Highlights
- VELSIPITY® offers a novel mechanism to treat ulcerative colitis for those unresponsive to current therapies.
- Ongoing studies aim to clarify VELSIPITY's long-term safety, enhancing treatment options for patients.
Overview and Background
VELSIPITY® (etrasimod) is an oral medication approved in 2025 for adults with moderately to severely active ulcerative colitis (UC) who have not responded to or tolerated conventional or advanced therapies. UC is a chronic autoimmune disease causing colon inflammation and symptoms like abdominal pain, diarrhea, and rectal bleeding. VELSIPITY works by selectively modulating the sphingosine-1-phosphate (S1P) receptor to reduce lymphocyte migration to the gut, thereby lowering inflammation. Traditional UC treatments include aminosalicylates, corticosteroids, thiopurines, JAK inhibitors, and biologics, but many patients require additional options.
Development and Mechanism of Action
VELSIPITY’s active ingredient, etrasimod, targets the S1P receptor to prevent lymphocytes from leaving lymph nodes, reducing their presence in the colon and mitigating inflammation. This novel approach directly addresses immune cell trafficking involved in UC. Developed by Pfizer, VELSIPITY underwent clinical trials with diverse patient populations and required close monitoring for immunomodulatory side effects, including infection risks. Baseline blood counts are recommended before starting therapy to ensure safety.
Clinical Trials and Efficacy
VELSIPITY’s approval was based on two Phase 3 randomized, placebo-controlled trials, ELEVATE UC 12 and ELEVATE UC 52, involving patients with moderate to severe UC who failed or were intolerant to prior therapies. ELEVATE UC 12 showed a 26.0% remission rate at 12 weeks with VELSIPITY versus 15.0% for placebo. ELEVATE UC 52 confirmed sustained remission at weeks 12 and 52. Trials included biologic- and JAK inhibitor-naïve patients and those with isolated proctitis, enhancing relevance. Common adverse events were headache, elevated liver enzymes, dizziness, and manageable hematologic abnormalities.
Regulatory Approvals and Guidelines
VELSIPITY received FDA approval in 2025 for adult UC patients with moderate to severe disease. Regulatory submissions have been made globally, including Canada, Australia, Europe, and Asia, with EMA’s decision expected in early 2024. Clinical guidelines recommend discontinuing VELSIPITY if progressive multifocal leukoencephalopathy (PML) is suspected. Monitoring clinical response and neurological status is emphasized to manage risks. Post-marketing studies are ongoing to evaluate long-term safety and use during pregnancy.
Clinical Use and Safety Profile
VELSIPITY is administered once daily and reimbursed under specific conditions in some regions. Clinical data show it induces and maintains remission, improves symptoms like stool frequency and rectal bleeding, and sustains corticosteroid-free remission at one year. Side effects occurring in ≥5% of patients include headache, elevated liver enzymes, and dizziness, with other less common effects such as arthralgia and infections. Drug interactions require careful medication review. Pediatric safety and efficacy have not been established, and some patients may experience loss of response over time. The estimated annual treatment cost is about $15,742 per patient.
Market Presence and Adoption
VELSIPITY is gaining global market presence with approvals in Macau, Singapore, Hong Kong, and pending decisions in major markets including China and Europe. In Canada, public reimbursement is recommended for eligible UC patients. The manufacturer provides educational resources and support programs to facilitate patient access and safe use, promoting wider adoption.
Future Directions
Ongoing research aims to clarify VELSIPITY’s long-term safety, potential pediatric use, and role in combination therapies. Its novel mechanism and demonstrated efficacy position it as a promising option for patients with limited alternatives. Continued innovation and expanded indications are anticipated to enhance UC management.
Criticisms and Safety Concerns
Despite its benefits, VELSIPITY has raised concerns about safety, particularly risks of infections, hematologic abnormalities, and limited data in older adults and special populations. Common side effects reported at rates higher than placebo include headache, elevated liver enzymes, dizziness, arthralgia, nausea, hypertension, and bradycardia. Vigilant monitoring and further study are necessary to fully assess its safety profile.
The content is provided by Jordan Fields, Scopewires
