The CALYPSO phase III trial (NCT05778071) is a randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of eneboparatide in adults with chronic hypoparathyroidism (HypoPT).1 After 24 weeks, the primary endpoint was achieved, with eneboparatide found to significantly normalize serum calcium levels in adults with chronic HypoPT, compared with placebo.2 Eneboparatide was well tolerated by patients, and all participants who received the treatment continued on eneboparatide for 52 weeks during the ongoing extension phase of the study.
On the 2 May 2024 eneboparatide was granted Fast Track and Orphan Drug designations by the US Food and Drug Administration (FDA), as well as Orphan Drug designation by the European Medicines Agency (EMA) for the treatment of HypoPT.3 HypoPT is a rare condition caused by a deficiency in parathyroid hormone (PTH); this disrupts calcium and phosphate regulation in the blood and impacts kidney and bone health. It is reported that the prevalence of chronic HypoPT is between 6.4–37 cases /100,000 people, while the incidence is between 0.8–2.3/100,000/year.4 The current primary treatment options for HypoPT are calcium supplements and activated vitamin D.5
Eneboparatide is an investigational parathyroid hormone receptor 1 (PTH1R) agonist, designed to bind with high affinity to a specific conformation of PTH1R, which is expressed in the kidneys and bone. The goal of treatment is to restore function by producing sustained and stable levels of calcium in the blood and by restoring calcium reabsorption by the kidney.2,3 Eneboparatide has been developed to have a short half-life in order to preserve bone health.
In the CALYPSO trial, 202 patients with chronic HypoPT receiving standard treatments were randomly assigned 2:1 to receive either eneboparatide or placebo for 24 weeks.1 The primary endpoint was a composite measure, assessing the proportion of patients who achieved albumin-adjusted serum calcium levels within a normal range and became independent from standard treatments after 24 weeks. Key secondary endpoints included normalization of 24-hour urinary calcium in patients with hypercalciuria at baseline and patient-reported outcomes reflecting physical symptoms and impact on quality of life.
References
- Clinicaltrials.gov. Evaluation of the Safety and Efficacy of Eneboparatide (AZP-3601) in Patients With Chronic Hypoparathyroidism (CALYPSO). ClinicalTrials.gov Identifier:NCT05778071. Available at: https://clinicaltrials.gov/study/NCT05778071 (accessed 19 March 2025).
- Astrazeneca. (2025) Eneboparatide met primary endpoint of normalizing serum calcium in adults with hypoparathyroidism at 24 weeks in CALYPSO Phase III trial (press release). Available at: https://www.astrazeneca.com/media-centre/press-releases/2025/eneboparatide-phase-iii-trial-met-primary-endpoint.html (accessed 19 March 2025).
- Globenewswire. (2024) Amolyt Pharma Granted FDA Fast Track Designation for Eneboparatide for the Treatment of Hypoparathyroidism. Available at: 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 (accessed 19 March 2025).
- Bjornsdottir S, Ing S, Mitchell DM, et al. (2022) Epidemiology and Financial Burden of Adult Chronic Hypoparathyroidism. J Bone Miner Res. 37(12):2602–14. DOI: 10.1002/jbmr.4675.
- National Organisation for Rare Diseases (NORD). (2024) Hypoparathyroidism https://rarediseases.org/rare-diseases/hypoparathyroidism/ (accessed 19 March 2025).
Disclosure: This article was created by the touchENDOCRINOLOGY team utilizing AI as an editorial tool (ChatGPT (GPT-4o) [Large language model]. https://chat.openai.com/chat.) The content was developed and edited by human editors. No funding was received in the publication of this article.
Cite: Eneboparatide meets primary endpoint in adults with hypoparathyroidism: CALYPSO topline phase III results. touchENDOCRINOLOGY. 20 March 2025.
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