Subcutaneous marzeptacog alfa (activated) for on-demand treatment of bleeding events in subjects with haemophilia A or B with inhibitors

Clin Pharmacol Ther. 2024 Jan 3. doi: 10.1002/cpt.3172. Online ahead of print.ABSTRACTMarzeptacog alfa (MarzAA) is under development for subcutaneous treatment of episodic bleeds in hemophilia A/B patients and was studied in a Phase 3 trial evaluating MarzAA compared to standard-of-care (SoC) for on-demand use. The work presented here aimed to evaluate MarzAA and SoC treatment of bleeding events on a standardized 4-point efficacy scale (poor, fair, good and excellent). Two continuous-time Markov modeling approaches were explored; a four-state model analyzing all four categories of bleeding improvement and a two-state model analyzing a binarized outcome (treatment failure [poor/fair], and treatment success [good/excellent]). Different covariates impacting improvement of bleeding episodes as well as a putative relationship between MarzAA exposure and improvement of bleeding episodes were evaluated. In the final four-state model, higher baseline diastolic blood pressure and higher age (>33 years of age) were found to negatively and positively impact improvement of bleeding condition, respectively. Bleeding events occurring in knees and ankles were found to improve faster than bleeding events at other locations. The covariate effects had most impact on early treatment success (=<3 hours) whereas at later timepoints (>12 hours), treatment success was similar for all patients indicating that these covariates might be clinically relevant for early treatment response. A stat...
Source: Clinical Pharmacology and Therapeutics - Category: Drugs & Pharmacology Authors: Source Type: research