US FDA approves Pfizer’s VELSIPITY™ for Ulcerative Colitis in Adults

Pfizer Inc. announced that the FDA has approved VELSIPITYTM (etrasimod), an oral, once-daily, selective sphingosine-1-phosphate (S1P) receptor modulator for individuals with moderately to severely active ulcerative colitis (UC). VELSIPITY’s official suggested dose is 2 mg.

UC is a chronic and frequently debilitating disease that affects an estimated 1.25 million persons in the United States Chronic diarrhea with blood and mucus, stomach pain, and urgency are all symptoms of Ulcerative Colitis. However, given to the chronic and unpredictable nature of symptoms, their impact might extend beyond the physical to other parts of life.5,6

“VELSIPITY allows adults with moderately to severely active UC to achieve steroid-free remission with an oral, once-daily pill that has a favorable benefit-risk profile,” said Angela Hwang, Chief Commercial Officer and President of Pfizer’s Global Biopharmaceuticals Business. “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 ELEVATE UC Phase 3 registrational program (ELEVATE UC 52 and ELEVATE UC 12) evaluated the safety and efficacy of VELSIPITY 2 mg once-daily on clinical remission in UC patients who had previously failed or were intolerant of at least one conventional, biologic, or Janus kinase (JAK) inhibitor therapy. Nearly two-thirds of patients in ELEVATE UC 52 and ELEVATE UC 12 had never received biologic or JAK inhibitor therapy, and these were the only advanced therapeutics for ulcerative colitis studies to include patients with isolated proctitis. Both studies met all primary and crucial secondary efficacy goals while maintaining a good safety profile similar with earlier VELSIPITY investigations.

“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.”

Clinical remission was 27.0% for VELSIPITY patients compared to 7.0% for placebo patients at week 12 (20.0% differential, P.001) and 32.0% compared to 7.0% at week 52 (26.0% differential, P=.001). Clinical remission was reached in 26.0% of VELSIPITY-treated patients vs to 15.0% of placebo-treated patients in ELEVATE UC 12 (11.0% difference, P=.05). At week 12, all critical secondary efficacy objectives, including endoscopic improvement and mucosal healing, were fulfilled. The safety of VELSIPITY was consistent with prior studies, with headache, increased liver tests, and dizziness being the most prevalent adverse effects (incidence 5%).

VELSIPITYTM (Etrasimod)

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

VELSIPITY regulatory applications in ulcerative colitis have been submitted for assessment in countries throughout the world, including Canada, Australia, Mexico, Russia, Switzerland, and Singapore. The European Medicines Agency (EMA) has approved the VELSIPITY Marketing Authorization Application (MAA), with a decision expected in early 2024.

Concerning ELEVATE UC 52 and ELEVATE UC 12

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

The ELEVATE UC 52 experiment is a randomized, double-blind, placebo-controlled study that used a treat-through design with a 12-week induction period followed by a 40-week maintenance term. Subjects were randomly assigned to either VELSIPITY or a placebo and were treated for the length of the research without re-randomization. Patients whose condition had not improved or worsened relative to baseline could withdraw and, if eligible, join in an open-label extension study beginning at week 12. The primary goal of this study was to determine the safety and efficacy of etrasimod 2 mg once day on clinical remission after 12 and 52 weeks. The modified Mayo score (MMS) is used as the primary outcome. Clinical remission was 27.0% for patients receiving etrasimod against 7.0% for patients receiving placebo at week 12 (20.0% difference, P.001) and 32.0% versus 7.0% at week 52 (26.0% difference, P.001). All critical secondary endpoints improved statistically significantly, including endoscopic improvement and mucosal healing at weeks 12 and 52, as well as corticosteroid-free remission and maintained clinical remission at week 52.

The ELEVATE UC 12 trial is a randomized, double-blind, placebo-controlled study that will look at the efficacy and safety of etrasimod 2 mg once day in people with moderately to highly active UC. The primary goal of this experiment was to evaluate the safety and efficacy of etrasimod on clinical remission at 12 weeks using the FDA-mandated 3-domain MMS. Clinical remission was attained in 26.0% of patients receiving etrasimod versus 15.0% of patients receiving placebo in ELEVATE UC 12 (11.0% difference, P.05). At week 12, all critical secondary goals, including endoscopic improvement and mucosal healing, were met.

In ELEVATE UC 12, the proportion of patients experiencing treatment-emergent adverse events (AEs) was comparable between the etrasimod 2 mg and placebo treatment groups, however it was greater in the etrasimod 2 mg group compared to placebo in ELEVATE UC 52. In both trials, the proportion of patients experiencing significant AEs was comparable across treatment groups. Headache, increased liver tests, worsening of UC, COVID-19 infection, dizziness, pyrexia, arthralgia, abdominal pain, and nausea were the most prevalent treatment-emergent AEs in 3% or more of etrasimod-treated patients and more than placebo up to week 52 in either trial. Data show that starting etrasimod medication does not necessitate a complicated up-titration plan.

In ELEVATE UC 52 and ELEVATE UC 12, nearly two-thirds of patients had never received biologic or JAK inhibitor therapy.

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