Axel Bolte, MSc, MBA, Co-Founder, President, and Chief Executive Officer, Inozyme Pharmaceuticals, discusses the positive preliminary data from the first 3 patients treated in the phase 1 portion of the phase 1/2 clinical trial of INZ-701 in ENPP1 deficiency patients.
The ENPP1 gene produces a critical enzyme called ectonucleotide pyrophosphatase/ phosphodiesterase 1 (ENPP1), which regulates inorganic pyrophosphate (PPi) levels in plasma. PPi is essential for preventing harmful soft tissue calcification and for regulating normal bone mineralization. Individuals who present in utero or in infancy are typically diagnosed with generalized arterial calcification of infancy (GACI), which is characterized by extensive vascular calcification and neointimal proliferation, resulting in myocardial infarction, stroke, or cardiac or multiorgan failure. Approximately 45% to 50% of infants with ENPP1 deficiency die within six months of birth. Children and adults with ENPP1 deficiency typically experience rickets and osteomalacia, a condition also known as autosomal-recessive hypophosphatemic rickets type 2 (ARHR2). These patients can also exhibit a range of signs and symptoms that include hearing loss, arterial calcification, and cardiac and/or neurological involvement. There are currently no approved therapies for ENPP1 deficiency.
Recently, Inozyme announced positive preliminary biomarker, safety, and pharmacokinetic data from the first 3 patients treated in the phase 1 portion of its ongoing phase 1/2 clinical trial of INZ-701 in adult patients with ENPP1 deficiency. The trial will primarily assess the safety and tolerability of INZ-701 in adult patients with ENPP1 deficiency, as well as characterize the PK/PD profile of INZ-701, including evaluation of PPi and other biomarker levels. 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 3 patients per dose cohort.
At the 0.2 mg/kg dose level of INZ-701, all 3 patients showed rapid, significant, and sustained increases in PPi levels. Preclinical findings also demonstrated PPi as a key predictive biomarker of therapeutic benefit in ENPP1 deficiency. The range of PPi levels across the 3 patients at screening was 132-333 nM while the range of PPi levels measured at 6 hours after the first dose was 581-1239 nM, an approximately 4-fold mean increase from screening. The mean PPi level during the 32-day dose evaluation period was 1356 nM, an approximately 5-fold mean increase. The range of peak PPi levels observed during the 32-day dose evaluation period across the 3 patients was 1082-2416 nM. This is comparable to healthy subject data (n=10), which showed PPi levels between 1002 nM and 2169 nM.
Following the conclusion of the 32-day dose evaluation period, an independent Data Safety Monitoring Board (DSMB) reviewed the preliminary data and recommended the trial continue as planned. Dosing is underway at the 0.6 mg/kg dose level of INZ-701 in the second cohort of the trial.
Inozyme plans to report topline data from the ongoing trial in the second half of 2022.
To learn more about this study and how to enroll, visit https://clinicaltrials.gov/ct2/show/NCT04686175
To learn more about ENPP1 deficiency and other genetic disorders, visit https://checkrare.com/diseases/congenital-and-genetic-conditions/
