General Information

Velsipity (etrasimod) is a sphingosine 1-phosphate receptor modulator.

Velsipity is specifically indicated for the treatment of moderately to severely active ulcerative colitis in adults.

Dosing/Administration

Velsipity is supplied as tablets for oral administration.

Before initiation of treatment with Velsipity, assess the following: (for more information, see Warning and Precautions section of the prescribing label)

Complete Blood Count
Obtain a recent (i.e., within the last 6 months or after discontinuation of prior UC therapy) complete blood count (CBC), including lymphocyte count
Cardiac Evaluation
Obtain an electrocardiogram (ECG) to determine whether preexisting conduction abnormalities are present. In patients with certain preexisting conditions, advice from a cardiologist should be sought
Liver Function Tests
Obtain recent (i.e., within the last 6 months) transaminase and bilirubin levels
Ophthalmic Assessment
Obtain a baseline evaluation of the fundus, including the macula, near the start of treatment with Velsipity
Current or Prior Medications: Determine if patients are taking drugs that could slow heart rate or atrioventricular (AV) conduction. If patients are taking anti-neoplastic, immune-modulating, or non-corticosteroid immunosuppressive therapies, or if there is a history of prior use of these drugs, consider possible unintended additive immunosuppressive effects before initiating treatment with Velsipity
Vaccinations: Patients without a healthcare professional-confirmed history of varicella (chickenpox) or without documentation of a full course of vaccination against varicella zoster virus (VZV) should be tested for antibodies to VZV before initiating Velsipity ; VZV vaccination of antibody-negative patients is recommended prior to commencing treatment with Velsipity. If live attenuated vaccine immunizations are required, administer at least 4 weeks prior to initiation of Velsipity. Update immunizations in agreement with current immunization guidelines prior to initiating Velsipity therapy.
Skin Examination: Obtain a skin examination prior to or shortly after initiation of Velsipit. If a suspicious skin lesion is observed, it should be promptly evaluated.

Recommended dosage

The recommended dosage of Velsipity is 2 mg orally once daily. Swallow the tablet whole, with or without food.

Mechanism of Action

Velsipity (etrasimod) is a sphingosine 1-phosphate (S1P) receptor modulator that binds with high affinity to S1P receptors 1, 4, and 5 (S1P1,4,5). Etrasimod has minimal activity on S1P3 (25-fold lower than Cmax at the recommended dose) and no activity on S1P2. Etrasimod partially and reversibly blocks the capacity of lymphocytes to egress from lymphoid organs, reducing the number of lymphocytes in peripheral blood. The mechanism by which etrasimod exerts therapeutic effects in UC is unknown but may involve the reduction of lymphocyte migration into the intestines.

Clinical Trial Results

The FDA approval of Velsipity 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 also included patients with isolated proctitis.

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) and was 32.0% compared to 7.0% at week 52 (26.0% differential). 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). All key secondary efficacy endpoints were met at week 12, including endoscopic improvement and mucosal healing.