WASHINGTON -- The FDA approved the biologic drug ocrelizumab (Ocrevus) for treatment of relapsing forms of multiple sclerosis and also the primary progressive form of the disease, the agency said early Wednesday.
Previously there had been no approved disease-modifying treatments specifically for primary progressive MS (PPMS).
"This therapy not only provides another treatment option for those with relapsing MS, but for the first time provides an approved therapy for those with primary progressive MS," said Billy Dunn, MD, director of the FDA's neurology drugs division, in a statement.
Ocrelizumab is an anti-CD20 monoclonal antibody targeting B cells. That's the same mechanism of action as rituximab (Rituxan), which some earlier studies found to be effective against both relapsing-remitting and progressive MS. Off-label use of rituximab in MS is not uncommon, especially in Europe where insurance coverage is more flexible.
However, the company that owns rituximab, Roche's Genentech unit, is also ocrelizumab's developer and chose not to fund additional studies of rituximab for these indications. The company maintained, and most MS specialists have agreed, that ocrelizumab is a better drug in several respects (for example, it's a humanized protein whereas rituximab is chimeric) and has focused on it exclusively .
Trial data supporting ocrelizumab for both primary progressive and relapsing-remitting MS were published last December in the New England Journal of Medicine after presentation at medical meetings. In summary, they showed:
- 24% reduction in risk of 12-week confirmed disability progression in PPMS relative to placebo
- About 46%-47% lower annualized relapse rates in RRMS
A novel concern with ocrelizumab, not seen with rituximab in inflammatory conditions, is that it seemed to carry a slight risk of inducing cancer. The trial data showed an overall incidence rate of first neoplasms of 0.4 per 100 patient-years of drug exposure, compared with 0.2 per 100 patient-years in comparator groups (placebo or beta-interferon).
The FDA's approval announcement noted that the drug "may increase the risk for malignancies, particularly breast cancer," but without special emphasis such as a boxed warning.
Other adverse effects listed were infusion reactions and increased risks of infection. Patients with hepatitis B infection should not receive ocrelizumab, and live-virus vaccines should not be given to patients on the drug. Infections, mostly minor, were the most common side effects seen in the drug's trials.
Genentech said the drug's list price will be $65,000 per year, with discounts and other support available for patients who can't afford co-pays or are without insurance coverage.