- Data from ongoing trial suggest clinical benefit for ENPP1 Deficiency, including improvement in key biomarkers, patient reported outcomes (PROs) and functional outcomes -
- Improvement in the Global Impression of Change (GIC) observed in all three dose cohorts in ABCC6 Deficiency (PXE) trial -
- INZ-701 was generally well tolerated and exhibited a favorable safety and immunogenicity profile in both trials -
- Company to host conference call and webcast today at 8:00 a.m. ET -
BOSTON, Sept. 26, 2023 (GLOBE NEWSWIRE) -- Inozyme Pharma, Inc. (NASDAQ:INZY) ("Inozyme" or the "Company"), a clinical-stage rare disease biopharmaceutical company developing novel therapeutics for the treatment of pathologic mineralization and intimal proliferation, today announced positive interim safety, pharmacokinetic (PK), pharmacodynamic (PD) and exploratory efficacy data from the Company's ongoing Phase 1/2 clinical trials of INZ-701 in adults with ENPP1 Deficiency and ABCC6 Deficiency (PXE, pseudoxanthoma elasticum).
"We are pleased that these trials have achieved their primary goals of demonstrating that INZ-701 was generally safe and well tolerated and meaningfully increased PPi levels in patients with ENPP1 Deficiency and ABCC6 Deficiency. We have also observed trends of clinical improvement which gives us confidence that we can design an informative pivotal trial in adults with ENPP1 Deficiency," said Kurt Gunter, M.D., senior vice president and chief medical officer of Inozyme Pharma. "The trends towards improvement in clinically meaningful markers of bone metabolism in adults with ENPP1 Deficiency point to the potential for INZ-701 to treat rickets in our planned pivotal trial in pediatric patients with the condition."
"Data from these first-in-human trials of INZ-701 are highly encouraging for both patients and physicians in the ENPP1 Deficiency and ABCC6 Deficiency communities. I am particularly excited to see early signs that INZ-701 may address symptoms in the adult population of ENPP1 Deficiency, which could translate to clinical benefits in the infant and adolescent patients who are in urgent need of a therapeutic option," said Michael Levine, M.D., Professor Emeritus, Pediatrics and Medicine and Chief Emeritus, Division of Endocrinology and Diabetes at the Center for Bone Health at the Children's Hospital of Philadelphia Research Institute.
ENPP1 Deficiency
Nine patients were initially enrolled in the ongoing Phase 1/2 clinical trial across three dose cohorts of INZ-701 (0.2 mg/kg (n=3), 0.6 mg/kg (n=3), and 1.8 mg/kg (n=3)). For trial design details, please see the section entitled "INZ-701 in ENPP1 Deficiency Phase 1/2 Clinical Trial Design" below.
Exploratory Biomarker Data
Exploratory biomarker data were collected throughout the study to provide evidence of the potential for disease modification with ongoing treatment with INZ-701. Notable changes in key biomarkers were observed and support the clinical hypothesis, including:
- Meaningful reduction of fibroblast growth factor-23 (FGF-23) observed. Most patients with ENPP1 Deficiency have elevated levels of FGF-23, which leads to increased phosphate wasting and hypophosphatemia, a key driver of osteomalacia and rickets.
- Serum phosphate (Pi) levels increased over time, in the absence of phosphate and active vitamin D supplementation, which were withheld from patients during the study.
- Statistically significant correlation between increase in plasma pyrophosphate (PPi) and decrease in FGF-23 observed at one week post first dose.
- Upward trends observed in bone specific alkaline phosphatase (BSAP) levels from baseline, which signal biological activity in bone tissue.
Exploratory Efficacy Data
Outcome measures were collected to assess potential clinical benefit with ongoing treatment with INZ-701 and to inform the design and patient selection of future trials in adolescents and adults. Notable changes in PROs and functional outcomes were observed in all cohorts, including:
- Concordant improvement in GIC scores reported by patients (P-GIC) and clinicians (C-GIC), and no patient showed a deterioration from baseline.
- High responder rates in Patient-Reported Outcome Measurement Information Scales (PROMIS) of Pain Intensity, Fatigue and Pain Interference.1
- Trend of improvement in 6-minute walk test (6-MWT). Subgroup analysis of 6-MWT results showed greater improvement in patients with lower baseline values and stable results over time in patients with higher baseline values.
- Subgroup analysis of patients who presented with arthritis/arthralgia at baseline showed improvement in 6-MWT, and increased spine bone mineral density (BMD) and bone mineral content (BMC), as measured by dual x-ray absorptiometry (DEXA).
Pharmacodynamic (PD) and Pharmacokinetic (PK) Data
- Rapid, significant, and sustained increase in PPi levels observed in all patients and significant elevation in PPi maintained for up to 18 months.
- Long half-life of approximately 126 hours and drug accumulation as shown by a greater than dose proportional exposure suggests the potential for once weekly dosing.
Safety Data
- INZ-701 was generally well-tolerated and exhibited a favorable safety profile, with no serious or severe adverse events attributed to INZ-701 and no adverse events leading to study withdrawal.
- 3/9 patients experienced mild adverse events related to INZ-701.
- Injection site reactions (bruising, hemorrhage, pain, pruritus, and/or swelling) occurred in 2/9 patients.
- Other related adverse ...