PK, PD Similarity Demonstrated for mAbxience's RTXM83 and MabThera

A study published yesterday in Cancer Chemotherapy and Pharmacology reports that pharmacokinetic (PK) and pharmacodynamic (PD) data from a randomized, double-blind, phase 3 clinical study show similarity between mAbxience’s proposed rituximab biosimilar, RTXM83, and its reference, MabThera (also marketed as Ritxuan in the United States), using a population PK model approach.

The study was conducted in patients with diffuse large B-cell lymphoma (DLBCL). Patients (n = 251) received intravenous doses of 375 mg/m² of either the biosimilar candidate plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (n = 127) or MabThera plus CHOP (n = 124).

PK similarity between the 2 products was assessed by comparing predicted serum concentratoins over time, derived from a population PK model, which “allows the use of sparse data to accurately calculate PK parameters,” according to the authors. Additionally, the schedule of treatment for DLBCL, which includes 6 treatment cycles that include 1 dose of rituximab every 21 days, allows for numerous PK measurements.

The primary PK endpoints of the study were area under the concentration—time curve (AUC) and the maximum serum concentration (C_max), levels of CD20+ and CD19+ B cells in peripheral blood were assessed for the PD evaluation, and anti-drug antibodies (ADAs) were assessed.

The authors report the following:

• The ratios (90% CI) of geometric least-square means for the RXTM83 treatment group versus the reference rituximab treatment group were 0.992 (0.936—1.05) for AUC and 0.996 (0.939–1.05) for C_max.
• Immediately after the first infusion, CD20+ B-cell counts reached 100% depletion in both groups.
• In both treatment groups, CD19+ B cells achieved nearly complete depletion (99.8% in the biosimilar arm and 99.6% in the reference arm) around day 7 after the first infusion.
• Complete depletion of CD20+ and CD19+ B cells was observed in the following treatment cycles in both groups.
• Overall ADA incidence in the studied population was low and was similar between the 2 groups.

The authors conclude that RTXM83 and MabThera have similar PK and PD and, to their knowledge, this study is the first to investigate the population PK of a rituximab biosimilar with a large sample size of patients, serum concentration, and multiple cycles of treatment.