Date: 2012-12-08
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the 54th annual meeting of the American Society of Hematology (ASH)
Company: Roche (Switzerland)
Product: MabThera® (rituximab)
Action
mechanism: monoclonal antibody. MabThera® (rituximab) is a therapeutic monoclonal antibody that binds to a particular protein – the CD20 antigen – on the surface of normal and malignant B-cells. It then recruits the body’s natural defenses to attack and kill the marked B-cells. Stem cells (B-cell progenitors) in bone marrow lack the CD20 antigen, allowing healthy B-cells to regenerate after treatment and return to normal levels within several months.
MabThera® subcutaneous uses Enhanze™ Technology, developed by Halozyme Therapeutics, Inc., which enables the injection of large volumes of a medication under the skin (subcutaneous). It temporarily modifies a gel-like substance (hyaluronan) that forms a barrier in the tissues between cells under the skin.
Disease: non-Hodgkin lymphoma
Therapeutic area: Cancer - Oncology
Country:
Trial
details: SABRINA is a two-stage international Phase III trial designed to investigate the pharmacokinetics, efficacy and safety of SC versus IV administration of MabThera® in FL patients receiving induction and maintenance therapy. In the first stage (dose-confirmation) with pharmacokinetics (Ctrough) as primary endpoint, treatment-naïve patients with FL, a common type of NHL, were randomized to receive 375 mg/m2 MabThera administered intravenously or a fixed dose of 1,400 mg of MabThera® via subcutaneous delivery, both given in combination with either CHOP or CVP chemotherapy. Patients who achieved a complete or partial response after 8 treatment cycles continued MabThera® maintenance therapy as per their initial randomization with either SC or IV administration. Exploratory efficacy analysis from SABRINA was also performed to demonstrate that a switch from IV to SC administration can be achieved without compromising on MabThera®’s anti-lymphoma efficacy: Similar overall response rates (ORR) [84.4% IV and 90.5% SC] and complete response (CR) rates [29.7% IV and 46% SC] support the conclusion of comparable efficacy. In the second stage with efficacy as the primary endpoint, additional patients will be randomized to either SC or IV administration of MabThera®.
The international Phase Ib study SPARKTHERA is a two-stage study comparing the SC and IV formulations of MabThera in terms of their pharmacokinetics and safety profiles during maintenance treatment in FL patients. In the first (dose-finding) stage of the trial, the dose was selected and in the second stage the selected MabThera® SC dose of 1,400mg was confirmed after randomizing patients to receive either SC or IV administration of MabThera® during maintenance treatment.
Latest
news: Roche has 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 (IV) infusion. Overall, SC and IV adverse event (AE) profiles were similar and administration related reactions (ARR) were mostly of mild to moderate intensity. These results formed the basis of the line-extension marketing application which was submitted to the European Medicines Agency (EMA) on December 4th 2012. 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.
