AstraZeneca announced today that eneboparatide (AZP-3601), its investigational parathyroid hormone (PTH) receptor 1 agonist, has met the primary endpoint in the Phase III CALYPSO trial for adults with chronic hypoparathyroidism (HypoPT).
The trial demonstrated that eneboparatide achieved statistically significant normalization of albumin-adjusted serum calcium levels while eliminating the need for active vitamin D and oral calcium therapy at 24 weeks compared to placebo.
"People living with HypoPT, a rare endocrine disease, are often at increased risk of hypercalciuria, osteopenia and osteoporosis," said Marc Dunoyer, Chief Executive Officer of Alexion, AstraZeneca Rare Disease. "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 characterize the risk-benefit profile."
Understanding Hypoparathyroidism
Hypoparathyroidism is a rare endocrine disorder characterized by insufficient production of parathyroid hormone (PTH), leading to impaired regulation of calcium and phosphate levels in the blood. This dysregulation can result in serious clinical manifestations affecting multiple body systems, particularly the kidneys and bones.
The condition affects over 200,000 people in the United States and European Union, with approximately 80% of patients being women. In about 75% of cases, the disease results from injury to or removal of the parathyroid glands during neck surgery.
Current standard of care typically involves supplementation with active vitamin D and oral calcium, which can be burdensome and may not adequately address all aspects of the disease. Many patients continue to experience significant symptoms and complications despite treatment.
The CALYPSO Trial Design and Results
The global Phase III CALYPSO trial enrolled 202 adult patients with chronic hypoparathyroidism who were receiving standard of care treatment. Participants were randomized in a 2:1 ratio to receive either eneboparatide or placebo.
The primary efficacy endpoint was a composite measure assessing the proportion of patients who achieved:
- Albumin-adjusted serum calcium within the normal range
- Independence from standard of care (active vitamin D and oral calcium supplementation)
After 24 weeks of treatment, eneboparatide met this primary endpoint with statistical significance compared to placebo. The drug was reported to be well-tolerated, though detailed safety data have not yet been released.
Key secondary endpoints in the trial include:
- Normalization of 24-hour urinary calcium in patients with hypercalciuria at baseline
- Assessment of patient-reported outcomes reflecting physical symptoms and quality of life
Following the 24-week randomized treatment period, all participants are now receiving eneboparatide in an ongoing long-term extension phase that will continue until the 52-week mark.
Mechanism of Action and Development Status
Eneboparatide is designed to bind with high affinity to a specific conformation of the PTH receptor 1, effectively restoring PTH function to manage the symptoms of hypoparathyroidism while preserving kidney function and bone health.
The drug has received significant regulatory support, having been granted:
- Fast track designation by the US Food and Drug Administration
- Orphan drug designation by both the FDA and the European Medicines Agency
These designations acknowledge the serious nature of hypoparathyroidism and the potential for eneboparatide to address substantial unmet needs in this patient population.
Looking Forward
AstraZeneca plans to analyze the full efficacy and safety data at the completion of the 52-week study period. These comprehensive results will be shared with global health authorities and presented at upcoming medical meetings.
If approved, eneboparatide would provide a targeted therapeutic option for patients with chronic hypoparathyroidism, potentially offering improved disease management beyond the limitations of current standard treatments.
The development of eneboparatide aligns with Alexion's three-decade commitment to rare disease research and AstraZeneca's broader mission to address significant unmet medical needs through innovative therapies.
For patients living with the challenging symptoms and complications of hypoparathyroidism, these positive Phase III results represent a promising step toward a potential new treatment option that more closely mimics the body's natural hormone function.
