A New Formulation for Rituxan Moves Ahead With FDA Committee Vote

In a unanimous (11-0) vote, the FDA’s Oncologic Drugs Advisory Committee (ODAC) recommended the approval of subcutaneous Rituxan for the treatment of patients with certain blood cancers, according to Genentech, the manufacturer of the treatment.

The company explained in a statement that the novel co-formulation includes the identical monoclonal antibody as intravenous (IV) Rituxan (rituximab), along with the molecule hyaluronidase, which facilitates the delivery of medicine beneath the skin.

The proposed indications for the treatment include previously untreated follicular lymphoma (FL), previously untreated diffuse large B-cell lymphoma (DLBCL), relapsed or refractory low grade or follicular lymphoma, and previously untreated and relapsed or refractory chronic lymphocytic leukemia (CLL). A final approval decision is expected from the FDA by June 26, 2017.

“Subcutaneous rituximab can be administered in five to seven minutes compared to an hour and a half or more for intravenous Rituxan,” Sandra Horning, M.D., chief medical officer and head of Global Product Development at Genentech, said in a statement. “The significant reduction in administration time could especially benefit people with blood cancer who may receive years of treatment, and we are pleased the committee unanimously supported this new co-formulation.”

ODAC based its recommendation on a review of data from five clinical trials that included 2,000 patients with the various blood cancers for which rituximab IV is currently approved. The results demonstrated that the efficacy, safety, and pharmacokinetics of the subcutaneous (SC) formulation were noninferior to IV Rituxan.

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 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 (P value not available). The complete response (CR) rates were 42.1 percent versus 47.0 percent, respectively.

The phase 3 SABRINA trial compared the Rituxan 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 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.

Subcutaneous Rituxan 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 FL, previously untreated DLBCL, relapsed or refractory low grade or follicular lymphoma, and previously untreated and relapsed or refractory CLL.

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