Experimental Medications: Monoclonal Antibody Medications
Companies: Genentech and Biogen
- Administered via intravenous infusion
- Rituxan is being studied in both RRMS and SPMS
Rituxan is a monoclonal antibody (CD20, from mouse tissue) that binds to a receptor on the surface of B cells. These cells are then destroyed and their levels in the circulation are decreased. It is approved for use in the treatment of lymphomas, leukemias, and autoimmune disorders.
A Phase II trial, completed in 2006, examined the effect of a single course of Rituxan treatment in RRMS, with two infusions of 1,000 mg each, administered two weeks apart. At 48 weeks, the number of active lesions was reduced by 91 percent and relapses were reduced by 58 percent.
The drug was also tested in a study of 30 people with RRMS who had experienced continued clinical activity despite treatment with one of the approved disease-modifying therapies. Participants received two doses of Rituxan, two weeks apart, while continuing to take their usual medication. Results showed gadolinium-enhancing lesions were reduced: 74 percent of post-treatment MRI scans were free of gadolinium-enhancing activity as compared with 26 percent that were free of gadolinium-enhancing activity at baseline. There was an 88-percent reduction in the average number of these lesions.
A Phase I/II double-blind study of 80 people with low-inflammatory SPMS, sponsored by the National Institute of Neurologic Diseases and Stroke, is testing Rituximab versus placebo (RIVITaLISe). The study is recruiting participants50 and expected to run until 2016. The primary outcome measure will be the progression of brain atrophy after two years of treatment, unless predetermined analysis shows that the secondary outcome measures of MRI and clinical assessment are more reliable measures of effectiveness than brain atrophy.
Serious adverse events have been reported in Rituxan-treated patients with other diseases, including Progressive Multifocal Leukoencephalopathy (PML), the same viral infection of the brain that has been seen with a small percentage of patients taking Tysabri. While no PML has been diagnosed in MS patients taking Rituxan, the number of individuals with MS treated with Rituxan is relatively small to date.
Rituxan is not likely to be further developed for FDA approval. However, next-generation anti-CD20 monoclonal antibodies have been developed to build on the encouraging data from Rituxan’s MS studies, including ocrelizumab (discussed on next page).