#AANAM – Early Ocrevus Treatment Helps to Protect Nervous System
“We are encouraged by these new analyses showing that early treatment with Ocrevus may significantly control disease progression in both relapsing-remitting MS and in primary progressive MS,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Genentech (a member of the Roche Group), which makes Ocrevus, said in a press release.
Ocrevus is approved to treat relapsing forms of MS, and is the only approved disease-modifying therapy for primary progressive MS (PPMS). It is administered via an infusion twice yearly and works by killing B-cells, a type of immune cell that drives inflammation in MS. In clinical trials, Ocrevus has been demonstrated to reduce the rate of MS relapses and ease disability.
At the American Academy of Neurology annual meeting (AANAM), researchers with Genentech and other institutions shared three posters highlighting new data on this therapy.
In one presentation, Timothy Vollmer, MD, a professor at the University of Colorado, shared interim data from an ongoing Phase 3b clinical trial called ENSEMBLE (NCT03085810). The poster was titled, “Recently Diagnosed Early-Stage RRMS: NEDA, ARR, Disability Progression, Serum Neurofilament and Safety: 1-Year Interim Data From the Ocrelizumab Phase IIIb ENSEMBLE Study.”
In ENSEMBLE, 678 people with relapsing-remitting MS (RRMS) are being treated with Ocrevus. The study only enrolled people with early disease (diagnosis up to three years ago). Most had active disease when enrolled, and none had received any prior treatment. Their mean age was 32.4, and the mean duration of symptoms was just over a year.
“ENSEMBLE was designed to study key outcomes in achievement of early phase MS with [Ocrevus],” Vollmer said.
After six months of treatment, 91.2% of these patients had no evidence of disease activity. This means they “had no relapses on therapy, no confirmed disability progression, and no MRI disease activity,” Vollmer said.
After a year of treatment, 84.8% of trial patients still had no evidence of disease activity. Their mean disability scores — measured with the Expanded Disability Status Scale — also decreased significantly, from 1.71 at the start of the trial, to 1.56 after six months and 1.55 after one year.
At the start of the ENSEMBLE study, most participants had higher-than-normal levels of a protein called neurofilament light (NfL) in their blood, which is indicative of damage to the nervous system. After a year of treatment, patients’ NfL levels were mostly within the range that is seen in the general population.
In another AANAM presentation, Robert Zivadinov, MD, PhD, with the University at Buffalo in New York, shared data from the Phase 3 clinical trial ORATORIO (NCT01194570), which is evaluating Ocrevus in people with PPMS. The poster was titled, “Evolution of Lesions that Shrink or Disappear into Cerebrospinal Fluid (Atrophied T2 Lesion Volume) in Primary-Progressive Multiple Sclerosis: Results from the Phase III ORATORIO Study.”
Specifically, Zivadinov focused on data pertaining to how treatment affects an MRI measurement called atrophied lesion volume. This measure reflects the volume of brain lesions that is replaced by cerebrospinal fluid, seen on MRI scans.
“Atrophied lesion volume reflects neurodegeneration [nervous system damage] and has demonstrated sensitivity for MS progression,” Zivadinov said, noting that accumulation of this imaging biomarker “is three to five fold higher in patients with progressive, compared to relapsing, disease.”
The ORATORIO trial recruited 732 PPMS patients, of whom 488 were treated with Ocrevus and 244 were given placebo; there were no noteworthy differences between the groups prior to treatment. Atrophied lesion volume was measured after 24, 48, and 120 weeks (2.5 years) of treatment.
Statistical analyses demonstrated that, relative to placebo, treatment with Ocrevus significantly reduced the accumulation of atrophied lesion volume over time.
Further analyses showed that this difference was evident in the subset of patients who had confirmed disability progression early on in the study (after 12 or 24 weeks). However, for those without such disability progression, there was no difference in atrophied lesion volume accumulation with Ocrevus treatment or placebo.
“We can conclude that significant reduction of atrophied lesion volume in [Ocrevus] versus placebo may be possibly explained by the fact that [Ocrevus] impacts mechanisms underlying progressive biology in MS, and that was particularly seen with respect to motor disability,” Zivadinov said.
In the third AANAM presentation, researchers analyzed insurance data to examine the economic impact of Ocrevus. This presentation was titled, “Adherence and Persistence to Disease-Modifying Therapies for Multiple Sclerosis and Their Impact on Clinical and Economic Outcomes in a US Claims Database.”
Data revealed that, compared with other disease-modifying therapies (DMTs), MS patients treated with Ocrevus had higher persistence and adherence. In other words, they were more likely to not switch to another DMT, to have no gaps in treatment (persistence), and to take the medication as prescribed (adherence).
Two years after starting treatment, patients on other therapies were 1.8 to 2.5 times more likely to be non-persistent, and 2.1 to 3 times more likely to be non-adherent, compared with those on Ocrevus.
Separate analyses demonstrated that both non-persistence and non-adherence were associated with higher non-DMT healthcare costs. These costs were on average $19,231 higher for non-persistent patients, and $16,091 higher for those who were not adherent, at two years after therapy start.
“This study was able to demonstrate that high persistence and adherence to MS DMTs is associated with a reduction in total all-cost, non-DMT costs,” Gabriel Pardo, MD, with the Oklahoma Medical Research Foundation, said at AANAM.
“In addition, patients initiating [Ocrevus] in a real-world setting had superior persistence and adherence at 12 and 24 months, compared to those initiating other MS disease-modifying therapies,” Pardo added.