Equivalence Confirmed: CT-P41 Paves the Way for Affordable Osteoporosis Care

CT-P41 was shown to be equivalent to US reference denosumab in efficacy, pharmacodynamics (PDs), pharmacokinetics (PKs), safety, and immunogenicity in patients with postmenopausal osteoporosis in a 78-week phase 3 trial.1

This study (NCT04757376), published in Osteoporosis International, was conducted to evaluate the equivalence of the biosimilar CT-P41 to US reference denosumab (Prolia/Xgeva) in treating postmenopausal osteoporosis, aiming to address treatment accessibility and reduce health care costs while maintaining efficacy, safety, and pharmacodynamic outcomes.

Between 2017 and 2018, osteoporosis prevalence among adults aged 50 and older was 12.6%, according to the National Center for Health Statistics.2 Throughout the 2010s, osteoporosis prevalence increased among women but remained stable for men, whereas low bone mass prevalence showed no significant change for either gender.

Osteoporosis not only significantly affects patient health, independence, and quality of life but also places a substantial economic burden on health care systems, particularly due to fracture treatment.1 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 alleviate the financial burden on health care systems and improve equitable access to treatment. In March 2024, the FDA approved the first denosumab biosimilars, Sandoz’ Wyost and Jubbonti (denosumab-bddz), both of which are awaiting market entry.3

The present study was a double-blind, randomized, active-controlled phase 3 clinical trial conducted at 20 sites across 4 countries to evaluate the efficacy and safety of CT-P41 compared with US-sourced denosumab. It included 440 postmenopausal women aged 50 to 80 years with osteoporosis. Participants underwent a 28-day screening period, followed by 2 treatment periods over 78 weeks and an end-of-study visit.

Patients were initially randomized 1:1 to receive either CT-P41 or US-denosumab (60 mg subcutaneous injection at weeks 0, 26, and 52). In the second treatment period, patients on US-denosumab were further randomized to either continue the treatment or switch to CT-P41.

Primary efficacy was measured as the percent change in lumbar spine bone mineral density (BMD) at week 52. Secondary end points included changes in BMD at other skeletal sites, fracture incidences, quality-of-life assessments, PKs, PDs, safety monitoring, and immunogenicity.

A total of 1238 patients were screened, with 479 randomized into 2 groups: CT-P41 (n = 240) and US-denosumab (n = 239). After correcting for eligibility errors, 239 and 238 patients initiated treatment, respectively. At week 52, 422 patients entered the maintenance phase, where patients receiving CT-P41 continued with CT-P41 (n = 221), while those on US-denosumab were re-randomized to either continue US-denosumab (n = 100) or switch to CT-P41 (n = 101). Discontinuation rates were higher in the US-denosumab group during the initial phase (15.5% vs. 7.5%), mostly due to patient withdrawal, but completion rates in the maintenance phase exceeded 97% across all groups.

Efficacy outcomes demonstrated equivalence between CT-P41 and US-denosumab for lumbar spine BMD at week 52, with changes in total hip and femoral neck BMD also comparable. 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, including serum denosumab concentrations and half-life, 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.

Limitations of the study included assay sensitivity affecting ADA impact assessment, smaller sample sizes in certain groups, and external disruptions impacting patient visits and dosing. Overall, the findings support CT-P41 as an effective and safe biosimilar to US-denosumab.

References

1. Reginster J-Y. Czerwinski E, Wilk K, et al. 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;35(11):1919-1930. doi:10.1007/s00198-024-07161-x

2. Sarafrazi N, Wambogo EA, Shepherd JA. Osteoporosis or low bone mass in older adults: United States, 2017–2018. CDC’s National Center for Health Statistics. March 2021. Accessed January 6, 2025. https://www.cdc.gov/nchs/products/databriefs/db405.htm#print

3. Jeremias S. FDA approves first denosumab biosimilars. The Center for Biosimilars®. March 5, 2024. Accessed January 7, 2025. https://www.centerforbiosimilars.com/view/fda-approves-first-denosumab-biosimilar