Roche announced today that its Phase III MUSETTE trial, designed to evaluate whether a higher dose of OCREVUS (ocrelizumab) would provide additional benefits for people with relapsing multiple sclerosis (RMS), did not meet its primary endpoint. The study results confirm that the currently approved intravenous (IV) 600 mg dose remains the optimal treatment regimen for slowing disability progression in MS patients.
The trial compared the standard OCREVUS IV 600 mg dose to higher doses (1,200 mg for patients under 75 kg or 1,800 mg for patients 75 kg or heavier) over a treatment period of at least 120 weeks. Researchers measured efficacy through a composite disability endpoint that tracked disease progression.
"These findings reaffirm that the current OCREVUS IV 600 mg is optimally dosed to significantly slow disability progression," said Levi Garraway, M.D., Ph.D., Roche's Chief Medical Officer and Head of Global Product Development. "Moreover, in several predefined analyses on disease activity, OCREVUS showed clinically meaningful results on relapses with a relapse occurring approximately once every 16 years, a first for an anti-CD20 RMS medicine."
Trial Design and Endpoints
The MUSETTE study (NCT04544436) was a randomized, double-blind, controlled, parallel-group, multicenter Phase III trial. The primary endpoint measured the time to first onset of 12-week composite confirmed disability progression (cCDP), defined by several criteria including increases in Expanded Disability Status Scale (EDSS) scores and performance deterioration in mobility and dexterity tests.
While the higher dose did not demonstrate superior efficacy, it was well tolerated with a safety profile comparable to the standard dose. No new safety signals were observed during the trial.
OCREVUS: Setting the Standard in MS Care
OCREVUS has established itself as a cornerstone therapy in multiple sclerosis treatment since its approval. It remains the first and only B-cell therapy approved for both RMS and primary progressive multiple sclerosis (PPMS), with more than 400,000 people treated globally. It is currently the most prescribed disease-modifying therapy for MS in the United States.
The humanized monoclonal antibody targets CD20-positive B cells, which are believed to be key contributors to myelin and axonal damage in MS. By binding to CD20 cell surface proteins expressed on certain B cells—but not on stem cells or plasma cells—OCREVUS may preserve important immune system functions while addressing the underlying disease mechanisms.
Multiple Sclerosis: A Global Health Challenge
Multiple sclerosis affects more than 2.9 million people worldwide. The chronic disease occurs when the immune system abnormally attacks the myelin sheath surrounding nerve cells in the central nervous system, causing inflammation and damage that can lead to a wide range of symptoms and eventual disability.
Approximately 85% of MS patients have the relapsing form of the disease (RMS), characterized by periods of new symptoms followed by remissions, along with worsening disability over time. The remaining 15% have primary progressive MS (PPMS), which features steadily worsening symptoms without distinct relapses or remissions.
Most people with MS experience their first symptoms between ages 20 and 40, making it the leading cause of non-traumatic disability in younger adults. Early diagnosis and treatment are crucial to slow disease progression and minimize long-term disability.
Expanding Treatment Options
Roche continues to innovate in MS treatment delivery. The company recently launched a subcutaneous formulation of OCREVUS (marketed as OCREVUS ZUNOVO in the U.S.) to improve the treatment experience and expand access to centers without IV infrastructure.
"With the recent launch of OCREVUS subcutaneous formulation we aim to improve the treatment experience for people living with multiple sclerosis and expand OCREVUS usage in centres without IV infrastructure or those with IV capacity limitations," the company stated. Roche is also developing a high-concentration formulation for on-body device delivery to bring treatment closer to patients' homes.
Beyond OCREVUS, Roche's neuroscience pipeline includes several promising candidates for MS treatment, including Brainshuttle CD20 and a monoacylglycerol lipase (MAGL) inhibitor in early-stage development. The company is also conducting Phase III studies of fenebrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, for both RMS and PPMS.
Full data from the MUSETTE trial will be presented at an upcoming medical meeting, providing the scientific community with a more detailed understanding of the findings.
