Experimental Medications: Monoclonal Antibody Medications
Company: 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 after treatment with Rituxan: 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 SPMS, sponsored by the National Institute of Neurologic Diseases and Stroke, tested a combination of intravenous (IV) and intrathecal (IT)(into the spinal fluid) rituximab versus placebo (the RIVITaLISe11 study). The study’s authors hypothesized that this combination method of Rituxan administration would cause more complete destruction of B cells both in the blood and the spinal fluid. Theoretically, the addition of the IT medication could be more effective for patients with progressive MS in which the immune cells provoking the continued attack may reside exclusively in the central nervous system, without circulating through the blood.
The study enrolled 27 patients but analyzed data in an interim analysis from 22 patients (14 on active drug and nine on placebo) who had received at least two doses of the drug. Though the study had originally aimed to measure progression of brain atrophy after two years of treatment, it was terminated early when the study authors did not find that the combination of IV and IT Rituxan was adequately decreasing B cells in the spinal fluid. Although there are multiple reasons that might account for this finding (including lower doses of Rituxan used in this study than in previous studies), this study raises questions about rituximab’s ability to decrease active inflammatory cells in the central nervous system. The small size of the study group did not allow for a true analysis of clinical outcome measures.
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, as discussed in the following entry.