On November 22, 2023, the FDA approved efbemalenograstim alfa-vuxw (Ryzneuta; Evive Biotech) subcutaneous injection, a novel long-acting granulocyte colony-stimulating factor (G-CSF), for the prevention and treatment of febrile neutropenia in adults with nonmyeloid malignancies who are receiving myelosuppressive chemotherapy associated with a clinically significant incidence of febrile neutropenia.
Efbemalenograstim alfa is a novel, dimeric G-CSF, long-acting fusion protein without PEGylation or polysorbate 80 (Tween-80). As a result of its unique molecular structure, efbemalenograstim alfa may possess stronger G-CSF receptor activation properties and avoid the potential adverse events (eg, allergic reactions) caused by PEGylation or Tween-80 that can occur with currently available G-CSFs. Through specific binding to its G-CSF receptor, efbemalenograstim alfa stimulates the survival, proliferation, differentiation, and function of neutrophil precursors and mature neutrophils, leading to enhanced immune function and the prevention of chemotherapy-induced neutropenia.
“Ryzneuta is a new treatment option that has demonstrated its efficacy and safety, building on the comprehensive global development program of Ryzneuta, which includes 12 clinical trials and has enrolled over 1200 subjects to date in multiple territories,” said John Glaspy, MD, Principal Investigator of efbemalenograstim alfa and Professor of Medicine at the Jonsson Comprehensive Cancer Center, University of California, Los Angeles School of Medicine, in a press release. “We hope that this promising therapy will benefit more CIN [chemotherapy-induced neutropenia] patients,” he added.
The FDA approved efbemalenograstim alfa based on the results of 2 pivotal phase 3 international clinical trials, Study GC-627-04 (NCT02872103) and Study GC-627-05 (NCT03252431). Study GC-627-04 was a randomized, double-blind, placebo-controlled phase 3 clinical trial that included 122 female patients with metastatic or nonmetastatic breast cancer who received chemotherapy with doxorubicin 60 mg/m2 and docetaxel 75 mg/m2 every 21 days, for up to 4 cycles. The patients were randomized to 20-mg efbemalenograstim alfa (n=83) or to placebo (n=39) during chemotherapy cycle 1, followed by 20-mg efbemalenograstim alfa in cycles 2 to 4.
The efficacy of efbemalenograstim alfa was based on the mean duration of grade 4 (severe) neutropenia in chemotherapy cycle 1, which was lower with efbemalenograstim alfa than with placebo (least square mean, 1.4 days vs 4.3 days, respectively; P<.001; 95% confidence interval [CI], 2.4-3.5). The incidence of febrile neutropenia (ie, temperature ≥38.3°C, or >38.0°C sustained for ≥1 hour, and absolute neutrophil count, <0.5×109/L) was also lower with efbemalenograstim alfa versus with placebo in cycle 1 (4.8% vs 25.6%, respectively; P=.0016; 95% CI, 1.8%-38.8%).
Study GC-627-05 was a multicenter, randomized, multidose, active-controlled phase 3 clinical trial that included 393 patients with nonmetastatic (stage I-III) invasive breast cancer who received chemotherapy with docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2 administered every 21 days for up to 4 cycles. The study compared the efficacy and safety of a single subcutaneous injection of 20-mg efbemalenograstim alfa (n=197) versus 6-mg pegfilgrastim (n=196) on day 2 of each chemotherapy cycle (cycles 1-4). The study met its primary and secondary end points of efficacy and safety: the mean days of grade 4 neutropenia in patients who received efbemalenograstim alfa did not exceed that of patients who received pegfilgrastim by >0.6 days in cycle 1 of chemotherapy. The mean days of grade 4 neutropenia in cycle 1 were 0.2 days in the 2 arms (difference in means, 0 days; 95% CI, 0.1-0.1). Subgroup analyses of the treatment-related adverse events were not useful because of the small subgroup sizes.
The most common (≥10%) adverse events in Study GC-627-04 in the efbemalenograstim alfa arm through cycle 1 were nausea (51%), anemia (15%), and thrombocytopenia (12%). In Study GC-627-05, the most common (≥20%) adverse events with efbemalenograstim alfa were fatigue and bone pain.
Efbemalenograstim alfa is contraindicated in patients with a history of serious allergic reactions to G-CSFs such as efbemalenograstim alfa, pegfilgrastim, or filgrastim.
The recommended dose of efbemalenograstim alfa is a single subcutaneous injection of 20 mg, administered once during a chemotherapy cycle, ≥24 hours after cytotoxic chemotherapy. Efbemalenograstim alfa should not be administered within 14 days before and <24 hours after the administration of cytotoxic chemotherapy.