#ECTRIMS2021 – Early Ocrevus Slows MS Better Versus 2-year Delay
Editor’s note: The Multiple Sclerosis News Today team is providing in-depth coverage of the virtual 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), Oct. 13–15. Go here to see the latest stories from the conference.
Early use of Ocrevus (ocrelizumab) continues to significantly slow disability progression after 7.5 years in people with relapsing multiple sclerosis (MS) and after eight years in those with primary progressive MS (PPMS), according to new analyses of Phase 3 trial data comparing immediate use with a two-year delay in starting therapy.
Also, the treatment’s safety profile remained consistent with that previously reported, supporting a favorable benefit-risk profile with long-term therapy.
“Many neurologists have had first-hand experience with Ocrevus over eight years in clinical trials and witnessed the consistently favorable efficacy and safety outcomes in RMS [relapsing MS] and PPMS, especially the reductions in progression to disability when given early in the disease,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Genentech, said in a press release. Genentech, a member of the Roche Group, is the developer of Ocrevus.
“We continue to see that early and ongoing treatment markedly improves outcomes, and we’ll continue to use scientific and real-world insights to improve our understanding and ways to support people living with these neurological disorders,” Garraway said in a separate press release.
These and other Ocrevus findings were shared through 21 Roche-funded oral and poster presentations at the 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held virtually Oct. 13–15.
Ocrevus is a twice-yearly infusion approved in the U.S. and the European Union to treat adults with relapsing forms of MS, as well as those with PPMS — for which it was the first therapy ever approved.
Its safety and effectiveness were demonstrated in the OPERA I and II (NCT01247324 and NCT01412333) and ORATORIO (NCT01194570) Phase 3 trials.
In the OPERA studies, 1,656 adults with relapsing MS were treated with either Ocrevus or Rebif (interferon beta-1a) for 96 weeks (about 1.8 years). In ORATORIO, 732 PPMS patients were assigned to either Ocrevus or a placebo for at least 120 weeks (about 2.3 years).
After completing the trials, participants were invited to enter open-label extension (OLE) phases, in which all would be given Ocrevus.
Newly presented findings concerned the results from the three completed trials and their ongoing extension phases, totaling about 7.5 (OPERA) to eight years (ORATORIO) of data.
Notably, 80% of OPERA’s participants and 71% of those in the ORATORIO study entered the respective extension periods, and about three-quarters continue to participate in the trials.
Now, researchers analyzed effectiveness results from patients initially assigned to the therapy (early treatment) or to a placebo (delayed treatment) in terms of time to confirmed disability progression (CDP), and to a need for a walking aid or wheelchair reliance.
CDP was defined as a disability worsening from study start that was sustained for 48 weeks (nearly one year), either based on the expanded disability status scale (EDSS) — a global measure of disability — or the 9-hole peg test (9HPT), which is a measure of arm and hand disability.
Changes in annualized relapse rates, called ARR, also were analyzed for the OPERA studies.
OPERA’s findings were presented by Gavin Giovannoni, PhD, a professor of neurology at Barts and The London School of Medicine and Dentistry, in a poster titled “Long-term reduction of relapse rate and confirmed disability progression after 7.5 years of ocrelizumab treatment in patients with relapsing multiple sclerosis in the OPERA OLE.”
Updated data showed that ARR was sustained at low levels in patients always on Ocrevus and that switching from Rebif to Ocrevus resulted in a “rapid and robust reduction in ARR that was maintained throughout [the extension phase],” Giovannoni said.
However, patients later switching to Ocrevus only reached the same ARR of the early treatment group at 7.5 years (0.03 annual relapses).
Compared with a delayed Ocrevus start, early treatment significantly reduced patients’ risk of CDP-EDSS by 23%. These patients’ need walking aid was cut by 35% after 7.5 years, the data show.
This means that people treated with Rebif in the first two years of the OPERA trials “just never catch up, so time is lost,” Giovannoni said.
Group differences in terms of the proportion of patients either showing CDP or needing walking aids became less pronounced in the OLE phases relative to the double-blind periods, failing to reach statistical significance.
A two-year delay in initiating a high-efficacy therapy such as Ocrevus “comes at a cost to patients,” Giovannoni said, adding that these data may prompt clinicians to start this therapy from the get-go.
In an oral presentation titled “Sustained reduction in 48-week confirmed disability progression in patients with PPMS treated with ocrelizumab in the ORATORIO OLE: 8-year follow-up,” Jerry S. Wolinsky, MD, of the University of Texas Health Sciences Center, shared updated ORATORIO findings.
Those results showed that, after eight years, PPMS patients who started on Ocrevus straight away had a significantly lower risk of confirmed disability progression compared with those beginning treatment two years later. Specifically, those given early Ocrevus saw their CDP-9HPT — the 9-hole peg test scores — reduced by 34%, and their CDP-EDSS, or scores on the expanded disability status scale, lowered by 29%. Scores on repeated CDP-EDSS were reduced 24%.
Early Ocrevus treatment also was associated with a 33% lower risk of requiring a wheelchair relative to delayed therapy, but this difference failed to reach statistical significance.
While the curves of disability progression “trend to track together” in the extension phase, “they never converge,” Wolinsky said, meaning that, as in relapsing MS, PPMS patients receiving delayed Ocrevus treatment do not catch up with those given the Genentech therapy from the start.
“My colleagues and I are grateful for the patients and their families, without whose sacrifices new therapies can never be achieved,” Wolinsky concluded.
Overall, data from all three trials suggest that Ocrevus effectively lowers the risk of disability and disease progression in both relapsing MS and PPMS, and that earlier and continuous use brings greater benefit.
Importantly, Ocrevus’ safety profile with longer-term use was consistent with that reported in the trials’ first two years, according to data presented by Stephen Hauser, MD, of the University of California, San Francisco. His poster was titled “Safety of ocrelizumab in multiple sclerosis: updated analysis in patients with relapsing and primary progressive multiple sclerosis.”
Rates of serious infections — excluding COVID-19 — and cancer in these patients “remain within the range reported for patients with MS in real-world registries,” the researchers wrote.
Also, safety data from 200,000 MS patients who initiated Ocrevus globally in the post-marketing setting up to December 2020 also remained generally consistent with those observed in trials.
“The reported rates of adverse events in these [Ocrevus-treated] populations, excluding COVID-19 infections, continued to be consistent with those seen during the controlled treatment periods of the Phase 3 trials,” Hauser said.
“These findings further demonstrate the consistently favorable benefit-risk profile of Ocrevus over eight years,” Genentech stated in the release.
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