Rituxan Hycela (rituximab) was granted approval by the Food and Drug Administration (FDA) for adult patients with previously untreated and relapsed or refractory follicular lymphoma, previously untreated diffuse large B-cell lymphoma (DLBCL) and previously untreated and previously treated chronic lymphocytic leukemia (CLL).
Genentech, the manufacturer of the treatment, explained in a statement that the novel co-formulation includes the identical monoclonal antibody as intravenous (IV) rituximab (Rituxan), along with the molecule hyaluronidase, which facilitates the delivery of medicine beneath the skin. The company reported that the treatment will be available in the United States in one to two weeks, and the IV formulation will continue to be available.
“With today’s approval of Rituxan Hycela, people with three of the most common blood cancers now have a new treatment option which provides efficacy comparable with intravenous Rituxan and can be delivered under the skin in minutes instead of hours through IV infusion,” Sandra Horning, M.D., chief medical officer and head of Global Product Development at Genentech, said in a statement. “People who benefit from Rituxan may receive years of repeated treatments for their blood cancer, so an option that reduces the administration time can be important.”
The approval, which follows a positive recommendation from the FDA’s Oncologic Drugs Advisory Committee, is based on data from five clinical trials that included 2,000 patients with the various blood cancers for which Rituxan IV is currently approved. The results demonstrated that the efficacy, safety, and pharmacokinetics of the subcutaneous (SC) formulation were noninferior to IV Rituxan Hycela.
The specific trials included in the clinical development program were as follows: SparkThera (NCT00930514), a phase 1b maintenance study in previously untreated or relapsed follicular lymphoma; SABRINA (NCT01200758), a phase 3 induction and maintenance study in previously untreated follicular lymphoma; SAWYER (NCT01292603), a phase 1b study in previously untreated CLL; MabEase (NCT01649856), a phase 3 study in previously untreated DLBCL; and PrefMab (NCT01724021), a phase 3 patient preference study in previously untreated follicular lymphoma and DLBCL.
As a sample of the pivotal data, the phase 3 MabEase trial evaluated SC (381 patients) versus IV (195 patients) Rituxan Hycela in combination with CHOP chemotherapy in patients with previously untreated CD20-positive DLBCL. The overall response rate (ORR) was 71.8 percent in the IV arm versus 72.7 percent in the SC arm. The complete response (CR) rates were 42.1 percent versus 47.0 percent, respectively. The hazard ratio (HR) for progression-free survival (PFS) was 1.23 and the HR for overall survival (OS) was 1.06.
The phase 3 SABRINA trial compared the Rituxan Hycela formulations in combination with CHOP or CVP chemotherapy in previously untreated patients with FL. The ORR was 84.9 percent in the IV arm (205 patients) and 84.4 percent in the SC arm (205 patients). The CR rates were 32.2 percent versus 32.2 percent, respectively. The HR for PFS was 0.84 and the HR for OS was 0.81.
The phase 1b SAWYER trial compared the two formulations in combination with chemotherapy in previously untreated patients with CLL. The ORR was 80.7 percent in the IV arm (88 patients) and 85.2 percent in the SC arm (88 patients). The CR rates were 33 percent versus 26.1 percent, respectively. The HR for PFS was 0.89 and the HR for OS was 0.60.
Subcutaneous Rituxan Hycela has been available in the European Union under the trade name MabThera since 2014, and is also approved in nearly 50 other countries.
The IV formulation of Rituxan is currently approved by the FDA for patients with previously untreated follicular lymphoma, previously untreated DLBCL, relapsed or refractory low grade or follicular lymphoma, and previously untreated and relapsed or refractory CLL.
“Today’s approval of subcutaneous rituximab marks an important advance in the development of new treatment options for people with lymphoma,” said Meghan Gutierrez, Chief Executive Officer of the Lymphoma Research Foundation. “Novel therapies and new methods of administration are important to ensuring that patients and their physicians, through shared decision making, are able to access the right treatments at the right time.”