FDA approves etrasimod for moderate to severe Ulcerative Colitis

USA: Etrasimod (Velsipity) has received approval from the US Food and Drug Administration (FDA) for adults with moderately to severely active ulcerative colitis (UC). The approved recommended dose for Velsipity is 2 mg.

VELSIPITY is an oral, once-daily, selective sphingosine-1-phosphate (S1P) receptor modulator for adults with moderately to severely active ulcerative colitis. 

UC is a chronic and often debilitating condition1 that affects an estimated 1.25 million people in the United States. Symptoms of UC can include chronic diarrhoea with blood and mucus, abdominal pain, and urgency. However, its impact can span beyond the physical to other aspects of life due to the chronic and unpredictable nature of symptoms.

“VELSIPITY provides adults living with moderately to severely active UC the opportunity to achieve steroid-free remission with an oral, once-daily pill that has a favourable benefit-risk profile,” said Angela Hwang, Chief Commercial Officer and President of Global Biopharmaceuticals Business, Pfizer. “VELSIPITY’s FDA approval today marks a significant milestone for UC patients who need new treatments for this chronic condition and are ready to start advanced therapy.”

The U.S. FDA approval was based on results from the ELEVATE UC Phase 3 registrational program (ELEVATE UC 52 and ELEVATE UC 12) that evaluated the safety and efficacy of VELSIPITY 2 mg once-daily on clinical remission in UC patients who had previously failed or were intolerant to at least one conventional, biologic, or Janus kinase (JAK) inhibitor therapy. Nearly two-thirds of patients in ELEVATE UC 52 and ELEVATE UC 12 were naïve to biologic or JAK inhibitor therapy, and these studies were also the only studies for advanced therapies for ulcerative colitis to include patients with isolated proctitis. Both studies achieved all primary and key secondary efficacy endpoints, with a favorable safety profile consistent with previous studies of VELSIPITY.

“Because of the unpredictable nature of UC, people living with the disease can cycle through several different treatments over time. Patients may also be apprehensive about using injectable therapies, like biologics,” said Dr. Michael Chiorean, Co-Director of the IBD Center at Swedish Medical Center and an investigator in the ELEVATE Registrational Program. “It’s important to have new, effective options like VELSIPITY for those patients who may require an advanced treatment option and prefer the convenience of a once-daily pill. VELSIPITY is a proven advanced treatment with a favorable benefit-risk profile.”

“UC can affect patients differently and many people living with this disease struggle with ongoing symptoms,” said Michael Osso, President and CEO of the Crohn’s & Colitis Foundation. “The introduction of a new treatment for UC could increase options for patients, and we look forward to seeing the impact of VELSIPITY for patients across the U.S.”

In ELEVATE UC 52, clinical remission was 27.0% for patients receiving VELSIPITY compared to 7.0% for patients receiving placebo at week 12 (20.0% differential, P˂.001) and was 32.0% compared to 7.0% at week 52 (26.0% differential, P=˂.001). In ELEVATE UC 12, clinical remission was achieved among 26.0% of patients receiving VELSIPITY compared to 15.0% of patients receiving placebo (11.0% differential, P=<.05). All key secondary efficacy endpoints were met at week 12, including endoscopic improvement and mucosal healing. The safety of VELSIPITY was consistent with previous studies, with the most common adverse reactions being headache, elevated liver tests, and dizziness (incidence ≥ 5%).

Full results from the program were published by The Lancet in March 2023.

About VELSIPITY™ (Etrasimod)

VELSIPITY is a once-daily, oral, sphingosine 1-phosphate (S1P) receptor modulator that selectively binds with S1P receptor subtypes 1, 4, and 5.

Regulatory applications for VELSIPITY in ulcerative colitis have been submitted to countries around the world for review, including Canada, Australia, Mexico, Russia, Switzerland, and Singapore. The European Medicines Agency (EMA) has accepted the Marketing Authorization Application (MAA) for VELSIPITY, with a decision anticipated in the beginning of 2024.

About ELEVATE UC 52 and ELEVATE UC 12

ELEVATE UC 52 and ELEVATE UC 12 are pivotal trials that are part of the ELEVATE UC Phase 3 registrational program.7

ELEVATE UC 52 is a randomized, double-blind, placebo-controlled trial that utilized a treat-through design comprising of a 12-week induction period followed by a 40-week maintenance period. Subjects were randomized to VELSIPITY or placebo and continued on treatment without re-randomization for the entire duration of the study. Beginning at week 12, all patients could continue their randomized treatment; patients whose disease had not improved or had worsened compared to baseline could discontinue and, if eligible, enroll in an open-label extension study. The primary objective of this trial was to assess the safety and efficacy of etrasimod 2 mg once daily on clinical remission after both 12 and 52 weeks. The primary endpoint is based on the 3-domain, modified Mayo score (MMS). In ELEVATE UC 52, clinical remission was 27.0% for patients receiving etrasimod compared to 7.0% for patients receiving placebo at week 12 (20.0% differential, P˂.001) and was 32.0% compared to 7.0% at week 52 (26.0% differential, P≤˂.001). Statistically significant improvements were attained in all key secondary endpoints, including endoscopic improvement and mucosal healing at weeks 12 and 52, and corticosteroid-free remission and sustained clinical remission at week 52.

ELEVATE UC 12 is a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of etrasimod 2 mg once-daily in subjects with moderately to severely active UC. The primary objective of this trial was to assess the safety and efficacy of etrasimod on clinical remission at 12 weeks assessed by the FDA-required, 3-domain, MMS. In ELEVATE UC 12, clinical remission was achieved among 26.0% of patients receiving etrasimod compared to 15.0% of patients receiving placebo (11.0% differential, P<.05). All key secondary endpoints were met at week 12, including endoscopic improvement and mucosal healing.

In ELEVATE UC 12, a similar proportion of patients experienced treatment-emergent adverse events (AEs) between etrasimod 2 mg and placebo treatment groups, while in ELEVATE UC 52, it was higher in the etrasimod 2 mg group compared to placebo. The proportion of patients experiencing serious AEs was similar between treatment groups in both trials. The most common treatment-emergent AEs in 3% or more of etrasimod-treated patients and greater than placebo up to week 52 in either trial were headache, elevated liver tests, worsening of UC, COVID-19 infection, dizziness, pyrexia, arthralgia, abdominal pain and nausea. Data support that initiation of etrasimod treatment does not require a complex up-titration regimen.

Nearly two-thirds of patients in ELEVATE UC 52 and ELEVATE UC 12, respectively, were naïve to biologic or JAK inhibitor therapy.