- Positive interim results in infants and young children with ENPP1 Deficiency showed improvements from baseline in multiple measures of disease, including survival, heart function, and stabilization or reduction in ectopic calcification and hypophosphatemia, with no radiographic evidence of rickets –
- Enrollment complete in ENERGY 3 pivotal trial in pediatric patients with ENPP1 Deficiency; on track to complete dosing in January 2026, with topline data to follow in early 2026 –
- Regulatory guidance from FDA and EMA supports planned ASPIRE pivotal trial focused on addressing severe complications of ABCC6 Deficiency in children –
Jan. 10, 2025 -- Inozyme Pharma, Inc. (Nasdaq: INZY) (“the Company” or “Inozyme”), a clinical-stage biopharmaceutical company developing innovative therapeutics for rare diseases that affect bone health and blood vessel function, today 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, completion of enrollment in the ENERGY 3 pivotal trial in pediatric patients with ENPP1 Deficiency and regulatory guidance for the ASPIRE pivotal trial in children with ABCC6 Deficiency.
“We believe these highly encouraging outcomes in infants and young children, combined with previously reported data from adult studies, provide strong support for the potential impact of INZ-701 on rickets, a key clinical endpoint in the ongoing pivotal ENERGY 3 trial, and underscore its potential to address the significant needs of pediatric patients,” said Douglas A. Treco, Ph.D., CEO and Chairman of Inozyme Pharma.
Matt Winton, Ph.D., Senior Vice President and COO of Inozyme Pharma added, “Our team and global collaborators worked tirelessly to identify and diagnose these rare patients and initiate treatment as quickly as possible. Tragically, in some cases, we have been unable to begin treatment before the infant passed. This only deepens our commitment to the patient community and strengthens our resolve to address unmet needs across all populations as we advance INZ-701.”
Interim data from the ENERGY 1 trial (three infants) and the EAP (two infants and one child -2.5 years old) evaluated patients with generalized arterial calcification of infancy (GACI), a severe manifestation of ENPP1 Deficiency. Patients were treated with INZ-701 for periods of three weeks to 22 months. The data presentation can be accessed here on Inozyme’s Investor Relations site. Key results include:
Improved Survival: 80% of infants treated with INZ-701 survived beyond their first year, compared to a historical survival rate of approximately 50%.
Reduction in Arterial Calcifications: Substantial reductions or stabilization of arterial calcifications were observed in all surviving patients, including complete resolution in some instances. There was no evidence of progression of arterial calcification in any patient.
Improved Heart Function: Stabilization or improvement in left ventricular ejection fraction (LVEF) was noted in all surviving patients.
Reduced Risk of Rickets: No radiographic evidence of rickets 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.
Favorable Safety Profile: 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. Across studies to-date low, often transient, anti-drug antibody (ADA) levels were noted in some children and adults, with no impact on pharmacokinetics (PK) or pharmacodynamics (PD). In the ENERGY 1 trial and EAP, higher ADA levels in some infants significantly affected PK and PD. In infants with high ADA levels, data collected pre- and post-dosing demonstrated substantial transient increases in PPi and drug exposure following INZ-701 administration, consistent with the clinical effects observed. ADAs were not associated with adverse events in any patient.
The Company today announced completion of enrollment in its ENERGY 3 pivotal trial of INZ-701 in patients with ENPP1 Deficiency aged >1 to
With 25 patients enrolled, the trial’s 2:1 randomized design provides >90% power to detect meaningful differences in RGI-C between treatment and control groups. Strong patient interest and scheduled screenings may result in the enrollment of additional participants in January 2025. Inozyme anticipates completing the one-year dosing period for all patients by January 2026, with topline data expected in early 2026.
Regulatory Progress for ASPIRE Pivotal Trial in Children with ABCC6 Deficiency: Preliminary Support from U.S. and EU Regulators
Inozyme is advancing the development of INZ-701 in ABCC6 Deficiency. In April 2024, the Company reported topline data from an open-label, dose-escalation study in adults, along with findings from a natural history study documenting the significant disease burden in patients with the early-onset form of the disease, known as GACI Type 2 (GACI-2). The adult study demonstrated positive improvements in vascular and retinal pathology after 48 weeks of treatment with INZ-701, as well as normalization of PPi levels at the highest dose tested, supporting further development in additional age groups. The natural history study revealed a high disease burden characterized by childhood strokes, arteriopathy, cardiovascular complications, and early mortality. Further research has identified a substantial pediatric population with ABCC6 Deficiency, underscoring the significant unmet medical need in this group.
