Pfizer’s S1P Therapy Scores Second Phase III Win in Ulcerative Colitis

 

Pfizer announced positive top-line results from its year-long Phase III trial of etrasimod for the treatment of ulcerative colitis (UC). The company plans to pursue regulatory filings for the drug later this year.

Ulcerative colitis is a chronic, debilitating inflammatory disease of the colon. It affects the lining of the colon and causes ulcers to form which secrete pus and mucous, inducing symptoms like abdominal pain and frequent bowel movements. UC can also cause other symptoms beyond the gastrointestinal system such as fatigue, fever and anemia.

Although several treatment options are available for UC, Pfizer has stated that the latest results from its trial of etrasimod underscore its best-in-class potential for patients.

The 52-week clinical trial, titled ELEVATE UC 52, enrolled 433 UC patients who had previously failed or were intolerant to at least one conventional therapy for the disease including biologics and Janus kinase (JAK) inhibitor therapy. Participants in the trial either received a placebo or a once-daily dose of etrasimod over the course of 12 weeks, with the option to extend their treatment beyond meeting the clinical primary endpoint at 12 weeks.

The primary objective of the trial was to assess the safety and efficacy of etrasimod on clinical remission at both week 12 and 52 based on the three-domain disease activity index for UC. Secondary measures included symptomatic remission, endoscopic improvement, corticosteroid-free remission and mucosal healing in participants. In its announcement, Pfizer stated that etrasimod patients achieved statistically significant improvements in primary endpoints of clinical remission and attained all key secondary endpoints as compared to those who had received placebo.

“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,” said Michael Corbo, chief development officer, inflammation & immunology, Pfizer Global Product Development. “Etrasimod can potentially provide a new, once-daily, oral option with a rapid onset of action and without first dose titration.”

Pfizer recently shared positive top-line results from a similar Phase III trial evaluating etrasimod in 354 UC patients in a 12-week trial. Patients who received etrasimod over the course of 12 weeks achieved statistically significant clinical remission. In both trials, etrasimod demonstrated a tolerable safety profile.

Etrasimod is a selective sphingosine 1-phosphate (S1P) receptor modulator that is designed to engage S1P receptors 1, 4 and 5. S1P immunomodulatory therapies prevent immune cells called lymphocytes from binding to S1P receptors which promote inflammatory responses. By binding to S1P receptors, etrasimod can prevent the colon from becoming overly inflamed in patients with UC. Etrasimod is also being investigated for the treatment of Crohn’s Disease, atopic dermatitis, eosinophilic esophagitis and alopecia areata.

In May 2021, the U.S. Food and Drug Administration approved the first S1P receptor modulator drug for the treatment of UC called Zeposia, a therapy marketed by Bristol Myers Squibb. S1P therapy is also being investigated in the treatment of multiple sclerosis, an autoimmune disease that targets the brain.