Ponesimod Safe, Effective Over 13 Years in RRMS

TOPLINELong-term use of ponesimod 20 mg showed no new safety concerns and was associated with low disease activity in patients with relapsing-remitting multiple sclerosis (RRMS), a combined analysis of a phase 2b trial and extension studies showed.METHODOLOGYResearchers conducted a combined analysis of a 24-week phase 2b core study and a long-term extension study spanning up to 13 years that included 435 adults with RRMS who received at least one dose of ponesimod during multiple treatment periods (TPs) across 23 countries.During TP1 (about 1.84 years), participants receiving ponesimod during the core study continued with their treatment doses (10, 20, or 40 mg once daily) and those receiving placebo were re-assigned (1:1:1) to receive ponesimod. During TP2, participants receiving 40 mg ponesimod were re-assigned (1:1) to receive 10 or 20 mg ponesimod. During TP3, all the participants received 20 mg ponesimod because it was identified as the optimal dose. The combined duration of TP2 and TP3 was about 10.4 years.Researchers assessed safety endpoints (treatment-emergent adverse events [TEAEs], clinical laboratory tests, ECG, blood pressure, and lung function tests) and exploratory efficacy endpoints (annualized relapse rate [ARR] for confirmed relapses, time to first confirmed relapse, and time to 24-week confirmed disability accumulation).MRI scans were examined at weeks 24, 48, and 96 and at the follow-up visit. Related efficacy endpoints comprised the cumulative number of T1 gadolinium-enhanced lesions, new or enlarging T2 lesions, and combined unique active lesions. Data were analyzed during three analysis periods (APs); AP3 included data from the core study and the three TPs.TAKEAWAYOf the 145 patients in the ponesimod 20 mg dose group, 92.4% reported experiencing at least one TEAE, most of which were of mild-to-moderate severity (73.1%). Serious TEAEs were reported by 24.1% of participants, and 13.1% of participants discontinued treatment due to TEAEs.In the 20 mg group, the mean ARR at the end of AP3 was 0.142, and 52.5% of participants experienced a confirmed relapse at nearly 13 years. About 31.3% of participants in the 20 mg group experienced 24-week confirmed disability accumulation at nearly 13 years, and 20% experienced 24-week confirmed disability accumulation during AP3.The mean total number of T1 gadolinium-enhanced lesions decreased substantially from 2.62 at baseline to 0.26 at week 648 in the 20 mg group. About 75% of participants were free from such new lesions at week 24, and over 80% were free at all subsequent timepoints.The mean number of new or enlarging T2 lesions per MRI time window decreased from 0.66 during weeks 0-48 to 0.10 during weeks 624-672 in the 20 mg group. About 89.1% of participants were free from these lesions during weeks 624-672 and 42.9% were free during AP3.IN PRACTICE“Ponesimod 20 mg treatment for up to 13 years in participants with RRMS showed no new safety concerns, and participants experienced low disease activity across relevant clinical and MRI outcomes,” the investigators wrote.SOURCEThe study was led by Tomas Olsson, Karolinska Institutet, Center for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden. It was published online on July 21 in Multiple Sclerosis and Related Disorders.LIMITATIONSThe study endpoints were exploratory in nature. Potential selection bias could be present. The study also lacked a placebo or an active control group. The effects of ponesimod on vaccine responsiveness were not assessed. Lastly, assignments were unblinded for the sponsor in TP1 for individuals receiving ponesimod.DISCLOSURESThe study was funded by Johnson & Johnson, the maker of ponesimod. Disclosure information for the study investigators is available in the original study publication.This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.