Sandoz's denosumab biosimilar, marketed as Jubbonti and Wyost, has been confirmed to be clinically safe and effective, demonstrating equivalence to the reference denosumab products Prolia and Xgeva. This finding, based on a comprehensive review of analytical, pharmacokinetic (PK), pharmacodynamic (PD), and clinical data, supports the biosimilar's approval and its potential to expand access to crucial treatments for osteoporosis and bone metastases.
The review, published in Clinical Therapeutics, consolidates evidence that led to the FDA's approval of Jubbonti and Wyost in March 2024. Denosumab, a monoclonal antibody targeting RANKL, is a vital therapy for managing conditions like osteoporosis and metastatic bone disease by inhibiting osteoclast activity, reducing bone resorption, and preserving bone density. While the reference denosumab has proven effective in trials like FREEDOM and ADAMO, its high cost has limited patient access.
Analytical and Functional Equivalence
Comprehensive analytical characterization revealed a high degree of similarity between denosumab-bddz and the reference product. The biosimilar shared key quality attributes, including over 98% purity and lower levels of aggregates and antibody fragments. Structural and chemical properties such as molecular mass, amino acid sequence, glycation, and N-glycosylation patterns were highly comparable, with minor differences deemed clinically irrelevant. Functionally, denosumab-bddz displayed equivalent binding affinity to RANKL and consistent neutralizing activity.
Clinical Trial Results
A Phase 1 study in 502 healthy males demonstrated PK, PD, safety, and immunogenicity equivalence between the biosimilar and reference products. Furthermore, a Phase 3 study involving 527 postmenopausal women with osteoporosis confirmed similar efficacy, PK, PD, safety, and immunogenicity over a 52-week period. No adverse effects were observed when switching between the biosimilar and the reference product. Pharmacokinetic endpoints were within pre-specified equivalence margins.
Implications for Treatment
The authors of the review concluded that the evidence supports extrapolating the equivalence of denosumab-bddz to Xgeva in studied populations to other indicated populations. This has the potential to lower development costs, reduce the number of clinical trials needed, and expedite the time to regulatory approval. Given the current evidence, denosumab-bddz is anticipated to be easily incorporated into the current treatment pathway, offering a more affordable alternative without compromising efficacy or safety.
