A randomized, double blind, parallel design, repeat dose, 2-arm, multicenter study comparing the efficacy, safety, immunogenicity, and pharmacokinetic profiles of a denosumab biosimilar, AVT03, in postmenopausal women with osteoporosis.

Abstract

Background: To demonstrate comparative efficacy of AVT03, a proposed denosumab biosimilar, versus reference product (RP) in postmenopausal women with osteoporosis.

Research design and methods: Participants received AVT03 or RP; 60 mg subcutaneous on Day 1 and Month 6. At Month 12, AVT03 group received 3^rd dose while RP group received either a 3^rd dose of RP or a dose of AVT03. Primary endpoints were percent change from baseline in lumbar spine bone mineral density (BMD) at 12 months and area under the effect curve (AUEC)_0-6 months of percent change from baseline (%Cfb) in serum C-terminal telopeptide of type I collagen (sCTX-1). Safety and immunogenicity were evaluated.

Results: The 95% confidence interval (CI)s of the least squares means difference between treatments for percent change from baseline in lumbar spine BMD to Month 12 (-0.58, 0.82) were entirely contained within the prespecified margin (-1.45%, 1.45%), supporting demonstration of comparative efficacy. The 95% CIs of the geometric mean ratio between treatments for AUEC_0-6 months of %Cfb sCTX-1 (0.97, 1.03) were entirely contained within the prespecified margin (0.80, 1.25), supporting demonstration of pharmacodynamic similarity. Safety and immunogenicity profiles were comparable throughout.

Conclusion: Data supported demonstration of comparative efficacy between AVT03 and RP denosumab. Safety and immunogenicity profiles were similar.

Trial registration: www.clinicaltrials.gov identifier is NCT05395091.