RINVOQ® (upadacitinib) Receives FDA Approval for the Treatment of Adults with Moderately to Severely Active Ulcerative Colitis

• In clinical trials, RINVOQ (upadacitinib) achieved the primary endpoints of clinical remission (per modified Mayo Score [mMS]) at weeks 8 and 52^1-4 
• A greater proportion of RINVOQ-treated patients achieved clinical response (per partial mMS [pmMS]) as early as week 2 and steroid-free clinical remission at one year, as well as key endoscopic and histologic improvement endpoints, at weeks 8 and 52⁴ 
• First approved in 2019, RINVOQ is a JAK inhibitor approved for four indications across gastroenterology, dermatology and rheumatology⁴

NORTH CHICAGO, IL, USA I March 16, 2022 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 ulcerative colitis (UC) who have had an inadequate response or intolerance to one or more tumor necrosis factor (TNF) blockers. This FDA approval is the first indication for RINVOQ in gastroenterology and is supported by efficacy and safety data from three Phase 3 randomized, double-blind, placebo-controlled clinical studies.

Experience the interactive Multimedia News Release here: https://www.multivu.com/players/English/8978351-abbvie-fda-ulcerative-colitis/ 

“There remains an unmet need for patients with moderately to severely active UC, who suffer from debilitating symptoms that are often unpredictable and burdensome,” said Thomas Hudson, MD, senior vice president of research and development, chief scientific officer, AbbVie. “With the approval of RINVOQ as a new treatment option, AbbVie continues our leadership in advancing research that can help impact the lives of people living with ulcerative colitis.” 

The two induction studies (U-ACHIEVE and U-ACCOMPLISH) utilized RINVOQ 45 mg once daily for 8 weeks, and then 15 mg or 30 mg once daily for the maintenance study (U-ACHIEVE maintenance) through 52 weeks.^1-4 Across all clinical trials, significantly more patients treated with RINVOQ achieved clinical remission at weeks 8 and 52, the primary endpoint based on the mMS: stool frequency subscore (SFS) ≤ 1 and not greater than Baseline, rectal bleeding subscore (RBS) = 0, endoscopy subscore (ES) of ≤ 1 without friability, compared to placebo. In addition, the studies met all ranked secondary endpoints, including endoscopic improvement and histologic-endoscopic mucosal improvement (HEMI), as well as corticosteroid-free clinical remission in the maintenance study. All primary and ranked secondary endpoints achieved p-values of <0.001 versus placebo.^1-3

“Ulcerative colitis patients live with unpredictable symptoms such as increased stool frequency and bleeding, which can make daily activities difficult,” said Maria T. Abreu, M.D., Professor of Medicine, Professor of Microbiology and Immunology, University of Miami Miller School of Medicine and Director, Crohn’s & Colitis Center, University of Miami Health System.* “In clinical trials, RINVOQ showed its ability to rapidly control symptoms in just eight weeks for many patients and sustained responses at one year. I believe these types of improvements can make a positive difference for my patients.”

Clinical Response and Durable Remission^1-4

• During the U-ACHIEVE and U-ACCOMPLISH induction trials at week 8, 26 percent and 33 percent of patients treated with RINVOQ 45 mg achieved clinical remission, the primary endpoint based on mMS, compared to 5 percent and 4 percent of patients who received placebo.
• Onset of response occurred as early as Week 2, with a greater proportion of patients receiving RINVOQ 45 mg once daily achieving clinical response, defined as a decrease of ≥1 point and ≥30 percent from Baseline and a decrease in RBS of ≥1 or an absolute RBS ≤1 per the pmMS, compared to placebo.
• During the maintenance trial, 42 percent and 52 percent of patients treated with RINVOQ 15 mg or 30 mg, respectively, achieved clinical remission at week 52, the primary endpoint, compared to 12 percent of patients who received placebo.
• Additionally, 57 percent and 68 percent of patients receiving RINVOQ 15 mg or 30 mg, respectively, achieved corticosteroid free remission, defined as clinical remission (per mMS) and corticosteroid free for ≥90 days immediately preceding Week 52 among patients who achieved clinical remission at the end of the induction treatment, compared to 22 percent of patients on placebo.

Endoscopic Improvement and Mucosal Healing^1-4

• Endoscopic improvement is defined as a ES of ≤1 without friability and was achieved in U-ACHIEVE and U-ACCOMPLISH.
  • In the induction studies at week 8, endoscopic improvement was observed in 36 percent and 44 percent of patients treated with RINVOQ 45 mg in U-ACHIEVE and U-ACCOMPLISH, respectively, compared to 7 percent and 8 percent, respectively, of patients on placebo.
  • In the maintenance study at week 52, endoscopic improvement was seen in 49 percent and 62 percent of patients with RINVOQ 15 mg and 30 mg, respectively, compared to 14 percent of patients on placebo.
• Mucosal healing was achieved in U-ACHIEVE and U-ACCOMPLISH and is defined by HEMI, which combines an ES of ≤1 without friability with a Geboes score of ≤ 3.1 (indicating neutrophil infiltration in <5 percent of crypts, no crypt destruction, and no erosions, ulcerations or granulation tissue); the relationship between HEMI and disease progression and/or long-term outcomes has not been established.
  • Mucosal healing was observed in 30 percent and 37 percent of patients treated with RINVOQ 45 mg in U-ACHIEVE and U-ACCOMPLISH, respectively, at week 8, compared to 7 percent and 6 percent of patients, respectively, who received placebo.
  • At Week 52, mucosal healing was seen in 35 percent and 50 percent of patients treated with RINVOQ 15 mg and 30 mg, respectively, compared to 12 percent patients who received placebo.

