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Evidence: MediumPeptideIn Clinical TrialsPTH1 receptor agonist peptidePhase 3 (CALYPSO) met its primary end pointNot approved

Eneboparatide

A once-daily injected peptide that does parathyroid hormone's job at its receptor, for people whose parathyroid glands no longer work

In hypoparathyroidism the body makes too little parathyroid hormone (PTH), so blood calcium falls and people live on calcium tablets and active vitamin D. Eneboparatide is a synthetic peptide that activates PTH's receptor and is injected once a day. In a phase 2 study most patients could stop their calcium and vitamin D within three months. Its phase 3 trial, CALYPSO, met its main goal in 2026, but in fewer patients (about a third), and most patients made antibodies to it. It is not approved anywhere.

Used in human trials: 10 or 20 µg to start, titrated to 60 or 80 µg, Once daily, Subcutaneous (Phase 2 (2024): chronic hypoparathyroidism) Details ↓

Overview

What is it?

The parathyroid glands, four rice-sized glands behind the thyroid, release parathyroid hormone to keep blood calcium steady: it frees calcium from bone, makes the kidneys hold on to calcium and lose phosphate, and switches on vitamin D. Most people who lose that hormone have had neck surgery. The standard treatment, calcium tablets and active vitamin D taken several times a day, raises blood calcium but does not replace the hormone's action on the kidney, so calcium spills into the urine, and over years that can damage the kidneys. Reviews from 2024 to 2026 describe the shift towards replacing the hormone itself.

Eneboparatide, first called AZP-3601, is one of those replacements. It is a synthetic peptide that activates the type 1 PTH receptor, the one PTH uses in bone and kidney. It is not a copy of PTH: its developers built it so that one daily injection keeps calcium up for the whole day, even though the drug itself leaves the blood quickly. In 104 healthy volunteers, blood levels peaked 5 to 20 minutes after injection and fell fast, yet calcium rose and phosphate fell for much longer, and urine calcium did not rise with dose.

The phase 2 study gave it to 28 adults with hypoparathyroidism for three months, starting at 10 or 20 micrograms a day and raising the dose while their usual calcium and vitamin D were withdrawn. At least 88% came off conventional therapy entirely while blood calcium stayed in the target range, and urine calcium fell, including in people who had too much calcium in their urine at the start. Bone turnover markers rose a little and bone density did not change, which the authors read as bone remodelling restarting. That study had no placebo group.

The phase 3 trial, CALYPSO, is the test that counts. Its sponsor is Alexion with Amolyt Pharma as collaborator (NCT05778071), and AstraZeneca reported the 24-week result on May 12, 2026: 31.1% of patients on eneboparatide met a strict composite goal (off active vitamin D, at most 600 mg of calcium a day, and normal blood calcium) against 5.9% on placebo, and urine calcium normalised in 56.6% of those with high levels at the start against 20%. The company also said that most patients developed antibodies to the drug, which reduced its effect in some. That is the maker's summary; the full paper had not appeared on PubMed by October 29, 2026.

The distance between 88% in phase 2 and 31% in phase 3 is the most important thing on this page. The goals differ (phase 3 demanded normal calcium on a fixed dose with almost no supplements), the phase 3 trial was blinded against placebo, and the antibodies may matter. An approved alternative already exists: palopegteriparatide, a long-acting PTH(1-34) prodrug, is approved by the FDA and in Europe.

Eneboparatide is not something sold legitimately outside a trial. Calcium control in hypoparathyroidism is fragile: too much drug pushes blood calcium too high, and too little lets it fall back while the tablets are being withdrawn. Trial patients titrated it under frequent blood tests.

≥88%
Off calcium and active vitamin D at 3 months, phase 2
28 patients, no placebo group · PMID 38449442
31.1%
Met the CALYPSO primary end point at week 24
Against 5.9% on placebo; AstraZeneca release, May 12, 2026, on NCT05778071
5-20 min
Time to peak level after injection
Calcium effect lasts much longer than the drug · PMID 40423237
Science

Mechanism of Action

Eneboparatide activates the type 1 parathyroid hormone receptor, standing in for the hormone the patient lacks.

