives."

In this study, the safety profile was consistent with that observed in the upadacitinib investigational rheumatoid arthritis clinical trials. While overall adverse events (AEs) and infections were numerically higher with upadacitinib than placebo, these events did not appear to be dose-related in this Phase 2 study.1 Serious AEs and discontinuations were similar in all groups, except for numerically greater events in the 12 mg twice daily group.1 One case of non-melanoma skin cancer was reported in the 24 mg twice daily group.1 One death was reported during screening, but the patient did not receive study drug.1

About CELEST Study1

CELEST is a Phase 2, multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of multiple dosing regimens of upadacitinib in adult patients with moderately to severely active Crohn's disease. Patients had a Crohn's Disease Activity Index score between 220-450, an average daily liquid/soft stool frequency (SF) ≥2.5 or daily abdominal pain (AP) score ≥2.0, and Simplified Endoscopic Score for Crohn's Disease (SES-CD) ≥6 or ≥4 for those with isolated ileal disease. A history of inadequate response to or intolerance to immunomodulators or TNF inhibitors was also required for enrollment in the study. Of the 220 enrolled patients, 96 percent had failed, or were intolerant to, one or more TNF inhibitors. Patients were randomized to double-blind induction therapy with placebo or upadacitinib at 3, 6, 12, 24 mg twice daily or 24 mg once daily for 16 weeks, followed by blinded extension therapy for 36 weeks. Of the 220 subjects, 180 (82 percent) completed 16 weeks of induction treatment. The co-primary endpoints were the proportion of patients who achieved clinical remission (SF ≤1.5 and AP ≤1, and both not worse than baseline) at week 16 and endoscopic remission (SES-CD ≤4 and ≥2 point reduction from baseline, no subscore >1) at week 12 or 16. Secondary endpoints included clinical response (≥30 percent reduction from baseline in SF or AP with neither worse than baseline) at week 16 and endoscopic response (≥25 percent decrease in SES-CD) at week 12 or 16.

The trial is ongoing and will evaluate patients up to 52 weeks. More information can be found on (NCT02365649).

About Upadacitinib
Pioneered by AbbVie, upadacitinib is an investigational oral compound engineered to selectively inhibit JAK1, which plays an important role in the pathophysiology of Crohn's disease. Phase 3 trials of upadacitinib in rheumatoid arthritis and psoriatic arthritis are ongoing and it is also being investigated to treat ulcerative colitis and atopic dermatitis.

Upadacitinib is an investigational medicine 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 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 Sandborn WJ, Feagan B, Panes J, et al. Safety and Efficacy of ABT-494, an oral JAK1 inhibitor, as induction therapy in patients with Crohn's disease: Results from CELEST. Digestive Disease Week; May 6-9, 2017; Chicago, IL. Presentation 874h.

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