Data Further Confirm Proposed Denosumab Biosimilar Shows Similar Efficacy to Originator

Key Takeaways

CT-P41 demonstrated equivalence to denosumab in efficacy, pharmacodynamics, pharmacokinetics, and safety in postmenopausal women with osteoporosis.
The study design included a double-blind, randomized, active-controlled approach with four distinct periods, ensuring robust data collection.
Participants aged 50-80 were included, with exclusions for prior biologic treatments, ensuring a focused study population.
No significant safety issues were identified during the transition from denosumab to the biosimilar, supporting its safety profile.

Investigators presented additional data from a clinical trial at the American College of Rheumatology Convergence, demonstrating similar safety for postmenopausal women with osteoporosis.

Additional data from a phase 3 trial investigating CT-P41 (Celltrion), a biosimilar candidate for denosumab (Prolia, Xgeva; Amgen) for postmenopausal women with osteoporosis (PMO), included data from the week 52 to week 78 expansion.¹

Osteoporosis, Biosimilar, Denosumab | Image Credit: © eddows | stock.adobe.com

In the phase 3 study (NCT04757376), investigators used a double-blind, randomized, active-controlled design that compared the drug with the reference product for PMO. There were 4 study periods: an initial 28-day screening period, treatment period 1 (week 0 to week 52), treatment period 2 (week 52 to week 78), and end-of-study visit at week 78. On the first day of the first treatment period, patients were assigned to received CT-P41 or denosumab and then went through a second randomization to maintain blinding before the first day of the second treatment period.²

Individuals included were aged 50 to 80 years but were excluded if they were previously treated with denosumab, a biosimilar, or other biologics for osteoporosis; received intravenous bisphosphonates, fluoride, or strontium; or received oral bisphosphonates, according to the study authors. The primary efficacy end point included the percent change from baseline in lumbar spine at week 52, and secondary end points included percent change from baseline in bone mineral density (BMD) for lumbar spine, total hip, and femoral neck at weeks 26, 52, and 78; incidences of new vertebral, non-vertebral, and hip fractures; and change from baseline in health-related quality of life at weeks 26, 52, and 78.²

About The Study

Trial: A Phase 3 Study to Compare Between CT-P41 and US-licensed Prolia in Postmenopausal Women With Osteoporosis

ClinicalTrials.gov ID: NCT04757376

Sponsor: Celltrion

Completion Date: November 2023

There were 239 individuals who started treatment with the biosimilar and 238 patients in the denosumab group. Furthermore, 422 patients continued onto the second treatment period, with 221 patients who received the biosimilar in treatment period 1 continuing on the biosimilar and 201 individuals who received the reference product randomized to continue on the reference product (n = 100) or switch to the biosimilar (n = 101). Investigators reported that the equivalence was demonstrated for the biosimilar in comparison with the reference product for efficacy, and secondary efficacy, pharmacodynamics, pharmacokinetics, and safety were also comparable.²

The new analysis included switching data from the reference product to the biosimilar, demonstrating comparability and sustained efficacy results to the reference product, according to the investigators. Further, the biosimilar was well tolerated and had a comparable safety profile compared to the reference product, with no notable safety issues being identified following the transition compared with the maintenance group. The investigators also said the data showed the impact of anti-drug antibody on pharmacokinetics, efficacy, safety, and treatment-emergence adverse events and were comparable between both treatment groups.¹

REFERENCES

1. Celltrion presents additional data from phase III randomized controlled trials to further support biosimilarity for CT-41 (biosimilar candidate of denosumab) and CT-P47 (biosimilar candidate of tocilizumab) at American College of Rheumatology (ACR) Convergence 2024. News release. Celltrion. November 18, 2024. Accessed November 21, 2024. https://www.prnewswire.com/news-releases/celltrion-presents-additional-data-from-phase-iii-randomized-controlled-trials-to-further-support-biosimilarity-for-ct-41-biosimilar-candidate-of-denosumab-and-ct-p47-biosimilar-candidate-of-tocilizumab-at-american-college-of--302308791.html

2. Reginster JY, 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