Regulatory Decision Summary for Rituxan SC

Rituximab (intravenous [IV] infusion), as currently authorized, has a proven positive benefit-risk ratio in combination chemotherapy (fludarabine and cyclophosphamide) in previously untreated Chronic Lymphocytic Leukemia (CLL) and is also a clinically established treatment option for patients with previously treated CLL. The current submission provides data to bridge this positive benefit-risk ratio to a new formulation of rituximab for administration using a new route of administration (i.e., subcutaneous [SC] injection). No added clinical benefit is expected; however, given the shortened administration time and reduced need for resources, it is expected that this new product will be more convenient for both patients and health care professionals.

Authorization is supported by a demonstration that exposure to rituximab resulting from SC rituximab (RITUXAN SC) is not unacceptably less than that achieved with the standard rituximab IV dose in patients with previously untreated CLL. To support this assumption, the efficacy of rituximab SC or IV, in combination with chemotherapy, was descriptively compared in patients with previously untreated CLL. The overall response rate was 85% and 81% in the SC arm and IV arm, respectively. In terms of risk, the overall proportion of patients having adverse events was similar between treatment arms; however, the number of adverse events was numerically increased among patients that received Rituxan SC. This was predominantly due to administration-related reactions that occurred at the site of subcutaneous injection and included increases in injection site erythema, injection site pain and erythema. Besides a difference in the occurrence of administration-related reactions, the overall safety profile of Rituxan SC was comparable to that of Rituxan IV except for small increases in neutropenia. While the rate of neutropenia was increased, there was no significant concomitant increase in the rate of febrile neutropenia although the incidence of serious febrile neutropenia was more frequently reported in patients that received Rituxan SC. It was noted during review that exposure to Rituxan SC resulted in clearly superior exposure to rituximab, which may account for the observed increases in some adverse events. The risk information on neutropenia and febrile neutropenia has been captured in a Rituxan SC-specific product monograph.

Despite increased exposures, the risks associated with Rituxan SC do not appear to be appreciably increased compared to the risks associated with Rituxan IV. Therefore, it can be considered that Rituxan SC has a benefit-risk ratio that is comparable to that of the currently authorized Rituxan for the indication proposed.