FDA Accepts Application for Rituximab Biosimilar for Several Indications

The U.S. Food and Drug Administration (FDA) accepted a biologics license application for the rituximab biosimilar GP2013 for the treatment of follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and chronic lymphocytic leukemia (CLL). The decision was based on results from the ASSIST-FL trial, which compared the safety, efficacy, and pharmacokinetics of GP2013 and rituximab.

The multinational, double-blind, randomized, controlled, confirmatory, phase III study enrolled 629 patients with untreated, advanced FL who were randomized 1:1 to receive eight cycles of GP2013 (n=314) or rituximab (n=315) in combination with CVP over 24 weeks.

GP2013 demonstrated similar efficacy to rituximab, with ORRs (primary endpoint) of 87 percent and 88 percent, respectively, for a between-group difference of -0.4 percent (95% CI -5.94-5.14; p value not provided). At the end of the combination phase, 55 patients in the GP2013 group and 59 patients in the rituximab group achieved CR, for a between-group difference of -1.1 percent (90% CI -7.46-5.25; p value not provided). The difference in CR between groups was 2.3 percent (90% CI -8-3.29) at 15 months, 0.6 percent (90% CI -5.59-6.75) at 27 months, and 0.4 percent (90% CI -6.61-5.88) at 33 months (p values not provided).

At data cutoff (median follow-up = 23.8 months; range not provided), the median PFS and OS had not been reached in either cohort; 30 percent of patients in the GP2013 cohort and 24 percent in the rituximab cohort had experienced a PFS event (HR=1.31; 95% CI 0.97-1.78). However, the study was not powered to show similarity in PFS and OS, the researchers cautioned.

Treatment was discontinued early in both groups (n=10 in each) because of disease progression. Rates of dose modifications (5% in each group) and dose delays or interruptions (41% in each group) were similar (p values not provided). Twenty-three patients (7%) in the GP2013 group and 29 patients (9%) in the rituximab group died (HR=0.77; 95% CI 0.45-1.33; p value not provided).

AEs occurring in the GP2013 and rituximab groups were similar: 93 percent and 91 percent, respectively, experienced any-grade AEs; 23 percent and 20 percent, respectively, experienced serious AEs (p values not provided). The most common AEs were neutropenia (26% and 30%), constipation (22% and 20%), and nausea (16% and 13%), and the most common grade 3/4 event was neutropenia (18% and 21%).

Five patients in the GP2013 group and three in the rituximab group developed anti-drug antibodies.

GP2013 has demonstrated an identical amino acid sequence, matched protein structures and modifications, and indistinguishable biological and functional properties. The clinical pharmacokinetic profile of GP2013 appears similar to rituximab.

Sources: Sandoz press release, September 12, 2017; Jurczak W, Illidia M, Govindbaby 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. Abstract #128. Presented at the 2016 ASH Annual Meeting, December 3, 2016; San Diego, CA.