Ocrelizumab Succeeds in Open-label Extension of OPERA Trials

Douglas Arnold, MD

Results from an open-label extension study show that patients with relapsing multiple sclerosis who were switched from interferon beta-1a to ocrelizumab (Ocrevus, Genentech) treatment showed swift improvement in MRI measures of disease activity and progression.

Patients who were assigned to ocrelizumab throughout the 4-year study sustained lower whole brain, white matter, and cortical grey matter tissue loss after 4 years of continuous treatment compared to those switched to ocrelizumab for the open-label extension (OLE) after 2 years of treatment with interferon beta-1a (IFN).

Douglas Arnold, MD, presented the first 2 years of data from the OLE of the ongoing phase 3 OPERA I and II studies at the 2018 American Academy of Neurology Annual Meeting.

Ocrelizumab is a monoclonal antibody that works by selectively depleting CD20+ B cells and sparing the early precursor cells and the plasma cells responsible for antibody formation.

“The OCREVUS data shared at AAN show the impact of this targeted B cell therapy on slowing disability progression in MS, and further support the approach of early treatment,” said Stephen Hauser, MD, chair of the Scientific Steering Committee of the OPERA studies, director of the Weill Institute for Neurosciences and chair of the Department of Neurology at the University of California, San Francisco. “In the extension studies, patients who received OCREVUS continuously experienced less disease progression than those who began treatment at a later time point.”

In annual MRIs during the OLE, researchers examined MRI lesion activity (T1 gadolinium-enhancing [T1Gd+] lesions, new/enlarging T2 [N/ET2] lesions) and the percentage change in whole brain volume (WBV), cortical grey matter volume (cGMV), and white matter volume (WMV).

Among patients who were switched from interferon-beta-1a to ocrelizumab (IFN-OCR) adjusted number of T1Gd+ lesions was 0.48 lesions/scan pre-switch, and decreased to 0.00 at years 1 and 2 of OLE. Additionally, decreases in N/ET2 lesions were seen from 2.16 lesions/scan in the year pre-switch to 0.33 and 0.08 at years 1 and 2 of OLE. Participants taking ocrelizumab during both study periods (OCR-OCR) maintained low numbers of T1Gd+ and N/ET2 lesions through 2 years of OLE.

OCR-OCR patients compared to IFN-OCR patients had lower brain atrophy from core study baseline to the end of years 1 and 2 of OLE measured by WBV change (—1.31%/–1.51% and –1.57%/–1.89%; p<0.01 for both); cGMV change (–1.47%/–1.56% and –1.72%/–1.91%; p=0.16 and p<0.01) and WMV change (–0.94%/–1.23% and –1.11%/–1.46%; p<0.01 for both).

The randomized, double-blind, and double-dummy OPERA trials previously showed the efficacy of ocrelizumab in treating relapsing and primary progressive multiple sclerosis (PPMS) and contributed to FDA approval of ocrelizumab. However, some clinicians caution that the drug is not ideal for all patients.

John Corboy, MD, professor and vice chair, Department of Neurology at the University of Colorado Anschutz Medical Campus, previously told MD Magazine that the OPERA trials’ data were “not surprising, unique, or groundbreaking.”

“The older the patient is and the longer they have had the disease, the less likely they are to benefit from those therapies,” Corboy added, referring to the average patient age in the trials—37.1 years in OPERA I and 37.2 years in OPERA II. “Sometimes, it’s the right patient, at the right time and that’s the key. A 35-year-old PPMS patient is not the same as a 75-year-old with PPMS. It’s just not the same situation.”

Nonetheless, Arnold’s presentation indicated how promising the initial OLE results are, given that patients who switched to ocrelizumab “showed almost complete suppression of gadolinium-enhancing activity during the open-label phase.” How both groups of patients respond to continued ocrelizumab treatment remains to be seen with the continuation of the OLE period.

The presentation, “Brain MRI Activity and Atrophy Measures in Patients Receiving Continuous Ocrelizumab or Switching from Interferon Beta-1a to Ocrelizumab Therapy in the Open-Label Extension Period of the Phase 3 Trials of Ocrelizumab in Patients with Relapsing Multiple Sclerosis,” was given at the American Academy of Neurology Annual Meeting in April 2018.

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