🦴

PTH1 receptor in bone and kidney

Activating the receptor raises blood calcium and lowers blood phosphate (PMIDs 40423237, 38449442).

💧

Less calcium lost in urine

Unlike calcium tablets, it lowered 24-hour urine calcium in patients, including those with high levels at baseline (PMID 38449442).

⏱️

Short in the blood, long in effect

Levels peak within 20 minutes and fall quickly, but the calcium effect lasts through the day, which supports once-daily dosing (PMID 40423237).

🔄

Bone turnover restarts

Bone formation and resorption markers rose slightly in patients while bone density was unchanged (PMID 38449442).

Evidence

Published Research

These are the studies of eneboparatide read from their PubMed abstracts on October 29, 2026: the phase 1 trial in healthy volunteers, the phase 2 trial in hypoparathyroidism, a mouse study, and four reviews of treatment that assess it. The reviews' titles do not name it; they are carded because their abstracts discuss eneboparatide by name. The phase 3 CALYPSO results are not yet published in a journal and are described from the company's release.

Human2024

Phase 2: off calcium and vitamin D

In an open-label study, 28 adults with hypoparathyroidism (mean age 58) injected eneboparatide daily for three months, starting at 20 or 10 micrograms and titrating up to 60 or 80 micrograms while conventional therapy was withdrawn. At least 88% became independent of calcium and active vitamin D with blood calcium in range, and 24-hour urine calcium fell quickly. There were no serious adverse events.

PMID: 38449442
Human2025

Phase 1 in healthy volunteers

In a randomised, placebo-controlled study of 104 healthy adults given single or repeated ascending doses, blood levels peaked 5 to 20 minutes after injection and the half-life was short, yet blood calcium rose and phosphate fell for longer, and urine calcium did not rise with dose. Bone markers did not change; adverse events were mild to moderate, none serious.

PMID: 40423237
Animal2026

Mice with an inherited low-calcium disorder

In mice modelling autosomal dominant hypocalcaemia type 1, where an overactive calcium sensor keeps calcium low, eneboparatide raised blood calcium without raising urine calcium. An animal result in a different form of the disease.

PMID: 41712458
Review2024

Re-establishing PTH's effects

A review of hypoparathyroidism treatment describes the shortfalls of calcium and active vitamin D, the phase 3 results of palopegteriparatide, and eneboparatide as another long-acting agent at the PTH receptor then in phase 3.

PMID: 38572533
Review2025

Current and emerging therapies

Compares PTH(1-34), PTH(1-84) and palopegteriparatide, now FDA- and EMA-approved, and lists eneboparatide among emerging therapies in phase 3, with the calcilytic encaleret for autosomal dominant hypocalcaemia type 1.

PMID: 40680836
Review2026

From laboratory to clinic

A broad review of diagnosis and treatment groups eneboparatide with palopegteriparatide and canvuparatide as PTH analogues with extended action that cut the need for active vitamin D and calcium, alongside calcilytics and cell-based therapies.

PMID: 42705258
Review2026

Clinical trials and recent approvals

Reviews the epidemiology, complications and treatment of hypoparathyroidism, with palopegteriparatide as the established long-acting option and eneboparatide among the investigational therapies.

PMID: 42907422
Dosing

Dosing Data

Eneboparatide has no approved label. The row below is the regimen of the published phase 2 study, from its abstract. In CALYPSO (NCT05778071), according to AstraZeneca's May 2026 release, patients started at 20 micrograms a day and titrated in 10-microgram steps, at least a week apart, up to 100 micrograms; that trial is not yet published in a journal, so it is not tabled.

A trial regimen titrated against frequent calcium blood tests while calcium and vitamin D were withdrawn, not a recommendation. Calcium can swing dangerously high or low; this is never something to try without a specialist.
ProtocolDoseFrequencyDurationRoute
Phase 2 (2024): chronic hypoparathyroidism Human studyPMID 3844944210 or 20 µg to start, titrated to 60 or 80 µgOnce daily3 monthsSubcutaneous

Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.

