Treating patients with primary progressive or relapsing multiple sclerosis (MS) early with Ocrevus (ocrelizumab) is key to slowing disease progression, according to Hideki Garren, global head of Multiple Sclerosis and Neuroimmunology at Genentech.
In an interview with Multiple Sclerosis News Today at the recent 34th congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), Garren, who is also group medical director of neuroscience at Genentech, discussed the latest long-term results of studies into Ocrevus’ use, and plans for future tests in progressive and pediatric patients.
Among data presented at ECTRIMS, the most important, he said, were five-year results from the pivotal Phase 3 trials ORATORIO (NCT01194570) and OPERA (NCT01247324 and NCT01412333), which evaluated Ocrevus in patients with primary progressive MS (PPMS) and relapsing MS, respectively.
In a first presentation of data from ORATORIO’s open-label, long-term extension, scientists showed that the proportion of primary progressive patients (PPMS) with disability worsening — as assessed through the Expanded Disability Status Scale (EDSS) — was lower in those given Ocrevus at 600 mg initially in this trial, or three-to-five years earlier, and who stayed on it continuously than in those who switched from placebo.
“What’s really important for patients is early and continuous treatment,” Garren said. “Patients who started off early and had treatment continuously had better outcomes than those that switched.”
Recent results demonstrated that, after more than two years of treatment, Ocrevus led to a three-fold greater proportion of PPMS patients showing no evidence of disease progression and no signs of inflammatory disease activity.
With OPERA, findings revealed that taking Ocrevus from the start led to superior results than were seen in patients switching from Rebif (interferon beta-1a, by EMD Serono), as demonstrated by lesser 12- and 24-week disability accumulation. This added to prior findings showing that both long-term treatment with Ocrevus and switching from Rebif significantly reduced disease activity in relapsing MS.
Results from a sub-group analysis of 72 patients of African descent, a population known for faster disease progression, in the OPERA trials were also presented. Similar to its effect on the overall MS population (1,656 patients), treatment with Ocrevus led to a better outcome than Rebif in African-descended patients, as evidenced by a lower rate of brain lesions seen on MRI scans, and a higher proportion of patients achieving no evidence of progression or disease activity.
People in these three trials will continue to be followed for as long as possible, said Garren, “because we do believe they will have better options long-term.”
These results are in line with the recent focus on early use of highly effective treatment in MS, as discussed by Cleveland Clinic neurologist Robert Bermel in a recent interview. Bermel also noted Ocrevus as a game-changer in moving beyond the so-called dose-escalation therapy approach.
“The field has changed because we’ve come to understand that progression in patients happens from very early on. Both in primary progressive [MS] but also in relapsing patients,” Garren said. “So it’s really important that we intervene and treat patients early on so that they don’t have this underlying progression.”
Previous data from ORATORIO, which included a total of 732 PPMS patients, found that Ocrevus, a B-cell depleting medication, delayed the relative risk of disability progression by 25% compared to placebo, and lowered the volume of chronic brain lesions and total brain volume loss.
This data, added to the fewer lesions and lower relapse rates seen in the OPERA trials, led to Ocrevus being the first disease-modifying treatment approved by the U.S. Food and Drug Administration and the European Commission for both PPMS and relapsing MS.
Turning to progressive and pediatric MS
“We’re very committed to progressive MS,” Garren said, noting that Genentech plans to open a placebo-controlled Phase 3b study called ORATORIO-HAND early next year. It will enroll around 1,000 patients — and, for a first time, those up to age 65 and with considerable disability.
This “brand-new trial in PPMS” will assess the long-term effectiveness of Ocrevus on upper limb function. Treatment with either Ocrevus or placebo will be given over at least 120 weeks, with study design informed by subgroup results of ORATORIO.
Its primary outcome is changes in the nine-hole peg test of finger skills, but will include measures of arm, wrist, and hand function.
“Maintaining that upper extremity arm and hand function is incredibly important for patients who are progressing,” Garren said. As these patients lose lower extremity function and may need a wheelchair, “maintaining their arm function is critically important, fundamental, to their independence,” he added.
Disability progression will also be evaluated.
Compared to ORATORIO, those entering ORATORIO-HAND may be older — its age limit is 65 rather than 55 — and have higher levels of disability, with EDSS score up to 8.0 vs. 6.5 (EDSS scores range from 0 to 10, and higher scores mark greater disability).
A new study is also planned for children with MS, part of a commitment the company made to regulators. But “[i]t’s much too early” for details, Garren said. “We’ll announce that when we’re ready.”
Still, Genentech’s goal is to make Ocrevus available “to as many patients as possible and as fast as possible.”
Recently, unfavorable cost-benefit estimates led the U.K. National Institute for Health and Care Excellence (NICE) to decide against including Ocrevus in the subsidized public health system for England and Wales as a treatment for early PPMS patients.
In a press release, Roche — which owns Genentech — said it remained committed to working with NICE for National Health Service inclusion. Garren agreed, noting “[w]e are working with regulators and with insurers.”
He added that Genentech also intends to provide six-month safety updates on Ocrevus’ use, based on data collected on clinical trial participants. “We’re committed to providing the community updates on safety,” Garren said.
He concluded by noting the progress made in treating MS, and his sense of satisfaction with Ocrevus coming into wide use.
“If I think back to when I was practicing many years ago, I only had interferon beta and Copaxone to offer patients,” Garren said. “Now, we have 14 different medicines to offer, including Ocrevus, of course. I think that’s just fantastic that patients have this choice.
“And we’re happy that patients and physicians are choosing Ocrevus.”