AbbVie Presents Upadacitinib Longer-Term (32-Week) and Patient-Reported Outcomes Data from Phase 2b Atopic Dermatitis Study at 27th European Academy of Dermatology and Venereology (EADV) Congress

- Across all doses, a significantly greater proportion of patients who remained on upadacitinib showed continuous improvements in skin lesions and pruritus (itch) at week 32 compared to patients re-randomized to placebo[1]

- At week 32, patients who switched from placebo to upadacitinib 30 mg at week 16 showed greater improvements in skin lesions and itch compared to those remaining on placebo[1]

- Results from an additional analysis of a subset of patients receiving upadacitinib 30 mg reported greater improvements in itch and sleep disturbance compared to those receiving placebo at week 16[2]

- Upadacitinib, an investigational oral agent engineered by AbbVie to selectively inhibit JAK1, is being studied as a once-daily therapy in atopic dermatitis and the Phase 3 clinical program was initiated in August 2018[3],[4]

News provided by

AbbVie

Sep 13, 2018, 09:20 ET

NORTH CHICAGO, Ill., Sept. 13, 2018 /PRNewswire/ -- AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced new results from the ongoing Phase 2b study including longer-term (32-week) efficacy and safety data and patient-reported outcomes data evaluating upadacitinib, an investigational, once-daily oral JAK1-selective inhibitor, in adult patients with moderate to severe atopic dermatitis.^1,2 Results from a pre-specified, interim analysis from the Phase 2b dose-ranging study showed that treatment with upadacitinib 7.5 mg, 15 mg or 30 mg resulted in greater improvements in itch and skin lesions, with statistically significant differences observed versus placebo at week 32.¹ Additionally, results from a further analysis of a subset of patients showed that upadacitinib improved patient-reported itch and impact on sleep due to atopic dermatitis in patients receiving upadacitinib (30 mg, once-daily) compared to placebo at week 16.² Data from these two analyses will be presented today at the 27th European Academy of Dermatology and Venereology (EADV) Congress in Paris. Upadacitinib is not approved by regulatory authorities and its safety and efficacy have not been established.

"Results from this study increase our understanding of upadacitinib's potential to be an important treatment option for patients living with atopic dermatitis," said Marek Honczarenko, M.D., Ph.D., vice president, global immunology development, AbbVie. "At AbbVie, we continuously strive to discover and develop innovative medicines for patients who are in need of more treatment options that advance standards of care and improve quality of life. Data from the mid-stage clinical study support the recent advancement of upadacitinib into Phase 3 clinical studies and underscore our commitment to patients with atopic dermatitis."

Atopic dermatitis is a common chronic, relapsing, inflammatory skin disease with associated comorbidities.⁵ One-third of atopic dermatitis patients have moderate to severe disease, which manifests as a debilitating, itchy rash with significant physical, psychological and economic burden.^5,6 There is a large unmet need for therapies that are effective to manage the signs and symptoms of moderate to severe atopic dermatitis.

"The symptoms associated with atopic dermatitis can have a profound impact on patients' quality of life, causing serious discomfort and pain, and impacting their ability to sleep," said Jonathan Silverberg, M.D., Ph.D., M.P.H., Associate Professor of Dermatology, Medical Social Sciences and Preventive Medicine, Northwestern University Feinberg School of Medicine and lead study investigator. "The patient-reported outcome results presented at EADV are encouraging, and provide further insight into the improvement provided by upadacitinib in patients with moderate to severe atopic dermatitis."

Longer-Term Results at Week 32¹

These results are from an interim analysis at week 32 of an ongoing Phase 2b study entitled, "Efficacy and Safety of Upadacitinib Treatment Over 32 Weeks for Patients with Atopic Dermatitis from a Phase 2b, Randomized, Placebo-Controlled Trial" (P0236).¹ At week 16, patients in each upadacitinib group were re-randomized in a 1:1 ratio to continue on the Period 1 dose (7.5/15/30 mg, once-daily) or to placebo (withdrawal), while the Period 1 placebo group was re-randomized to receive upadacitinib (30 mg, once-daily) or placebo.¹ Four weeks following re-randomization (week 20), blinded rescue therapy with upadacitinib (30 mg, once-daily) was provided after the first instance of a less than EASI 50 response.¹

Results showed that patients treated with upadacitinib across all dose groups (7.5/15/30 mg, once-daily) achieved significant improvement in extent and severity of atopic dermatitis, as measured by the mean percent improvement from baseline in the Eczema Area and Severity Index (EASI) score.¹ For patients receiving upadacitinib, the mean percent improvement from baseline in the EASI score was 48/44/69 percent for the 7.5/15/30 mg doses, respectively, compared to 34 percent for patients receiving placebo.¹Among patients receiving placebo in Period 1 and re-randomized to receive the upadacitinib 30 mg dose in Period 2, the mean percent improvement from baseline in the EASI score was 97 percent at week 32.¹

Additionally, significant improvement in pruritus (itch) from baseline was observed across all upadacitinib treatment groups at week 32.¹Patients re-randomized to upadacitinib achieved a 53/44/61 percent improvement in itch across the 7.5/15/30 mg doses, respectively, compared to 6 percent worsening in itch for patients receiving placebo, as measured by the pruritus numerical rating scale (NRS).¹

