INZ-701 shows early promise in treating ENPP1 Deficiency in pediatric patients

Inozyme Pharma

Inozyme Pharma has announced interim results from its phase 3 ENERGY 3 trial evaluating INZ-701 in pediatric patients with ENPP1 deficiency, a rare genetic disorder that affects bone development and vascular health. According to the company’s Q1 2025 update, the study's findings show promising trends in safety, immunogenicity, and improvements in serum phosphate levels.^1,2

“The consistency we have observed across safety, immunogenicity, and increases in phosphate levels reinforces our conviction in INZ-701’s ability to address the underlying biology of ENPP1 Deficiency,” said Douglas A. Treco, PhD, CEO and chairman of Inozyme. “With no dropouts or dose modifications to date, the emerging profile in pediatric patients is highly encouraging.”¹

ENERGY 3 trial progressing without safety concerns

Enrollment in the ENERGY 3 trial was completed in January 2025, with dosing scheduled to conclude in early 2026. Currently, the trial has reported no discontinuations, dose adjustments, or pauses related to tolerability or adverse events. The Data Safety Monitoring Board has not identified any new safety signals.

INZ-701 is being studied as a potential first therapy for ENPP1 Deficiency, which can cause hypophosphatemia and result in rickets, osteomalacia, and other complications. The drug is designed to increase levels of serum phosphate and pyrophosphate (PPi), both of which are critical to bone health.

Preliminary immunogenicity data supports continued development

An evaluation of anti-drug antibodies (ADAs) among 17 of 19 patients who had received at least 13 weeks of INZ-701 treatment showed that 15 had either undetectable or low-titer responses. Two patients developed higher-titer responses, but still demonstrated potential clinical benefit with transient increases in PPi. “At this time, ADAs have not been associated with any impact on patient tolerability or adverse events,” the company stated.

Similar patterns were noted in other pediatric patients treated with INZ-701 in the ENERGY 1 trial and Expanded Access Program. In infants who developed high ADA titers, responses stabilized or declined over time, particularly after dosing adjustments. These findings suggest that longer treatment duration or more frequent dosing may help manage immunogenicity.

Serum phosphate levels rise with INZ-701 treatment

A key focus of the ENERGY 3 trial is whether INZ-701 can correct hypophosphatemia, a hallmark of ENPP1 Deficiency that contributes to rickets and other skeletal abnormalities. According to interim data:

• At Week 13, mean serum phosphate increased by 8.2% from baseline in the INZ-701 group (n = 17), while it declined by 0.04% in the conventional treatment group (n = 7).
• By Week 26, the mean change was +6.8% in the INZ-701 group (n = 11) versus -5.5% in the conventional group (n = 6).
• At Week 39, among the few patients with longer-term data, phosphate levels increased by 12.1% (n = 4) in the INZ-701 group, compared to a 9.0% decline in the conventional group (n = 2).

Six of the 17 INZ-701–treated patients reached normal phosphate levels at least once during the study. No patients in the control arm reached that threshold.

“These emerging data on serum phosphate levels suggest that INZ-701 may have a meaningful impact on the severity of rickets and other skeletal complications in children with ENPP1 Deficiency,” said Thomas Carpenter, MD, professor of Pediatrics and Orthopaedics at Yale School of Medicine, who is not involved in the trial. “The consistency of the safety profile and biomarker responses to date is encouraging and supports further clinical development.”

Topline data from the ENERGY 3 trial are expected in the first quarter of 2026.

Reference:

1. Inozyme Pharma Reports First Quarter 2025 Financial Results and Provides Business Highlights. Inozyme Pharma. May 14, 2025. Accessed May 14, 2025. https://investors.inozyme.com/news-releases/news-release-details/inozyme-pharma-reports-first-quarter-2025-financial-results-and

2. ENPP1 Deficiency. Inozyme Pharma. Accessed May 14, 2025. https://www.inozyme.com/patients-and-families/enpp1-deficiency/