The European Commission (EC) has approved the rituximab (Rituxan) biosimilar Rixathon (GP2013) to treat patients with follicular lymphoma, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia.
Rixathon is approved for use in all indications of the reference medicine, subcutaneous rituximab. Subcutaneous rituximab has been available in the European Union since 2014, and is approved in nearly 50 other countries.
Sandoz, the manufacturer of Rixathon and a division of Novartis, announced the approval in a press release Monday.
“Today’s approval of Rixathon represents a big win for patients in Europe with blood cancers or immunological diseases because it enables increased access to biologics,” said Carol Lynch, Sandoz global head of biopharmaceuticals. “It also allows healthcare systems to redeploy resources to other areas of high need, particularly innovative therapies. Sandoz is committed to increasing patient access to biologic medicines, and Rixathon will be one of the five major launches we plan in the next four years.”
The approval for indications in cancer is based on results from the phase III confirmatory ASSIST-FL study. 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 segregated 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)
, and Ctrough
between the two 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 anti-drug antibodies.
In March, the FDA’s Oncologic Drugs Advisory Committee unanimously recommended approval of subcutaneous rituximab for the treatment of patients with follicular lymphoma, previously untreated diffuse large B-cell lymphoma, relapsed or refractory low grade or follicular lymphoma, and previously untreated and relapsed or refractory chronic lymphocytic leukemia. The FDA is slated to issue a final ruling by June 26, 2017.
Today’s EU approval for Rixathon also includes indications for immunological diseases, such as rheumatoid arthritis, granulomatosis with polyangiitis, and microscopic polyangiiti.
Jurczak W, Ilidia M, Govindbabu KS, et al. A phase III efficacy and safety study of the proposed rituximab biosimilar GP2013 versus rituximab in patients with previously untreated advanced follicular lymphoma. Presented at: 58th American Society of Hematology Annual Meeting; San Diego, CA; December 3-6, 2016. Abstract 1151.