– Significantly more upadacitinib-treated (45 mg) patients achieved clinical remission (primary endpoint per Adapted Mayo Score) at week 8 compared to placebo in adults with moderate to severe ulcerative colitis[1]
– All ranked secondary endpoints, including clinical, endoscopic and histologic outcomes, were met[1]
– The safety results in this study were consistent with the known profile of upadacitinib, with no new safety risks observed[1-5]
– Upadacitinib, a selective and reversible JAK inhibitor discovered and developed by AbbVie, is being studied as an oral therapy for moderate to severe ulcerative colitis and several other immune-mediated diseases[1,6-14]
– Ulcerative colitis is a chronic, systemic, inflammatory disease caused by inflammation of the large intestine[15-17]
NORTH CHICAGO, IL, USA I December 9, 2020 I AbbVie (NYSE: ABBV) today announced positive results from the Phase 3 induction study, U-ACHIEVE, which showed upadacitinib (45 mg, once daily) met the primary endpoint of clinical remission (per Adapted Mayo Score) at week 8, as well as all ranked secondary endpoints, in adult patients with moderate to severe ulcerative colitis.1 In the study, 26 percent of patients receiving upadacitinib achieved clinical remission compared to 5 percent of patients receiving placebo (p<0.001).1 U-ACHIEVE is the first of two Phase 3 induction studies to evaluate the safety and efficacy of upadacitinib in adults with moderate to severe ulcerative colitis.1
“Despite the availability of multiple treatment options with varying mechanisms of action, many patients still do not achieve disease control,” said Michael Severino, M.D., vice chairman and president, AbbVie. “We are encouraged by these results showing upadacitinib’s potential to improve clinical, endoscopic and histologic outcomes in patients with ulcerative colitis.”
Significantly more upadacitinib-treated patients achieved endoscopic improvement at week 8 compared to patients receiving placebo (36 percent versus 7 percent; p<0.001).1 Furthermore, 30 percent of patients treated with upadacitinib achieved histologic-endoscopic mucosal improvement at week 8, versus 7 percent of those receiving placebo (p<0.001).1 A greater proportion of patients treated with upadacitinib achieved clinical response (per Adapted Mayo Score) at week 8 compared to placebo (73 percent versus 27 percent; p<0.001), and 60 percent of upadacitinib-treated patients experienced clinical response (per partial Adapted Mayo Score) at week 2, versus 27 percent on placebo (p<0.001).1
“Ulcerative colitis is a complex disease to manage, and many patients do not achieve relief from symptoms,” said Silvio Danese, M.D., lead study investigator and head of the Inflammatory Bowel Diseases Centre at Humanitas Research Hospital, Milan, Italy. “I am excited about these positive results showing the potential of upadacitinib to alleviate symptoms and control mucosal inflammation in patients with moderate to severe ulcerative colitis.”
U-ACHIEVE Efficacy Results at Week 8*,1 | ||
Upadacitinib 45 mg, once daily (n=319) |
Placebo (n=154) |
|
Clinical remission (Adapted Mayo Score)a,† | 26% | 5% |
Clinical response (Adapted Mayo Score)b,† | 73% | 27% |
Endoscopic improvementc,† | 36% | 7% |
Histologic-endoscopic mucosal improvementd,† | 30% | 7% |
*Primary endpoint was clinical remission (per Adapted Mayo Score). Clinical response (per Adapted Mayo Score), endoscopic improvement and histologic-endoscopic mucosal improvement were ranked secondary endpoints. Not all ranked secondary endpoints are shown. All primary and ranked secondary endpoints achieved p-values of <0.001 versus placebo. | ||
aClinical remission per Adapted Mayo Score is defined as stool frequency subscore (SFS) ≤1 and not greater than baseline, rectal bleeding subscore (RBS) of 0 and endoscopic subscore ≤1. | ||
b Clinical response per Adapted Mayo Score is defined as a decrease from baseline in the Adapted Mayo score ≥2 points and ≥30 percent from baseline, plus a decrease in RBS ≥1 or an absolute RBS ≤1. | ||
cEndoscopic improvement is defined as endoscopic subscore ≤1. | ||
dHistologic-endoscopic mucosal improvement is defined as endoscopic subscore of 0 or 1 and Geboes score ≤3.1. | ||
†Evidence of friability during endoscopy in subjects with otherwise “mild” endoscopy activity will confer an endoscopic subscore of 2. |
The safety profile of upadacitinib (45 mg) was consistent with safety findings in previous studies across indications, with no new safety risks observed.1-5 During the 8-week study period, the most common adverse events (AEs) observed in the upadacitinib group were acne, blood creatine phosphokinase increase and nasopharyngitis.1 The increases in blood creatine phosphokinase were non-serious and did not lead to study drug discontinuation. 1 Patients with blood creatine phosphokinase increase were usually asymptomatic and no cases of rhabdomyolysis were reported.1 Serious adverse events (SAEs) occurred in 2.5 percent of patients in the upadacitinib group and 5.8 percent of patients in the placebo group.1 Serious infections were reported infrequently (1.6 percent in the upadacitinib group and 1.3 percent in the placebo group).1 No deaths, gastrointestinal perforation, malignancy, major cardiovascular or thromboembolic events were reported.1
Full results from the U-ACHIEVE study will be presented at a future medical meeting and submitted for publication in a peer-reviewed journal. Use of upadacitinib in ulcerative colitis is not approved and its safety and efficacy have not been evaluated by regulatory authorities.
