AAN 2023: Early use of Ocrevus lowers disease activity in relapsing MS
Starting patients on treatment soon after diagnosis seen as 'highly efficacious'
Nearly half of the people with relapsing forms of multiple sclerosis (MS) treated early with Ocrevus (ocrelizumab) in Phase 3 clinical trials showed no evidence of disease activity after up to nine years on the therapy, data show.
In contrast, about one-quarter of enrolled patients who started on the therapy two years later were without any evidence of disease activity at nine years.
These findings cover a subgroup of recently diagnosed MS patients who received first-line treatment in the OPERA trials and their ongoing open-label extension study.
João Cerqueira, MD, PhD, a professor of neurology at the University of Minho in Portugal, shared these data at the American Academy of Neurology (AAN) 2023 Annual Meeting, held in late April in Boston and virtually.
His presentation was titled, “Long-Term Treatment With First-Line Ocrelizumab in Patients With Early RMS: 9-Year OPERA Subgroup Analysis.” The work was funded by the Roche subsidiary Genentech, which markets Ocrevus.
Data cover 757 people diagnosed within two years of entering OPERA trials
Findings suggest that Ocrevus “started early as a first-line drug in this very early [relapsing] MS population is highly efficacious,” Cerqueira said.
Ocrevus is an approved MS treatment that works by destroying B-cells. In the U.S., the medication is approved to treat relapsing types of MS, as well as primary progressive MS (PPMS).
The Phase 3 OPERA I (NCT01247324) and OPERA II (NCT01412333) clinical trials, which helped to support Ocrevus’ approval, enrolled 1,656 adults with relapsing MS.
In the main studies, participants were treated with either Ocrevus or Rebif (interferon beta-1a) for about two years (96 weeks). Results showed that Ocrevus outperformed Rebif at reducing relapse rates and preventing disability progression.
After these studies concluded, most patients entered into an open-label extension, where all are being treated with Ocrevus and followed for long-term outcomes. Cerqueira’s presentation covered data for 757 people diagnosed with MS less than two years before entering the OPERA studies, and not using any MS treatment before starting in the trial.
These patients were followed for a total of nine years, two years in the original study plus seven in the extension.
Among this group, 375 people were randomized to Ocrevus in the two-year OPERA trials, while 382 others initially were treated with Rebif. When the OPERA studies started, patients’ average age was around 36, and most were less than a year out from a diagnosis.
Nearly half (48.2%) of the patients on continuous use of Ocrevus were seen to have no evidence of disease activity (NEDA) — defined as no relapses, no worsening of disability, and no new MRI activity — after nine years. In contrast, about 1 in 4 (25.7%) of those given Rebif in the main studies had reached NEDA at nine years.
“This highlights the fact that it’s really beneficial … to start these patients on [Ocrevus] early on, as compared to … a delayed start,” Cerqueira said.
After nine years, less than a third of these patients had any confirmed disability progression. The rate of disability progression was slightly lower for patients on continuous Ocrevus, compared with those who switched to the therapy two years later (27% vs. 31%).
The difference between the two groups was not statistically significant, “but nevertheless this is a numerical difference that is important to highlight,” Cerqueira said.
He noted that the difference largely was attributable to more patients experiencing disability progression while on Rebif in the original OPERA trials.
“We lose these patients by not treating them earlier” with Ocrevus, Cerqueira said, adding that rates of disability progression over time were generally comparable for both groups during the extension trial when all were given Ocrevus.
Long-term safety data generally were consistent with prior findings. Serious infections, a known risk of the immune-suppressing therapy, were reported in less than 3% of patients. Data suggested that patients with low levels of an antibody called immunoglobulin G (IgG) were more likely to have a serious infection, though the types of infection were similar regardless of IgG status.
“The rates of infection in this long period of follow-up didn’t go above what was expected and what was seen in other trials,” Cerqueira said.
Four-year update on early RRMS patients given Ocrevus in ENSEMBLE trial
In a separate AAN presentation, Robert Bermel, MD, a neurologist with the Cleveland Clinic, shared four years of treatment data from another Phase 3 clinical trial, called ENSEMBLE (NCT03085810), which is testing Ocrevus in people with early stage relapsing-remitting multiple sclerosis (RRMS).
His talk was titled, “Low Disease Activity Over 4 Years of Ocrelizumab Therapy in Treatment-Naive Patients With Early-Stage Relapsing-Remitting Multiple Sclerosis; the Phase IIIb ENSEMBLE Study.”
ENSEMBLE enrolled more than 1,200 adults, ages 18 to 55, who were less than three years out from their first attack of MS symptoms; most had experienced their first attack less than a year before entering the study. None had received prior MS therapies.
All patients are being treated with Ocrevus according to its approved dosing schedule. Prior data showed that most patients (77.3%) achieved NEDA after two years of treatment.
At the four year analysis, nearly 2 in every 3 patients (66.4%) with available data continued to have NEDA. Specifically, 90.9% had no relapses, 81.8% had no disability worsening, and 85% had no new MRI activity. In total, more than three-quarters of patients (77.9%) had neither relapses nor worsening disability over four years on Ocrevus.
The average relapse rate was 0.02 relapses per year, which Bermel noted equates to one relapse every 50 years. In most patients (82.1%), scores on the Expanded Disability Status Scale (EDSS) indicated that disability either was stable (in 59.3%) or improved (in 22.8%) over the course of the trial. ENSEMBLE is due to conclude in August 2024.
“Disease activity based on clinical and MRI measures was really very minimal in most patients treated with [Ocrevus] over four years. Patients most commonly remained stable, or some improved, over the course of the study,” Bermel concluded.
Safety data in ENSEMBLE were consistent with other studies of Ocrevus, with common side effects including infusion reactions, headache, and the common cold. “No new safety signals were identified here,” Bermel said.
Note: The Multiple Sclerosis News Today team is providing coverage of the American Academy of Neurology (AAN) 2023 Annual Meeting April 22-27. Go here to see the latest stories from the conference.
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