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Positive Phase 2b Data for AbbVie's Upadacitinib Show Significant Induction of Clinical Remission and Response in Patients with Ulcerative Colitis

Rinvoq (upadacitinib) Now FDA Approved - August 16, 2019

NORTH CHICAGO, Ill., Oct. 22, 2018 /PRNewswire/ -- AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced positive results from U-ACHIEVE, an ongoing Phase 2b/3 dose-ranging study evaluating upadacitinib, an investigational JAK1-selective inhibitor, for induction and maintenance therapy in adult patients with moderately to severely active ulcerative colitis.1 After 8 weeks, upadacitinib (15/30/45 mg, once daily) met the primary endpoint of clinical remission (per Adapted Mayo Score) and all ranked secondary endpoints.1 These clinical data, in addition to patient-reported outcomes data from the study, are being presented at United European Gastroenterology (UEG) Week 2018 in Vienna, Austria. Upadacitinib is not approved by regulatory authorities and its safety and efficacy have not been established.

"While treatment of ulcerative colitis has come a long way, patients are still in need of therapies like upadacitinib that have the potential to provide disease control," said Marek Honczarenko, M.D., Ph.D., vice president, global immunology development, AbbVie. "These results support the initiation of the Phase 3 clinical trial program to further evaluate upadacitinib in ulcerative colitis, underscoring AbbVie's unwavering commitment to the development of treatment options for those living with inflammatory bowel disease."

The study showed that significantly more patients achieved clinical remission (per Adapted Mayo score) with upadacitinib (14/14/20 percent of patients in the 15/30/45 mg groups) compared to placebo (0 percent) at week 8.1 Additionally, key secondary endpoints were also achieved at week 8 across the upadacitinib 15/30/45 mg groups, including endoscopic improvement, clinical remission (per Full Mayo Score) and clinical response (per Adapted Mayo Score).1 The upadacitinib 7.5 mg group did not meet the primary endpoint.1 These results are being presented today during an oral presentation entitled "Efficacy and safety of upadacitinib as an induction therapy for patients with moderately to severely active ulcerative colitis: data from the phase 2b study U-ACHIEVE" from 2:12 – 2:24 p.m. CEST.

U-ACHIEVE Efficacy Results at Week 81

Upadacitinib

Placebo

(n=46)

7.5 mg

once-daily

(n=47)

15 mg

once-daily

(n=49)

30 mg

once-daily

(n=52)

45 mg

once-daily

(N=56)

Clinical remission (per Adapted Mayo Score)a

9%

14%*

14%*

20%**

0%

Endoscopic improvementb

15%*

31%***

27%***

36%***

2%

Clinical remission (per Full Mayo Score)c

9%

10%*

12%*

20%**

0%

Clinical response (per Adapted Mayo Score)d

30*

45%***

44%***

50%***

13%

*p<0.05, **p<0.01, ***p<0.001
aClinical remission (Adapted Mayo Score [Mayo Score without Physician Global Assessment]) is defined as stool frequency subscore (SFS)<1, rectal bleeding subscore (RBS)=0, and endoscopic subscore (ES)<1.
bEndoscopic improvement is defined as an ES<1.
cClinical remission (per Full Mayo Score) is defined as a Full Mayo Score < 2 with no subscore >1.
dClinical response (per Adapted Mayo Score) is defined as a decrease from baseline in the Adapted Mayo score >2 points and >30% from baseline, plus a decrease in RBS >1 or an absolute RBS <1.

In this study, the safety profile was consistent with that observed in the previously reported Phase 2 Crohn's disease study.1 No new safety signals were detected.1 Serious adverse events occurred in 0/4/6/5 percent of the 7.5/15/30/45 mg upadacitinib groups, respectively, compared to 11 percent in the placebo group.1 Serious infections occurred in 0/2/0/4 percent of the 7.5/15/30/45 mg upadacitinib groups, respectively, compared to 4 percent in the placebo group.1 One event of herpes zoster with the upadacitinib 45 mg dose and one malignancy (malignant melanoma) with the upadacitinib 7.5 mg dose were reported. No venous thromboembolic events, major adverse cardiovascular events or deaths occurred.1

"Ulcerative colitis can be a difficult disease to manage with symptoms that can significantly impact patients' daily lives," 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 and lead study investigator. "The U-ACHIEVE study included patients with difficult-to-treat ulcerative colitis, the majority of whom had failed multiple previous therapies, including biologics. These results further extend our understanding of upadacitinib's potential as an important treatment option for ulcerative colitis patients."

Data from two separate analyses of U-ACHIEVE showing the impact of upadacitinib on patient-reported outcomes were also presented at UEG Week. Results from one analysis showed that patients treated with upadacitinib reported greater improvements in ulcerative colitis symptoms, including bowel urgency, abdominal pain, rectal bleeding and stool frequency, compared to placebo.2 This presentation, entitled "Induction Therapy of Upadacitinib is Associated with Improved Symptoms in Bowel Urgency and Abdominal Pain for Patients with Ulcerative Colitis: Data from U-ACHIEVE," was featured during the Poster Champ Session on Monday, October 22 from 12:40 – 12:45 p.m. CEST. This session highlights the top 12 poster presentations of the day, selected by the UEG Week Scientific Committee. In another analysis, more patients treated with upadacitinib reported significant and clinically meaningful improvements in disease-specific and general health-related quality of life, fatigue, work productivity and the ability to perform daily activities after 8 weeks of treatment compared to placebo.3 This poster, entitled "Improved Patient-Reported Outcomes with Upadacitinib as an Induction Therapy for Patients with Ulcerative Colitis: Data from U-ACHIEVE" was presented during the poster session IBD I on Monday, October 22.

