Efficacy and safety of candidate biosimilar CT-P41 versus reference denosumab: a double-blind, randomized, active-controlled, Phase 3 trial in postmenopausal women with osteoporosis

Osteoporos Int. 2024 Nov;35(11):1919-1930. doi: 10.1007/s00198-024-07161-x. Epub 2024 Jul 23.

Abstract

This 78-week (18-month) study conducted in 479 postmenopausal women with osteoporosis evaluated the efficacy, pharmacodynamics, pharmacokinetics, safety, and immunogenicity of candidate biosimilar CT-P41 relative to US reference denosumab. CT-P41 had equivalent efficacy and pharmacodynamics to US-denosumab, with similar pharmacokinetics and comparable safety and immunogenicity profiles.

Purpose: To demonstrate equivalence of candidate biosimilar CT-P41 and US reference denosumab (US-denosumab) in postmenopausal women with osteoporosis.

Methods: This 78-week (18-month), double-blind, randomized, active-controlled Phase 3 study (NCT04757376) comprised two treatment periods (TPs). In TPI, patients (N = 479) were randomized 1:1 to 60 mg subcutaneous CT-P41 or US-denosumab. At Week 52, those who had received CT-P41 in TPI continued to do so. Those who had received US-denosumab were randomized (1:1) to continue treatment or switch to CT-P41 in TPII. The primary efficacy endpoint was percent change from baseline in lumbar spine bone mineral density at Week 52. Efficacy equivalence was concluded if associated 95% confidence intervals (CI) for least squares (LS) mean group differences fell within ± 1.503%. The primary pharmacodynamic (PD) endpoint was area under the effect curve for serum carboxy-terminal cross-linking telopeptide of type I collagen through the first 26 weeks, with an equivalence margin of 80-125% (for 95% CIs associated with geometric LS mean ratios).

Results: Equivalence was demonstrated for CT-P41 and US-denosumab with respect to primary efficacy (LS mean difference [95% CI]: - 0.139 [- 0.826, 0.548] in the full analysis set and - 0.280 [- 0.973, 0.414] in the per-protocol set) and PD (geometric LS mean ratio [95% CI]: 94.94 [90.75, 99.32]) endpoints. Secondary efficacy, PD, pharmacokinetics, and safety results were comparable among all groups up to Week 78, including after transitioning to CT-P41 from US-denosumab.

Conclusions: CT-P41 was equivalent to US-denosumab in women with postmenopausal osteoporosis, with respect to primary efficacy and PD endpoints.

Keywords: Biosimilar; CT-P41; Denosumab; Equivalence; Osteoporosis.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Multicenter Study
  • Comparative Study

MeSH terms

  • Aged
  • Biosimilar Pharmaceuticals* / adverse effects
  • Biosimilar Pharmaceuticals* / pharmacokinetics
  • Biosimilar Pharmaceuticals* / therapeutic use
  • Bone Density Conservation Agents* / administration & dosage
  • Bone Density Conservation Agents* / adverse effects
  • Bone Density Conservation Agents* / pharmacokinetics
  • Bone Density Conservation Agents* / pharmacology
  • Bone Density Conservation Agents* / therapeutic use
  • Bone Density* / drug effects
  • Denosumab* / administration & dosage
  • Denosumab* / adverse effects
  • Denosumab* / pharmacokinetics
  • Denosumab* / pharmacology
  • Denosumab* / therapeutic use
  • Double-Blind Method
  • Female
  • Humans
  • Injections, Subcutaneous
  • Lumbar Vertebrae / physiopathology
  • Middle Aged
  • Osteoporosis, Postmenopausal* / drug therapy
  • Therapeutic Equivalency*
  • Treatment Outcome

Substances

  • Denosumab
  • Biosimilar Pharmaceuticals
  • Bone Density Conservation Agents