1700PSafe switch of treatment from the reference product to RGB-02, a proposed biosimilar pegfilgrastim: Analysis of the results of three clinical trials

Background: Treatment with recombinant human granulocyte-colony stimulating factor (G-CSF) is an accepted standard for prevention of chemotherapy-induced neutropenia. RGB-02, a pegylated G-CSF (pegfilgrastim) developed by Gedeon Richter is a proposed biosimilar to the reference product Neulasta®. Therapy switch from a reference product to its biosimilar is expected to occur in the daily practice. Here we are presenting the outcome of treatment switch in two randomized cross-over design comparative PK/PD studies (EudraCT nr: 2011-001737-17 and 2016-005051-25) and a randomized, comparative, multicenter efficacy and safety study of RGB-02 (EudraCT nr: 2013-003166-14). Methods: Efficacy, safety and PD data of two PK/PD studies (enrolling 110 and 150 healthy volunteers, respectively) and a comparative efficacy and safety study (enrolling 239 breast cancer patients) were analyzed in order to assess whether treatment switch from Neulasta® to RGB-02 has any impact on the PD response, efficacy or safety. The PK/PD studies had a cross-over design. Patients in the reference arm of the comparative efficacy and safety study were switched to RGB-02 treatment following the first two chemotherapy cycles. Endpoints assessed were related to the change in ANC count in healthy volunteers, duration of severe neutropenia (DSN; ANC < 0.5 x109/L) in the comparative efficacy and safety study, as well as safety data including immunogenicity collected in each clinical study. Results: None of the PD endpoints showed any difference following the cross-over in the comparative PK/PD studies. The mean DSN values after the therapy switch were similar to the values prior to the switch and the switched arm (mean DSN: 0.6) did not show decreased efficacy compared to the arm received RGB-02 from the first cycle (mean DSN: 0.9). Safety results, including immunogenicity of the 3 studies did not reveal any negative impact of the treatment switch. Conclusions: Treatment switch from Neulasta® to RGB-02 can be considered safe while maintaining the therapeutic effect of pegfilgrastim therapy. Clinical trial identification: EudraCT: 2011-001737-17; EudraCT: 2016-005051-25; EudraCT: 2013-003166-14. Legal entity responsible for the study: Gedeon Richter Plc. Funding: Gedeon Richter Plc. Disclosure: A. Illes L. Perjesi, K. Horvat-Karajz, N. Jeszenoi, I. Aradi: Employee: Gedeon Richter Plc. N.K. Singh, S.J. Mair, Z. Kahan: Principal investigator of one of the studies (EudraCT Nr. 2016-005051-25) sponsored by Gedeon Richter Plc; Investigator grant from the sponsor.