Genentech shared new insights into the workings of Ocrevus (ocrelizumab) and its effectiveness in reducing disease activity and slowing progression in relapsing and primary progressive multiple sclerosis (MS) at the recent 3rd Congress of the European Academy of Neurology (EAN).
The new findings, previously reported here, built on analyses of information gathered during the three Phase 3 clinical trials assessing Ocrevus’ safety and efficacy, as well as through monitoring patients in extension studies.
To better understand this new data’s relevance to the patient community, Multiple Sclerosis News Today turned to Dr. Hideki Garren, group medical director of ocrelizumab at Genentech.
The many aspects of disease progression
One of the issues researchers evaluated in-depth at the congress was NEPAD, short for No Evidence of Progression or Active Disease, a new measure of treatment efficacy used in the trials. NEPAD is a composite measure, similar to NEDA (No Evidence of Disease Activity), but it holds additional information.
To achieve NEDA, an MS patient must have no relapses, no new or enhancing brain lesions on magnetic resonance imaging (MRI), and no disability progression assessed by the Expanded Disability Status Scale (EDSS). To fulfill NEPAD, all the requirements of NEDA must be met, plus no confirmed disability progression equal to or above 20% on a timed 25-foot walk — measuring mobility and leg function — and on 9-hole peg tests — measuring finger dexterity.
“NEPAD represents an expansion of NEDA and integrates more aspects of disability, which are highly meaningful to people with MS,” said Garren, explaining that since the 1990s, researchers have been striving to develop more sensitive measures of clinically meaningful outcomes, as well as methods to determine how well a patient responds to a medicine.
Combined measures are a rather recent addition to these efforts, and go beyond what EDSS alone is able to measure.
“The development of NEPAD is a testament to Genentech’s commitment to provide new insights about how best to measure and improve the quality of life of MS patients, and our commitment to move the MS field forward,” Garren said.
The studies showed that nearly 40 percent of Ocrevus-treated relapsing patients and nearly 30 percent of primary progressive patients achieved NEPAD during the Phase 3 trials. In contrast, only 21.5 percent of those treated with Rebif and 9.4 percent receiving placebo achieved NEPAD — figures that demonstrate Ocrevus’ impact on patients’ lives.
But Genentech also performed specific analyses of walking ability in trial participants. Researchers found that, among relapsing patients, Ocrevus lowered the risk of losing the ability to walk long distances unassisted, or of requiring a cane or crutch. It also reduced the risk of becoming wheelchair-bound among primary progressive patients.
We wondered if Ocrevus specifically impacts walking ability, or if Genentech chose to focus on walking ability because it is a good mirror of other types of disability progression.
“One of the main treatment goals for people with MS is to slow disability progression and extend the time before they need to use a cane or wheelchair,” Garren said. “The new data, shown at EAN, was based on meeting specific milestones on the EDSS scale, which measure walking ability but also takes into account other aspects of disability progression. These milestones were chosen because they are clinically meaningful to people with MS.”
Garren also underscored that Ocrevus’ ability to slow the decline in walking ability and other types of disabilities are comparable between patients with relapsing and primary progressive disease — data that demonstrate that the treatment acts on disease mechanisms that drive disability in both disease forms.
Among the many presentations at the EAN meeting was an analysis that specifically looked at Ocrevus effectiveness in primary progressive patients with varying rates of disability progression.
Earlier analyses of Ocrevus’ effectiveness in these patients did not take this range into account. Therefore, in showing that the drug benefitted a certain proportion of PPMS patients, it was theoretically possible that those who did not benefit were people with very rapid disease progression. The new analysis, however, showed that this was not the case.
Rather, researchers found that Ocrevus reduces disability progression even in people with a rapid disease course.
“The implication is that not only does Ocrevus reduce the rate of overall disability progression, Ocrevus may reduce the severity of any disability progression that people with primary progressive MS still have,” Garren said.
How these effects play out in the long-term is the subject of ongoing research, as Genentech continues to follow these patients in an extension study.
Ocrevus’ prescription label strongly advises against pregnancy while on the treatment. Despite precautions, some women became pregnant during the trials. One of the meeting presentations narrated outcomes of these pregnancies; one healthy baby born at term and two ongoing pregnancies in women exposed to the drug.
But while Genentech monitors women who become pregnant while on Ocrevus, Garren explained that the number of reported pregnancies is too small to draw conclusions about the treatment’s safety in pregnancy.
He further underscored that researchers do not know if Ocrevus also depletes B-cells in the fetus or in the baby born to a treated woman.
“Patient safety is very important to us, and we are committed to learning about any risks of Ocrevus associated with pregnancy through an ongoing registry in women with MS treated with Ocrevus,” said Garren, adding that the information will be used to define the appropriate use of Ocrevus for women who wish to become pregnant.
Technology for quality of life
Ocrevus was not Genentech’s only focus at the EAN Congress, Garren pointed out. The company also presented preliminary data from a pilot study assessing the feasibility of using digital technology, such as smartphones or watches, to monitor how MS impacts patients’ quality of life.
The prospective study, called FLOODLIGHT, compares data gathered by technological solutions to conventional measures compiled during physician visits.
“Initial studies have shown smartphone-based technologies are a viable way to monitor patient-reported assessments in MS,” Garren said. “The FLOODLIGHT method may be more sensitive than conventional outcomes recorded at periodic physician visits, especially for detecting subtle progressive subclinical changes that may predict disease activity and long-term outcomes,” he added.
The data — Garren explained — might also correlate with MRI features of progressive MS types.
“This initiative should provide new insights about how best to measure and improve the quality of life of MS patients. It is a testament to Genentech’s commitment to develop and apply innovative measures to improve outcomes for people with MS, and we look forward to sharing additional results from this study at upcoming medical meetings,” Garren concluded.