Ponesimod in Relapsing Forms of Multiple Sclerosis - Long-Term Pooled Safety Results from the Clinical Development Program

Background: Ponesimod is a selective sphingosine-1-phosphate receptor 1 modulator approved for the treatment of relapsing multiple sclerosis (RMS). The Phase 2/3 clinical development program of ponesimod monotherapy in MS includes 2 double-blind, controlled studies and 2 ongoing long-term extension (LTE) studies.

Objectives: To provide a comprehensive perspective of the safety of ponesimod 20 mg in RMS and to characterize the safety profile in a large and robust ‘long-term’ pooled dataset.

Methods: The long-term pool included patients who received at least 1 dose of ponesimod in the completed double-blind studies or their ongoing LTE studies (data collected up to and including 18 March 2020). This analysis focusses only on patients in the ponesimod 20 mg arm.

Results: A total of 1148 patients treated with ponesimod 20 mg were included in this analysis. The total mean exposure to ponesimod in the 20 mg arm was 2.834 years (3253.21 patient years). Of these, 855 (74.5%) patients were receiving ongoing ponesimod 20 mg treatment as of March 2020. The incidence of treatment emergent adverse events (TEAEs) and serious AEs (SAEs) was 87.1% and 11.1%, respectively. Most TEAEs were mild or moderate in intensity. TEAEs classified as severe were reported in 8.8% of patients.. TEAEs leading to discontinuation occurred in 8.9% of patients. One death was reported (sudden death in a patient with multiple cardiovascular factors and history of peripheral vascular disease and vascular surgery - not considered related to ponesimod treatment). The most frequently reported (≥10% of patients) TEAEs by preferred term were: nasopharyngitis (19.7%), alanine aminotransferase increased (17.9%), headache (13.0%), and upper respiratory tract infection (11.0%). The most frequent SAEs (> 1.5%) by system organ class were infections and infestations (2.2%) and nervous system disorders (1.7%). Overall, the incidence of malignancies was low with 0.3% of patients reporting basal cell carcinoma and one patient, malignant melanoma. There were no cases of progressive multifocal leukoencephalopathy, cryptococcal meningitis infection or any other opportunistic infections with fatal outcome.

Conclusions: The safety profile, including the pattern and nature of TEAEs, was consistent with TEAEs reported from the individual clinical trials as reflected within the product labelling. No unexpected safety findings were identified in this analysis.