AstraZeneca's Eneboparatide Frees 31% of Hypoparathyroidism Patients From Calcium and Vitamin D at Week 24 in CALYPSO Phase III

Overview

AstraZeneca’s investigational rare-disease drug eneboparatide met the composite primary endpoint of its CALYPSO Phase III trial in adults with chronic hypoparathyroidism, with 31.1% of treated patients reaching a normal blood-calcium range while dropping their oral calcium and active vitamin D supplements at week 24, compared with 5.9% on placebo, Pharmaceutical Executive reported. The full late-breaking dataset, including a 52-week open-label extension, was presented on 12 May 2026 at the European Congress of Endocrinology in Prague, according to the AstraZeneca release carried by Mirage News.

It is the largest controlled trial ever run in this small endocrine disease, and the strongest sign yet that eneboparatide — the lead asset AstraZeneca picked up in last year’s $1.05 billion acquisition of Amolyt Pharma — is on track for regulatory submission.

What We Know

Eneboparatide, also designated AZP-3601, is a once-daily subcutaneous parathyroid hormone (PTH) type 1 receptor agonist designed to bind a specific conformation of the receptor to restore PTH function in patients whose own glands cannot, as Clinical Trials Arena describes. Chronic hypoparathyroidism deprives patients of the hormone that regulates blood calcium, leaving them dependent on high-dose oral calcium and active vitamin D — a regimen that controls symptoms only imperfectly and carries long-term kidney risk.

CALYPSO randomized 202 adults across 12 countries in a 2:1 ratio to eneboparatide or placebo on top of standard supplementation, per Pharmaceutical Executive. Treated patients started at 20 micrograms daily and could be titrated upward in 10-microgram steps at minimum seven-day intervals over a 20-week titration period, up to a maximum of 100 micrograms.

The composite primary endpoint required patients to bring albumin-adjusted serum calcium into the normal 8.3 to 10.6 mg/dL band and to come off active vitamin D entirely while taking no more than 600 milligrams of oral calcium per day. At week 24, Pharmaceutical Executive reported, 41 of 132 eneboparatide patients (31.1%) cleared that bar versus 4 of 68 in the placebo arm (5.9%), with a p-value of 0.0001.

After week 24 the study converted to a 28-week open-label extension. Patients originally on the drug stayed on it; patients originally on placebo were switched over. In the continued-treatment group, the AstraZeneca release notes, clinical benefits were maintained through week 52, with some residual use of oral supplements. The release also reports no clinically significant reduction in bone mineral density as measured by BMD T- and Z-scores — a key safety question for any PTH analog, given that long-term over-stimulation of the receptor has historically raised concerns about bone turnover.

The drug was, per AstraZeneca’s own summary, well tolerated over 52 weeks of treatment, with the majority of treatment-emergent adverse events balanced between the eneboparatide and placebo arms through week 24.

Gianluca Pirozzi, Senior Vice President, Head of Development, Regulatory and Safety at Alexion, AstraZeneca Rare Disease, framed CALYPSO as the largest global trial ever run in adults with hypoparathyroidism and said the dataset shows the drug delivering sustained benefits in calcium regulation, symptom burden, physical function, and bone health, the release states.

Eneboparatide carries fast track and orphan drug designations from the US Food and Drug Administration and orphan designation from the European Medicines Agency, Clinical Trials Arena notes.

The Amolyt Backstory

AstraZeneca did not develop eneboparatide in-house. It acquired the drug — along with Amolyt Pharma’s broader endocrine pipeline — for up to $1.05 billion in a deal that closed on 15 July 2024, according to the AstraZeneca press release distributed by GlobeNewswire. The structure was an $800 million upfront cash payment, with a further $250 million contingent on a specified regulatory milestone.

The acquisition was first announced in March 2024 to bolster the Alexion rare-disease unit’s bone-metabolism franchise, Pharmaceutical Executive reported at the time. CALYPSO is the first pivotal trial under AstraZeneca ownership to deliver topline data, and a positive readout takes the $250 million contingent payment a meaningful step closer to triggering — though AstraZeneca has not publicly disclosed what specific milestone the language refers to.

What We Don’t Know

AstraZeneca has not given a date for its planned regulatory filings or said whether it will file simultaneously in the US, EU, and Japan. The full CALYPSO efficacy and safety package — including the week-52 endpoint hierarchy, specific eGFR data on the kidney-protection hypothesis, and per-group adverse event tables — was delivered as a late-breaking ECE presentation; the company has not confirmed when, or in which journal, the data will appear as a peer-reviewed publication.

The headline 31.1% versus 5.9% endpoint is a categorical composite, not a continuous calcium difference. The trial’s published summary does not break out how many additional patients in the eneboparatide arm achieved partial responses — for example, normal calcium but still on a minimal supplement dose — that fell short of the binary composite. Those data will matter to clinicians weighing whether to switch a patient from a controlled-but-symptomatic supplement regimen to a daily injection of a peptide hormone.

Finally, while AstraZeneca has framed CALYPSO as the largest trial ever conducted in chronic hypoparathyroidism — a disease estimated to affect more than 250,000 people across the US, EU5, and Japan, per the AstraZeneca release — 202 randomized patients remains a small absolute number, and durability beyond one year is not yet established.