2021 CMSC Annual Meeting

Recently Diagnosed Treatment-Naive RRMS: 1-Year Safety Data from the Ocrelizumab Phase IIIb ENSEMBLE Study


Background: ENSEMBLE (NCT03085810) is a multicenter, open-label, single-arm Phase IIIb study evaluating the effectiveness and safety of ocrelizumab (OCR) in an early-stage, treatment-naive, relapsing-remitting MS (RRMS) population with active disease. In the initial cohort (N=678), patients responded consistently well to OCR treatment based on clinical, MRI, and biomarker measures; however, it is also important to understand the short- and long-term safety profile of OCR as an early, first-line treatment in this population. Objectives: To evaluate the safety of OCR after 1 year (48 weeks) of treatment in the full cohort of patients (N=1,225) with early-stage, treatment-naive RRMS, in ENSEMBLE. Methods: Patients (treatment-naive, diagnosis of early-stage RRMS [age 18–55 years inclusive; Expanded Disability Status Scale score ?3.5], disease duration ?3 years and active disease [?1 clinically reported relapse and/or ?1 sign of MRI activity within 12 months of enrollment]) received 600 mg OCR every 24 weeks. Safety assessments consisted of monitoring and recording adverse events (AEs) including serious AEs (SAEs), discontinuations due to AEs, protocol-specified safety laboratory assessments, and protocol-specified tests deemed critical to the safety evaluation. Results: AEs were reported in 85.1% of patients (n/N=1042/1225) and SAEs were reported in 4.6% of patients (n/N=56/1225). The majority of AEs were mild to moderate (Grade 1 or 2), with 67 patients (5.5%) experiencing Grade 3 AEs. Grade 4 AEs were reported in five patients (0.4%); all resolved, and no action was taken with OCR. One fatal (Grade 5) AE occurred (<0.1%; bronchopneumonia). There were nine discontinuations due to AEs (0.7%). A total of 600 patients (49.0%) experienced infections and 13 patients (1.1%) experienced serious infections. A total of 497 patients (40.6%) experienced infusion-related reactions (IRRs); only 18 were Grade 3 and there were no Grade 4 or Grade 5 IRRs. Six serious IRRs were observed in total. From the main ENSEMBLE study, n=745 patients were randomized into the ENSEMBLE PLUS shorter infusion substudy; one of the serious IRRs (Grade 2 with preventive hospitalization) was in relation to the shorter infusion protocol. At the start of the COVID-19 pandemic (March 2020), n=197 patients were in the first year of treatment, however, no cases of COVID-19 were reported. Conclusions: Safety outcomes in ENSEMBLE were quantitively and qualitatively consistent with the known safety profile of ocrelizumab. No new safety signals were observed.