Inozyme's INZ-701 Shows Promise in ENPP1 and ABCC6 Deficiencies
Key Insights
Inozyme Pharma's INZ-701 demonstrated improved survival rates in infants with ENPP1 Deficiency (search), with 80% surviving beyond one year compared to a historical 50%.
The ENERGY 3 pivotal trial of INZ-701 in pediatric patients with ENPP1 Deficiency (search) has completed enrollment, with topline data expected in early 2026.
Preliminary regulatory support has been received for the ASPIRE pivotal trial of INZ-701 in children with ABCC6 Deficiency (search), targeting major adverse clinical events.
Inozyme Pharma has announced positive interim data from its ENERGY 1 trial and Expanded Access Program (EAP) evaluating INZ-701 in infants and young children with ENPP1 Deficiency (search). The company also reported the completion of enrollment in the ENERGY 3 pivotal trial in pediatric patients with ENPP1 Deficiency and provided updates on regulatory guidance for the ASPIRE pivotal trial in children with ABCC6 Deficiency (search).
Significant Improvements in ENPP1 Deficiency with INZ-701
Interim data from the ENERGY 1 trial and EAP showcased notable improvements in infants treated with INZ-701. Survival rates increased to 80% beyond the first year, a significant improvement compared to the historical survival rate of approximately 50%. Furthermore, substantial reductions or stabilization of arterial calcifications were observed in all surviving patients, with complete resolution in some instances. There was no evidence of progression of arterial calcification in any patient.
Improvements in heart function were also noted, with stabilization or improvement in left ventricular ejection fraction (LVEF) in all surviving patients. Additionally, no radiographic evidence of rickets (search) was observed in patients evaluated beyond one year of age and at-risk of rickets development (n=3), supported by stabilization or increases in serum phosphate levels.
INZ-701 was well-tolerated, with no serious treatment-related adverse events in infants and young children. Observed treatment-related events were limited to mild injection site reactions. While some children and adults showed low, often transient, anti-drug antibody (ADA) levels, these did not impact pharmacokinetics (PK) or pharmacodynamics (PD) in most cases. In infants with high ADA levels in the ENERGY 1 trial and EAP, data collected pre- and post-dosing demonstrated substantial transient increases in PPi (search) and drug exposure following INZ-701 administration, consistent with the clinical effects observed. ADAs were not associated with adverse events in any patient.
ENERGY 3 Pivotal Trial Enrollment Complete
Enrollment is now complete in the ENERGY 3 pivotal trial of INZ-701 in patients with ENPP1 Deficiency (search) aged >1 to <13 years. The trial has enrolled 25 patients in a 2:1 randomized design, providing >90% power to detect meaningful differences in radiographic global impression of change (RGI-C) between treatment and control groups. Topline data is expected in early 2026.
Regulatory Progress for ASPIRE Trial in ABCC6 Deficiency
Inozyme is also advancing the development of INZ-701 in ABCC6 Deficiency (search). Preliminary support from U.S. and EU regulators has been received for the planned randomized, controlled ASPIRE trial of INZ-701 in children with ABCC6 Deficiency. The proposed primary endpoint, comprising major adverse clinical events over a two-year treatment period, has been reviewed and received preliminary support. The trial is expected to enroll approximately 70 patients from infancy up to <18 years old with biallelic or monoallelic ABCC6 Deficiency. Inozyme aims to initiate the ASPIRE trial in early 2026, pending ongoing regulatory review and the availability of financial resources.
About ENPP1 and ABCC6 Deficiencies
ENPP1 Deficiency (search) is a serious and progressive rare disease affecting blood vessels, soft tissues, and bones. Infants often present with generalized arterial calcification of infancy (search) (GACI Type 1), with approximately 50% not surviving beyond six months. Children may develop rickets (search), while adolescents and adults may develop osteomalacia (search). Biallelic ENPP1 Deficiency affects approximately 1 in 64,000 pregnancies worldwide.
ABCC6 Deficiency (search) is another progressive and debilitating rare disease affecting blood vessels and soft tissues. Infants may be diagnosed with generalized arterial calcification of infancy (search) (GACI Type 2). Older individuals may develop pseudoxanthoma elasticum (search) (PXE). Biallelic ABCC6 Deficiency is estimated to affect 1 in 25,000 to 1 in 50,000 individuals worldwide.
Currently, there are no approved therapies for either ENPP1 or ABCC6 Deficiency (search), highlighting the significant unmet medical need.
Inozyme's Approach
Inozyme Pharma is focused on developing innovative therapeutics for rare diseases affecting bone health and blood vessel function. Their lead candidate, INZ-701, is an ENPP1 Fc fusion protein enzyme replacement therapy (ERT) designed to increase PPi (search) and adenosine, potentially treating multiple diseases caused by deficiencies in these molecules.