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AbbVie (NYSE: ABBV) today announced that upadacitinib (45 mg, once daily) met the primary endpoint of clinical remission (per Adapted Mayo Score) and all ranked secondary endpoints in the Phase 3 induction study, U-ACCOMPLISH.1 In the study, 33 percent of patients receiving upadacitinib achieved clinical remission (per Adapted Mayo Score) at week 8 compared to 4 percent of patients receiving placebo (p<0.001).1 U-ACCOMPLISH is the second of two Phase 3 induction studies to evaluate the safety and efficacy of upadacitinib in adults with moderate to severe ulcerative colitis.1

"We remain steadfast in our pursuit of transforming the treatment landscape for people living with ulcerative colitis," said Tom Hudson, senior vice president of research and development, AbbVie. "These positive results confirm the findings of the previous induction study and underscore the potential impact upadacitinib could have on patients struggling to manage their disease."

In this study, all ranked secondary endpoints were met, including clinical, endoscopic, and histologic outcomes.1 A greater proportion of patients treated with upadacitinib achieved clinical response compared to placebo, with 74 percent of upadacitinib-treated patients experiencing clinical response (per Adapted Mayo Score) at week 8 versus 25 percent of patients receiving placebo (p<0.001).1 Additionally, 63 percent of patients treated with upadacitinib achieved clinical response (per partial Adapted Mayo Score) at week 2 versus 26 percent of those receiving placebo (p<0.001).1 At week 8, 44 percent of patients treated with upadacitinib achieved endoscopic improvement versus 8 percent of patients receiving placebo (p<0.001).1 And significantly more upadacitinib-treated patients achieved histologic-endoscopic mucosal improvement at week 8 compared to patients receiving placebo (37 percent versus 6 percent; p<0.001).1

"People living with moderate to severe ulcerative colitis continue to suffer from the significant burden of this disease," said Silvio Danese, M.D., lead study investigator and head of the Inflammatory Bowel Diseases Centre at Humanitas Research Hospital, Milan, Italy. "I am very impressed with the consistent results seen in both ulcerative colitis induction studies, suggesting that upadacitinib could be a potential new treatment option for patients."

The safety profile of upadacitinib (45 mg) was consistent with the safety findings in the previously reported Phase 3 induction study in ulcerative colitis and safety findings in previous studies across indications, with no new safety risks observed.1-6 During the 8-week study period, the most common adverse events observed in the upadacitinib group were acne, blood creatine phosphokinase increase, and anemia.1 The increases in blood creatine phosphokinase were non-serious and did not lead to study drug discontinuation.1 Patient with blood creatine phosphokinase increase was usually asymptomatic and no cases of rhabdomyolysis were reported.1 Serious adverse events occurred in 3.2 percent of patients in the upadacitinib group and 4.5 percent of patients in the placebo group.1 Similar rate of serious infections (0.6 percent) was observed in the two treatment groups.1 No deaths, gastrointestinal perforation, malignancy, major cardiovascular or thromboembolic events were reported in the upadacitinib group.1 One case of venous thromboembolism (deep vein thrombosis and pulmonary embolism) and one case of gastrointestinal perforation were reported in the placebo group.1

Full results from the U-ACCOMPLISH study will be presented at a future medical meeting and submitted for publication in a peer-reviewed journal. Top-line results from the Phase 3 portion of the first induction study, U-ACHIEVE, were announced in December 2020 and the maintenance study for both is ongoing. The 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-ACCOMPLISH Study1,9

U-ACCOMPLISH is a Phase 3 multicenter, randomized, double-blind, placebo-controlled induction study to evaluate the efficacy and safety of upadacitinib 45 mg once daily for induction therapy compared to placebo in subjects with moderate to severe ulcerative colitis. U-ACCOMPLISH is the second of two Phase 3 induction studies.

The primary endpoint is the 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 (NCT03653026).

About the Upadacitinib Ulcerative Colitis Program9,19,20

The global upadacitinib 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 the efficacy and safety 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 (NCT03653026, NCT02819635, 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.1,7-14 It was engineered to have greater inhibitory potency for JAK1 versus JAK2, JAK3, and TYK2.3 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. RINVOQ is also approved by the European Commission for the treatment of adult patients with moderate to severely active rheumatoid arthritis who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs); active psoriatic arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more DMARDs and active ankylosing spondylitis in adult patients who have responded inadequately to conventional therapy. The approved dose for RINVOQ in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis is 15 mg. Phase 3 trials of RINVOQ in ulcerative colitis, rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, Crohn's disease, atopic dermatitis, and giant cell arteritis are ongoing.8-14 Use of RINVOQ in ulcerative colitis is not approved and its safety and efficacy have not been evaluated by regulatory authorities.

 Important Safety Information about RINVOQ (upadacitinib)21

RINVOQ U.S. Use and Important Safety Information
RINVOQ is a prescription medicine used to treat adults with moderate to severe rheumatoid arthritis in whom methotrexate did not work well or could not be tolerated. It is not known if RINVOQ is safe and effective in children under 18 years of age.

What is the most important information I should know about RINVOQ?
RINVOQ is a medicine that can lower the ability of your immune system to fight infections. You should not start taking RINVOQ if you have any kind of infection unless your healthcare provider (HCP) tells you it is okay.

• Serious infections have happened in some people taking RINVOQ, including tuberculosis (TB) and infections caused by bacteria, fungi, or viruses that can spread throughout the body. Some people have died from these infections. Your HCP should test you for TB before starting RINVOQ and check you closely for signs and symptoms of TB during treatment with RINVOQ. You may be at higher risk of developing shingles (herpes zoster).
• Lymphoma and other cancers, including skin cancers, can happen in people taking RINVOQ.
• Blood clots in the veins of the legs or lungs and arteries are possible in some people taking RINVOQ. This may be life-threatening and cause death.
• Tears in the stomach or intestines and changes in certain laboratory tests can happen. Your HCP should do blood tests before you start taking RINVOQ and while you take it. Your HCP may stop your RINVOQ treatment for a period of time if needed because of changes in these blood test results.