U.S. FDA Approves RINVOQ® (upadacitinib) as a Once-Daily Pill for Moderately to Severely Active Crohn’s Disease in Adults

–  The co-primary endpoints of endoscopic response (visible reduction of intestinal lining damage) and clinical remission were achieved by significantly more patients treated with RINVOQ (upadacitinib) at week 12 and week 52 versus placebo¹
–  Clinical response was achieved by significantly more patients treated with RINVOQ (upadacitinib) versus placebo as early as week 2 in induction studies¹
–  This indication marks the seventh FDA approval for RINVOQ across gastroenterology, rheumatology and dermatology¹

NORTH CHICAGO, IL, USA I May 18, 2023 I AbbVie (NYSE: ABBV) today announced that the U.S. Food and Drug Administration (FDA) has approved RINVOQ^® (upadacitinib) for the treatment of adults with moderately to severely active Crohn’s disease who have had an inadequate response or intolerance to one or more TNF blockers.¹ This is the seventh FDA approval for RINVOQ across rheumatology, dermatology, and gastroenterology, where it is now indicated in both ulcerative colitis and Crohn’s disease.¹

Access the multimedia news release here: https://www.multivu.com/players/English/9145751-abbvie-fda-crohns-disease/

“AbbVie recognizes the need for more treatment options for Crohn’s disease that can help address both rapid relief of symptoms along with the visible reduction of intestinal lining damage,” said Thomas Hudson, M.D., senior vice president of research and development, chief scientific officer, AbbVie. “We’re pleased that RINVOQ may provide this relief and is now available to treat Crohn’s disease.”

Endoscopic Response and Clinical Remission
The approval is supported by data from two induction studies, U-EXCEED and U-EXCEL, and the U-ENDURE maintenance study.¹ Statistical significance was achieved for the co-primary endpoints and key secondary endpoints with RINVOQ 45 mg in the induction studies and RINVOQ 15 mg and 30 mg in the maintenance study compared to placebo.

• Endoscopic response: In the two induction studies, 34% and 46% of patients treated with RINVOQ 45 mg achieved endoscopic response (defined as a decrease of greater than 50% from the baseline Simplified Endoscopic Score for CD [SES-CD] or for patients with isolated ileal disease and a baseline SES-CD of 4, at least a 2-point reduction from baseline) at week 12, respectively, compared to 3% and 13% of patients receiving placebo.¹ In the maintenance study, 28% and 41% of patients treated with RINVOQ 15 mg and 30 mg achieved endoscopic response at week 52, respectively, compared to 7% of patients receiving placebo.
• Clinical remission: In the two induction studies, 36% and 46% of patients treated with RINVOQ 45 mg achieved clinical remission (defined as a Crohn’s Disease Activity Index [CDAI] of less than 150) at 12 weeks, respectively, compared to 18% and 23% of patients receiving placebo. Additionally, in the maintenance trial, 42% and 55% of patients treated with RINVOQ 15 mg and 30 mg achieved clinical remission at 52 weeks, respectively, compared to 14% of patients receiving placebo.¹

“Symptoms of moderately to severely active Crohn’s disease can be disruptive and uncomfortable for patients, so relief as early as possible is key. Given the progressive nature of the disease, endoscopic response is just as important,” said Edward V. Loftus, Jr., M.D., professor of medicine in the division of gastroenterology and hepatology at Mayo Clinic in Rochester, Minnesota and U-EXCEL study investigator.* “Based on the clinical trial results, treatment with RINVOQ shows both early and long-term symptom relief along with evidence of a visible reduction of damage to the intestinal lining caused by excess inflammation.”

“I started feeling better within a couple weeks. My symptoms lessened – less cramping, firmer stools, and the bleeding stopped. When I stopped bleeding, I had more energy,” said Danielle, who is living with Crohn’s disease and received RINVOQ in an open-label treatment arm in one of the clinical trials.

