Randomized Double-Blind Comparative Study of First Global Denosumab Biosimilar in Oncology

Abstract

Purpose The aim of this study was to compare first global biosimilar denosumab for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors. Methods It was a randomized, double-blind, comparative clinical study. Total of 136 patients of solid tumor were dosed (i.e., 102 subjects in study arm and 34 subjects in the reference arm) with initial double-blind period of 24 weeks (primary efficacy) followed by open-label phase till week 36. Primary endpoint was the incidence of first on-study SRE including hypercalcemia of malignancy with co-primary endpoint of median time to first on-study SRE. Secondary endpoints included mean number and time to first and subsequent on-study SREs (week 12, 24, 36), incidence/proportion of patients with first and subsequent on-study SREs (week 24, 36), change from baseline in nuclear bone scan, quality of life assessment, pharmacokinetics, pharmacodynamic, and safety. Results In biosimilar study arm, 06 (5.83%) patients suffered SRE from baseline to week 24 compared with 02 (5.71%) patients in reference arm with one (0.97%) patient showing pathological fracture in study arm and one (2.86%) patient having spinal cord compression in reference arm. There was no statistically significant difference in median time to first SRE, mean number of SRE/patient in both arms and improvement in bone repair on nuclear scan at 12, 24 and 36 weeks. Though the study arm showed better health-related quality of life (HRQoL), mean change in HRQoL was statistically not different in both the arms. Pharmacodynamics, serum bone-specific alkaline phosphatase, pharmacokinetic and safety evaluation did not show any statistical difference between arms. Conclusion There was no clinically meaningful difference in the biosimilar denosumab and reference product after detailed efficacy and safety evaluation.

Autoreactive IgE: Pathogenic role and therapeutic target in autoimmune diseases

“…However, it also implies that repeated injections of OMZ are required in order to trap IgE as it slowly detaches from FcεRI. Several OMZ biosimilars such as GBR 310, CT‐P39, and CMA007 are now at various stages of clinical development 148–150 …”

Clinical inertia in asthma

“…For example, generic medications and biosimilars to salmeterol/fluticasone generics have been shown to improve ACT scores and respiratory function 86 , and their clinical benefit in the short term is similar to that of the original medication 87 . A biosimilar of omalizumab has been shown to be non-inferior to the existing product in terms of clinical efficacy and toxicity 88 , 89 . This approach to medications can remove psychological constraints on medication safety and cost for patients and healthcare providers, and the widespread availability of medications is likely to promote a comprehensive approach by the healthcare team.…”

Autoreactive IgE: pathogenic role and therapeutic target in autoimmune diseases

“…However, it also implies that repeated injections of OMZ are required in order to trap IgE as it slowly detaches from FcεRI. Several OMZ biosimilars such as GBR 310, CT-P39 and CMA007 are now at various stages of clinical development [146][147][148] .…”