Investigative Treatment for ENPP1 Deficiency Has Moved to Phase 1/2 Clinical Trial

Inozyme Pharma has recently announced that the first patient was dosed in its Phase 1/2 clinical trial of INZ-701 in adult patients with ABCC6 Deficiency and the second cohort in the ongoing Phase 1/2 clinical trial in ENPP1 Deficiency has been fully enrolled.

Preclinical data with this treatment has demonstrated that inorganic pyrophosphate, or PPi, levels are a predictive biomarker of how therapeutic a treatment is. Inozyme recently reported positive preliminary biomarker, safety, and pharmacokinetic (PK) data from the first three patients (cohort 1) treated in the Phase 1 portion of its ongoing first-in-human Phase 1/2 clinical trial of INZ-701 in adult patients with ENPP1 Deficiency. At the 0.2 mg/kg dose level of INZ-701, all three patients showed rapid, significant, and sustained increases in PPi levels.

ENPP1 Deficiency

ENPPi deficiency is a rare and progressive condition. Some present with the condition in infancy, and others aren’t diagnosed until they are children or adults.

For those diagnosed either in utero or in infancy, a diagnosis of generalized arterial calcification of infancy (GACI) is typically provided. GACI patients have vascular calcification as well as an overgrowth of the smooth muscle cells within the blood vessels. Infants can face stroke, myocardial infarction, cardiac failure, and multi organ failure. GACI leads to death for 45% to 50% of infants within six months of birth.

Children as well as adults with the condition face osteomalacia, rickets, arterial calcification, hearing loss, and more. There is often neurological and cardiac involvement.

ABCC6 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 is believed to affect more than 67,000 individuals worldwide. The condition is characterized by pathological mineralization in blood vessels and soft tissues clinically affecting the skin, eyes, and cardiovascular system that can drive devastating medical problems.

Some infants with ABCC6 Deficiency are diagnosed with generalized arterial calcification of infancy (GACI) type 2, a vascular condition that resembles GACI type 1, the acute infantile form of ENPP1 Deficiency. In older patients, ABCC6 Deficiency presents as pseudoxanthoma elasticum (PXE), a rare, inherited disorder in which individuals develop calcification of soft connective tissues, including in the eyes, cardiovascular system, and skin.

There have yet to be any approved treatments for ENPPI Deficiency or ABCC6 Deficiency in infants, children, or adults.


INZ-701 is a type of enzyme replacement therapy which has demonstrated an ability to generate PPi. INZ-701 has also shown potential to restore PPi to its normal levels and ultimately, prevent calcification within the kidneys and normalize mineralization in the bone.

This treatment is also being developed for other genetic conditions such as ABCC6 Deficiency.

INZ-701 in ENPP1 Deficiency Phase 1/2 Clinical Trial Design

This Phase 1/2 clinical trial is a multiple dose trial which includes 9 patients. All patients are adults  located in either Europe or the United States. Its primary aim is to understand the safety and tolerability of this therapy across various ascending doses. Additionally, the research team will document pharmacodynamic and pharmacokinetic benefits such as PPi levels.

The dose escalation part of this trial (Phase 1) is evaluating doses of the treatment (.2 mg/kg, .6 mg/kg, and 1.8 mg/kg) across 32 days . These doses were chosen based on the preclinical data. From this data, the proper dosage will be documented and used in the open-label section of the trial.

The Phase 2 component of this trial will document the long-term safety of this therapy as well as its pharmacodynamics and pharmacokinetics for up to 48 weeks. Researchers will document physical function, vascular function, and skeletal function, in addition to outcomes reported by patients themselves.

The aim is to present topline data from this trial within the second half of this year.

INZ-701 in ABCC6 Deficiency Phase 1/2 Clinical Trial Design

The ongoing Phase 1/2 open-label clinical trial is expected to enroll up to nine adult patients with ABCC6 Deficiency at sites in the United States and Europe. The trial will primarily assess the safety and tolerability of INZ-701 in adult patients with ABCC6 Deficiency, as well as characterize the pharmacokinetic (PK) and pharmacodynamic (PD) profile of INZ-701, including the evaluation of levels of plasma PPi and other biomarkers.

In the Phase 1 dose-escalation portion of the trial, Inozyme is assessing INZ-701 for 32-days at doses of 0.2 mg/kg, 0.6 mg/kg, and 1.8 mg/kg administered via subcutaneous injection twice weekly, with three patients per dose cohort. Doses were selected based on preclinical studies and PK/PD modeling. The Phase 1 dose-escalation portion of the trial seeks to identify a safe, tolerable dose for further development that increases PPi levels.

The open-label Phase 2 extension portion of the trial will assess long-term safety, pharmacokinetics, and pharmacodynamics of continued treatment with INZ-701 for up to 48 weeks, where patients may receive doses of INZ-701 at home depending on site-specific protocols. Exploratory endpoints will include evaluations of vascular,  ophthalmologic, physical function and patient-reported outcomes.

The aim is to present preliminary biomarker and safety data from this trial in the second quarter of this year.

You can read more about this investigative treatment here.

If you are a family dealing with ENPP1deficiency, Generalized Arterial Calcification of Infancy, or ARHR2 AUTOSOMAL RECESSIVE HYPOPHOSPHATEMIC RICKETS TYPE 2 contact: for more information and support.

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