Rapid Clinical Response and Corticosteroid-free Clinical Remission¹ 

• Onset of clinical response based on CDAI was observed as early as two weeks in U-EXCEED and U-EXCEL, with a greater proportion of patients achieving clinical response at week 2 in RINVOQ-treated patients compared with placebo.¹
• This is the first clinical program of an approved moderate-to-severe Crohn’s disease treatment to require steroid taper during the induction period, with a corticosteroid taper regimen initiated at week 4. Corticosteroid-free clinical remission (defined as discontinuation of steroid and achievement of clinical remission per CDAI [CDAI less than 150]) among patients on steroid at baseline was achieved at week 12 by more patients treated with RINVOQ in U-EXCEED and U-EXCEL (30% and 40%, respectively) compared to placebo (11% and 13%, respectively). In U-ENDURE, corticosteroid-free remission (defined as no corticosteroids for 90 days prior to week 52 and achievement of clinical remission) was achieved by more patients treated with RINVOQ 15 mg and 30 mg (42% and 53%, respectively) compared to 14% with placebo.

RINVOQ Safety Considerations¹

• Overall, the safety profile observed in patients with Crohn’s disease treated with RINVOQ was consistent with the known safety profile for RINVOQ in other indications.
• RINVOQ may cause serious side effects, including:
  • Serious infections. RINVOQ can lower ability to fight infections. Serious infections, some fatal, occurred, including tuberculosis (TB) and infections caused by bacteria, fungi, or viruses.
  • Increased risk of death in people age 50+ with at least 1 heart disease risk factor.
  • Cancer and immune system problems. Increased risk of some cancers, including lymphoma and skin. Current or past smokers have higher risk for lymphoma and lung cancer.
  • Increased risk of major cardiovascular events such as heart attack, stroke, or death in people 50+ with at least 1 heart disease risk factor, especially in current or past smokers.
  • Blood clots, some fatal, in veins of the legs or lungs and arteries. This occurred more often in people 50+ with at least 1 heart disease risk factor.
  • Serious allergic reactions. Do not take if allergic to RINVOQ or its ingredients.
  • Tears in the stomach or intestines; changes in certain laboratory test results.

For more information about RINVOQ, visit RINVOQ.com.

Patient Access & Support
AbbVie is committed to helping people access RINVOQ and other medicines, including offering a patient support program and a co-pay card that may reduce out-of-pocket costs to $5 per month for eligible, commercially insured patients. For those with limited or no health insurance, AbbVie offers myAbbVie Assist, a patient assistance program that provides RINVOQ at no charge to those who qualify. For more details, please visit AbbVie.com/myAbbVieAssist.

About Crohn’s Disease
Crohn’s disease is a chronic, systemic disease that manifests as inflammation within the gastrointestinal (or digestive) tract, causing persistent diarrhea and abdominal pain.^2-4 It is a progressive disease, meaning it gets worse over time, and in many cases leads to surgery.^3,4 Because the signs and symptoms of Crohn’s disease are unpredictable, it causes a significant burden on people living with the disease.⁵

About the U-EXCEED and U-EXCEL Induction and the U-ENDURE Maintenance Studies^1,6-8
The three Phase 3 studies are multicenter, randomized, double-blind, placebo-controlled studies to evaluate the efficacy and safety of RINVOQ 45 mg as induction therapy and RINVOQ 15 mg and 30 mg as maintenance therapy in patients with moderately to severely active Crohn’s disease. Topline results of the U-EXCEED and U-EXCEL induction studies were announced in December 2021 and February 2022. Topline results of the U-ENDURE maintenance study were announced in May 2022. More information can be found on https://clinicaltrials.gov (U-EXCEED: NCT03345836, U-EXCEL: NCT03345849, U-ENDURE: NCT03345823).

*Dr. Loftus is a consultant and advisor for AbbVie.

About RINVOQ^® (upadacitinib)
Discovered and developed by AbbVie scientists, RINVOQ is a selective JAK inhibitor that is being studied in several immune-mediated inflammatory diseases. Based on enzymatic and cellular assays, RINVOQ demonstrated greater inhibitory potency for JAK-1 vs JAK-2, JAK-3, and TYK-2.¹ The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness and safety is not currently known.

