Pegfilgrastim Biosimilar Shows Therapeutic Equivalence to Neulasta

A new granulocyte-colony stimulating factor biosimilar demonstrated therapeutic equivalence to a reference brand of pegfilgrastim (Neulasta®, Amgen) for use in patients with breast cancer receiving chemotherapy, according to results from a recent study.

The authors, publishing in BMC Cancer, noted in their background section that biosimilars for a related therapy, filgrastim (approved in 1991), had been approved in Europe since 2009 and in the United States in 2015, but that biosimilars for pegfilgrastim are still in various stages of development. The present study looked at proposed biosimilar RGB-02 (Gedeon Richter) in comparison to Neulasta (approved in 2002) in a double-blind clinical trial setting.

The study was conducted across 35 centers located in Hungary, Romania, Russia, Ukraine, Serbia, Croatia, Bulgaria, and Czech Republic between January 2014 and April 2015. The randomized, double-blind, phase III clinical study included 239 women, who were randomized (1:1) to receive either RGB-02 (n=121) or the reference product (n=118). The study population was limited to chemotherapy-naïve women between 18 and 65 with invasive Stage IIB and III breast cancer. Patients were assigned to up to six cycles of docetaxel (60 mg/m2)/doxorubicin (75 mg/m2) chemotherapy as myelosuppressive chemotherapy combination, as well as a once-per-cycle injection of pegfilgrastim (6 mg).

The primary study endpoint was the duration of severe neutropenia (absolute neutrophil count [ANC] < 0.5 × 109/L) in Cycle 1, with secondary endpoints of severe neutropenia incidence and duration, incidence of febrile neutropenia, time to ANC recovery, and depth of ANC nadir in Cycles 1 and 2.

According to the results, RGB-02 demonstrated therapeutic equivalence with the reference pegfilgrastim. The mean duration of severe neutropenia in Cycle 1 and Cycle 2 was comparable between the two study groups. The researchers also reported no statistically significant differences in secondary endpoints between study groups, and no clinically relevant differences either. The incidence and duration of severe neutropenia and episodes fever and treatment with antibiotics were “almost identical in both groups, according to the authors.

“The mean duration of severe neutropenia in Cycles 3 and 4, after patients in the reference arm switched to RGB-02, was less than one day in the RGB-02 arm (0.9 days) and the reference arm switched to RGB-02 (0.6 days), indicating that the switch from reference to RGB-02 treatment did not increase the patient’s risk to develop longer lasting grade 4 neutropenia,” they wrote.

The safety profile suggested equivalence, with similar numbers of adverse events occurring in both study groups. Two deaths were reported in the RBG-02 arm but were unrelated to the investigational medication.

“The safety profile of RGB-02 is comparable with the reference pegfilgrastim and no immunogenicity was found, even after switching from the originator product to RGB-02,” the researchers added in the study. “The incidence and severity of bone pain associated with the use of pegfilgrastim was comparable between treatment arms and was similar to previous studies.”

The researchers also looked at immunogenicity, which they noted could occasionally cause problems for biologics if the body produces antidrug antibodies leading to a loss of efficacy or to adverse reactions. The screening assay test was negative in 96.1% of immunogenicity samples for the double-blind treatment period. The results, the authors said, suggested no immunogenic responses to the study drug and no detection of anti-pegfilgrastim antibodies during the study period.

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