Patient-reported outcomes are an important component of understanding how patients perceive the physical, psychological and social burden of their disease.12 Using patient-reported outcomes data to assess the impact of the disease provides valuable insight to healthcare teams.12

About the U-ACHIEVE Study1

U-ACHIEVE is an ongoing Phase 2b/3 multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of upadacitinib for induction and maintenance therapy in subjects with moderately to severely active ulcerative colitis. The objective of the Phase 2b part of the study was to characterize the dose-response, efficacy and safety of upadacitinib compared to placebo in inducing clinical remission in order to identify the induction dose of upadacitinib for further evaluation in Phase 3 studies. Patients enrolled in the study had an inadequate response, loss of response or intolerance to corticosteroids, immunosuppressants or biologic therapies. Patients were randomized to receive induction therapy with placebo or upadacitinib 7.5, 15, 30 or 45 mg once daily for 8 weeks. The primary endpoint of the Phase 2b study was the proportion of patients who achieved clinical remission (defined as stool frequency subscore [SFS] ≤1, rectal bleeding subscore [RBS] of 0 and endoscopic subscore [ES] ≤1) at week 8. Secondary endpoints included endoscopic improvement (ES ≤1), clinical remission (per Full Mayo score ≤2 with no subscore >1) and clinical response (decrease from baseline in the Adapted Mayo score >2 points and >30 percent from baseline in the Adapted Mayo Score, plus a decrease in RBS >1 or an absolute RBS <1) at week 8. More information can be found on www.clinicaltrials.gov (NCT02819635).

About the Upadacitinib Phase 3 Ulcerative Colitis Program10,13,14

The global upadacitinib Phase 3 ulcerative colitis program evaluates more than 1,300 patients with moderately to severely active ulcerative colitis across three pivotal studies. These studies include assessments of efficacy, safety and tolerability of upadacitinib. Key measures of efficacy include clinical remission per Adapted Mayo Score, clinical response per Adapted Mayo Score, endoscopic improvement and endoscopic response. More information on these trials can be found at www.clinicaltrials.gov (NCT02819635, NCT03653026, NCT03006068).

About Upadacitinib

Discovered and developed by AbbVie, upadacitinib is a once-daily oral, small molecule JAK1-selective inhibitor being developed for moderately to severely active ulcerative colitis and other immune-mediated diseases.4,5 Phase 3 trials of upadacitinib in rheumatoid arthritis, psoriatic arthritis, Crohn's disease, ulcerative colitis and atopic dermatitis are ongoing and it is also being investigated to treat ankylosing spondylitis.6-11

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, LinkedIn or Instagram.

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:

1. Sandborn, W.J., et al. Presentation #OP195. United European Gastroenterology (UEG) Week 2018. October 23, 2018.
2. Ghosh, S., et al. Presentation #P0348. United European Gastroenterology (UEG) Week 2018. October 22, 2018.
3. Ghosh, S., et al. Presentation #P0336. United European Gastroenterology (UEG) Week 2018. October 22, 2018.
4. Parmentier J, Voss J, Graff C et al. In vitro and in vivo characterization of the JAK1 selectivity of upadacitinib (ABT-494). BMC Rheumatology. 2018;2(1).
5. Pipeline – Our Science | AbbVie. AbbVie. 2018. Available at: https://www.abbvie.com/our-science/pipeline.html. Accessed on September 25, 2018.
6. A Study Comparing Upadacitinib (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). ClinicalTrials.gov. 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT02675426. Accessed on September 25, 2018.
7. 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 25, 2018.
8. 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 25, 2018.
9. 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 25, 2018.
10. A Study to Evaluate the Safety and Efficacy of Upadacitinib (ABT-494) for Induction and Maintenance Therapy in Subjects With Moderately to Severely Active Ulcerative Colitis (UC). ClinicalTrials.gov. 2018. Available at: https://clinicaltrials.gov/ct2/show/record/NCT02819635. Accessed on September 25, 2018.
11. A Study to Evaluate ABT-494 (Upadacitinib) in Adult Subjects with Moderate to Severe Atopic Dermatitis. ClinicalTrials.gov. 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT02925117. Accessed on September 25, 2018.
12. Deshpande, PR et al. Patient-reported outcomes: A new era in clinical research. Perspect Clin Res. 2011 Oct-Dec; 2(4): 137–144.
13. A Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Participants With Moderately to Severely Active Ulcerative Colitis. ClinicalTrials.gov. 2018. Available at: https://clinicaltrials.gov/ct2/show/record/NCT03653026. Accessed on September 25, 2018.
14. A Study to Evaluate the Long-Term Safety and Efficacy of Upadacitinib (ABT-494) in Subjects With Ulcerative Colitis (UC). ClinicalTrials.gov. 2018. Available at: https://clinicaltrials.gov/ct2/show/record/NCT03006068. Accessed on September 25, 2018.

SOURCE AbbVie

Posted: October 2018

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