A recent 78-week phase 3 trial has demonstrated that CT-P41, a biosimilar to the US reference denosumab, is equivalent in efficacy, pharmacodynamics (PDs), pharmacokinetics (PKs), safety, and immunogenicity for patients with postmenopausal osteoporosis. This study, published in Osteoporosis International, aimed to evaluate the equivalence of CT-P41 to US reference denosumab (Prolia/Xgeva) to improve treatment accessibility and reduce healthcare costs while maintaining treatment efficacy and safety.
Osteoporosis affects 12.6% of adults aged 50 and older, with a significant impact on patient health, independence, and quality of life, as well as placing a substantial economic burden on healthcare systems due to fracture treatment. Denosumab, a biologic therapy approved for osteoporosis treatment in high-risk patients, increases bone mineral density and reduces fracture risk by inhibiting bone resorption. However, the high costs of biologic therapies can limit patient access. Biosimilars like CT-P41 offer a solution by alleviating the financial burden on healthcare systems and improving equitable access to treatment.
The study was a double-blind, randomized, active-controlled phase 3 clinical trial conducted at 20 sites across 4 countries, involving 440 postmenopausal women aged 50 to 80 years with osteoporosis. Participants were randomized to receive either CT-P41 or US-denosumab, with primary efficacy measured as the percent change in lumbar spine bone mineral density (BMD) at week 52. Secondary endpoints included changes in BMD at other skeletal sites, fracture incidences, quality-of-life assessments, PKs, PDs, safety monitoring, and immunogenicity.
Results showed equivalence between CT-P41 and US-denosumab for lumbar spine BMD at week 52, with comparable changes in total hip and femoral neck BMD. Secondary efficacy measures, including vertebral and nonvertebral fracture rates, were low and similar between groups. Health-related quality-of-life scores were consistent across groups, with no significant differences observed. PD analyses showed equivalent suppression of bone turnover markers, and PK parameters were similar across groups, even after switching to CT-P41.
Safety profiles were comparable, with treatment-emergent adverse events (TEAEs) reported in 75.7% and 70.2% of patients in the CT-P41 and US-denosumab groups, respectively, during the initial phase. The most common TEAEs were COVID-19 and upper respiratory tract infections. Serious AEs were rare and balanced between groups, with 1 death in each phase unrelated to the study drug. Immunogenicity assessments revealed low antidrug antibody (ADA) incidence and no neutralizing antibodies in either treatment phase.
Despite some limitations, such as assay sensitivity affecting ADA impact assessment and external disruptions impacting patient visits and dosing, the findings support CT-P41 as an effective and safe biosimilar to US-denosumab, paving the way for more affordable osteoporosis care.
