AstraZeneca Reports Positive Phase 3 Data for Eneboparatide in Chronic Hypoparathyroidism

AstraZeneca announced positive results from the Phase 3 CALYPSO trial evaluating eneboparatide, an investigational parathyroid hormone (PTH) receptor 1 agonist, in adults with chronic hypoparathyroidism (HypoPT). According to the company, 31.1% of patients receiving eneboparatide achieved the composite primary endpoint of normalized serum calcium levels and independence from active vitamin D and oral calcium supplements at 24 weeks, compared with 5.9% in the placebo arm.¹

The global CALYPSO trial enrolled 202 adults with chronic HypoPT who were receiving standard-of-care therapy. Participants were randomized in a 2:1 ratio to receive either eneboparatide or placebo. The study’s primary endpoint assessed the proportion of patients achieving albumin-adjusted serum calcium within the normal range while discontinuing active vitamin D and reducing oral calcium supplementation to 600 mg/day or less.¹

According to a company press release, eneboparatide demonstrated statistically significant improvement compared with placebo. The company also reported that serum calcium remained controlled in many patients despite reduced reliance on supplements. However, immunogenicity was observed in most of the treated patients, resulting in reduced treatment effects in some participants.¹

Addressing challenges in hypoparathyroidism management

HypoPT is a rare endocrine disorder characterized by inadequate secretion or action of parathyroid hormone (PTH), resulting in hypocalcemia and, in some cases, hyperphosphatemia and hypercalciuria. Conventional treatment typically consists of oral calcium salts and active vitamin D supplementation, but this approach can lead to fluctuating calcium levels, high pill burden, and increased risk of long-term renal complications, including nephrocalcinosis and nephrolithiasis.²

Investigators and clinicians continue to evaluate whether PTH replacement therapies may provide more physiologic calcium regulation compared with conventional supportive care. Eneboparatide is designed to selectively activate the PTH1 receptor with the goal of restoring calcium homeostasis through sustained receptor signaling.³

Expansion of AstraZeneca’s rare disease pipeline

Eneboparatide became part of AstraZeneca’s rare disease portfolio through its acquisition of Amolyt Pharma in 2024. The acquisition expanded AstraZeneca’s pipeline of peptide-based therapies targeting rare endocrine diseases and metabolic disorders.

The CALYPSO study remains ongoing through 52 weeks to further evaluate long-term efficacy and safety outcomes. Detailed findings were presented during the 2026 European Congress of Endocrinology.

Competitive landscape continues to evolve

The positive Phase 3 findings add momentum to a competitive but evolving HypoPT treatment landscape. Several companies are developing PTH analogs or receptor agonists aimed at reducing dependence on high-dose calcium and vitamin D supplementation. Analysts note that successful hormone replacement therapies could help address unmet needs in a patient population where disease management remains challenging despite available supportive care.

For BioPharm stakeholders, the CALYPSO data underscore continued investment in rare endocrine disorders and highlight growing industry interest in peptide therapeutics targeting endocrine signaling pathways. While additional long-term data will be important to clarify durability of response and immunogenicity considerations, the latest results position eneboparatide as a potentially significant entrant in the chronic HypoPT pipeline.

References

1. Eneboparatide normalised serum calcium and achieved independence from supplements in adults with HypoPT in CALYPSO Phase III trial. (2026 May 12). AstraZeneca. https://www.astrazeneca.com/media-centre/press-releases/2026/eneboparatide-normalised-serum-calcium-and-achieved-independence-from-supplements-in-31-1-percent-of-adults-with-HypoPT-in-CALYPSO-Phase-iii-trial.html
2. Khan, S., & Khan, A. A. (2025 Feb 4). Hypoparathyroidism: Diagnosis, management and emerging therapies. Nature Reviews Endocrinology. https://www.nature.com/articles/s41574-024-01075-8
3. Takacs, I., et al. An open-label phase 2 study of eneboparatide, a novel PTH receptor agonist, in chronic hypoparathyroidism. (2024 Aug 13). Journal of Clinical Endocrinology & Metabolism. https://pubmed.ncbi.nlm.nih.gov/38449442/
4. Evaluation of the safety and efficacy of eneboparatide (AZP-3601) in patients with chronic hypoparathyroidism (CALYPSO) (NCT05778071). (2026). ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT05778071