UK-based AstraZeneca’s acquired rare disease drug has met the primary endpoint in a Phase III trial in patients with chronic hypoparathyroidism.
The Calypso trial (NCT05778071) of eneboparatide, an investigational parathyroid hormone (PTH) receptor 1 agonist, met its primary endpoint of a composite of normalisation of albumin-adjusted serum calcium levels and independence from active vitamin D and oral calcium therapy.
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The key secondary efficacy endpoints include the normalisation of 24-hour urinary calcium in patients with hypercalciuria at baseline and patient-reported outcomes.
AstraZeneca added eneboparatide to the Alexion and AstraZeneca rare disease pipeline through the acquisition of Amolyt Pharma in July 2024, in a deal valued around $1.05bn. Shareholders received an $800m upfront payment and will receive $250m payment upon the drug meeting a specified regulatory milestone.
The trial enrolled 202 patients who were evaluated for 24 weeks. The randomised, double-blind, placebo-controlled study has now become an open-label study that will continue to evaluate patients for 52 weeks. In this open-label period, all patients will receive eneboparatide.
The rare disease drug was well tolerated across the 24 weeks. Full efficacy and safety data will be analysed again at 52 weeks. At that point, Alexion will share data with global health authorities.
Alexion and AstraZeneca rare disease CEO Marc Dunoyer said: “People living with hypoparathyroidism 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. We look forward to reviewing clinical results at 52 weeks to fully characterise the risk-benefit profile.”
Eneboparatide acts by binding to a specific conformation of the PTH receptor 1 to restore PTH function and manage the symptoms of hypoparathyroidism, while preserving kidney function and bone health.
The therapy has been granted fast track and orphan drug designations by the US Food and Drug Administration (FDA) and orphan designation by the European Medicines Agency (EMA).
Hypoparathyroidism is a rare endocrine disease caused by a deficiency of PTH. Symptoms include impaired regulation of calcium and phosphate levels in the blood. This dysregulation of the physiological action of PTH can lead to clinical manifestations, including a negative impact on the kidney and bone. It is one of the largest known rare diseases and affects over 200,000 people in the US and European Union (EU), and approximately 80% of patients are female.
The clinical space for hypoparathyroidism has been limited, with the standard treatment typically involving oral calcium and vitamin D supplementation. On 12 August 2024, Ascendis Pharma announced that the FDA-approved Yorvipath (palopegteriparatide) as the first and only dedicated treatment for adults with hypoparathyroidism in the US.
GlobalData predicts that Yorvipath will benefit from its first-to-market advantage and generate $1.66bn of sales in 2030. Meanwhile, eneboparatide will likely bring in $492m in the same year.
GlobalData is the parent company of Clinical Trials Arena.
On 17 March, AstraZeneca signed an executive licence agreement deal with bio-platform company Alteogen worth up to $1.35bn. The deal allows AstraZeneca to use Alteogen’s hyaluronidase using Hybrozyme platform technology, ALT-B4, to develop subcutaneous formulations of oncology assets.
