PRAGUE, Czech Republic, May 12, 2026
AstraZeneca and Alexion announced positive Phase III clinical trial results for eneboparatide (AZP-3601), an investigational therapy for chronic hypoparathyroidism (HypoPT), demonstrating significant improvements in calcium regulation, kidney health, physical functioning, and quality of life in adults living with the rare endocrine disorder. The findings from the global CALYPSO Phase III study were presented at the European Congress of Endocrinology in Prague and highlighted the therapy’s potential to become a major advancement in HypoPT treatment.
The trial achieved its primary endpoint by showing that 31.1% of patients treated with eneboparatide achieved normalized serum calcium levels while becoming independent from active vitamin D and oral calcium supplements at week 24, compared with only 5.9% in the placebo group. Researchers described the results as statistically significant and clinically meaningful for patients living with a condition that currently has limited long-term treatment options.
Hypoparathyroidism is a rare endocrine disease caused by inadequate parathyroid hormone production, leading to disruptions in calcium and phosphate balance that can result in neuromuscular complications, kidney dysfunction, skeletal abnormalities, and severe impacts on quality of life. AstraZeneca noted that more than 250,000 people across the United States, Europe, and Japan are living with the disease, with women representing the majority of affected patients.
CALYPSO Study Demonstrates Strong Clinical Benefits
The global CALYPSO trial enrolled 202 patients across 12 countries and evaluated the safety and efficacy of once-daily subcutaneous eneboparatide in adults with chronic hypoparathyroidism. Patients receiving the investigational therapy demonstrated significant improvements in multiple clinical endpoints beyond serum calcium normalization.
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One of the most important secondary findings involved urinary calcium regulation. The study showed that 56.6% of patients with elevated urinary calcium levels at baseline achieved normalized urinary calcium excretion, compared with 20% in the placebo group. Researchers emphasized that controlling urinary calcium is critical because hypercalciuria can contribute to kidney damage and long-term renal complications in HypoPT patients.
The investigational therapy also produced statistically significant improvements in patient-reported outcomes related to physical symptoms, physical functioning, and overall quality of life. Investigators stated that the results suggest eneboparatide may help restore more natural parathyroid hormone activity while reducing disease burden and treatment complexity.
Importantly, clinical benefits remained durable during the study’s open-label extension period through week 52. Patients continuing eneboparatide maintained positive treatment responses, including stable calcium control and preservation of bone health. Researchers reported balanced bone turnover biomarkers and no clinically significant reductions in bone mineral density during long-term treatment.
Rare Disease Pipeline Gains Momentum
AstraZeneca and Alexion described the CALYPSO study as the largest global clinical trial conducted in adults with chronic hypoparathyroidism. Company executives stated that the broad range of positive data supports eneboparatide’s potential to address several unmet medical needs simultaneously, including calcium regulation, symptom control, kidney preservation, and bone health maintenance.
Eneboparatide is designed as a parathyroid hormone receptor agonist intended to restore physiological PTH function rather than simply replacing calcium through supplements. The investigational therapy has already received Fast Track and Orphan Drug Designations from the U.S. FDA as well as orphan designation in Europe and Japan, reflecting growing regulatory interest in innovative rare disease therapies.
The therapy was generally well tolerated throughout the 52-week treatment period, with AstraZeneca reporting a consistent safety profile and balanced treatment-emergent adverse events between the treatment and placebo groups.
The positive Phase III findings strengthen AstraZeneca’s expanding rare disease portfolio and position eneboparatide as a potentially transformative therapy for patients living with chronic hypoparathyroidism, a disease area that has historically lacked effective long-term therapeutic options.
Source: AstraZeneca, Alexion press release
