AbbVie Presents New Phase 2b Data on Upadacitinib in Atopic Dermatitis

NORTH CHICAGO, Ill., Feb. 17, 2018 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global research and development-based biopharmaceutical company, today presented new positive results from a Phase 2b dose-ranging study evaluating upadacitinib, an investigational, once-daily oral JAK1-selective inhibitor, in adult patients with moderate to severe atopic dermatitis. These results were featured during the “Late-Breaking Research: Clinical Trials” session at the 2018 American Academy of Dermatology (AAD) Annual Meeting in San Diego. Upadacitinib is not approved by regulatory authorities and its safety and efficacy have not been established.

In September of 2017, AbbVie announced positive top-line results from this Phase 2b study, including an evaluation of the primary endpoint - mean percent change in Eczema Area and Severity Index (EASI) at week 16 versus placebo.¹ The press release is available here.

In today’s presentation, across all doses (30/15/7.5 mg once-daily), additional exploratory results showed significant reduction of select symptoms of atopic dermatitis in upadacitinib patients, including reduction in itch (pruritus) at week 1 and improvement in the extent and severity of skin lesions at week 2.¹

“Patients living with atopic dermatitis are seeking relief from the intense itching and skin lesions - which can have a profound impact,” 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. “For this patient population, given the severity of their disease and available targeted therapies, additional options are needed.”

Evaluation of Signs and Severity (Eczema Area and Severity Index)

• In an exploratory analysis, results at week 2 of treatment with upadacitinib showed all dose groups (30/15/7.5 mg once-daily) achieved significant improvement in extent and severity of atopic dermatitis, as measured by the mean percent change in Eczema Area and Severity Index (EASI) score.¹

 Mean Percentage Change from Baseline in EASI Score*** ---------------------------------------------------- Dose Week 2 Week 16 (Primary Endpoint) ---- ------ -------------------------- 30 mg (n=42) 59%* 74%* ----------- --- --- 15 mg (n=42) 56%* 62%* ----------- --- --- 7.5 mg (n=42) 39%* 39%** ------------ --- ---- Placebo (n=39) 9% (n=37) 23% ------------- -------- --- 

 *P<0.001, **P<0.05 ***Eczema Area and Severity Index (EASI) score is a tool used to measure the extent (area) and severity of atopic eczema. 

Evaluation of Reduction in Itch (Pruritus)

• In an exploratory analysis, results at week 1 showed reduction in itch in patients treated with upadacitinib, as measured by the pruritus numerical rating scale (NRS).¹

 Mean Percent Change from Baseline in Pruritus (Itch) Numerical Rating Scale***** -------------------------------------------------------------- Dose Week 1 Week 2 Week 16 ---- ------ ------ ------- 30 mg (n=42) 36%* 58%* 69%* ------- --- --- --- 15 mg (n=37) 28%* 46%* 48%* ------- --- --- --- 7.5 mg (n=40) 19%*(n=39) 29%* (n=39) 40%**** ------- --------- ---------- ------ Placebo (n=37) -1% -2% 10% ------- --- --- --- 

 *P<0.001, ****P<0.01 *****Itch will be rated from 0 (no itch) to 10 (worst imaginable itch). 

The most common adverse events were upper respiratory tract infection, atopic dermatitis worsening and acne.¹ Serious adverse events across treatment groups occurred in 0/1/2 patients in the 30/15/7.5 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 the first 16 weeks of this Phase 2b study.¹

“This study showed that upadacitinib significantly reduced itch and improved skin lesions supporting its potential to be a meaningful treatment option for patients,” said Marek Honczarenko, M.D., Ph.D., vice president, immunology development, AbbVie. “We strive to make a remarkable impact on patients’ lives and we look forward to advancing this development program into registration-enabling studies this year.”

About Atopic Dermatitis
Atopic dermatitis, a chronic inflammatory skin disease, is characterized by skin erosion, oozing and crusting, redness, intense itching and dry skin.¹⁰ Symptoms can appear as a rash on the skin, or the skin may become thickened and leathery.¹¹

About the Phase 2b Upadacitinib Study¹
This dose-ranging 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 not adequately controlled by topical treatments, or for whom topical treatments were not medically advisable. In Period 1, subjects were randomized in a 1:1:1:1 ratio to one of four treatment groups (three dosing groups, 30/15/7.5 mg once-daily, and one placebo group) for 16 weeks. The primary endpoint of the study was mean percentage change from baseline in Eczema Area and Severity Index (EASI) score at 16 weeks in comparison with placebo. 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 disorders.^2,3 Phase 3 trials of upadacitinib in rheumatoid arthritis, psoriatic arthritis and Crohn’s disease are ongoing.^4-6 Upadacitinib is also being evaluated as a potential treatment for ankylosing spondylitis.⁷ AbbVie plans to begin registration-enabling studies in atopic dermatitis, ulcerative colitis and giant cell arteritis this year.^8,9

In January 2018, the U.S. Food and Drug Administration granted Breakthrough Therapy Designation for upadacitinib in adult patients with moderate to severe atopic dermatitis who are candidates for systemic therapy. Breakthrough Therapy Designation is intended to expedite the development and review of medicines with preliminary clinical evidence that indicate that the investigational treatment may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.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 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 are, or may be considered, 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,” of AbbVie’s 2017 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.

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¹ Guttman-Yasky, E et al. Primary Results from a Phase 2b, Randomized, Placebo-Controlled Trial of Upadacitinib for Patients with Atopic Dermatitis. American Academy of Dermatology. February 2018.
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 Pipeline - Our Science | AbbVie. AbbVie. 2017. Available at: https://www.abbvie.com/our-science/pipeline.html. Accessed on January 29, 2018.
⁴ A Study Comparing ABT494 to Placebo in Subjects With Rheumatoid Arthritis on a Stable Dose of Conventional Synthetic DiseaseModifying Antirheumatic Drugs (csDMARDs) Who Have an Inadequate Response to csDMARDs Alone (SELECT-NEXT). ClinicalTrials.gov. 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT02675426. Accessed on January 29, 2018.
⁵ A Study Comparing Upadacitinib (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). ClinicalTrials.gov. 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT03104400. Accessed on January 29, 2018.
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. ClinicalTrials.gov. 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT02365649. Accessed on January 29, 2018.
⁷ A Study Evaluating the Safety and Efficacy of Upadacitinib in Subjects With Active Ankylosing Spondylitis (SELECT Axis 1). ClinicalTrials.gov. 2018. Available at: https://clinicaltrials.gov/ct2/show/study/NCT03178487. Accessed on January 29, 2018.
⁸ 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. ClinicalTrials.gov. 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT02819635. Accessed on January 29, 2018.
⁹ Phase 2b AD Dose Ranging Study (40wk) N=160. ClinicalTrials.gov. 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT02925117. Accessed on January 29, 2018.
¹⁰ Hebert AA. Review of pimecrolimus cream 1% for the treatment of mild to moderate atopic dermatitis. Clin Ther. 2006;28(12): 1972-82.
¹¹ Williams HC. Clinical practice. Atopic dermatitis. N Engl J Med. 2005;352(22):2314-24. ¹² U.S. Food and Drug Administration.
¹² Fact Sheet: Breakthrough Therapies. https://www.fda.gov/RegulatoryInformation/LawsEnforcedbyFDA/SignificantAmendmentstotheFDCAct/FDASIA/ucm329491.htm. Accessed on January 29, 2018.

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