Tony Hagen is senior managing editor for The Center for Biosimilars®.
The rituximab biosimilar candidate ABP 798 met primary and secondary end points for safety, efficacy, and immunogenicity in a study presented at ASCO20 Virtual, the annual meeting of the American Society of Clinical Oncology (ASCO).
Results of a study presented at ASCO20 Virtual, the annual meeting of the American Society of Clinical Oncology, confirmed the clinical equivalence of the rituximab biosimilar candidate ABP 798.
Efficacy results demonstrated no clinically meaningful differences, and safety and immunogenicity were found to be similar between the reference product and ABP 798, according to Dietger Niederwieser, MD, a professor of medicine and head of the Division of Hematology and Oncology at University Hospital Leipzig in Germany.
The safety profile for the biosimilar candidate also was similar to that of the reference product (Rituxan in the United States and MabThera in the European Union).
“Together with analytical, functional, and clinical [pharmacokinetic (PK)/pharmacodynamic (PD) findings], these clinical efficacy, safety, and immunogenicity results provide the totality of evidence to support similarity of ABP 798 with [reference] rituximab,” Niederwieser and other investigators wrote.
The biosimilar is the subject of a Biologics License Application submitted for review to the FDA in December 2019 by Amgen and Allergan, which are collaborating on multiple oncology biosimilars. Since that time, Allergan has been merged into AbbVie.
Rituximab is a CD20-directed cytolytic antibody that in the United States has been approved for the treatment of non-Hodgkin lymphoma, chronic lymphocytic leukemia, and rheumatoid arthritis.
Investigators enrolled rituximab-naïve adult patients (N = 250) with grade 1, 2, or 3a follicular B-cell lymphoma expressing CD20. They were randomized 1:1 to ABP 798 or reference rituximab at a dose of 375 mg/m2 every week for 4 weeks followed by repeated dosing at weeks 12 and 20.
The primary and secondary end points were efficacy as measured by the risk difference (RD) of overall response rate (ORR). Additional end points were trough serum concentrations and the percent of patients with complete depletion of CD19-positive cell count at day 8. Adverse events and immunogenicity, or the incidence of developing antidrug antibodies, were also measured.
Clinical equivalence for the primary end point was measured by comparing performance of ABP 798 with the one-sided, 95% upper and lower confidence limits of the reference product at week 28, with noninferiority margins established at —15% and 35.5%.
In the primary analysis, investigators found that the biosimilar candidate efficacy was within the predefined equivalence margins (lower, —1.4%; upper, 16.8%) and results at week 12 also supported similarity (–9.3%, 11.2%).
Serum concentrations over time were similar, meeting the PK end point. Investigators said the percent of patients with complete depletion of CD19-positive cell count at day 8 also was similar between the groups, indicating equivalent B-cell depletion between the biosimilar candidate and the reference product.
The adverse event (AE) profiles also were similar: 83.6% of patients in the ABP 798 cohort (n = 128) experienced any AE, and 10.9% experienced grade ≥3 AE; the respective AE numbers for the reference product were 75.4% (126) and 10.3%.
“Overall, the severities of all AEs observed were within the grades of severity expected for the reference product; no new safety signals were identified,” investigators wrote. ABP 798 also passed the immunogenicity test. Investigators said there were no clinically meaningful differences between treatment groups with regard to the incidence of developing antidrug antibodies.
Niederwieser D, Hamm C, Cobb P, et al. Efficacy of ABP 798 compared with rituximab RP: results from the comparative clinical study in patients with non-Hodgkin lymphoma. Presented at ASCO20 Virtual, May 30-31, 2020. Poster 8044