A pre-filled pen in the trials
Trial patients injected a daily dose of tens of micrograms from a pre-filled pen and adjusted it against blood calcium; there is no approved product and nothing to reconstitute.
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For Buyers

What a Buyer Needs to Know

What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.

What is sold

Unknown: we hold no label and no published test that says what forms or vial sizes Eneboparatide is sold in. A vial's own label is a seller's claim, not a source.

Mixing a vial: a worked example

An arithmetic example, not a recommendation: a 5 mg vial mixed with 2 mL of bacteriostatic water holds 2,500 mcg per mL, so 10 µg, the first amount in the “Phase 2 (2024): chronic hypoparathyroidism” row (10 or 20 µg to start, titrated to 60 or 80 µg) would be 0.4 units, too little to measure on a U-100 syringe. Put your own vial's numbers into the reconstitution calculator.

Source: dose: Used in human trials, PMID 38449442 (Dosing Data below); vial and water: the calculator's default example, not a vial size we have a source for.

Storage before and after mixing

Unknown: no label or published stability study on file says how to store Eneboparatide, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Eneboparatide stays intact once mixed.

How it is taken

As it was given in human studies: Subcutaneous (Once daily; Phase 2 (2024): chronic hypoparathyroidism).

For injection technique, sites and needle disposal, see the mixing guide.

Source: Used in human trials: the route and frequency of each row in Dosing Data below.

What to expect, and when

How long it stays in the body: a half-life of short; peak 5-20 minutes after injection. After about five half-lives almost none is left.

How long the doses were given: Phase 2 (2024): chronic hypoparathyroidism: 3 months.

When effects appear: unknown; no source on this page gives a time to effect for Eneboparatide. Results reported in the studies are under Published Research.

Source: half-life: PMID 40423237; Used in human trials, the duration of each row in Dosing Data below.

Side effects, and when to stop or get help

From the Side Effects section: No serious adverse events in the phase 2 study of 28 patients (PMID 38449442); Adverse events in healthy volunteers were mild to moderate, none serious (PMID 40423237); In CALYPSO most patients developed antibodies to the drug, which reduced its effect in some (AstraZeneca, May 12, 2026); Adverse events in CALYPSO were balanced between drug and placebo through week 24, according to the company. Full list and cautions ↓

When to stop or get help: unknown; no label or trial on file sets rules for stopping Eneboparatide. Treat a severe or unexpected reaction as a reason to stop and see a doctor.

Source: the Side Effects section below (“From the trials read and AstraZeneca's phase 3 release”).

Interactions

Unknown: a PubMed search for human interaction studies of Eneboparatide (reviewed 2026-10-28) found none. Unknown is not the same as safe to combine.

Every peptide's record, with its source: the interaction matrix.

Checking what you bought

Unknown: no published independent test of Eneboparatide products is in our lab-results database yet, so how products sold under this name measure up is not known.

To read a certificate of analysis, paste it into the COA decoder; it checks the measured mass against Eneboparatide's expected mass, 4,265.0 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.

Legal status

US: In Clinical Trials (Not approved anywhere). Sport: Prohibited (S0 catch-all).

Country by country ↓ · Regulatory tracker

Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.

Safety

Side Effects & Contraindications

Reported Side Effects

From the trials read and AstraZeneca's phase 3 release.

● No serious adverse events in the phase 2 study of 28 patients (PMID 38449442)
● Adverse events in healthy volunteers were mild to moderate, none serious (PMID 40423237)
● In CALYPSO most patients developed antibodies to the drug, which reduced its effect in some (AstraZeneca, May 12, 2026)
● Adverse events in CALYPSO were balanced between drug and placebo through week 24, according to the company

Contraindications & Cautions

There is no label. These cautions come from the trial designs and from the condition.

● Only for diagnosed chronic hypoparathyroidism, under an endocrinologist with frequent calcium checks
● Calcium has to be checked often while the dose is set: in the trials it was titrated against blood tests
● CALYPSO excluded people at increased risk of osteosarcoma (NCT05778071)
● CALYPSO excluded pregnant and breastfeeding women (NCT05778071)
Questions

Frequently Asked Questions

?What is eneboparatide?

