Pivotal study data presented at ASH shows that subcutaneous administration enables the delivery of MabThera over approximately 5 minutes without compromising MabThera’s proven efficacy and safety.
Roche last week announced results from two studies which showed that a fixed dose of MabThera (rituximab) can be administered subcutaneously (SC), potentially allowing patients to spend less time in infusion centers receiving their MabThera treatment. Specifically, the studies showed that SC injection resulted in non-inferior MabThera concentrations in the blood (pharmacokinetics; PK) compared with standard intravenous infusion. Overall, SC and IV adverse event profiles were similar and administration related reactions were mostly of mild to moderate intensity. The results were presented at the 54th annual meeting of the American Society of Hematology (ASH) and formed the basis of the line-extension marketing application which was submitted to the European Medicines Agency (EMA) on December 4th 2012.
“MabThera SC has the potential to offer patients an effective and more convenient delivery option for MabThera, which has revolutionized the treatment of B-cell malignancies,” said Hal Barron, Chief Medical Officer and Head, Global Product Development. “As a leader in innovative treatments for cancer, Roche is committed to a broad research program of investigational medicines and innovative ways to administer them.”
Administering MabThera SC shortens the treatment time significantly, enabling administration over approximately 5 minutes compared with 2.5 hours during IV infusion. The ready-to-use SC formulation may also significantly reduce pharmacy time and the impact on hospital resources as medicine preparation time and hospital staff time per administration are significantly reduced.
A non-inferiority endpoint was chosen to ensure that patients are not under-dosed as compared to the established IV dose and treatment intervals, and the study met its primary endpoint by confirming that the minimum drug concentration during a given dosing interval (Ctrough) was non-inferior for MabThera SC vs. IV administration (134.6 vs. 83.1 µg/mL respectively – ratio 1.62). Furthermore, an exploratory efficacy analysis (response rates) demonstrated that the switch from IV to SC administration did not compromise MabThera’s proven anti-lymphoma efficacy.
Additionally, the SparkThera study (phase Ib) also met its primary endpoint of demonstrating non-inferior Ctrough values of MabThera SC relative to IV when both formulations were given in the follicular lymphoma (FL) maintenance setting. Specifically, the minimum MabThera concentration ratio for SC vs. IV was 1.24 when MabThera was given once every two months and 1.12 when MabThera was given once every three months.
MabThera subcutaneous uses Enhanze™ Technology, developed by Halozyme Therapeutics, Inc., which enables the injection of large volumes of a medication under the skin. It temporarily modifies a gel-like substance (hyaluronan) that forms a barrier in the tissues between cells under the skin.
Roche is also developing a subcutaneous formulation of Herceptin (trastuzumab) using this technology and has submitted a Line Extension Application for Herceptin SC to the European Medicines Agency (EMA) for the treatment of HER2-positive breast cancer.
MabThera is known as Rituxan in the United States, Japan and Canada. Genentech, a member of the Roche family, and Biogen Idec collaborate on Rituxan in the United States, and Roche markets MabThera in the rest of the world, except Japan, where MabThera is co-marketed by Chugai and Zenyaku Kogyo Co. Ltd.
Source: Roche press release