First Person Treated in Phase 1 Trial Testing AZP-3601 for Hypoparathyroidism
Note: This story was updated on Nov. 12, 2020, to clarify key scientific concepts.
The study will evaluate the safety, tolerability, pharmacological properties, and preliminary efficacy of AZP-3601 in up to approximately 130 people — both those with hypoparathyroidism and healthy participants. Single and multiple increasing doses will be tested.
Patients with hypoparathyroidism will be treated at several study sites in Europe that specialize in this disorder, while healthy participants will receive the therapy at a single site.
“This achievement marks a significant milestone for Amolyt Pharma in the development of AZP-3601,” Thierry Abribat, PhD, CEO of Amolyt, said in a press release. “We are implementing an ambitious and efficient Phase 1 program to demonstrate proof-of-concept and rapidly advance AZP-3601 for patients with hypoparathyroidism.”
Hypoparathyroidism is characterized by insufficient blood levels of the parathyroid hormone (PTH), which promotes calcium absorption and reduces calcium loss in urine. Low PTH levels result in calcium deficiency and abnormally high levels of phosphorus in the blood.
The disorder is more common in women than men, with perimenopausal and menopausal women being the most affected population. Because menopause increases the risk of osteoporosis, a condition that causes brittle bones, calcium deficiency is of particular concern in this population.
Current treatment options for hypoparathyroidism include PTH replacement therapy and supplements to correct blood levels of calcium and phosphorus. However, even with available treatments, many patients experience a diminished quality of life and an increased risk of chronic kidney disease resulting from decreased calcium reabsorption.
AZP-3601 is an analog that selectively targets a specific configuration of the PTH receptor to help sustain normal levels of calcium in the blood. An analog is a compound with similar structure but slight differences in composition compared with another molecule.
In preclinical studies, the potential therapy has outperformed natural PTH at boosting and maintaining calcium levels, without increasing urine calcium excretion, a key risk factor for kidney disease, according to Amolyt.
“Current treatments for hypoparathyroidism fail not only to effectively control symptoms and to regulate 24-hour serum [blood] calcium, but also to normalize 24-hour urinary calcium, a key contributor to long-term kidney disease,” Abribat said.
“Through its unique mechanism of action, AZP- 3601 is expected to preserve bone integrity, an important advantage since hypoparathyroidism disproportionately affects peri and postmenopausal women who are at an increased risk of osteoporosis,” he added.