Proposed Biosimilar for Denosumab Has Similar Safety, Efficacy as Reference

MW032, a proposed biosimilar for denosumab, had similar efficacy, population pharmacokinetics, and safety compared with the reference product, according to results of a study published in JAMA Oncology. The investigators hope that the availability of biosimilars for denosumab will help increase access to the drug and reduce the burden for those with solid tumor-related bone metastases.

According to the study authors, metastatic bone disease affects more than 1.5 million patients with cancer, particularly those with breast and prostate cancer.

“Patients frequently experienced osteoclast-mediated bone destruction that resulted in clinically important complications, such as fracture, need for bone radiation or surgery, spinal cord compression, hypercalcemia, or bone pain,” the study authors said.

A phase 1 study previously demonstrated that MW032 and denosumab were bioequivalent in pharmacokinetics, pharmacodynamics, safety, and immunogenicity. In the current study, investigators aimed to determine the biosimilarity in efficacy, safety, and population pharmacokinetics between the biosimilar and the reference product for those with solid tumor bone metastases, according to the study authors.

The study was conducted at 46 clinical centers in China and included individuals aged 18 years and older with a histologically confirmed malignant tumor, excluding blood cancer and radiographic evidence of at least 1 bone metastasis. Treatment was assigned on a 1:1 ratio with either the biosimilar or the reference product. Individuals received 120 mg of their assigned drug subcutaneously every 4 weeks until week 39 and were advised to take daily supplements containing 500 mg of elemental calcium and at least 400 international units of vitamin D, according to the study authors.

The primary endpoint included percentage change in natural logarithmic transformed urinary N-telopeptide/creatinine ratio (uNTx/uCr) from baseline to week 13 and secondary endpoints included percentage change in uNTx/uCr and bone-specific alkaline phosphates from baseline to weeks 5, 25, 37, and 53. Safety endpoints included prevalence and severity of adverse events and laboratory measures, according to the study authors.

From January 17, 2020, to April 30, 2021, 708 individuals were included in the study, with 701 completing the assessment for the primary endpoint. The mean age was 56.1 years and 65.6% were woman. Additionally, 47.2% had breast cancer as their primary tumor. The baseline uNTx/uCr was similar between groups.

The mean percent change of 13-week uNTx/uCr from baseline was -72% and -72.7% for the biosimilar and reference product groups, respectively, according to the study authors. The percent changes also corresponded to mean logarithmic ratios, equating to a 0.02 difference according to the study results.

Further, the mean changes of uNTx/uCr and bone-specific alkaline phosphatase were similar at each time point for the 53 weeks. The differences in uNTx/uCr changes were 0.015, -0.02, -0.05, and 0.001 at 5, 25, 37, and 53 weeks, respectively, according to the study authors. For bone-specific alkaline phosphatase, the differences of change were -0.006, 0.00, -0.085, -0.09, and -0.13, respectively.

Treatment related adverse events (TRAEs) in the biosimilar and reference product groups included hypocalcemia (35.6% vs 41.2%), hypophosphatemia (15.7% vs 10.7%), and hyperuricemia (6.8% vs 5.9%). Patients who experienced grade 3 or worse TRAEs were similar in both groups and had no notable differences for special interest reactions. There were no differences observed in incidence skeletal related events or time to first on-study skeletal-related events in either group.

Reference

Zhang S, Yin Y, Xiong H, Wang J, et al. Efficacy, Safety, and Population Pharmacokinetics of MW032 Compared With Denosumab for Solid Tumor-Related Bone Metastases: A Randomized, Double-Blind, Phase 3 Equivalence Trial. JAMA Oncol. doi:10.1001/jamaoncol.2023.6520