Phase 3 trials of RINVOQ in rheumatoid arthritis, atopic dermatitis, psoriatic arthritis, axial spondyloarthritis, Crohn’s disease, ulcerative colitis, giant cell arteritis, and Takayasu arteritis are ongoing.^9-17

Please click here for the Full Prescribing Information and Medication Guide.

Globally, prescribing information varies; refer to the individual country product label for complete information.

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.

References:

1. RINVOQ [Package Insert]. North Chicago, IL: AbbVie Inc.; 2023.
2. Kaplan G. The Global Burden of IBD: from 2015 to 2025. Nat Rev Gastroenterol Hepatol. 2015 Dec;12(12):720-7. doi: 10.1038/nrgastro.2015.150.
3. The Facts about Inflammatory Bowel Diseases. Crohn’s & Colitis Foundation of America. 2014. Available at: https://www.crohnscolitisfoundation.org/sites/default/files/2019-02/Updated%20IBD%20Factbook.pdf. Accessed March 24, 2023.
4. Crohn’s disease. Symptoms and Causes. Mayo Clinic. 2020. Available at: https://www.mayoclinic.org/diseases-conditions/crohns-disease/symptoms-causes/syc-20353304. Accessed March 24, 2023.
5. 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 March 24, 2023.
6. A Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Participants With Moderately to Severely Active Crohn’s Disease Who Have Inadequately Responded to or Are Intolerant to Biologic Therapy. ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT03345836?term=NCT03345836&draw=2&rank=1. Accessed March 30, 2023
7. A Study of the Efficacy and Safety of Upadacitinib in Participants With Moderately to Severely Active Crohn’s Disease Who Have Inadequately Responded to or Are Intolerant to Conventional and/or Biologic Therapies (U-EXCEL). ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT03345849?term=NCT03345849&draw=2&rank=1. Accessed March 30, 2023.
8. A Maintenance and Long-Term Extension Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Participants With Crohn’s Disease Who Completed the Studies M14-431 or M14-433. ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT03345823?term=NCT03345823&draw=2&rank=1. Accessed March 30, 2023.
9. A Study to Evaluate Efficacy and Safety of Upadacitinib in Adult Participants With Axial Spondyloarthritis (SELECT AXIS 2). ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT04169373. Accessed March 24, 2023.
10. A Study Comparing Upadacitinib (ABT-494) to Placebo and to Adalimumab in Adults with Rheumatoid Arthritis Who Are on a Stable Dose of Methotrexate and Who Have an Inadequate Response to Methotrexate (SELECT-COMPARE). ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT02629159. Accessed March 24, 2023.
11. 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. Available at: https://clinicaltrials.gov/ct2/show/NCT02819635. Accessed March 24, 2023.
12. 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. Available at: https://clinicaltrials.gov/ct2/show/NCT02365649. Accessed March 24, 2023.
13. A Study to Evaluate the Safety and Efficacy of Upadacitinib in Participants With Giant Cell Arteritis (SELECT-GCA). ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT03725202. Accessed March 24, 2023.
14. 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. Available at: https://clinicaltrials.gov/ct2/show/NCT03104400. Accessed March 24, 2023.
15. A Study to Compare Safety and Efficacy of Upadacitinib to Dupilumab in Adult Participants With Moderate to Severe Atopic Dermatitis (Heads Up). ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT03738397. Accessed March 24, 2022.
16. A Study to Evaluate the Safety and Efficacy of Upadacitinib in Participants with Giant Cell Arteritis (SELECT-GCA). ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT03725202. Accessed March 30, 2023.
17. A Study to Evaluate the Efficacy and Safety of Upadacitinib in Participants with Takaysu Arteritis (TAK) (SELECT-TAK). ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT04161898?term=upadacitinib&cond=Takayasu%E2%80%99s+arteritis&draw=2&rank=1. Accessed March 30, 2023.

SOURCE: AbbVie