ECE2023 Poster Presentations Calcium and Bone (83 abstracts)
A Phase 1/2, Open-Label, Multiple Ascending Dose Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INZ-701 in Adults with ENPP1 Deficiency
Robert Wermers 1 , Rainard Fuhr 2 , Dirk Schnabel 3 , Terra Arnason 4 , Alix Bensacon 5 , Borut Cizman 6 , Deborah Wenkert 7 , Yves Sabbagh 6 & Kurt Gunter 6
1Mayo Clinic, Division of Medicine, Division of Endocrinology, Diabetes, Metabolism, and Nutrition and Department of Medicine, Rochester, United States; 2Parexel International GmbH, Early Phase Clinical Unit Berlin, Berlin, Germany; 3Charitè, Universitätsmedizin, Center for Chronic Sick Children, Pediatric Endocrinology, Berlin, Germany; 4University of Saskatchewan, Division of Endocrinology, Department of Medicine, Saskatoon, Canada; 5Hôpital Universitaire Necker Enfants Malades, Endocrino-diabetologie pediatrique, Paris, France; 6Inozyme Pharma, Boston, United States; 7Wenkert & Young, LLC (Former Employee, Inozyme Pharma), Thousand Oaks, United States
Background: ENPP1 Deficiency is a rare disorder due to inactivating mutations in the ENPP1 gene. It is characterized by low levels of inorganic pyrophosphate (PPi), a critical regulator of mineralization; subsequent pathologic soft tissue calcification results in ~50% infant mortality and life-long musculoskeletal and cardiovascular morbidities. No targeted therapy exists for this disease. INZ-701 is a recombinant ENPP1-Fc investigational product.
Purpose: To determine the safety, tolerability, immunogenicity, pharmacokinetics and pharmacodynamics of INZ-701 following subcutaneous administration in adults with ENPP1 Deficiency.
Methods: Phase 1/2, multicenter, open-label, multiple ascending dose study including three cohorts of three adults each, with genetic confirmation and PPi <1300 nM (NCT04686175). Following ethical committee approval, participants were dosed at Day 1, then twice weekly from Day 8 through Day 32.
Results: In the first patient cohort receiving 0.2 mg/kg INZ-701, INZ-701 was well-tolerated with no serious adverse events or injection site reactions. A rapid (≤ 6 hrs) ~4-fold increase in PPi was noted in all three participants. Mean PPi increased from 262 ± 114 nM (screening) to a mean sustained level through Day 32 of 1374 ± 457nM (in the normal range), representing a ~5-fold increase in PPi. Steady state was reached approximately by Day 29 with a ~4-fold accumulation from Day 1, based on AUC0-72hrs and showed good correlation with INZ-701 activity. The half-life of INZ-701 (~126 hrs) suggests the potential for once-weekly dosing. Participants from the first cohort have enrolled in an open label extension study.
Conclusions: At the lowest dose studied, INZ-701 demonstrated a rapid and sustained increase in PPi levels in all participants, was well tolerated, and exhibited a favorable safety profile with a potential for once weekly dosing. Results from cohorts two (0.6 mg/kg dose) and three (1.8 mg/kg dose) are anticipated in early 2023.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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