Adverse events were reported for 83% of patients receiving CT-P10 (compared with 80% of those in the rituximab control group) and 93% of patients receiving GP2013 (vs 91% in the rituximab group). The most common grade 3 to 4 adverse event among all patients in both studies was neutropenia.CT-P10 and GP2013 are just two of 7 rituximab biosimilars that have undergone clinical testing for follicular and other B-cell non-Hodgkin lymphomas.3 Others include Amgen’s ABP798 for treating B-cell non-Hodgkin lymphoma, Pfizer’s PF-05280586 is for first-line treatment of follicular lymphoma, and Mabion’s MabionCD20 for first-line treatment of diffuse large B-cell lymphoma.3
“Because small changes in chemical properties can affect in-vivo activity associated with the complex mechanism of action of monoclonal antibodies, confirmatory clinical trials with correct endpoints are needed to introduce biosimilars into clinical practice, noted Shinichi Makita, MD, PhD, and Kensei Tobinai, MD, PhD, of the National Cancer Center Hospital in Tokyo, Japan, who coauthored a commentary published alongside the 2 studies.3
Although the US Food and Drug Administration (FDA) and the European Medicines Agency both permit overall response rate (ORR) as a surrogate endpoint for comparing biosimilars and originator biologics, it is not a “robust” endpoint for evaluating biosimilar efficacy, the authors noted. Nor is CVP a common regimen for patients with follicular lymphoma, who more frequently receive cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and bendamustine.
Despite these limitations, CT-P10 and GP2013 have both been approved in Europe based on the study findings. The trial data are expected to hasten these biosimilars’ arrival in clinical practice here in the US as well.
The anti-CD20 monoclonal antibody, obinutuzumab, plus chemotherapy is more effective than rituximab among patients with advanced follicular lymphoma.4 Nevertheless, rituximab and its biosimilars are “expected to remain an important drug in the treatment of B cell malignancies for the time being” and the biosimilars’ anticipated lower cost should translate to improved accessibility for patients.
“While it’s still very early in the market development lifecycle for [cancer] biosimilars, they do appear to provide savings in the range of 15% to 35%, as each of these molecules has additional biosimilar entrants and competition,” Mr Picard said.
“FDA approval is typically one of the largest challenges. I anticipate that the originator companies will vigorously defend their intellectual property with patent litigation.”
- Kim WS, Buske C, Ogura M, et al. Efficacy, pharmacokinetics, and safety of the biosimilar CT-P10 compared with rituximab in patients with previously untreated advanced-stage follicular lymphoma: a randomised, double-blind, parallel-group, non-inferiority phase 3 trial. Lancet Haematol. 2017;4(8):e362-73. doi: 10.1016/S2352-3026(17)30120-5
- Jurczak W, Moreira I, Kanakasetty GB, et al. Rituximab biosimilar and reference rituximab in patients with previously untreated advanced follicular lymphoma (ASSIST-FL): primary results from a confirmatory phase 3, double-blind, randomised, controlled study. Lancet Haematol. 2017;4(8):e350-61. doi: 10.1016/S2352-3026(17)30106-0
- Makita S, Tobinai K. Rituximab biosimilars: introduction into clinical practice. Lancet Haematol. 2017;4(8):e342-3. doi: 10.1016/S2352-3026(17)30124-2]
- Marcus RE, Davies AJ, Ando K, et al. Obinutuzumab-based induction and maintenance prolongs progression-free survival (PFS) in patients with previously untreated follicular lymphoma: primary results of the randomized phase 3 GALLIUM study. Paper presented at: American Society of Hematology (ASH) 58th Annual Meeting and Exposition; December 3-6, 2016; San Diego, CA.