Inozyme Pharma Reports Positive Interim Data for INZ-701 in Young ENPP1 Deficiency Patients and Program Updates

Inozyme Pharma, a clinical-stage biopharmaceutical company, has reported promising interim results from its ENERGY 1 trial and Expanded Access Program (EAP) for infants and young children suffering from ENPP1 Deficiency. This rare genetic disorder significantly impacts bone health and blood vessel function. The aim of Inozyme’s treatment, INZ-701, is to improve disease markers such as survival rates, heart function, and the stabilization of ectopic calcification and hypophosphatemia, without any signs of rickets.

The ENERGY 1 trial, focusing on infants with generalized arterial calcification of infancy (GACI), a severe form of ENPP1 Deficiency, demonstrated encouraging results. Patients treated with INZ-701 showed improved survival, with 80% living beyond their first year, as opposed to the historical survival rate of around 50%. Additionally, there was a notable reduction or stabilization of arterial calcifications in all surviving patients, with some experiencing complete resolution. Improved heart function was also observed, particularly in the stabilization or enhancement of the left ventricular ejection fraction.

The data also highlighted a decreased risk of rickets among patients, with no radiographic evidence of the condition in those evaluated beyond one year. This was supported by stable or increased serum phosphate levels. Moreover, INZ-701 was well-tolerated, presenting mainly mild injection site reactions without any serious adverse events related to the treatment. Some children and adults exhibited low levels of anti-drug antibodies (ADAs) with no effect on drug pharmacokinetics or pharmacodynamics, although higher ADA levels in infants did influence these parameters to some extent.

Enrollment for the ENERGY 3 pivotal trial, aimed at evaluating INZ-701 in children over one year old with ENPP1 Deficiency, has been completed. The trial involves 25 participants in a 2:1 randomized design, with more than 90% power to detect significant differences between the treatment and control groups. All patients are expected to finish the one-year dosing period by January 2026, with top-line results anticipated shortly afterward.

In parallel, Inozyme is preparing for the ASPIRE pivotal trial in children with ABCC6 Deficiency. This condition, similar to ENPP1 Deficiency, affects the vascular and soft tissue systems and can lead to severe complications. Preliminary data from adult studies have shown positive outcomes, including improvements in vascular and retinal health and normalization of PPi levels, paving the way for further development.

The ASPIRE trial, supported by regulatory guidance from both the FDA and EMA, is set to address significant unmet medical needs in pediatric patients. The planned trial will focus on major adverse clinical events over a two-year period and involve approximately 70 young patients. Inozyme aims to initiate this pivotal trial in early 2026, contingent on regulatory approvals and financial resources.

ENPP1 Deficiency manifests as GACI Type 1 in infants, leading to severe complications such as rickets and osteomalacia, impacting mobility and leading to pain. The condition's prevalence is estimated at 1 in 64,000 pregnancies, but monoallelic cases may suggest wider occurrence than current figures indicate. Similarly, ABCC6 Deficiency, which manifests as GACI Type 2 in infants and pseudoxanthoma elasticum (PXE) in older individuals, affects blood vessel and soft tissue mineralization. Prevalence is estimated between 1 in 25,000 and 1 in 50,000 individuals, but monoallelic cases could reveal higher actual prevalence.

Inozyme Pharma’s commitment to addressing these rare diseases is underscored by its focus on the PPi-Adenosine Pathway, which is crucial in regulating mineralization and blood vessel health. INZ-701, the company's lead candidate, is being developed to potentially treat ENPP1 Deficiency, ABCC6 Deficiency, and other related conditions by targeting this pathway to correct pathological processes.