Kurt Gunter, MD, Senior Vice President and Chief Medical Officer at Inozyme Pharma, discusses data presented on ENPP1 deficiency and ABCC6 deficiency at the 2024 American Society for Bone and Mineral Research meeting.
ENPP1
ENPP1 deficiency is a rare metabolic disease caused by mutations in the ENPP1 enzyme. This enzyme is responsible for the cleavage of ectonucleotides that prevent mineralization. In ENPP1 deficiency, calcium phosphate precipitates throughout the body, accumulating in the wrong places such as blood vessels, skin, eyes, joints, and tendons. This is due to low levels of pyrophosphate and ATP production.
Pyrophosphate is also essential in the formation of the skeletal system. Insufficient pyrophosphate can lead to skeletal abnormalities such as rickets and soft bone. Patients with ENPP1 deficiency also commonly experience walking and mobility issues, pain, inflammation, and bones that fracture easily. Adults may also experience hearing loss, arterial calcification, and cardiac and/or neurological involvement. Approximately half of infants with ENPP1 deficiency die within six months of birth.
There are no approved therapies for ENPP1 deficiency.
ABCC6
ABCC6 is a rare metabolic disease caused by mutations in the ABCC6 gene, the gene responsible for transporting ATP from the inside of cells to the outside. Mutations cause reduced levels of systemic ATP, leading to low levels of pyrophosphate and adenosine in the blood. Due to its similarity to ENPP1 deficiency, many patients experience identical symptoms and difficulties.
There are no approved therapies for ABCC6 deficiency.
INZ-701
INZ-701 is a subcutaneous investigational ENPP1 enzyme replacement therapy (ERT). It is currently in development for the treatment of ENPP1 deficiency, ABCC6 deficiency, and calciphylaxis. The therapy has so far shown a rapid, significant, and sustained increase in pyrophosphate levels. The efficacy and safety profile has been positive as well.
ENERGY 3 Clinical Trial
The ENERGY 3 study is an ongoing phase 3, multicenter, randomized, controlled, open-label trial evaluating the safety and efficacy of INZ-701 in children with ENPP1 deficiency. For more information, click here.
Results from this study are expected in the second half of 2025. Additionally, a phase 1/2 study of INZ-701 for ABCC6 deficiency and a phase 1b trial for calciphylaxis have been completed.
Data Presented at the American Society for Bone and Mineral Research 2024 Meeting
The presentations discussed the following:
- Findings emphasizing the significant medical burden of ENPP1 deficiency and ABCC6 deficiency
- Data from a natural history study with information on the progression of ENPP1 deficiency
- The launch of a global registry in efforts to better understand these rare diseases
The data highlighted the necessity for therapies that address both the cardiovascular and musculoskeletal manifestations of these deficiencies as well as the long-term systemic impact. Within the first few months of life of patients with ENPP1 deficiency, 88% experienced ectopic calcifications and 76% experienced serious cardiovascular complications. In another study, patients with early-onset ABCC6 deficiency experienced significant cardiovascular complications and 44% experienced stroke.
To better understand these diseases, a global registry, PROPEL, is looking to collect clinical data and patient information.
For more information, click here.
To learn more about these deficiencies and other rare metabolic disorders, visit https://checkrare.com/diseases/metabolic-disorders/