Ponesimod Treatment in Early Multiple Sclerosis Reduced Likelihood of Severe Relapses and Was Safe in Long-Term Studies

As previously reported, ponesimod (Ponvory; Janssen Pharmaceuticals, Titusville, NJ) significantly reduced the annualized rate of relapse (ARR) in relapsing multiple sclerosis (RMS) in the phase 3 OPTIMUM study (NCT02425644). Treatment with 20 mg ponesimod resulted in a 30.5% reduction in ARR relative to treatment with teriflunomide (Aubagio; Genzyme, Cambridge, MA). 

The ARR for those treated with 20 mg of ponesimod was 0.202 vs 0.290 for 14 mg of teriflunomide (P=.0003). Of those treated with 20 mg/day ponesimod, 29.3% (166/567) experienced a relapse compared with 39.4% (223/566) of those treated with 14 mg/day teriflunomide. 

A new post hoc analysis of OPTIMUM data being presented at the European Academy of Neurology Congress June 25-28 in Vienna, Austria and online, showed that relapse severity was also significantly reduced with ponesimod vs terifluomide. 

Participants treated with ponesimod had a 42% lower likelihood of having a highly or moderately severe relapse than those treated with teriflunomide (odds ratio [OR] 0.58; 95% CI, 0.44-0.76). Among a subgroup of participants who had Expanded Disability Status Scale scores of at least 3 at baseline, those treated with ponesimod vs teriflunomide had a 56% lower likelihood of having a highly or moderately severe relapse (OR 0.44; 95%, CI 0.30-0.64). The likelihood of a low severity relapse was similar for those treated with ponesimod or teriflunomide, regardless of EDSS score. 

Severity of relapse was defined as high if treatment was withdrawn or the individual being treated was hospitalized and high/moderate if more than 1 functional domain was affected and corticosteroid treatment was needed. All other relapses were defined as low severity. 

Data from the open-label extension period of OPTIMUM are also being presented. All participants in the open-label extension study received 20 mg/day ponesimod for a mean 30.3 months. 

During the extension period, rates of serious adverse events were similar between those treated with ponesimod (3.2%, n=439) vs teriflunomide (3.9%; n=438) in the double-blind period. Serious adverse events that occurred in more than 1 participant included appendicitis, abdominal pain, induced abortion, lumbar radiculopathy, and multiple sclerosis relapse. No cases of skin cancer or PML or death occurred in the double-blind or open-label periods. 

The rates of any adverse events in the open-label period were also similar at 59.9% and 66% in participants who had ponesimod vs terifluomide in the double-blind period.