The natural history study data, supplemented by literature reports, has informed the design of the Company’s 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 from U.S. and EU regulators. The trial is expected to enroll approximately 70 patients from infancy up to
The Company plans to continue regulatory engagement over the coming months to finalize the trial protocol. Pending ongoing regulatory review and the availability of financial resources, Inozyme aims to initiate the ASPIRE trial in early 2026.
ENPP1 Deficiency is a serious and progressive rare disease that affects blood vessels, soft tissues, and bones. Individuals who present in utero or in infancy are typically diagnosed with generalized arterial calcification of infancy (GACI Type 1), with about 50% of these infants not surviving beyond six months. Children with this condition typically develop rickets, specifically autosomal-recessive hypophosphatemic rickets type 2 (ARHR2), while adolescents and adults may develop osteomalacia, or softened bones. ARHR2 and osteomalacia cause pain and difficulty with movement. Additionally, patients may experience hearing loss, calcification in arteries and joints, and heart problems. Biallelic ENPP1 Deficiency affects approximately 1 in 64,000 pregnancies worldwide. Initially, it was believed to only impact individuals with two copies of the mutated gene. However, many individuals with just one copy of the mutated gene (monoallelic ENPP1 Deficiency) also exhibit severe symptoms. This suggests that the worldwide prevalence of ENPP1 Deficiency may be much higher than current estimates, which are based solely on biallelic cases. Currently, there are no approved therapies for ENPP1 Deficiency.
ABCC6 Deficiency is a progressive and debilitating rare disease that affects blood vessels and soft tissues. Infants with ABCC6 Deficiency are diagnosed with generalized arterial calcification of infancy (GACI Type 2), which is similar to GACI Type 1, the infant form of ENPP1 Deficiency. Pediatric patients who survive beyond the first year of life may develop neurological disease, including strokes, and cardiovascular diseases due to ongoing vascular calcification and stenosis. In older individuals, ABCC6 Deficiency manifests as pseudoxanthoma elasticum (PXE), characterized by abnormal mineralization in blood vessels and soft tissues, affecting the skin, visual function, and vascular system. Biallelic ABCC6 Deficiency is estimated to affect 1 in 25,000 to 1 in 50,000 individuals worldwide. Initially, it was believed to only impact individuals with two copies of the mutated gene. However, many people with just one copy of the mutated gene (monoallelic ABCC6 Deficiency) also exhibit severe symptoms. This suggests that the worldwide prevalence of ABCC6 Deficiency may be much higher than current estimates, which are based solely on biallelic cases. Currently, there are no approved therapies for ABCC6 Deficiency.
Inozyme Pharma is a pioneering clinical-stage biopharmaceutical company dedicated to developing innovative therapeutics for rare diseases that affect bone health and blood vessel function. We are experts in the PPi-Adenosine Pathway, where the ENPP1 enzyme generates inorganic pyrophosphate (PPi), which regulates mineralization, and adenosine, which controls intimal proliferation (the overgrowth of smooth muscle cells inside blood vessels). Disruptions in this pathway impact the levels of these molecules, leading to severe musculoskeletal, cardiovascular, and neurological conditions, including ENPP1 Deficiency, ABCC6 Deficiency, calciphylaxis, and ossification of the posterior longitudinal ligament (OPLL).
Our lead candidate, INZ-701, is an ENPP1 Fc fusion protein enzyme replacement therapy (ERT) designed to increase PPi and adenosine, enabling the potential treatment of multiple diseases caused by deficiencies in these molecules. It is currently in clinical development for the treatment of ENPP1 Deficiency, ABCC6 Deficiency, and calciphylaxis. By targeting the PPi-Adenosine Pathway, INZ-701 aims to correct pathological mineralization and intimal proliferation, addressing the significant morbidity and mortality in these devastating diseases.
The content above comes from the network. if any infringement, please contact us to modify.
