Upadacitinib Achieved Primary and Key Secondary Endpoints in First Phase 3 Induction Study in Patients with Crohn’s Disease

AbbVie has announced positive top-line results from U-EXCEED, a Phase 3 induction study, showing upadacitinib (45 mg once daily) achieved both primary endpoints of clinical remissiona,b and endoscopic responsec at week 12.1 The U-EXCEED study enrolled patients with moderate to severe Crohn’s disease who had an inadequate response or were intolerant to biologic therapy, with over 60 percent having previously failed two or more biologics.1 U-EXCEED is the first of two Phase 3 induction studies to evaluate the safety and efficacy of upadacitinib in adults with moderate to severe Crohn’s disease.1

“The data from this first Phase 3 induction study in Crohn’s disease suggest upadacitinib may help address the needs of patients suffering from this disease, as demonstrated in stringent endpoints such as endoscopic response,” said Michael Severino, M.D., vice chairman and president, AbbVie. “We continue to leverage our expertise in IBD by driving research and development that help shape the IBD landscape and elevate standards of care for patients.”

In U-EXCEED, clinical remission was measured by the Crohn’s Disease Activity Index (CDAI) and by the patient-reported symptoms of stool frequency/abdominal pain (SF/AP).1 A significantly greater proportion of patients treated with a 12-week induction regimen of upadacitinib 45 mg daily achieved clinical remission per CDAI at week 12 compared to placebo (39 percent, versus 21 percent; p<0.0001).1 Similar results were seen with clinical remission per SF/AP (40 percent in upadacitinib-treated patients versus 14 percent in placebo-treated patients; p<0.0001).1 In this study, all patients were also evaluated for improvement in the intestinal mucosa by endoscopy.1 At week 12, a significantly greater proportion of patients treated with upadacitinib 45 mg achieved endoscopic response compared to the placebo group (35 percent versus 4 percent; p<0.0001).1

Among patients taking corticosteroids at baseline, a significantly higher proportion of patients receiving upadacitinib 45 mg achieved steroid-free clinical remissiond per CDAI and per SF/AP compared to placebo at week 12.1 A significantly higher proportion of patients receiving upadacitinib compared to placebo also achieved early symptom improvement measured by CR-100 (defined as reduction of CDAI ≥100 points from baseline) at week 2 as well as clinical remission at week 4.1

“I am thrilled to see the results of this first Phase 3 induction study of upadacitinib, particularly in this difficult-to-treat refractory patient population,” said Jean-Frederic Colombel, M.D., professor of medicine and director of Inflammatory Bowel Disease Center, Icahn School of Medicine, Mount Sinai, and U-EXCEED study investigator. “These results demonstrate upadacitinib’s potential to achieve endoscopic response and clinical remission, including steroid-free clinical remission, at 12 weeks in patients living with Crohn’s disease.”

Efficacy Results at Week 121
Placebo

(n=171)

Upadacitinib 45 mg

(n = 324)

Clinical Remission (per CDAI)a 21% 39%*
Clinical Remission (per SF/AP)b 14% 40%*
Endoscopic Responsec 4% 35%*

 

* Co-primary endpoints were clinical remission (per CDAI for the U.S. FDA and per SF/AP for the EU EMA) and endoscopic response at week 12. All primary endpoints achieved statistical significance with p-values of <0.0001 versus placebo.
Clinical remission (per CDAI) is defined as CDAI <150.
b Clinical remission per SF (stool frequency)/AP (abdominal pain) (also referred to as PRO-2) is defined as average daily very soft or liquid stool frequency ≤2.8 AND average daily abdominal pain score ≤1.0, and both not greater than baseline.
Endoscopic response is defined as a decrease in simple endoscopic score for Crohn’s disease (SES-CD) of >50 percent from baseline (or at least a 2-point reduction from baseline for subjects with a baseline SES-CD of 4), as scored by central reviewer.

 

During the 12-week, double-blind, placebo-controlled period, the safety profile of upadacitinib 45 mg was consistent with the safety profile observed in previous studies across indications, with no new safety risks observed.1 The most common adverse event was nasopharyngitis for upadacitinib and exacerbation of Crohn’s disease for placebo1. Serious adverse events occurred in 9.3 percent of patients in the upadacitinib 45 mg group compared to 9.9 percent of patients in the placebo group1 . Rates of serious infections were 2.8 percent in those treated with upadacitinib 45 mg and 1.8 percent in patients who received placebo.1 All events of herpes zoster (1.5 percent of patients) were nonserious and reported in the upadacitinib group only.1 There was one case of adjudicated gastrointestinal perforation in the upadacitinib group.1

In the study, no treatment-emergent cases of adjudicated cardiovascular event, malignancy, thromboembolic event or death were reported across treatment groups.1

Full results from the U-EXCEED study will be presented at upcoming medical conferences and published in a peer-reviewed medical journal. Use of upadacitinib in Crohn’s disease is not approved and its safety and efficacy have not been evaluated by regulatory authorities.

More information can be found on www.clinicaltrials.gov

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