Efficacy Results at Week 32¹
Period 1 Dose	PBO		UPA 7.5 mg		UPA 15 mg		UPA 30 mg
Period 2 Dose	PBO (n=10)	UPA 30 mg (n=10)	PBO (n=15)	UPA 7.5 mg (n=16)	PBO (n=19)	UPA 15 mg (n=18)	PBO (n=19)	UPA 30 mg (n=19)
Mean Percent Improvement from Baseline in EASI Score^a	34%	97%***	9%	48%*	12%	44%*	22%	69%**
Mean Percent Improvement from Baseline in Pruritus/Itch Numerical Rating Scale^b	-6%	94%***	-6%	53%**	3%	44%**	-13%	61%***

*p<0.05, **p<0.01, ***p<0.001

^aEczema Area and Severity Index (EASI) score is a tool used to measure the extent (area) and severity of atopic dermatitis

^bItch was rated from 0 (no itch) to 10 (worst imaginable itch)

In this study, no new safety signals were detected.¹ There were two serious adverse events in the placebo group re-randomized to receive upadacitinib 30 mg, including one serious infection and one case of non-melanoma skin cancer.¹No cardiovascular events (adjudicated), malignancies other than non-melanoma skin cancer, deep vein thrombosis (DVT) or pulmonary embolism (PE) occurred through week 32 in the Phase 2b study.¹

AbbVie has previously announced positive results from the Phase 2b study in February 2018 and September 2017.

Patient-Reported Outcomes at Week 16: Itch, Skin Pain and Impact on Sleep Due to Atopic Dermatitis²

Results from an additional analysis in a subset of patients through week 16 showed that patients treated with upadacitinib had improvements on patient-reported outcomes covering itch and the impact of atopic dermatitis on sleep.² In the study, patients completed a symptom and impact questionnaire daily, which included three items to assess itch and skin pain (itch during sleep, itch while awake, skin pain) and three items to assess impact on sleep (difficulty falling asleep, sleep impact, bother from waking up at night).²

Improvements on all measures were observed as early as week 2 for all upadacitinib dose groups compared to placebo.² At week 16, only the upadacitinib 30 mg group showed improvements on all measures except skin pain.²

Patient-reported outcomes are an important component of understanding how patients perceive the physical, psychological and social burden of their disease.⁷ Using patient-reported outcomes data to assess the impact of the disease allows patients to take an active role in their treatment journey, providing valuable insight to their healthcare teams.

About the Phase 2b Upadacitinib Study¹

Interim results were reported from an ongoing, 88 week dose-ranging, randomized, double-blind, parallel-group, placebo-controlled multicenter Phase 2b 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 (16 weeks), subjects were randomized in a 1:1:1:1 ratio to one of four treatment groups (three upadacitinib dosing groups, 7.5/15/30 mg, once-daily, and one placebo group). In Period 2 (72 weeks), each upadacitinib group was re-randomized in a 1:1 ratio to continue the Period 1 dose or placebo (withdrawal). Patients randomized to placebo in Period 1 were re-randomized at week 16 to either upadacitinib 30 mg once-daily or placebo. After four weeks of re-randomization (week 20), rescue therapy with upadacitinib 30 mg once-daily was provided after the first instance of a less than EASI 50 response. The primary endpoint of the study was the mean percentage change from baseline in Eczema Area and Severity Index (EASI) score at 16 weeks. Secondary endpoints included the proportion of patients achieving EASI 90, EASI 75, Investigator Global Assessment (IGA) of 0 or 1 and percent change in pruritus/itch numerical rating scale (NRS). More information on this trial can be found at www.clinicaltrials.gov (NCT02925117).

About Upadacitinib

Discovered and developed by AbbVie, upadacitinib is a once-daily oral, small molecule JAK1-selective inhibitor being developed for moderate to severe atopic dermatitis and other immune-mediated diseases.^3,4Phase 3 trials of upadacitinib in rheumatoid arthritis, psoriatic arthritis and Crohn's disease are ongoing and it is also being investigated to treat ulcerative colitis, ankylosing spondylitis and atopic dermatitis.^8-13

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.

References

Guttman-Yassky, E et al. ePoster #P0236. 27th European Academy of Dermatology and Venerology (EADV) Congress. September 2018.
Silverberg, J et al. Presentation #FC04.03. 27th European Academy of Dermatology and Venerology (EADV) Congress. September 2018.
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.
Pipeline – Our Science | AbbVie. AbbVie. 2018. Available at: https://www.abbvie.com/our-science/pipeline.html. Accessed on September 6, 2018.
Nutten S, Atopic Dermatitis: Global Epidemiology and Risk Factors. Ann Nutr Metab 2015;66(suppl 1):8-16 2. Accessed on September 6, 2018.
Wei, W, et al. Discordance Between Physician- and Patient-Reported Disease Severity in Adults with Atopic Dermatitis: A US Cross-Sectional Survey. Am J Clin Dermatol. 2017; 18(6): 825–835.
Deshpande, PR et al. Patient-reported outcomes: A new era in clinical research. Perspect Clin Res. 2011 Oct-Dec; 2(4): 137–144.
A Study Comparing ABT494 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). ClinicalTrials.gov. 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT02675426. Accessed on September 6, 2018.
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 September 6, 2018.
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 September 6, 2018.
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 September 6, 2018.
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 September 6, 2018.
Phase 2b AD Dose Ranging Study (40wk) N=160. ClinicalTrials.gov. 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT02925117. Accessed on September 6, 2018.