Eneboparatide
Eneboparatide (AZP-3601), a 36-amino-acid hybrid analog of PTH and PTH-related peptide (PTHrP) that acts as a parathyroid hormone receptor 1 agonist for chronic hypoparathyroidism (DOI 10.1210/jendso/bvae163.415; DOI 10.1210/jendso/bvad114.562)
Eneboparatide (AZP-3601) is an investigational PTH1 receptor agonist developed by Amolyt Pharma (now Alexion/AstraZeneca) for chronic hypoparathyroidism, with published phase 1 and phase 2 human data and positive phase 3 CALYPSO results reported via press release in March 2025 (PMID 38449442; PMID 40423237; NCT05778071; AstraZeneca press release March 2025).
Last updated: 2026-03-09
Safety Summary
Across the published human studies in the source set, phase 1 reported only mild-to-moderate adverse events and no serious adverse events (N=104, PMID 40423237), and phase 2 likewise reported no serious adverse events (N=28, PMID 38449442). The phase 3 CALYPSO press release stated eneboparatide was well tolerated at 24 weeks (AstraZeneca press release March 2025, MANUFACTURER_STUDY). Individual adverse event types and their frequencies are not itemized in available abstracts or publications.
Who Should NOT Use This
Talk to Your Doctor
Before considering Eneboparatide, discuss it with your healthcare provider. Ask about potential interactions with your current medications, whether it is appropriate for your health conditions, and what monitoring may be needed.
Sources: [1-6]
Evidence Assessment
The CALYPSO phase 3 randomized placebo-controlled trial (NCT05778071) randomized 202 patients and met its primary composite endpoint with statistical significance at 24 weeks, per AstraZeneca press release in March 2025 and corroborated by multiple independent news sources (AstraZeneca press release; BiotechReality; Xtalks; EMPR). Published peer-reviewed evidence also includes a phase 1 RCT in 104 healthy volunteers (PMID 40423237) and a phase 2 open-label study in 28 patients (PMID 38449442). IMPORTANT CAVEAT: The phase 3 results are currently available only via manufacturer press release and news coverage; the full peer-reviewed publication is pending. If the published Phase 3 data do not confirm the press-release claims, the tier should be downgraded to 3.
1An Open-label Phase 2 Study of Eneboparatide, a Novel PTH Receptor 1 Agonist, in Hypoparathyroidism.PMID 38449442
Takacs et al. - The Journal of Clinical Endocrinology and Metabolism (2024) - open-label phase 2 study - 28 patients with hypoparathyroidism
After 3 months, at least 88 percent of patients achieved independence from conventional therapy while mean albumin-adjusted serum calcium stayed in target range; mean 24-hour urinary calcium fell rapidly and persistently; no serious adverse events were reported.
Limitations: Open-label, non-randomized study with small sample size and 3-month follow-up; manufacturer-affiliated authors were included.
2Phase 1 clinical trial of eneboparatide, a novel PTH receptor 1 agonist.NCT05239221PMID 40423237
Ovize et al. - Endocrine Connections (2025) - randomized, double-blind, placebo-controlled phase 1 trial - 104 healthy volunteers
Single and multiple ascending dose cohorts showed dose-dependent increases in serum calcium and decreases in serum phosphorus; urinary calcium did not increase with dose; no serious adverse events were reported.
Limitations: Conducted in healthy volunteers rather than target patients, and manufacturer-affiliated authors were included.
3Evaluation of the Safety and Efficacy of Eneboparatide (AZP-3601) in Patients With Chronic Hypoparathyroidism (CALYPSO)NCT05778071
Alexion Pharmaceuticals, Inc. - ClinicalTrials.gov / AstraZeneca press release (2023) - phase 3 randomized placebo-controlled double-blind trial - 202 patients randomized (165 originally estimated)
The CALYPSO trial met its primary composite endpoint with statistical significance at 24 weeks per AstraZeneca press release (March 2025). Primary endpoint required normal albumin-adjusted serum calcium with independence from active vitamin D and oral calcium. Eneboparatide was reported as well tolerated. A 132-week open-label extension is ongoing.
Limitations: Results available only via manufacturer press release as of evaluation date. No peer-reviewed publication. Full efficacy data, effect sizes, and detailed safety data not yet publicly available.
4OR23-04 Treatment Of Chronic Hypoparathyroidism With Eneboparatide (AZP-3601), A Novel PTH 1 Receptor Agonist: Results From A Phase 2 Trial
Kamenicky et al. - Journal of the Endocrine Society (2023) - conference abstract from phase 2 trial - 14 patients in the reported second cohort
In the reported cohort, over 90 percent of patients were off active vitamin D and oral calcium at 3 months, serum calcium averaged 8.32 mg/dL at Day 84, and mean 24-hour urinary calcium fell 49 percent by Day 14 in hypercalciuric patients.
Limitations: Conference abstract only, reporting one cohort rather than the entire trial; manufacturer employees were among authors.
58041 Eneboparatide, A Potent Stimulator Of Urinary Calcium Reabsorption, Induces Prolonged Renal Cortex Retention And PTH1 Receptor Signaling
Ravel et al. - Journal of the Endocrine Society (2024) - conference abstract with translational preclinical data - Rats, HEK293 cells, and referenced human chronic hypoparathyroidism observations
Conference data reported higher R0-conformation affinity than PTH1-34 (IC50 1.5 nM vs 30.9 nM), longer renal cortex retention (only 61.4% cleared at 6h vs 96.3%), cAMP EC50 of 0.32 nM vs 0.48 nM, and prolonged cAMP signaling for over 16 hours after washout, offering a mechanistic explanation for reduced urinary calcium with eneboparatide.
Limitations: Conference abstract and largely preclinical, not a definitive human efficacy study; manufacturer-affiliated authors were included.
6Chronic Hypoparathyroidism-Current and Emerging Therapies.PMID 40680836
Khan et al. - Endocrine Practice (2025) - review - Narrative review
This review positions eneboparatide as an emerging phase 3 therapy for chronic hypoparathyroidism within the current treatment landscape, discussed separately from the approved palopegteriparatide.
Limitations: Review article, not primary efficacy data.