17 March 2025
Eneboparatide met primary
endpoint of normalising serum calcium in adults with
hypoparathyroidism at 24 weeks in CALYPSO Phase III
trial
Trial continues as planned to
52 weeks to further characterise the risk-benefit
profile
High-level results from the CALYPSO
Phase III trial showed that eneboparatide (AZP-3601),
an investigational parathyroid hormone (PTH)
receptor 1 agonist, met its primary endpoint with statistical
significance in adults with chronic hypoparathyroidism (HypoPT) at
24 weeks, compared to placebo. The primary endpoint is a composite
of normalisation of albumin-adjusted serum calcium levels and
independence from active vitamin D and oral calcium
therapy.
HypoPT is a rare endocrine disease
caused by a deficiency of PTH and characterised by impaired
regulation of calcium and phosphate levels in the blood. This
dysregulation of the physiological action of PTH can lead to
clinical manifestations, including negative impact on the kidney
and bone.1 HypoPT is one of the largest known rare
diseases, affecting over 200,000 people in the United States and
the European Union, approximately 80% of whom are
women.2-4
Marc Dunoyer, Chief Executive
Officer, Alexion, AstraZeneca Rare Disease, said: "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. We look forward to
reviewing clinical results at 52 weeks to fully characterise the
risk-benefit profile."
Eneboparatide was well
tolerated. After the 24-week randomised treatment
period, all patients receive eneboparatide in the ongoing long-term
extension period until 52 weeks. Full efficacy and safety data will
be analysed at 52 weeks. Alexion plans to
share these data with global health
authorities and present them at forthcoming medical
meetings.
Notes
Hypoparathyroidism
Hypoparathyroidism (HypoPT) is a rare endocrine
disease caused by a deficiency of parathyroid hormone (PTH) and
characterised by decreased calcium and elevated phosphate levels in
the blood, which can lead to a variety of neuromuscular, renal and
skeletal manifestations.1,5,6 The primary cause in
approximately 75% of people with HypoPT is injury to or removal of
the parathyroid glands during neck surgery.5,6 There are
over 200,000 people in the United States and the European Union
living with HypoPT, approximately 80% of whom are women.2-4
Despite available treatments, people living with HypoPT
continue to experience a significant unmet
need.1,8
CALYPSO
CALYPSO is a global Phase III, randomised,
double-blind, placebo-controlled, multicentre trial designed to
evaluate the efficacy and safety of eneboparatide in adults with
chronic hypoparathyroidism. A total of 202 patients treated with
standard of care (active vitamin D and oral calcium
supplementation) were randomised in a 2:1 ratio to receive
eneboparatide or placebo.9
The primary efficacy endpoint is a composite of
the proportion of patients that achieve albumin-adjusted serum
calcium within the normal range and independence from standard of
care after 24 weeks of treatment. The key secondary efficacy
endpoints include normalisation of 24-hour urinary calcium in
patients with hypercalciuria at baseline and assessment of
patient-reported outcomes that reflect physical symptoms and impact
on quality of life.9
After the 24-week randomised main
treatment period, all patients receive eneboparatide treatment in
the ongoing long-term extension period.9
Eneboparatide
(AZP-3601)
Eneboparatide (AZP-3601) is an investigational
parathyroid hormone (PTH) receptor 1
agonist for the treatment of chronic hypoparathyroidism
(HypoPT). It is designed to bind with high affinity to a specific
conformation of the PTH receptor 1 to restore PTH function to
manage the symptoms of HypoPT, while preserving kidney function and
bone health.6 Eneboparatide has been granted fast
track designation and orphan drug designation by the US Food and
Drug Administration and orphan designation by the European
Medicines Agency for the treatment of HypoPT.
Alexion
Alexion, AstraZeneca Rare Disease, is focused
on serving patients and families affected by rare diseases and
devastating conditions through the discovery, development and
delivery of life-changing medicines. A pioneering leader in rare
disease for more than three decades, Alexion was the first to
translate the complex biology of the complement system into
transformative medicines, and today it continues to build a
diversified pipeline across disease areas with significant unmet
need, using an array of innovative modalities. As part of
AstraZeneca, Alexion is continually expanding its global geographic
footprint to serve more rare disease patients around the world. It
is headquartered in Boston, US.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global,
science-led biopharmaceutical company that focuses on the
discovery, development, and commercialisation of prescription
medicines in Oncology, Rare Diseases, and BioPharmaceuticals,
including Cardiovascular, Renal & Metabolism, and Respiratory
& Immunology. Based in Cambridge, UK, AstraZeneca's innovative
medicines are sold in more than 125 countries and used by millions
of patients worldwide. Please visit astrazeneca.com and
follow the Company on social media @AstraZeneca.
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References
1. Bilezikian JP. Hypoparathyroidism. J Clin Endocrinol Metab.
2020;105(6):1722-1736. doi:10.1210/clinem/dgaa113.
2. Vadiveloo T, et al. A population-based study of the
epidemiology of chronic hypoparathyroidism. J Bone Miner Res.
2018;33(3):478-485.
3. Villarroya-Marquina I, et al. Influence of gender and women's age on the prevalence of
parathyroid failure after total thyroidectomy for multinodular
goiter. Gland Surg.
2020;9(2):245-251.
4. Deering KL, et al. Economic burden of patients with
post-surgical chronic and transient hypoparathyroidism in the
United States examined using insurance claims data. Orphanet J Rare Dis.
2024;19(1):164.
5. Gafni RI, Collins MT. Hypoparathyroidism. N Engl J Med. 2019;380(18):1738-1747.
doi:10.1056/NEJMcp1800213
6. Shoback DM, Bilezikian JP, Costa AG, et al. Presentation of
hypoparathyroidism: etiologies and clinical features. J Clin Endocrinol Metab.
2016;101(6):2300-2312. doi:10.1210/jc.2015-3909
7. Clarke BL, et al. Epidemiology and diagnosis of
hypoparathyroidism. J Clin
Endocrinol Metab. 2016;101(6):2284-99.
8. Abate EG, et al. Review of hypoparathyroidism. Front Endocrinol (Lausanne).
2017;7:172.
9. ClinicalTrials.gov. Evaluation of the safety and efficacy of
eneboparatide (AZP-3601) in patients with chronic
hypoparathyroidism (CALYPSO). NCT Identifier: NCT05778071.
Available here.
Accessed March 2025.
Adrian Kemp
Company Secretary
AstraZeneca PLC