FDA Approves Etrasimod for Moderately to Severely Active Ulcerative Colitis

The US Food and Drug Administration (FDA) has approved etrasimod (Velsipity) 2 mg for adults with moderately to severely active ulcerative colitis (UC).

Announced by Pfizer on October 13, 2023, the approval is supported by data from the the ELEVATE UC Phase 3 registrational program, including the ELEVATE UC 52 and ELEVATE UC 12 trials, assessing the safety and efficacy of etrasimod 2 mg once-daily on clinical remission in patients with UC who had previously failed or were intolerant to at least 1 conventional, biologic, or Janus kinase (JAK) inhibitor therapy.¹

In ELEVATE UC 52, 27.0% of patients receiving etrasimod achieved clinical remission at week 12 and 32.0% at week 52. In ELEVATE UC 12, clinical remission was achieved among 26.0% of patients receiving etrasimod.¹

“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 Michael Chiorean, MD, co-director of the IBD Center at Swedish Medical Center.¹ “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.”

A sphingosine 1-phosphate (S1P) receptor modulator, etrasimod selectively binds with S1P receptor subtypes 1, 4, and 5. Regulatory applications for etrasimod in UC have been submitted for review in Canada, Australia, Mexico, Russia, Switzerland, and Singapore. The European Medicines Agency has accepted the Marketing Authorization Application for etrasimod, with a decision anticipated in 2024.¹

The ELEVATE UC program included a pair of independent randomised, multicenter, double-blind, placebo-controlled, phase 3 trials, in ELEVATE UC 52 and ELEVATE UC 12, which assessed the safety and efficacy of of etrasimod in adult patients with moderately to severely active UC. ELEVATE UC 52 included a 12-week induction period followed by a 40-week maintenance period with a treat-through design, while ELEVATE UC 12 independently assessed induction at week 12.²

To be included in the trials, participants were required to be diagnosed with UC ≥ 3 months prior to screeningand have active UC confirmed by endoscopy. In total, 433 participants were enrolled in ELEVATE UC 52 and 354 were enrolled in ELEVATE UC 12. The full analysis set of ELEVATE UC 52 comprised 289 patients assigned to etrasimod and 144 to placebo. In ELEVATE UC 12, 238 patients were assigned to etrasimod and 116 to placebo.^3,4

Participants were randomly assigned 2:1 to once-daily oral etrasimod 2 mg or placebo, stratified by previous exposure to biologicals or JAK inhibitor therapy, baseline corticosteroid use, and baseline disease activity. The primary endpoints were the percentage of participants achieving clinical remission at week 12 and at week 52.¹

According to the release, clinical remission was achieved in 27.0% for patients receiving etrasimod compared to 7.0% of patients receiving placebo at week 12 (P ˂ .001) and was 32.0% compared to 7.0% at week 52 (P ≤ .001) in ELEVATE UC 52. In ELEVATE UC 12, clinical remission was achieved among 26.0% of patients receiving etrasimod compared to 15.0% of patients receiving placebo (P < .05). 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 52.¹

The release pointed out the safety of etrasimod was consistent with previous studies, with the most common adverse reactions being headache, elevated liver tests, and dizziness (incidence ≥ 5%). In ELEVATE UC 12, a similar proportion of patients experienced treatment-emergent adverse events between etrasimod 2 mg (47%) and placebo treatment groups (47%), while in ELEVATE UC 52, it was higher in the etrasimod 2 mg group (71%) compared to placebo (56%).²

“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.¹ “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.”

References:

1. Pfizer. U.S. FDA Approves Pfizer’s VELSIPITY™ for Adults with Moderately to Severely Active Ulcerative Colitis (UC). Press Releases. October 13, 2023. Accessed October 13, 2023. https://www.pfizer.com/news/press-release/press-release-detail/us-fda-approves-pfizers-velsipitytm-adults-moderately
2. Sandborn WJ, Vermeire S, Peyrin-Biroulet L, et al. Etrasimod as induction and maintenance therapy for ulcerative colitis (ELEVATE): two randomised, double-blind, placebo-controlled, phase 3 studies [published correction appears in Lancet. 2023 Mar 25;401(10381):1000]. Lancet. 2023;401(10383):1159-1171. doi:10.1016/S0140-6736(23)00061-2
3. Clinicaltrials.gov. Etrasimod Versus Placebo for the Treatment of Moderately to Severely Active Ulcerative Colitis (ELEVATE UC 52). December 20, 2022. Accessed October 13, 2023. https://clinicaltrials.gov/study/NCT03945188
4. Clinicaltrials.gov. Etrasimod Versus Placebo as Induction Therapy in Moderately to Severely Active Ulcerative Colitis (ELEVATE UC 12). December 21, 2022. Accessed October 13, 2023. https://clinicaltrials.gov/study/NCT03996369