RINVOQ Safety Profile⁴

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

Patient Access and Support
AbbVie is committed to helping people access RINVOQ and other medicines, including offering a patient support program and co-pay card that may reduce out-of-pocket costs to as little as $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. More information about this assistance program can be found at www.AbbVie.com/myAbbVieAssist.

About Ulcerative Colitis
Ulcerative colitis is a chronic, idiopathic, immune-mediated inflammatory bowel disease (IBD) of the large intestine that causes continuous mucosal inflammation extending, to a variable extent, from the rectum to the more proximal colon.^5,6 The hallmark signs and symptoms of ulcerative colitis include rectal bleeding, abdominal pain, bloody diarrhea, tenesmus (a sense of pressure), urgency and fecal incontinence.^7,8 The disease course of ulcerative colitis varies between patients and can range from quiescent disease to chronic refractory disease.^5,8 The severity of symptoms and unpredictability of disease course can lead to substantial burden among those living with the disease.⁹

About the U-ACHIEVE Induction, U-ACCOMPLISH and U-ACHIEVE Maintenance Studies^1-4
The three Phase 3 studies are multicenter, randomized, double-blind, placebo-controlled studies to evaluate the efficacy and safety of upadacitinib 45 mg once daily as induction therapy, and upadacitinib 15 mg and 30 mg once daily as maintenance therapy in subjects with moderately to severely active ulcerative colitis. The primary endpoints were clinical remission per mMS at week 8 for the induction clinical trials and at week 52 for the maintenance trial. Topline results of the U-ACHIEVE induction study were announced in December 2020, topline results of the second induction study, U-ACCOMPLISH, were announced in February 2021, and topline results of the U-ACHIEVE maintenance study were announced in June 2021. More information can be found on www.clinicaltrials.gov (NCT03006068, NCT03653026, NCT02819635).

*Dr. Abreu 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.^4,10 Based on enzymatic and cellular assays, RINVOQ demonstrated greater inhibitory potency for JAK-1 vs JAK-2, JAK-3, and TYK-2.⁴ The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness and safety is not currently known.

In the U.S., RINVOQ 45 mg is approved for use in adult patients with moderately to severely active ulcerative colitis who have had an inadequate response or intolerance to one or more TNF blockers as an induction therapy once daily for 8 weeks. The recommended dose of RINVOQ for maintenance treatment is 15 mg once daily. A dosage of 30 mg once daily may be considered for patients with refractory, severe or extensive disease. Discontinue RINVOQ if an adequate response is not achieved with the 30 mg dose. Use the lowest effective dosage needed to maintain response. RINVOQ 15 mg once daily can be initiated in adults and children 12 years of age and older weighing at least 40 kg with refractory, moderate to severe atopic dermatitis whose disease is not adequately controlled with other system drug products, including biologics or when use of those therapies is inadvisable. In these children and adults less than 65 years of age who do not achieve an adequate response, the dose may be increased to 30 mg once daily. RINVOQ 15 mg is also approved in the U.S. for adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more TNF blockers as well as adults with active psoriatic arthritis who have had an inadequate response or intolerance to one or more TNF blockers.⁴ In the EU, RINVOQ 15 mg is approved for the treatment of adults with moderate to severe active rheumatoid arthritis, adults with active psoriatic arthritis and adults with active ankylosing spondylitis. RINVOQ is also approved in the EU for adults (15 mg and 30 mg) and adolescents (15 mg) with moderate to severe atopic dermatitis.⁴

Phase 3 trials of RINVOQ in rheumatoid arthritis, atopic dermatitis, psoriatic arthritis, axial spondyloarthritis, Crohn’s disease, giant cell arteritis and Takayasu arteritis are ongoing.^11-17

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 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 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, LinkedIn or Instagram.

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13. 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. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT03104400. Accessed on March 9, 2021.
14. A Study to Evaluate Efficacy and Safety of Upadacitinib in Adult Participants With Axial Spondyloarthritis (SELECT AXIS 2). ClinicalTrials.gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT04169373. Accessed on March 9, 2021.
15. 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. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT03345836. Accessed on March 10, 2021.
16. A Study to Evaluate the Safety and Efficacy of Upadacitinib in Participants With Giant Cell Arteritis (SELECT-GCA). ClinicalTrials.gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT03725202. Accessed on March 10, 2021.
17. A Study to Evaluate the Efficacy and Safety of Upadacitinib in Subjects With Takayasu Arteritis (TAK) (SELECT-TAK). ClinicalTrials.gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT04161898. Accessed on March 10, 2021

SOURCE: AbbVie