Inozyme Reports Positive Topline Data from Ongoing Phase 1/2 Trials of Therapy for Rare Mineralization Disorders
February 17, 2023
Rare Daily Staff
Inozyme Pharma reported positive, topline pharmacokinetic, pharmacodynamic, and safety data from the ongoing phase 1/2 clinical trials of its experimental therapy INZ-701 in ENPP1 deficiency and ABCC6 deficiency, two rare mineralization disorders.
ENPP1 deficiency is a progressive condition that manifests as a spectrum of diseases. Individuals who present in utero or in infancy are typically diagnosed with generalized arterial calcification of infancy (GACI), which is characterized by extensive vascular calcification and intimal proliferation (overgrowth of smooth muscle cells inside blood vessels), resulting in myocardial infarction, stroke, or cardiac or multiorgan failure. Approximately 50 percent of infants with ENPP1 deficiency die within six months of birth. Children with ENPP1 deficiency typically experience rickets, a condition also known as autosomal-recessive hypophosphatemic rickets type 2 (ARHR2), while adults experience osteomalacia (softened bones), and they can exhibit a range of signs and symptoms that include hearing loss, arterial calcification, and cardiac and/or neurological involvement. There are no approved therapies for ENPP1 deficiency.
ABCC6 deficiency is a rare, severe, inherited disorder caused by mutations in the ABCC6 gene, leading to low levels of PPi. PPi is essential for preventing harmful soft tissue calcification and regulating bone mineralization. ABCC6 deficiency is a systemic and progressively debilitating condition, which affects more than 67,000 individuals worldwide. Infants with ABCC6 deficiency are diagnosed with generalized arterial calcification of infancy (GACI) type 2, a condition that resembles GACI type 1, the infant form of ENPP1 deficiency. In older individuals, ABCC6 deficiency presents as pseudoxanthoma elasticum, which is characterized by pathological mineralization in blood vessels and soft tissues clinically affecting the skin, eyes, and vascular system. There are no approved therapies for ABCC6 deficiency.
The topline data today demonstrated that INZ-701 rapidly restored PPi to normal levels in all dose cohorts in the ENPP1 deficiency trial, with normal PPi levels sustained during the trial. Additionally, emerging patient-reported outcome data, as measured by GIC, showed six of eight patients reported concordant improvements in overall health compared to baseline on clinician-GIC and patient-GIC.
The ABCC6 deficiency trial showed pharmacodynamic activity in all dose cohorts and sustained PPi levels in the highest dose cohort.
“Data reported today are highly encouraging and show that INZ-701 significantly increased PPi levels into normal physiological ranges with a favorable safety profile,” said Michael Levine, professor emeritus of pediatrics and medicine and chief emeritus of the Division of Endocrinology and Diabetes at the Center for Bone Health at the Children’s Hospital of Philadelphia Research Institute. “The data presented today represent strong evidence to warrant continued clinical development of INZ-701 in ENPP1 deficiency and ABCC6 deficiency.”
Photo: Michael Levine, professor emeritus of pediatrics and medicine and chief emeritus of the Division of Endocrinology and Diabetes at the Center for Bone Health at the Children’s Hospital of Philadelphia Research Institute
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