About Ulcerative Colitis
Ulcerative colitis is a chronic, systemic, inflammatory disease caused by inflammation of the large intestine, which triggers abdominal pain, bloody diarrhea, severe urgency for a bowel movement, weight loss and fatigue.15-17 The severity of symptoms and uncertainty surrounding flares cause a substantial burden and often disability among those living with the disease.18
About the U-ACHIEVE Study1,8
U-ACHIEVE is an ongoing, seamless Phase 2b/3 multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of upadacitinib for induction and maintenance therapy in subjects with moderate to severe ulcerative colitis. Results from the Phase 2b part of the study were announced in October 2018. The objective of this first of two Phase 3 induction studies is to evaluate the efficacy and safety of upadacitinib 45 mg once daily compared to placebo.
The primary endpoint is achievement of clinical remission (per Adapted Mayo Score) at week 8. Ranked secondary endpoints included clinical response (decrease from baseline in the Adapted Mayo score ≥2 points and ≥30 percent from baseline, plus a decrease in RBS ≥1 or an absolute RBS ≤1), endoscopic improvement (endoscopic subscore ≤1) and histologic-endoscopic mucosal improvement (endoscopic subscore of 0 or 1 and Geboes score ≤3.1) at week 8. More information can be found on www.clinicaltrials.gov (NCT02819635).
About the Upadacitinib Phase 3 Ulcerative Colitis Program8,19,20
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 (RINVOQ)
Discovered and developed by AbbVie scientists, RINVOQ is an oral, once daily, selective and reversible JAK inhibitor studied in several immune-mediated inflammatory diseases.1,6-14 It was engineered to have greater inhibitory potency for JAK1 versus JAK2, JAK3 and TYK2.2 In August 2019, RINVOQ received U.S. Food and Drug Administration approval for adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate. In December 2019, RINVOQ also received approval by the European Commission for the treatment of adult patients with moderate to severe active rheumatoid arthritis who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs. The approved dose for RINVOQ in rheumatoid arthritis is 15 mg. Phase 3 trials of RINVOQ in atopic dermatitis, rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, Crohn’s disease, ulcerative colitis, giant cell arteritis and Takayasu arteritis are ongoing.7-14 Use of RINVOQ in ulcerative colitis is not approved and its safety and efficacy have not been evaluated by regulatory authorities.
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About AbbVie in Gastroenterology
With a robust clinical trial program, AbbVie is committed to cutting-edge research to drive exciting developments in inflammatory bowel diseases (IBD), like ulcerative colitis and Crohn’s disease. By innovating, learning, and adapting, AbbVie aspires to eliminate the burden of IBD and make a positive long-term impact on the lives of people with the IBD. For more information on AbbVie in gastroenterology, visit https://www.abbvie.com/our-science/therapeutic-focus-areas/immunology/immunology-focus-areas/gastroenterology.html.
About AbbVie
AbbVie’s mission is to discover and deliver innovative medicines that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people’s lives across several key therapeutic areas: immunology, oncology, neuroscience, eye care, virology, women’s health and gastroenterology, in addition to products and services across its Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook, Instagram, YouTube and LinkedIn.
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- Van der Heijde D., et al. Efficacy and Safety of Upadacitinib in a Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase 2/3 Clinical Study of Patients With Active Ankylosing Spondylitis. 2019 ACR/ARP Annual Meeting; 2728.
- Guttman-Yassky, E., et al. Safety and Efficacy of Upadacitinib Monotherapy in Adolescents and Adults with Moderate-to-severe Atopic Dermatitis: Results From 2 Pivotal, Phase 3, Randomized, Double-blinded, Monotherapy, Placebo-controlled Studies (Measure Up 1 and Measure Up 2). European Academy of Dermatology and Venerology Congress. 2020. D3T03.4B.
- Pipeline – Our Science | AbbVie. AbbVie. 2019. Available at: https://www.abbvie.com/our-science/pipeline.html. Accessed on December 3, 2020.
- Burmester G.R., et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018 Jun 23;391(10139):2503-2512.
- 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. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT02819635. Accessed on Accessed on December 3, 2020.
- 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. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT02365649. Accessed on Accessed on December 3, 2020.
- 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. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT03104400. Accessed on December 3, 2020.
- A Study to Evaluate Efficacy and Safety of Upadacitinib in Adult Participants With Axial Spondyloarthritis (SELECT AXIS 2). ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT04169373. Accessed on December 3, 2020.
- A Study to Compare Safety and Efficacy of Upadacitinib to Dupilumab in Adult Participants With Moderate to Severe Atopic Dermatitis (Heads Up). ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT03738397. Accessed on December 3, 2020.
- A Study to Evaluate the Safety and Efficacy of Upadacitinib in Participants With Giant Cell Arteritis (SELECT-GCA). ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT03725202. Accessed on December 3, 2020.
- A Study to Evaluate the Efficacy and Safety of Upadacitinib in Subjects With Takayasu Arteritis (SELECT-TAK). ClinicalTrials.gov. 2020. Available at https://clinicaltrials.gov/ct2/show/record/NCT04161898. Accessed on Accessed on December 3, 2020.
- The Economic Costs of Crohn’s Disease and Ulcerative Colitis. Access Economics Pty Limited. 2007. Available at: https://www.crohnsandcolitis.com.au/site/wp-content/uploads/Deloitte-Access-Economics-Report.pdf. Accessed on December 3, 2020
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SOURCE: AbbVie