Eneboparatide Hits Primary Phase 3 Endpoint for Hypoparathyroidism

Eneboparatide (AZP-3601) met the primary endpoint at 24 weeks in the Phase 3 CALYPSO trial, normalizing serum calcium levels with statistical significance in adults with chronic hypoparathyroidism, compared with placebo.1

Announced by AstraZeneca, on March 17, 2025, eneboparatide will continue to be studied in CALYPSO until 52 weeks to explore further the risk-benefit profile of the investigational parathyroid hormone (PTH) receptor 1 agonist.

“People living with HypoPT, a rare endocrine disease, are often at increased risk of hypercalciuria, osteopenia, and osteoporosis, and these results from the CALYPSO trial underscore eneboparatide’s potential to be another option for these patients,” said Marc Dunoyer, chief executive officer of Alexion and AstraZeneca Rare Disease.1

A rare endocrine disease tied to a deficiency of PTH, hypoparathyroidism is characterized by the impaired regulation of calcium and phosphatase levels in the blood, which can negatively implicate the kidney and bone. More than 200,000 people in the US and European Union are affected by the rare disease, comprising primarily women (80%).2

Citing a significant unmet medical need, despite available treatments, AstraZeneca designed eneboparatide to bind with high affinity to the PTH receptor 1 to restore PTH function and manage the symptoms of hypoparathyroidism while preserving kidney function and bone health.1

The global, randomized, double-blind, placebo-controlled CALYPSO trial measured the efficacy and safety of eneboparatide for 202 adults with chronic hypoparathyroidism treated with standard of care of active vitamin D and oral calcium supplementation. Trial participants were randomized in a 2:1 ratio to eneboparatide or placebo.

Efficacy endpoints for the trial were a composite of the proportion of patients who achieved normal-range albumin-adjusted serum calcium alongside independence from standard of care after 24 weeks of treatment. Key secondary efficacy endpoints included the normalization of 24-hour urinary calcium in individuals with baseline hypercalciuria and a review of patient-reported outcomes on physical symptoms and impact on quality of life.

Trial results portrayed a tolerable profile of eneboparatide for patients with hypoparathyroidism. After the 24-week randomized period, all patients received eneboparatide in the ongoing long-term extension period.

“We look forward to reviewing clinical results at 52 weeks to fully characterize the risk-benefit profile,” Dunoyer added.1

Eneboparatide has been awarded Fast Track and Orphan Drug Designations from the US Food and Drug Administration (FDA) and Orphan designation by the European Medicines Agency (EMA) for HypoPT.3 AstraZeneca announced the full efficacy and safety data will be analyzed at 52 weeks, shared with global health authorities, and presented at upcoming medical meetings.1

References

1. Eneboparatide met primary endpoint of normalizing serum calcium in adults with hypoparathyroidism at 24 weeks in calypso phase III trial. March 17, 2025. Accessed March 19, 2025. https://www.astrazeneca-us.com/media/press-releases/2025/Eneboparatide-met-primary-endpoint-of-normalizing-serum-calcium-in-adults-with-hypoparathyroidism-at-24-weeks-in-CALYPSO-Phase-III-trial.html.

2. Hans SK, Levine SN. Hypoparathyroidism. [Updated 2024 Feb 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441899/

3. Amolyt Pharma. AMOLYT Pharma granted FDA Fast Track designation for Eneboparatide for the treatment of hypoparathyroidism. GlobeNewswire News Room. May 2, 2024. Accessed March 19, 2025. https://www.globenewswire.com/news-release/2024/05/02/2874145/0/en/Amolyt-Pharma-Granted-FDA-Fast-Track-Designation-for-Eneboparatide-for-the-Treatment-of-Hypoparathyroidism.html.