Recently Diagnosed Early-Stage RRMS: NEDA, ARR, Disability Progression, Serum Neurofilament and Safety: 1-Year Interim Data From the Ocrelizumab Phase IIIb ENSEMBLE Study
Timothy Vollmer1, Mark S Freedman2, Joep Killestein3, Carlos Nos4, Ludo Vanopdenbosch5, Regine Buffels6, Karen Kadner6, Thomas Kuenzel6, Inessa Kulyk6, Hans-Peter Hartung7
1Department of Neurology, University of Colorado, 2University of Ottawa, Department of Medicine and the Ottawa Hospital Research Institute, 3Department of Neurology, VU University Medical Center, 4Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Vall d’Hebron Hospital Universitari, 5Department of Neurology, AZ Sint Jan Brugge Oostende, 6F. Hoffmann-La Roche Ltd, 7Department of Neurology, UKD, Center of Neurology and Neuropsychiatry and LVR-Klinikum, Heinrich Heine University Duesseldorf

To report 1-year interim efficacy and safety data in ENSEMBLE (NCT03085810), a Phase IIIb study evaluating ocrelizumab in patients with early-stage relapsing-remitting multiple sclerosis (RRMS).


Early treatment of MS and rapid onset of therapeutic effect provide long-term benefits on disease outcomes. Individual and composite measures of MRI and clinical disease activity and progression were assessed in ENSEMBLE, a treatment-naive early-stage RRMS population with active disease.


Patients (treatment-naive, diagnosis of early-stage RRMS [age 18–55 years inclusive; Expanded Disability Status Scale (EDSS) score ≤3.5], disease duration ≤3 years and active disease [≥1 clinically reported relapse or ≥1 sign of MRI activity within 12 months of enrollment]) received ocrelizumab 600 mg every 24 weeks. Biomarker and clinical assessments included: NEDA (with MRI rebaselining at Week 8; defined as absence of protocol-defined relapses, 24-week confirmed disability progression, T1-weighted contrast-enhancing and new/enlarging T2-weighted lesions), annualized relapse rate (ARR), EDSS score and serum neurofilament-light (NfL) levels.


Baseline demographics and disease characteristics of 678 patients (64.6% female) were consistent with early-stage disease (mean [SD]: age, 32.4 [9.1] years; baseline EDSS, 1.71 [0.95]; time since RRMS diagnosis, 0.36 [0.40] years; time since MS symptom onset, 1.10 [0.84] years) of which 74.6% had both MS relapse and MRI activity. At Weeks 24 and 48 most patients (91.2% [n/N=618/678] and 84.8% [n/N=545/643]) had NEDA. Adjusted ARR at Week 48 was 0.005 (95%CI, 0.003-0.009). EDSS score (mean [SD]) remained stable at Weeks 24 (1.56 [1.04]) and 48 (1.55 [1.07]). Age-adjusted serum NfL levels (geometric mean, pg/mL [coefficient of variance]) at baseline and Week 48 were 10.5 (107.8%) and 4.55 (59.5%), versus 4.12 (36.2%) in age-matched healthy controls. Safety results were consistent with prior studies.


Treatment-naive patients with early-stage RRMS in ENSEMBLE responded consistently well to ocrelizumab treatment based on clinical, MRI and biomarker measures; no new safety signals were observed.