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Date: 02-Jul-2021

AbbVies Phase 3 Trial Of Upadacitinib To Treat Ulcerative Colitis Meets Primary And Secondary Endpoints

AbbVie announced that upadacitinib (15 mg or 30 mg, once daily) met the primary endpoint of clinical remission (per Adapted Mayo Score) and all secondary endpoints at one-year (week 52) in the phase 3 ulcerative colitis maintenance study. Significantly more upadacitinib-treated patients achieved clinical remission at week 52 compared to placebo (15 mg: 42 percent and 30 mg: 52 percent versus placebo: 12 percent; p<0.001).

“Ulcerative colitis is a disease with unpredictable symptoms and frequent flares, which can make daily life challenging,” said Michael Severino, M.D., vice chairman and president, AbbVie. “We are encouraged by these results that demonstrate upadacitinib's potential as a treatment option for patients with moderate to severe ulcerative colitis.”

In this study, adults with moderate to severe ulcerative colitis who achieved a clinical response (per partial Adapted Mayo Score) following an 8-week study period of once-daily upadacitinib (45 mg) induction treatment were re-randomized to receive upadacitinib 15 mg, upadacitinib 30 mg or placebo for an additional 52 weeks.

All secondary endpoints were met, including the achievement of endoscopic improvement, histologic-endoscopic mucosal improvement (HEMI) and corticosteroid-free clinical remission at week 52. 49 percent of patients treated with upadacitinib 15 mg and 62 percent of patients treated with upadacitinib 30 mg achieved endoscopic improvement at 52 weeks versus 14 percent of patients in the placebo group (p<0.001). In addition, 35 percent of patients on upadacitinib 15 mg and 49 percent of patients on upadacitinib 30 mg achieved HEMI compared to 12 percent of patients in the placebo group (p<0.001). Of patients who were in remission at the completion of the 8-week induction studies, corticosteroid-free remission was achieved in 57 percent of patients in the upadacitinib 15 mg group and 68 percent of patients in the upadacitinib 30 mg group compared to 22 percent of patients in the placebo group (p<0.001).

“Ulcerative colitis is a challenging disease to manage, and many patients do not find relief from their most burdensome symptoms,” said Remo Panaccione, M.D., professor of medicine and director of the IBD unit, University of Calgary. “These positive results demonstrate upadacitinib's potential to achieve improvements in clinical, endoscopic and histological outcomes at 52 weeks. This is promising news for the IBD community.”

A total of 746 patients who completed the 8-week upadacitinib induction treatment with clinical response and received at least one dose of the study drug in the maintenance period were included in the safety analysis. The safety results of upadacitinib (15 mg or 30 mg) were consistent with the safety profile observed in the phase 3 induction studies in ulcerative colitis, as well as in previous studies across indications. No new safety risks were identified. The most common adverse events observed in the upadacitinib groups during the 52-week study period were nasopharyngitis, exacerbation of ulcerative colitis and blood creatine phosphokinase increase. The exposure-adjusted event rates of adverse events per 100 patient years were 16.0 events in the upadacitinib 15 mg group, 13.8 events in the upadacitinib 30 mg group and 26.1 events in the placebo group. The rates of infections were 6.2, 3.9 and 7.5 events per 100 patient years in the upadacitinib 15 mg, upadacitinib 30 mg and placebo groups, respectively. The rates of adverse events leading to treatment discontinuation per 100 patient years were 7.6 events and 7.9 events in patients receiving upadacitinib 15 mg and upadacitinib 30 mg, respectively, compared with 24.3 events in the placebo group.

Malignancies (excluding non-melanoma skin cancer) reported in the study included one event in the upadacitinib 15 mg group, two events in the upadacitinib 30 mg group and one event in the placebo group.1 Adjudicated thrombotic events were reported in the upadacitinib 15 mg group (two events of pulmonary embolism), 30 mg group (two events of deep vein thrombosis) and the placebo group (one event of ovarian vein thrombosis).

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.

The phase 3 maintenance study is an ongoing, phase 3 multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of upadacitinib in patients with moderate to severe ulcerative colitis. Results from the induction studies, U-ACHIEVE and U-ACCOMPLISH, were announced in December 2020 and February 2021, respectively. The objective of this maintenance study is to evaluate the efficacy and safety of upadacitinib 15 mg and 30 mg, once daily, as a maintenance therapy compared to the placebo group.

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 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.

Discovered and developed by AbbVie scientists, Rinvoq is a selective and reversible JAK inhibitor that is being studied in several immune-mediated inflammatory diseases. In human cellular assays, Rinvoq preferentially inhibits signaling by JAK1 or JAK1/3 with functional selectivity over cytokine receptors that signal via pairs of JAK2. In August 2019, Rinvoq received US FDA approval for adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate.