The drug met the co-primary endpoints of clinical remission at both weeks 12 and 52 and all key secondary endpoints in the study.
Pfizer Inc’s etrasimod, an investigational, once-a-day, oral selective sphingosine 1-phosphate (S1P) receptor modulator in development for the treatment of moderately to severely active ulcerative colitis (UC), produced positive top-line results in a second phase 3 study, the company said in a statement.
The positive 12- and 52-week results from ELEVATE UC 52 (NCT03945188) follow the announcement of positive 12-week findings from the ELEVATE UC 12 trial on March 23.
In the ELEVATE UC 52 trial, patients taking etrasimod achieved statistically significant improvements in the co-primary endpoints of clinical remission at weeks 12 and 52 compared with a placebo. Statistically significant improvements also occurred in all key secondary endpoints at both 12 and 52 weeks. Etrasimod, which Pfizer subsidiary Arena Pharmaceuticals developed, demonstrated a safety profile consistent with previous studies, including the phase 2 OASIS trial.
The double-blind, global, phase 3 multi-center, placebo-controlled, randomized study enrolled 433 patients with UC who had been unsuccessful or were unable to tolerate at least 1 biologic, conventional, or Janus kinase (JAK) inhibitor therapy. Participants received etrasimod 2 mg or a placebo once daily. ELEVATE UC 52 used a treat-through design in which patients were eligible to continue with their randomized treatment regardless of whether they reached the objective criteria of clinical response at week 12.
“For patients suffering with moderate to severe ulcerative colitis, these most recent data further demonstrate the substantial potential benefits of this medicine and clearly confirm its ability to achieve significant induction of remission at 12 weeks and now clinical remission at week 52. These data underscore etrasimod’s potential, if approved, as a best-in-class therapy,” Michael Corbo, chief development officer of inflammation and immunology at Pfizer Global Product Development, said in the statement.
“Etrasimod can potentially provide a new, once-daily, oral option with a rapid onset of action and without first dose titration,” he said. “Further, we believe the treat-through design of the ELEVATE UC 52 study more accurately reflects a real-world treatment approach than the re-randomization design often used in UC clinical trials.”
The primary objective of the latest trial is to assess the efficacy and safety of etrasimod on clinical remission after both 12 and 52 weeks. The primary endpoint is based on the 3-domain, modified Mayo score. Key secondary measures corticosteroid-free remission, efficacy, endoscopic improvement, mucosal healing, and symptomatic remission in study participants at time points up to 52 weeks of treatment.
UC is a chronic and often debilitating inflammatory bowel disease that affects millions of individuals worldwide, including an estimated 3.8 million people in Europe and North America, Pfizer said in the statement.
UC symptoms can include abdominal pain, chronic diarrhea with blood and mucus, cramping, and weight loss. UC can have a significant effect on family, social activities, and work.
Etrasimod is being investigated for a range of immuno-inflammatory diseases apart from UC, including alopecia areata, atopic dermatitis, Crohn disease, and eosinophilic esophagitis.
Pfizer plans to submit full results from the studies for future scientific publication and presentation. The company expects these data, along with results from the ELEVATE UC 12 study and the long-term extension from these 2 trials, ELEVATE UC OLE, to form the basis for planned future regulatory filings, which Pfizer said it expects to initiate later this year.
Pfizer plans announces positive top-line results from yearlong phase 3 trial of etrasimod in ulcerative colitis, underscoring best-in-clase potential. Pfizer. News release. March 29, 2022. Accessed March 29, 2022. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-positive-top-line-results-yearlong-phase-3