After 192 weeks, more than 90% of patients on ocrelizumab had no relapses and slightly more than 80% had no 24-week confirmed disability progression.
New data from the phase 3b ENSEMBLE study (NCT03085810) assessing ocrelizumab (Ocrevus; Genentech) in patients with relapsing-remitting multiple sclerosis (RRMS) showed stable or improved disability progression in most patients treated up to 4 years. Safety results were consistent with the known ocrelizumab safety profile, with no new safety signals.
The analysis included 678 individuals with early-stage RRMS with a disease duration of less than 3 years who received ocrelizumab 600 mg every 24 weeks for 192 weeks. At week 192, 77.9% of patients showed no evidence of clinical activity and 85.0% achieved no evidence of MRI activity. Above all, 66.4% of patients treated with first-line ocrelizumab maintained no evidence of disease activity (NEDA) after 4 years of treatment.
These findings were presented at the 2023 American Academy of Neurology (AAN) Annual Meeting, held April 22-27, in Boston, Massachusetts, by lead author Robert Bermel, MD, staff neurologist, Mellen Center for Multiple Sclerosis, Cleveland Clinic. The patient cohort featured individuals aged 18 to 55 years, who had Expanded Disability Status Scale (EDSS) scores between 0-3.5, 1 relapse or T1-weighted contrast enhancing lesion in the prior 12 months, and were treatment-naïve.
In the trial, patients received ocrelizumab 300 mg intravenously on days 1 and 15 for the first dose, followed by 600 mg IV every 24 weeks for 4 years. At the conclusion of the 4-year period, 90.9% (n = 539) of patients had no relapses, and 81.8% (n = 485) had no 24-week confirmed disability progression (CDP). Furthermore, 90.6% and 90.4% of patients, respectively, showed no T1-weighted contrast enhancing lesions or T2-weighted lesions by the end of the observed period.
Over a total of 2385 patient-years followed, there were 54 relapses total, equating to an adjusted annualized relapse rate of 0.023 (95% CI, 0.02-0.03). In terms of 24-week CDP, 15.9% (n = 108) of the cohort had an event while the remaining 84.1% (n = 570) did not. At 4 years, 82.1% of those on ocrelizumab had either stable or improved EDSS. More specifically, 22.8% improved, 59.3% remained stable, and 18.0% worsened.
In total, 95.4% (n = 647) of patients experienced an adverse event (AE) throughout the trial, 3.1% (n = 21) of which were grade 3 and above. Serious AEs were recorded by 15.5% (n = 105) of the cohort, and death occurred in 6 patients (0.6%). Fatalities included 2 cases of COVID-19, 2 cases of COVID-19 pneumonia, 1 case of pneumonia, and 1 case of immune reconstitution inflammatory syndrome. Infusion-related reactions, infections, and serious infections were found in 51.8%, 75.2%, and 6.9% of patients, respectively. Of the IRRs (n = 351), none were grade 4 and above, and 13 were grade 3.
Ocrelizumab, an anti-CD20 monoclonal antibody, has been approved for relapsing MS and primary progressive MS. In 2020, the FDA approved a shorter 2-hour infusion time for ocrelizumab based on findings from ENSEMBLE-PLUS, a prospective substudy to the open-label, single-arm, phase 3b ENSEMBLE trial. Findings from ENSEMBLE-PLUS showed a similar frequency and severity of infusion reactions for a 2-hour ocrelizumab infusion time compared to the previously approved 3.5-hour time in patients with RRMS.2