A synthetic peptide, first called AZP-3601, that activates the parathyroid hormone receptor. It is being developed as a once-daily injection for chronic hypoparathyroidism.

?Does it work?

In a three-month phase 2 study, at least 88% of 28 patients stopped calcium and active vitamin D with calcium in range. In the larger placebo-controlled phase 3, 31.1% met a stricter goal against 5.9% on placebo, according to AstraZeneca.

?Why did phase 3 look weaker than phase 2?

The phase 3 goal was stricter and was tested against placebo, and the company reports that most patients made antibodies to the drug, which reduced its effect in some. The full results are not yet published.

?Is it approved?

No. It has FDA fast track and orphan designations, according to AstraZeneca, but no approval anywhere as of October 29, 2026.

?How is it different from palopegteriparatide?

Palopegteriparatide releases PTH(1-34) slowly from a prodrug and is already approved. Eneboparatide is a different peptide that acts quickly and briefly in the blood but has a calcium effect lasting the day.

?How long does it last?

Blood levels peak 5 to 20 minutes after injection and the half-life is short; the calcium-raising effect lasts much longer, which is why it is given once a day.

Bibliography

References

  1. [clinical-trial] Takacs I, et al. "An Open-label Phase 2 Study of Eneboparatide, a Novel PTH Receptor 1 Agonist, in Hypoparathyroidism." J Clin Endocrinol Metab, 2024;109(9):2199-2209. PMID: 38449442.
  2. [clinical-trial] Ovize M, et al. "Phase 1 clinical trial of eneboparatide, a novel PTH receptor 1 agonist." Endocr Connect, 2025;14(6). PMID: 40423237.
  3. [pubmed] Hannan FM, et al. "Long-acting parathyroid hormone receptor agonist rectifies hypocalcemia in autosomal dominant hypocalcemia type 1 mice." J Clin Invest, 2026;136(7). PMID: 41712458.
  4. [review] Rejnmark L. "Treatment of Hypoparathyroidism by Re-Establishing the Effects of Parathyroid Hormone." Endocrinol Metab (Seoul), 2024;39(2):262-266. PMID: 38572533.
  5. [review] Khan S, et al. "Chronic Hypoparathyroidism-Current and Emerging Therapies." Endocr Pract, 2025;31(11):1478-1487. PMID: 40680836.
  6. [review] Brandi ML, et al. "Hypoparathyroidism: translating science from the laboratory to the clinic." Lancet Diabetes Endocrinol, 2026;14(11):927-951. PMID: 42705258.
  7. [review] De Leo S, et al. "Hypoparathyroidism: a review of clinical trials and recent approvals." Expert Opin Pharmacother, 2026. PMID: 42907422.
  8. [manufacturer] AstraZeneca press release, May 12, 2026: eneboparatide normalised serum calcium and achieved independence from supplements in 31.1% of adults with hypoparathyroidism at week 24 in the CALYPSO phase 3 trial (5.9% on placebo).
  9. [clinicaltrials] ClinicalTrials.gov NCT05778071: "A Phase 3 Multicenter, Randomized, Placebo-controlled, Double-blind Study to Evaluate the Efficacy and Safety of Eneboparatide (AZP-3601), a Parathyroid Hormone Receptor Agonist, in Patients With Chronic Hypoparathyroidism (CALYPSO)" Alexion Pharmaceuticals, Inc.. Phase 3, active not recruiting, June 2023 to November 2024 (primary completion), 165 participants. Registry record read October 28, 2026.
  10. [other] PubChem CID 172915634, Eneboparatide: formula C191H312N60O49S, molecular weight 4265. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/172915634

Sources & Citations

Every study on this page was read from its PubMed record on October 29, 2026. The phase 3 results come from AstraZeneca's press release of May 12, 2026 and will be replaced by the journal paper when it appears; trial status from ClinicalTrials.gov, checked October 29, 2026. Grey Peptides sells nothing and links to no vendor.

Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.

Last reviewed: 2026-10-29