New Phase III clinical trial results presented at the European Congress of Endocrinology in Prague showed that Eneboparatide achieved significant improvements in calcium regulation and reduced dependence on supplements in adults with chronic Hypoparathyroidism, further supporting the drug’s potential as a novel treatment option for the rare endocrine disease.
The findings come from the CALYPSO Phase III trial, the largest global study conducted in adults with chronic hypoparathyroidism. Researchers reported that the investigational therapy met its composite primary endpoint at week 24 by demonstrating statistically significant normalization of albumin-adjusted serum calcium levels while allowing patients to discontinue active vitamin D and oral calcium supplements.
According to the data, 31.1% of patients treated with eneboparatide achieved normal serum calcium levels without requiring oral supplements, compared with 5.9% of patients receiving placebo. Investigators described the results as both clinically meaningful and statistically significant.
The therapy also met all key secondary endpoints in the study. Among patients who experienced excessive urinary calcium excretion, or hypercalciuria, at baseline, 56.6% of those treated with eneboparatide achieved normalization of urinary calcium levels. This compared with 20% of patients in the placebo arm.
Researchers additionally observed improvements in patient-reported outcomes related to physical symptoms, physical functioning, and overall quality of life. Measures using the SF-36 Physical Function Subscore also showed statistically significant gains among patients receiving the investigational treatment.
Hypoparathyroidism is a chronic disorder caused by insufficient parathyroid hormone activity, resulting in disrupted calcium and phosphate balance throughout the body. Patients often experience muscle cramps, fatigue, cognitive impairment, kidney complications, and reduced quality of life. Current treatment options mainly rely on calcium and vitamin D supplementation, which may not fully address the underlying hormonal deficiency.
The CALYPSO trial evaluated eneboparatide, also known as AZP-3601, as a parathyroid hormone receptor agonist designed to restore more natural PTH activity. Investigators said the therapy demonstrated potential benefits beyond calcium stabilization, including kidney protection and preservation of bone health.
After the initial 24-week treatment period, patients either continued eneboparatide therapy or switched from placebo to eneboparatide during a 28-week open-label extension phase. Clinical improvements observed during the main study were largely maintained through week 52, although some patients continued to use oral supplements.
Maria Luisa Brandi, an investigator in the trial from the IRCCS European Institute of Oncology in Milan, said inadequate parathyroid hormone activity affects multiple body systems and significantly reduces quality of life for patients with hypoparathyroidism. She noted that the trial results suggest eneboparatide may help stabilize calcium levels while also supporting kidney and bone health, outcomes considered critical for long-term disease management.
Gianluca Pirozzi, Senior Vice President and Head of Development, Regulatory and Safety at Alexion, part of AstraZeneca Rare Disease, said the breadth of evidence from the CALYPSO study highlights the therapy’s potential to provide sustained improvements across multiple aspects of the disease burden.
The safety profile of eneboparatide was generally manageable, although researchers noted that immunogenicity was observed in many patients, reducing treatment effects in some cases. Investigators said calcium levels could still be managed through supplement adjustments and dose titration.
The results strengthen the potential role of eneboparatide as a future treatment option for patients living with chronic hypoparathyroidism, an area where therapeutic choices remain limited.