ASCO 2024 Posters Showcase Positive Data on Denosumab, Pegfilgrastim Biosimilars

Posters from the American Society of Clinical Oncology (ASCO) 2024 annual meeting demonstrate positive safety and efficacy data for denosumab and pegfilgrastim biosimilars.

Denosumab Biosimilar Data in Postmenopausal Osteoporosis¹

One study supported the therapeutic equivalence and similar safety profiles of a denosumab biosimilar candidate (FKS518) compared with the originator (Prolia/Xgeva) in postmenopausal women with osteoporosis.

FKS518, a candidate biosimilar of denosumab (a RANKL inhibitor used for bone metastases and multiple myeloma), was studied to establish biosimilarity through the LUMIADE-3 trial (NCT04934072).

The study included 553 women aged 55 to 85, randomized to receive either FKS518 (n = 276) or the denosumab originator (n = 277). The primary efficacy end point was the percent change in lumbar spine bone mineral density (LS-BMD) at week 52. Patients were administered three 60 mg doses, with those on the originator product being re-randomized at week 52 to continue their treatment or switch to the biosimilar.

Results showed significant increases in LS-BMD in both the FKS518 and originator groups. The lower bound of the 90% CI for non-inferiority (–0.05) was above –1.45, and the upper bound for non-superiority (1.20) was below 1.45, confirming therapeutic equivalence. Secondary end points, including changes in bone mineral density at the femoral neck and total hip, also demonstrated similar percent changes from baseline in both groups.

Safety evaluation indicated no notable differences between FKS518 and the originator, with treatment-emergent adverse events occurring in 67.6% of patients: 66.8% in the FKS518 group and 68.5% in the originator group.

Pegfilgrastim Biosimilar in Patients Receiving Cytotoxic Chemotherapy²

A second study found that biosimilar pegfilgrastim was safe and effective in patients with various cancer types receiving cytotoxic chemotherapy.

Despite pegfilgrastim being essential for preventing chemotherapy-induced neutropenia and newer biosimilars emerging as promising alternatives with trials showing comparable efficacy, conclusive clinical benefit evidence is lacking, likely due to low statistical power in these trials.

A systematic review and meta-analysis were conducted, analyzing data from 10 randomized controlled trials published before October 2023 featuring 2,237 patients being treated with cytotoxic chemotherapy to compare the efficacy and safety of conventional pegfilgrastim and its biosimilars.

Studies included had to report at least one primary outcome: duration of severe neutropenia (DSN) after the first chemotherapy cycle, incidence of febrile neutropenia (FN), or bone pain. The analysis calculated pooled risk ratios (RR) and weighted mean differences (WMD).

Biosimilars showed a significant reduction in DSN (WMD, n = –0.08 days; 95% CI, –0.15 to –0.01; P = .03). There were no significant differences in FN incidence (RR, 0.98; 95% CI, 0.62-1.53) or bone pain (RR, 0.98; 95% CI, 0.82-1.17).

Additionally, eflapegrastim, another long-acting granulocyte-colony stimulating factor agent, significantly reduced DSN compared to conventional pegfilgrastim (WMD, n = –0.13 days; 95% CI –0.24 to –0.03; P = .01). The researchers recommended “exploring the impact of the drug in clinical settings on costs and patient-reported outcomes could provide valuable insights into optimizing the management of chemotherapy-related neutropenia.”

References

1. Sadek J, Valter I, de Souza A, Szeles P, Monnet J. A randomized, double-blind study to evaluate the efficacy, pharmacodynamics, safety and immunogenicity of FKS518, a proposed denosumab, with the originator in postmenopausal women with osteoporosis (LUMIADE-3 study). Presented at: ASCO; May 31-June 4, 2024; Chicaco, IL. Abstract 3155.

2. Nasir S, Ali I, Salim SS, Alidina Z, Idrees H, Moosajee M, et al. Comparative efficacy and safety profiles between conventional pegfilgrastim and its biosimilar agents in patients receiving cytotoxic chemotherapy: A systemic review and meta-analysis. Presented at: ASCO; May 31-June 4, 2024; Chicaco, IL. Abstract 12115.