MB09, a denosumab biosimilar candidate: Biosimilarity demonstration in a phase I study in healthy subjects
Abstract This was a Phase I, randomized, double‐blinded, three‐arm, single‐dose, parallel study aimed to demonstrate pharmacokinetic (PK) similarity between MB09 (a denosumab biosimilar candidate) and reference denosumab (XGEVA® from European Union [EU‐reference] and United States [US‐reference]) in...
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| Format: | Article |
| Language: | English |
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Wiley
2024-09-01
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| Series: | Clinical and Translational Science |
| Online Access: | https://doi.org/10.1111/cts.70013 |
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| author | Monika Tomaszewska‐Kiecana Elisabete Carapuça Amalia Florez‐Igual Javier Queiruga‐Parada |
| author_facet | Monika Tomaszewska‐Kiecana Elisabete Carapuça Amalia Florez‐Igual Javier Queiruga‐Parada |
| author_sort | Monika Tomaszewska‐Kiecana |
| collection | DOAJ |
| description | Abstract This was a Phase I, randomized, double‐blinded, three‐arm, single‐dose, parallel study aimed to demonstrate pharmacokinetic (PK) similarity between MB09 (a denosumab biosimilar candidate) and reference denosumab (XGEVA® from European Union [EU‐reference] and United States [US‐reference]) in a healthy male population. The primary PK endpoints included: Area under the serum concentration versus time curve from time 0 to the last quantifiable concentration timepoint (AUC0–last); and maximum observed serum concentration (Cmax). Secondary endpoints included: AUC from time 0 extrapolated to infinity (AUC0–∞), time to reach maximum observed concentration, clearance, terminal phase half‐life, pharmacodynamic, safety, and immunogenicity assessments. A total of 255 subjects were randomized (1:1:1) to receive a subcutaneous 35 mg dose of MB09 or reference denosumab. Cmax was reached after denosumab administration, followed by a decline in the concentration with similar terminal phase half‐live across treatment arms. Systemic exposure of MB09 (AUC0–last and Cmax) was equivalent to the reference denosumab, as the 90% confidence intervals around the geometric least square mean ratios laid within the predefined acceptance limits (80.00%, 125.00%) across all comparisons. Pharmacodynamic parameters, based on the percent of change from baseline in serum C‐terminal telopeptide of Type 1 collagen levels, were similar across the three arms. The treatments were considered safe and generally well tolerated, with 92 treatment‐emergent adverse events reported (most Grade 2 and 3) and similarly distributed. Immunogenicity was low and similarly distributed. These results provide strong evidence that supports the biosimilarity between MB09 and denosumab reference products. |
| format | Article |
| id | doaj-art-57c1e8cb07884d4692bbf9f7180b3eae |
| institution | OA Journals |
| issn | 1752-8054 1752-8062 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Science |
| spelling | doaj-art-57c1e8cb07884d4692bbf9f7180b3eae2025-08-20T01:55:12ZengWileyClinical and Translational Science1752-80541752-80622024-09-01179n/an/a10.1111/cts.70013MB09, a denosumab biosimilar candidate: Biosimilarity demonstration in a phase I study in healthy subjectsMonika Tomaszewska‐Kiecana0Elisabete Carapuça1Amalia Florez‐Igual2Javier Queiruga‐Parada3Biokinetica S.A. Józefów PolandMedical Department mAbxience Research S.L.U. Madrid SpainMedical Department mAbxience Research S.L.U. Madrid SpainMedical Department mAbxience Research S.L.U. Madrid SpainAbstract This was a Phase I, randomized, double‐blinded, three‐arm, single‐dose, parallel study aimed to demonstrate pharmacokinetic (PK) similarity between MB09 (a denosumab biosimilar candidate) and reference denosumab (XGEVA® from European Union [EU‐reference] and United States [US‐reference]) in a healthy male population. The primary PK endpoints included: Area under the serum concentration versus time curve from time 0 to the last quantifiable concentration timepoint (AUC0–last); and maximum observed serum concentration (Cmax). Secondary endpoints included: AUC from time 0 extrapolated to infinity (AUC0–∞), time to reach maximum observed concentration, clearance, terminal phase half‐life, pharmacodynamic, safety, and immunogenicity assessments. A total of 255 subjects were randomized (1:1:1) to receive a subcutaneous 35 mg dose of MB09 or reference denosumab. Cmax was reached after denosumab administration, followed by a decline in the concentration with similar terminal phase half‐live across treatment arms. Systemic exposure of MB09 (AUC0–last and Cmax) was equivalent to the reference denosumab, as the 90% confidence intervals around the geometric least square mean ratios laid within the predefined acceptance limits (80.00%, 125.00%) across all comparisons. Pharmacodynamic parameters, based on the percent of change from baseline in serum C‐terminal telopeptide of Type 1 collagen levels, were similar across the three arms. The treatments were considered safe and generally well tolerated, with 92 treatment‐emergent adverse events reported (most Grade 2 and 3) and similarly distributed. Immunogenicity was low and similarly distributed. These results provide strong evidence that supports the biosimilarity between MB09 and denosumab reference products.https://doi.org/10.1111/cts.70013 |
| spellingShingle | Monika Tomaszewska‐Kiecana Elisabete Carapuça Amalia Florez‐Igual Javier Queiruga‐Parada MB09, a denosumab biosimilar candidate: Biosimilarity demonstration in a phase I study in healthy subjects Clinical and Translational Science |
| title | MB09, a denosumab biosimilar candidate: Biosimilarity demonstration in a phase I study in healthy subjects |
| title_full | MB09, a denosumab biosimilar candidate: Biosimilarity demonstration in a phase I study in healthy subjects |
| title_fullStr | MB09, a denosumab biosimilar candidate: Biosimilarity demonstration in a phase I study in healthy subjects |
| title_full_unstemmed | MB09, a denosumab biosimilar candidate: Biosimilarity demonstration in a phase I study in healthy subjects |
| title_short | MB09, a denosumab biosimilar candidate: Biosimilarity demonstration in a phase I study in healthy subjects |
| title_sort | mb09 a denosumab biosimilar candidate biosimilarity demonstration in a phase i study in healthy subjects |
| url | https://doi.org/10.1111/cts.70013 |
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