Thierry Abribat, PhD, Chief Executive Officer of Amolyt Pharmaceuticals, discusses the mechanism of action of AZP-3601, a PTH analog, which is currently being investigated to treat patients with hypoparathyroidism.
Hypoparathyroidism is a rare endocrine disorder characterized by a deficiency of parathyroid hormone (PTH), which leads to decreased serum calcium and increased phosphorus levels in the blood. This can lead to weakness, muscle cramps, excessive nervousness, headaches, and/or uncontrollable twitching and cramping spasms of certain muscles such as those of the hands, feet, arms, legs, and/or face. Numbness and tingling around the mouth, fingers, and toes may also occur. Patients living with hypoparathyroidism often develop kidney disease and have abnormal bone architecture as well. This rare endocrine disorder is usually due to damage to/removal of the parathyroid glands via surgery for another condition, however other etiologies do exist.
Historically, the standard treatment strategy for hypoparathyroidism has been short-term management of symptoms using large doses of oral calcium and active vitamin D. Recently, however, Amolyt Pharma announced that the FDA has cleared its Investigational New Drug (IND) application for the ongoing clinical proof-of-concept trial of AZP-3601 in patients with hypoparathyroidism.
As Dr. Abribat explains, AZP-3601 is a PTH analog that has an increased affinity and selectivity for a specific conformation of the PTH receptor called R0 which allows for prolonged activation and effect on calcium metabolism. Additionally, AZP-3601 is designed to have a short half-life to potentially preserve bone integrity, an important benefit, since the majority of hypoparathyroid patients are peri- and postmenopausal women who have an increased risk of developing osteoporosis.
In October 2021, Amolyt Pharmaceuticals presented positive phase 1 data in healthy volunteers at the American Society for Bone and Mineral Research (ASBMR) 2021 Annual Meeting, which provided strong scientific rationale for continued development. However, hypoparathyroid patient data is not yet available – it will likely be available in approximately 3 months.
The phase 1 trial is currently only recruiting in Europe. As Dr. Abribat states, Amolyt Pharmaceuticals intends to develop the drug in the U.S. as well, since they now have an open IND in the U.S. This will likely occur in the next clinical trial of AZP-3601, a larger phase 2 study expected to begin in early 2023.
To learn more about hypoparathyroidism and other rare endocrine disorders, visit checkrare.com/diseases/endocrine-disorders/
