Abstract Details

Early and sustained treatment of MS with high-efficacy therapy reduces the risk of long-term disease progression. ENSEMBLE is a multicenter, open-label, single-arm Phase IIIb study, evaluating the efficacy and safety of OCR in patients with early-stage RRMS.

To report 4-year efficacy and safety data from the ENSEMBLE trial (NCT03085810) of ocrelizumab (OCR) in patients with early-stage relapsing-remitting multiple sclerosis (RRMS).

At the time of enrollment, eligible patients were treatment naive, aged 18–55 years, had an active early-stage RRMS with a disease duration ≤3 years, Expanded Disability Status Scale (EDSS) ≤3.5 and ≥1 clinically reported relapse(s) or ≥1 signs of magnetic resonance imaging (MRI) activity (T1-weighted contrast-enhancing lesions or new/enlarging T2-weighted lesions, with MRI measurements rebaselined at W8) in the prior 12 months. Patients received OCR 600 mg every 24 weeks for 192 weeks. Key endpoints were no evidence of disease activity (NEDA)-3 (defined as no relapses, no 24-week [W] confirmed disability progression [CDP] and no MRI activity), annualized relapse rate (ARR), mean change in EDSS score from baseline (BL) and safety.

BL characteristics (N=678) were consistent with early-stage RRMS (patients ≤40 years with a median age of 31.0 years; duration since MS symptom onset, 0.78 years; duration since RRMS diagnosis, 0.24 years; mean BL EDSS score [SD], 1.71 [0.95]). At W192, the majority of patients had NEDA (n=394/593, 66.4%), 85.0% had no MRI activity, 90.9% had no relapses and 81.8% had no 24W-CDP. Adjusted ARR at W192 was low, 0.020 (95% CI, 0.015–0.027). No new or unexpected safety signals were observed.

Disease activity based on clinical and MRI measures was minimal in most patients treated with ocrelizumab over 4 years in the ENSEMBLE study. Safety was consistent with the known profile of ocrelizumab, with no new signals.