Phase III Trial Data Show Eneboparatide Normalizes Serum Calcium Levels in Chronic Hypoparathyroidism
In the Phase III CALYPSO trial, eneboparatide demonstrated statistical significance in achieving albumin-adjusted serum calcium normalization while eliminating the need for active vitamin D and oral calcium therapy in chronic hypoparathyroidism.
Image Credit: Adobe Stock Images/Dr_Microbe
Results from the Phase III CALYPSO trial show that eneboparatide (AZP-3601; Alexion, AstraZeneca Rare Disease) normalized serum calcium levels in adults with chronic hypoparathyroidism (HypoPT) at 24 weeks. According to the study, eneboparatide also showed statistical significance in achieving albumin-adjusted serum calcium normalization while eliminating the need for active vitamin D and oral calcium therapy.1
Eneboparatide was previously granted Fast Track Designation and Orphan Drug Designation by the FDA.1
“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, CEO, Alexion, AstraZeneca Rare Disease, in a press release. “We look forward to reviewing clinical results at 52 weeks to fully characterize the risk-benefit profile.”
The global, randomized, double-blind, placebo-controlled, multicenter CALYPSO trial evaluated the safety and efficacy of eneboparatide in 202 patients with HypoPT. Patients were randomly assigned in a 2:1 ratio to receive either eneboparatide or placebo after previously receiving standard of care, which included active vitamin D and oral calcium supplements. The primary endpoint of the study was percentage of patients who achieved albumin-adjusted serum calcium levels within the normal range and no longer requiring standard care after 24 weeks of treatment. Secondary endpoints included evaluating the normalization of 24-hour urinary calcium in those who had hypercalciuria at the start of the study and analyzing patient-reported outcomes related to physical symptoms and overall quality of life.
Eneboparatide was well tolerated, and all participants have continued treatment in the long-term extension phase, with full efficacy and safety data expected at 52 weeks. Alexion intends to share these results with global regulatory authorities and at upcoming medical conferences.1
AstraZeneca gained the rights to eneboparatide in May 2024 when it acquired Amolyt Pharma, a biotech company focused on developing novel treatments for rare endocrine diseases. In return for the rights to eneboparatide as well as the Amolyt brand, AstraZeneca provided an upfront payment of $800 million, with a potential for an additional payout of up to $250 million, pending the completion of specific milestones.2
According to AstraZeneca, 75% of all HypoPT cases result from injury to or removal of the parathyroid glands during neck surgery. Currently, there are over 200,000 people living with HypoPT in the United States and the EU combined, 80% of whom are women.1
According to a study published in Oxford Academic, the global prevalence of chronic HypoPT ranges from 5.3 to 40 cases per 100,000 people. In patients with postoperative HypoPT and nonoperative HypoPT, the prevalence is 6.4 to 26 and 0.2 to 17 per 100,000 people, respectively.3
According to the National Organization for Rare Disorders, an estimated 70,000 people in the United States are currently living with chronic HypoPT, which can occur in patients at any age. In most cases, HypoPT can be temporary, depending on the extent of the damage sustained during surgery. In an estimated 25% of cases, transient post-surgical HypoPT can be permanent.4
According to Medscape, 74% of patients with HypoPT in the United States are over 45 years of age. Around 75% of all HypoPT cases in the United States occur in females.5
References
1. Eneboparatide met primary endpoint of normalising serum calcium in adults with hypoparathyroidism at 24 weeks in CALYPSO Phase III trial. AstraZeneca. March 17, 2025. Accessed March 17, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/eneboparatide-phase-iii-trial-met-primary-endpoint.html#!
2. AstraZeneca Acquires Amolyt Pharma with the Aim of Developing Rare Endocrine Disease Treatments. PharmExec. March 14, 2025. Accessed March 17, 2025. https://www.pharmexec.com/view/astrazeneca-acquires-amolyt-pharma-with-the-aim-of-developing-rare-endocrine-disease-treatments
3. Prevalence and characteristics of postoperative and nonoperative chronic hypoparathyroidism in Japan: a nationwide retrospective analysis. Oxford Academic. Accessed March 17, 2025. https://academic.oup.com/jbmrplus/article/8/9/ziae100/7723491
4. Hypoparathyroidism. NORD. Accessed March 17, 2025. https://rarediseases.org/rare-diseases/hypoparathyroidism/#disease-overview-main
5. Hypoparathyroidism Follow-up. Medscape. Accessed March 17, 2025. https://emedicine.medscape.com/article/122207-followup
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