Treatment-naive patients with early-stage relapsingremitting multiple sclerosis showed low disease activity after 2-year ocrelizumab therapy, with no new safety signals' the Phase IIIb ENSEMBLE study

ABSTRACT

Background: Early high-efficacy treatment of multiple sclerosis (MS) may provide long-term clinical benefits, improving disease outcomes and patient quality of life. ENSEMBLE is a multicentre, open-label, single-arm Phase IIIb study, evaluating the effectiveness and safety of ocrelizumab (OCR) in patients with early-stage relapsing-remitting MS (RRMS). Aim(s) To report 2-year interim efficacy and safety data of the full cohort of patients with early-stage RRMS from the ENSEMBLE trial (NCT03085810), using no evidence of disease activity (NEDA)-3 as the primary endpoint. Method(s) Treatment-naive patients with early-stage RRMS (age 18-55 years;disease duration <=3 years;Expanded Disability Status Scale [EDSS] <=3.5;with one or more clinically reported relapse(s) or one or more signs of MRI activity in the prior 12 months) received OCR 600 mg every 24 weeks for 192 weeks (planned study duration). Key endpoints were NEDA-3 (defined as no relapses, 24-week [W] confirmed disability progression [CDP] and MRI activity [T1-weighted contract enhanced images or new/enlarging T2-weighted lesions, with MRI measurements rebaselined at W8]), annualised relapse rate (ARR), mean change in EDSS score from baseline (BL) and a safety overview. Result(s) BL demographics and disease characteristics of the ENSEMBLE population (N=1,225) were consistent with earlystage RRMS disease (patients <=40 years, 78.9%;female, 64.0%;median Age, 32.0 years;duration since MS symptom onset, 0.74 years;duration since RRMS diagnosis, 0.22 years;BL EDSS score, 1.75;mean BL EDSS score [SD], 1.80 [0.93]). At W96, the majority of patients (n=857, 77.3%) had NEDA, 88.9% had no MRI activity, 93.4% had no relapses and 90.7% had no 24W-CDP. The adjusted ARR at W96 was low, 0.033 (95% CI, 0.026-0.042), and the mean (SD) EDSS score showed a statistically significant improvement between BL and W96, decreasing by 0.13 (0.89;p<0.0001), from 1.80 (0.93) to 1.67 (1.12). Safety results were consistent with prior OCR studies. Infections were reported by 760 (62.0%) patients;rates of serious infections were low (n=33 [2.7%] patients);32 (2.6%) of patients contracted a COVID-19 infection. Conclusion(s) In the ENSEMBLE study of treatment-naive patients with early-stage RRMS, disease activity based on clinical and MRI measures was minimal in most patients treated with ocrelizumab over 2 years;safety was consistent with prior ocrelizumab experience, with no new safety signals.