Higher Ocrelizumab Exposure Further Reduces Disability Progression in MS

New data presented at the American Academy of Neurology Annual Meeting show the positive impact of ocrelizumab (Ocrevus, Genentech) in significantly reducing disease progression in relapsing and primary progressive multiple sclerosis (MS).

Ocrelizumab, a humanized monoclonal antibody designed to target CD20-positive B cells, is the first and only therapy with a 6-month dosing approved for patients with relapsing MS (RMS) and primary progressive MS (PPMS). Ocrelizumab is administered by intravenous infusion every 6 months, with the initial dose given as two 300 mg infusions 2 weeks apart, according to Genentech. Subsequent doses are given as single 600 mg infusions.

The findings include long-term data from the phase 3 OPERA and ORATORIO open-label extension (OLE) trials in patients with RMS and PPMS, as well as interim results from the phase 3 Ocrelizumab Biomarker Outcome Evaluation (OBOE).

Overall, the data showed that higher exposure to ocrelizumab was correlated with lower B-cell levels and lower rates of disability progression in patients. Ocrelizumab was shown to reduce the risk of 24-week confirmed disability progression (CDP) at all exposure levels compared with interferon beta-1a in patients with RMS. In patients with PPMS, ocrelizumab reduced the risk of 24-week CDP at all exposure levels compared with a placebo, according to the study.

In both RMS and PPMS patients, ocrelizumab reduced T1 gadolinium-enhancing and new/enlarging T2 MRI lesions to nearly undetectable levels. The analyses found that patients with RMS also demonstrated reduced annualized relapse rates to low levels across all exposure segments.

The findings also indicated that higher exposure levels did not increase the likelihood of adverse events, as safety results remained consistent across all ocrelizumab exposure levels in the studies.

“There are the first data to show that higher Ocrevus exposure is associated with greater control of disability progression without impacting safety,” Stephen Hauser, MD, chair of the Scientific Steering Committee of the OPERA studies and director of the Weill Institute for Neurosciences at the University of California, San Francisco, said in a statement. “These analyses, along with long-term data that show Ocrevus reduced the risk of permanent disability progression, create a compelling case for initiating therapy early in the disease course and provide important information that clinicians can use to inform treatment decisions.”

Other key findings from the studies included:

• In the OPERA OLE, the proportion of patients with RMS with 48-week CDP was lower for those treated with continuous ocrelizumab compared with patients who switched to ocrelizumab after 2 years of interferon beta-1a treatment (10.4% versus 15.7%; p=0.004).
• In the ORATORIO OLE, the proportion of patients with PPMS with 48-week CDP was lower in those treated with continuous ocrelizumab over 5 and a half years compared with patients who switched to ocrelizumab from placebo after the 120-week double-blind period (43.7% versus 53.1%; p=0.03).
• In the OBOE study, ocrelizumab reduced the presence of a nerve cell damage and inflammation biomarker in serum and cerebrospinal fluid at 12, 24, and 52 weeks in patients with RMS.

Reference

Genentech to Present New Ocrevus (ocrelizumab) Data Analyses Showing Significant Reduction of Disability Progression in Relapsing and Primary Progressive Multiple Sclerosis at the AAN Annual Meeting [news release]. Genentech. https://www.gene.com/media/press-releases/14788/2019-05-07/genentech-to-present-new-ocrevus-ocreliz. Accessed May 8, 2019.