Research Highlights Filgrastim and Pegfilgrastim Biosimilars

Three posters presented on September 10, 2017, at the European Society for Medical Oncology (ESMO) 2017 meeting in Madrid, Spain, covered research on 2 proposed pegfilgrastim biosimilars and evaluated the use of filgrastim in oncology practice.

In their presentation, Paul Cornes, MD, and Andriy Krendyukov conclude that physicians and payers need to be aware that Health Technology Assessment (HTA)—based decisions require constant reevaluation, especially following the launch of biosimilar alternatives to biologic medications, because biosimilars can transform healthcare. “This explains the first inclusion of filgrastim in the World Health Organization (WHO) essential drug list for cancer more than 20 years after its original approval in 1991,” they note.¹

In their value evaluation of the evolution of the granulocyte colony stimulating factor filgrastim in oncology practice, the 2 researchers conducted a literature search of 25 systematic reviews and 55 economic evaluations of filgrastim to examine its value over time, as new evidence for risks and benefits of use emerged and the economics of the drug changed. HTAs initially suggested a low value for filgrastim because of its high cost and (at the time) no evidence of significant gain in overall survival (OS). However, more recent meta-analyses of placebo-controlled randomized clinical trial data show absolute overall survival gains of 3.2% (95% CI, 2.1% to 4.2%) resulting from filgrastim support of cytotoxic chemotherapy and falling costs due to biosimilar competition.

In their poster, Karsten Roth, PhD, and coworkers demonstrated the comparability of Cinfa Biotech’s proposed pegfilgrastim biosimilar, B12019, with reference drug Neulasta in 2 highly sensitive clinical study settings in 172 and 96 healthy volunteers.²

The pharmacokinetic comparability of B12019 and Neulasta was demonstrated at the clinical dose of 6 mg, and the pharmacodynamic comparability of B12019 and Neulasta was shown at the clinical dose of 6 mg and the reduced dose of 3 mg. The researchers reported that the safety and immunogenicity profile of B12019 did not show any clinically meaningful differences to Neulasta.

K. Horvat-Karajz and colleagues demonstrated the therapeutic equivalence and similar safety profiles in clinical trials comparing RGB-02 (Gedeon Richter’s proposed pegfilgrastim biosimilar to reference Neulasta) as once-per-cycle administration in their poster presentation.³ The researchers concluded that RGB-02 can provide a biosimilar alternative for the prevention of neutropenia.

Their randomized, comparative, double-blind, multicenter study evaluated the efficacy and safety of RGB-02 compared with Neulasta in 239 breast cancer patients receiving up to 6 cycles of cytotoxic docetaxel and doxorubicin, and a once-per-cycle injection of a fixed 6-mg dose of pegfilgrastim. The duration of severe neutropenia (defined as an absolute neutrophil count [ANC] of less than 0.5x10⁹/L) in cycle 1 was the primary endpoint; secondary endpoints included incidence and duration of severe neutropenia, incidence of febrile neutropenia, time to ANC recovery, depth of ANC nadir, and safety outcomes.

The mean duration of severe neutropenia in cycle 1 was 1.7 days for the biosimilar RGB-02 and 1.6 days for the reference drug. Therapeutic equivalence was established, they said, as the results were within the predefined range of ±1 day. The incidence of severe neutropenia decreased from cycle 1 to cycle 2 in both groups, with no statistically significant differences: from 84.6% (99 patients) to 54.1% (60 patients) for RGB-02 and from 77.0% (87 patients) to 43.7% (45 patients) in the comparator group. Both groups were similar regarding mean time to ANC recovery with 3.4 ±1.88 days during cycle 1. Safety profiles were comparable between groups.

References

1. Cornes P, Krendyukov A. The revolution of value with filgrastim in oncology. Presented at the European Society for Medical Oncology 2017 Congress; September 8-12, 2017; Madrid, Spain. Abstract 1126P. cslide.ctimeetingtech.com/library/esmo/browse/search/51E#2Bb4e.

2. Roth K, Wessels H, Hoefler, J, et al. Pharmacokinetic and pharmacodynamic comparability of B12019: a proposed pegfilgrastim biosimilar. Presented at the European Society for Medical Oncology 2017 Congress; September 8-12, 2017; Madrid, Spain. Abstract 1573P. cslide.ctimeetingtech.com/library/esmo/browse/search/51E#2Bb4e.

3. Horvatz-Karajz K, Grecea D, Smakal M, et al. Efficacy and safety of RGB-02, a proposed biosimilar pegfilgrastim to prevent chemotherapy-induced neutropenia: results of a randomized, double-blind, phase 3 clinical study versus reference pegfilgrastim in patients with breast cancer receiving docetaxel/doxorubicin. Presented at the European Society for Medical Oncology 2017 Congress; September 8-12, 2017; Madrid, Spain. Abstract 1574P. cslide.ctimeetingtech.com/library/esmo/browse/search/51E#2Bb4e.