Safety, pharmacokinetics, and pharmacodynamics of efzimfotase alfa, a second-generation enzyme replacement therapy: phase 1, dose-escalation study in adults with hypophosphatasia.

ABSTRACT: Hypophosphatasia (HPP) is a rare, inherited metabolic disease caused by deficient activity of tissue-nonspecific alkaline phosphatase (TNSALP). Efzimfotase alfa (ALXN1850) is a second-generation TNSALP enzyme replacement therapy in development for HPP. This first-in-human open-label, dose-escalating phase 1 trial evaluated efzimfotase alfa safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity. Fifteen adults (5/cohort) with HPP received efzimfotase alfa in doses of 15 mg (cohort 1), 45 mg (cohort 2), or 90 mg (cohort 3) as one intravenous (i.v.) dose followed by 3 weekly subcutaneous (s.c.) doses. The primary objective was to assess safety and tolerability. Secondary objectives included pharmacokinetics, pharmacodynamics of ALP substrates known to be biomarkers of di

SUBMITTER: Dahir KM 

PROVIDER: S-EPMC11425692 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature