Velsipity From Pfizer

The FDA has approved etrasimod (Velsipity) oral tablets from Pfizer for the treatment of moderately to severely active ulcerative colitis (UC) in adults.¹ UC affects approximately 1.25 million individuals in the US. Symptoms include abdominal pain, chronic diarrhea with blood and mucus, and urgency to urinate.²

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PHARMACOLOGY AND PHARMACOKINETICS

Etrasimod is a sphingosine 1-phosphate (S1P) receptor modulator that selectively binds with S1P receptors 1, 4, and 5. The median time to maximum plasma concentrations is approximately 4 hours after oral administration, and steadystate plasma concentrations are observed within 7 days of treatment. Etrasimod displays a mean plasma elimination half-life of approximately 30 hours. No clinically significant differences in its pharmacokinetics were observed based on age (> 65 years), body weight, disease, ethnicity, race, sex, and severe renal impairment (estimated glomerular filtration rate ≤ 29 mL/min).^1,2

DOSAGE AND ADMINISTRATION

The recommended dose of etrasimod is 2 mg orally once daily. The medication should be swallowed whole and may be taken with or without food. Before beginning treatment, patients should have a complete blood count, electrocardiogram, liver function tests, ophthalmic assessment, skin examination, and a review of both immunization status and medication history.¹

CLINICAL TRIALS

Etrasimod was evaluated for efficacy in 2 double-blind, placebo-controlled, randomized studies (ELEVATE UC-1, NCT03945188; and ELEVATE UC-12, NCT03996369) of adults with moderately to severely active ulcerative colitis who had an inadequate response, loss of response, or intolerance to biologic therapies, corticosteroids, Janus kinase inhibitors, oral aminosalicylates, and/or thiopurines. In both studies, participants were randomly assigned to receive either etrasimod or placebo.

The co-primary end points of UC-1 were the proportion of participants who achieved clinical remission at weeks 12 and 52, which the study met. Statistically significant improvements were demonstrated in the study’s secondary end points, including the proportion of participants who achieved endoscopic improvement, histologic-endoscopic mucosal improvement, corticosteroid-free clinical remission, and maintenance of clinical remission.

UC-12 met both its primary and secondary end points. The primary end point was the proportion of participants who achieved clinical remission at week 12, and the secondary end points included the proportion of participants who achieved endoscopic improvement and histologicendoscopic mucosal improvement at week 12.^1,2

CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS

Treatment with etrasimod is contraindicated in patients who have experienced class III or IV heart failure, decompensated heart failure requiring hospitalization, myocardial infarction, stroke, transient ischemic attack, or unstable angina pectoris within the past 6 months. Treatment is also contraindicated in patients with a history or presence of Mobitz type II second-degree or third-degree atrioventricular block, sick sinus syndrome, or sinoatrial block, unless a functioning pacemaker is in place.

Treatment with etrasimod may increase the risk of infections or macular edema. Atrioventricular conduction delays, decreased pulmonary function, elevated aminotransferases, increased blood pressure, or a transient decrease in heart rate may occur. Because etrasimod may cause fetal harm, women of reproductive potential should use effective contraception during treatment and for 1 week after stopping the medication. Malignancies, including skin malignancies, have been reported in patients using S1P receptor modulators. If symptoms of posterior reversible encephalopathy syndrome occur, neurological and physical exams should be performed and an MRI considered. When switching to etrasimod from agents with prolonged immune effects, the half-life and mode of action of these agents should be considered to avoid unintended additive immunosuppressive effects. Because the use of immunosuppressants within 4 to 5 weeks of stopping etrasimod may lead to an additive effect on the immune system, patients should be monitored for up to 5 weeks after the last dose of etrasimod when receiving concomitant immunosuppressants for infectious complications. Etrasimod should not be used in patients with severe hepatic impairment.

The most common adverse reactions with etrasimod are dizziness, elevated liver tests, and headache.¹

References

1. Velsipity. Prescribing information. Pfizer Inc; 2023. Accessed November 2, 2023. https://labeling.pfizer.com/ShowLabeling.aspx?id=19776

2. U.S. FDA Aapproves Pfizer’s Velsipity for Aadults with Mmoderately to Sseverely Aactive Uulcerative Ccolitis (UC). News release. Pfizer Inc.;. October 13, 2023. Accessed November 2, 2023.https://www.pfizer.com/news/press-release/press-release-detail/us-fda-approves-pfizers-velsipitytm-adults-moderately