FDA Accepts Application for Rituximab Biosimilar

The FDA has accepted a biologics license application (BLA) for the rituximab (Rituxan) biosimilar Rixathon (GP2013), according to Sandoz (Novartis), the company developing the treatment.

If approved, Rixathon would be indicated for the hematologic malignancies follicular lymphoma, diffuse large B-cell lymphoma (DLBCL), and chronic lymphocytic leukemia (CLL), as well as for rheumatoid arthritis. In June, the European Commission approved Rixathon to be marketed for these indications in the EU.

“The cost of treating cancer in the United States is a major concern for many patients and their families, as well as for the healthcare system” Mark Levick, MD, PhD, Sandoz global head of development, biopharmaceuticals, said in a press release. “With the FDA acceptance of our regulatory submission for proposed biosimilar rituximab, we plan to deliver patients a high-quality Sandoz biosimilar that, following approval, could help drive healthcare savings and increase competition, while freeing up resources for and supporting patient access in other areas of cancer care, including innovative therapies.”

Sandoz supported the BLA with a series of data, including results from the ASSIST-RA study in rheumatoid arthritis and the phase III confirmatory ASSIST-FL study in follicular lymphoma.

ASSIST-FL compared the efficacy, safety, pharmacokinetics (PK) and pharmacodynamics (PD) of Rixathon plus cyclophosphamide, vincristine, prednisone (GP2013-CVP) versus rituximab-CVP in patients with previously untreated, advanced stage follicular lymphoma (N = 629).

The treatment phase lasted 6 months, with a 2-year maintenance phase, and a 3-year follow-up. Patients were randomly assigned to 8 cycles of GP2013-CVP (n = 314) or rituximab-CVP (n = 315). Patients with complete or partial response then entered the double-blind maintenance phase, and received treatment with either GP2013 or rituximab.

Patients were separated into low-, intermediate-, or high-risk groups as determined by Follicular Lymphoma International Prognostic Index (FLIPI) score risk group, and by geographic region.

Overall response rate was 87.1% in the GP2013-CVP arm versus 87.5% in the rituximab-CVP arm. The rate of complete response was 14.8% and the partial response rate was the 72.3% in the GP2013-CVP arm. Complete response rate was 13.4% with a partial response rate of 74.1% in the rituximab-CVP group.

Median progression-free survival and overall survival had not been reached.

Investigators found that the PK and PD of Rixathon were similar to rituximab. The ratio of geometric mean for Cmax at cycle 4, day 1 was 1.00 (90% CI, 0.925-1.09). Investigators also observed comparable results for AUC(0-21d), AUCall, and Ctrough between the 2 groups.

Investigators assessed peripheral CD19+ B-cell counts were assessed as PD outcome. Ratio of AUEC(0-21d) was 0.939 (90% CI, 0.845-1.04), confirming the similarity between both the 2 drugs.

Incidence of serious adverse events (AEs) was similar between GP2013-CVP (22.8%) and rituximab-CVP (20.0%) arms. The most common serious AE for both groups was febrile neutropenia, 4.8% in the GP2013-CVP arm and 2.9% in the rituximab-CVP arm.

Four patients in the GP2013-CVP and 7 in the rituximab-CPV group died during the treatment phase. As of the July 10, 2015, data cutoff, 35 patients (18 in GP2013-CVP arm and 17 in the rituximab-CVP arm) died during the study. The most common cause was non-Hodgkin lymphoma, 2.6% in GP2013-CVP arm versus 1.9% in the rituximab-CVP arm.

Overall, 5 (1.9%) patients in the GP2013-CVP and 3 (1.1%) in the rituximab-CVP arm developed antidrug antibodies.

Sandoz plans to introduce 5 oncology and immunology biosimilars by 2020, the company noted in a statement.