Researchers found that a denosumab biosimilar appeared comparably safe and effective to reference drug Prolia.
Researchers in China found that a denosumab biosimilar (LY06006) increased lumbar spine bone mineral density (BMD) and decreased bone resorption in postmenopausal women with a high risk of fracture, indicating that LY06006 might be an effective osteoporosis treatment.
This study, published in the Journal of Orthopaedic Translation, attempted to determine the efficacy, safety, pharmacokinetics, and immunogenicity profiles of the denosumab biosimilar (LY06006) in Chinese postmenopausal women with osteoporosis and a high fracture risk.
A randomized, double-blind, placebo-controlled, multicenter phase 3 study was conducted within various hospitals throughout China to examine the bioequivalence of LY06006 to reference denosumab (Prolia), an already available therapy for osteoporosis. Prolia is a fully human monoclonal antibody for nuclear factor-kappa B ligand (RANKL) and has been used to treat patients with osteoporosis for more than 10 years.
In the study, LY06006, a recombinant anti-RANKL whole human monoclonal antibody injection, displayed high similarity with reference denosumab when studied in the pharmaceutical and nonclinical spheres and showed clinical localization consistent with that of the reference. Researchers found LY06006 to be well tolerated with no unexpected adverse reactions.
Across 49 medical centers in China, 448 postmenopausal women aged 50 to 85 years with osteoporosis were randomly assigned (3:1) to receive 60 mg of LY06006 or placebo subcutaneously every 6 months for 1 year. Change in lumbar spine BMD was the primary end point. This study was performed from June 2019 to August 2021.
Of the 448 participants, 409 (LY06006, n = 311; placebo, n = 98) finished the study. All participants were involved in the intent-to-treat trial, 427 (95.3%) were in the full analysis set, 408 (91.1%) were in the per protocol set, 446 (99.6%) were in the safety set, and 336 (75.0%) were in the pharmacokinetics concentration set.
Study participants were also given daily 500 mg oral calcium and 600 IU vitamin D supplements during the study.
In terms of efficacy, a 4.71% (95% CI, 3.81%-5.60%) treatment difference in percent change in lumbar spine BMD from baseline to month 12 was seen in the LY06006 group compared with the placebo group (P < .0001). Rising lumbar spine BMD levels were associated with LY06006 at the 6-month mark.
The serum C-terminal telopeptide of type 1 collagen (CTX) change rate in the LY06006 group decreased by 78.42% (95% CI, 75.30%-81.64%), 58.66% (95% CI, 54.07%-63.41%), and 61.15% (95% CI, 54.97%-66.68%) compared with the placebo group at months 1, 6, and 12, respectively (all P < .0001).
Serum procollagen type I N-terminal propeptide (PINP) change rates at the 1-, 6-, and 12-month marks in the LY06006 group compared with the placebo group were decreased by 15.69% (95% CI, 12.58%-18.71%), 53.89% (95% CI, 49.74%-58.15%), and 55.31% (95% CI, 50.33%-59.88%), respectively (all P < .0001).
Adverse events were experienced by 264 (78.6%) LY06006 group participants and 83 (75.5%) placebo group participants. The most common treatment-emergent adverse events experienced by participants were urinary tract infections and upper respiratory tract infections.
The PubMed database contains only 1 other phase 3 clinical study on a denosumab biosimilar, which had a smaller sample size, suggesting that the results of this study might be more illustrative of the benefits of LY06006 across a larger sample size.
However, a limitation was that Prolia was not approved in China at the start of the study, so researchers were unable to directly compare LY06006 with Prolia.
A denosumab biosimilar such as LY06006 could help additional patients by increasing drug accessibility and lowering health care costs, the authors noted.
They concluded that ostmenopausal women with a high risk of fracture can be helped by a denosumab biosimilar such as LY06006, especially if biologics for the condition are high in cost or difficult to access.
Gu J, Zhang H, Xue Q, et al. Denosumab biosimilar (LY06006) in Chinese postmenopausal osteoporotic women: a randomized, double-blind, placebo-controlled, multicenter phase III study. J Orthop Translat. 2022;38:117-125. doi:10.1016/j.jot.2022.06.007