Phase III CALYPSO data presented at ECE showed eneboparatide met its primary endpoint in chronic hypoparathyroidism, significantly improving serum calcium control and reducing dependence on active vitamin D and oral calcium supplements through 24 weeks.
Written By: Farha Farheen, PharmD
Reviewed By: Pharmacally Editorial Team
Phase III CALYPSO trial (NCT05778071) results presented at the European Congress of Endocrinology (ECE) in Prague showed that eneboparatide (AZP-3601), an investigational parathyroid hormone receptor 1 agonist, met its composite primary endpoint in adults with chronic hypoparathyroidism (HypoPT).
At week 24, 31.1% of patients receiving eneboparatide achieved normal albumin-adjusted serum calcium levels (8.3–10.6 mg/dL) without active vitamin D or oral calcium supplementation, compared with 5.9% in the placebo group (41/132 vs. 4/68; p=0.0001). Immunogenicity was observed in most patients, reducing treatment effects in some cases, though calcium control was maintained with dose adjustments and supplemental support.
All key secondary endpoints were met. Among patients with baseline hypercalciuria, 56.6% of those on eneboparatide achieved normalization of urinary calcium excretion versus 20% in the placebo arm (43/76 vs. 9/45; p=0.0001). Statistically significant improvements were also seen in disease-related physical symptoms, physical functioning, and SF-36 Physical Function Subscore.
Patients continuing into the 28-week open-label extension maintained clinical benefits through week 52, including sustained calcium control with reduced supplement use. Bone health remained stable, with biomarkers of bone turnover within normal ranges and no clinically significant decline in bone mineral density.
Eneboparatide was generally well tolerated. Treatment-emergent adverse events were balanced between groups through week 24, with a consistent safety profile through week 52.
Maria Luisa Brandi, MD, PhD, investigator at the IRCCS European Institute of Oncology in Milan, said the findings highlight eneboparatide’s potential to stabilize serum calcium while supporting kidney and bone health in HypoPT.
Gianluca Pirozzi, Senior Vice President and Head of Development, Regulatory and Safety at Alexion, AstraZeneca Rare Disease, added that the CALYPSO data support eneboparatide’s potential to deliver sustained improvements in calcium regulation, symptom burden, physical function, and bone health.
CALYPSO is a global Phase III, randomized, double-blind, placebo-controlled trial evaluating once-daily subcutaneous eneboparatide in 202 adults with chronic HypoPT across 12 countries.
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About the Writer
Farha Farheen, PharmD (LinkedIn) is a pharmacy professional with a strong interest in pharmacovigilance and clinical research. She has completed her Doctor of Pharmacy (Pharm.D) along with her internship as a Clinical Pharmacist. She has hands-on experience in adverse drug reaction (ADR) reporting, safety data documentation, and pharmacovigilance workflows, and is proficient in using VigiFlow. She is also a patent holder for an antibacterial formulation enriched with bioactive substances, granted by the German Patent and Trademark Office.
About the Writer