COVID-19 Vaccine Antibody Response in RMS Patients Treated with Ponesimod: Results from the Long-Term Extension Study AC-058B202

Background: Ponesimod is a sphingosine-1-phosphate (S1P) receptor modulator indicated for the treatment of RMS in adults. Limited clinical data suggest that S1P receptor modulators may impact the humoral immune response to non-live vaccines, including those for COVID-19.

Objectives: To characterize the SARS-CoV-2 humoral response and COVID-19 infection adverse events (AEs) in RMS patients who have received COVID-19 vaccination while on ponesimod treatment.

Methods: Participants in Phase 2 study AC-058B202 receiving ponesimod 20 mg who reported COVID-19 vaccination were analyzed. Blood samples collected before and at least 3 weeks after COVID-19 vaccination were tested for SARS-CoV-2 anti-spike-protein (spike) antibody concentrations (Human SARS-CoV-2 PreSpike IgG ELISA, Nexelis). Response to vaccination was defined as seroconversion in case of negative pre-vaccination antibody testing, or a 4-fold antibody concentration increase in case of a positive pre-vaccination antibody result. COVID-19 infection adverse events (AEs) were evaluated in vaccinated participants.

Results: Based on data cut-off on 03/17/2022, 134 study participants received COVID-19 vaccines (64.9% mRNA, 17.9% viral vector, 9.0% inactivated, 6.0% mixed, 2.2% unspecified). Median exposure to ponesimod at time of vaccination was 10.7 (range 9.8-11.8) years. Of the 134 participants, 49 participants had both pre- and post-vaccination blood samples tested for spike antibody concentrations. Out of these 49 participants, 40 (81.6%) met the definition of response to COVID-19 vaccination. Of the 38 antibody-negative participants, 33 (86.8%) achieved seroconversion post-vaccination. As for clinical outcomes in the 134 vaccinated participants, 20 and 17 participants reported pre-vaccination and post-vaccination AEs of COVID-19 infection, respectively. None of these AEs were serious, severe or fatal, and none led to permanent treatment discontinuation.

Conclusions: In patients with RMS on ponesimod, the majority (>80%) appear to develop a measurable SARS-CoV-2 humoral response after COVID-19 vaccination. Further investigations on the efficacy and safety of COVID-19 vaccination in MS patients on ponesimod are warranted.