Eneboparatide Advances in Hypoparathyroidism Trial: Key Phase III Update

Eneboparatide (AZP-3601), an investigational parathyroid hormone 1 receptor (PTH1R) agonist, met its primary endpoint in the CALYPSO Phase III trial, offering new data for adults with chronic hypoparathyroidism.

While detailed outcome data were not shared, suggested that the therapy significantly improved albumin-adjusted serum calcium levels and reduced reliance on active vitamin D and oral calcium therapies.

AstraZeneca received eneboparatide during its $1.05 billion acquisition of Amolyt Pharma — a clinical-stage biotech focused on novel treatments for rare endocrine diseases — expanding its late-stage pipeline in rare diseases and bone metabolism.

Hypoparathyroidism is a rare endocrine disorder caused by a deficiency of parathyroid hormone (PTH), which is key to balancing calcium and phosphate in the blood.

Without proper PTH function, patients may face kidney and bone complications. Many rely on daily calcium and vitamin D supplements, which help but can lead to fluctuations and risks such as excessive calcium loss through urine.

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Eneboparatide is engineered to bind with high affinity to a specific conformation of the PTH1R, essentially mimicking the hormone’s natural action.

In doing so, it helps regulate calcium and phosphate more naturally, potentially limiting urinary calcium excretion and supporting kidney and bone health.

If successful, eneboparatide may offer an alternative for those who have not found sufficient relief with standard treatments, entering a market now served by Ascendis Pharma’s Yorvipath (palopegteriparatide), recently introduced in the US as a once-daily subcutaneous option.

The CALYPSO trial was a global, randomized, double-blind, placebo-controlled, multicenter study involving 202 adults with chronic hypoparathyroidism. Participants were randomized in a 2:1 ratio to receive eneboparatide or a placebo.

The study measured a composite endpoint — patients achieving normalized serum calcium levels and independence from conventional therapies — and also assessed reductions in elevated urinary calcium and patient-reported outcomes.

The investigational therapy was well tolerated over 24 weeks.

Following these results, all patients will continue eneboparatide in a Long-Term Extension Phase until 52 weeks. This extension aims to further characterize its long-term efficacy and safety, with data to be shared with global health authorities and presented at upcoming medical meetings.

AstraZeneca anticipates the first Phase III data for seven new medicines in 2025, along with key indication opportunities for existing therapies.

In 2024, the company’s rare disease revenue grew by 13%, driven by treatments for conditions such as paroxysmal nocturnal hemoglobinuria and hypophosphatasia.

Beyond eneboparatide, AstraZeneca has continued its M&A activity — including the acquisition of Esobiotec towards cell therapy innovation and a licensing agreement with Alteogen for subcutaneous formulations of oncology assets.

In related news, MBX Biosciences recently completed enrollment in its Phase II trial for its PTH peptide prodrug, canvuparatide, while Septerna discontinued its Phase I trial for SEP‑786, an oral small molecule PTH1R agonist, and is pivoting toward next-gen oral therapies.