EB612 (Oral Long-Acting PTH Tablet)
Also known as: Oral long-acting PTH replacement, Entera oral PTH replacement, Oral hypoparathyroidism tablet
Overview
EB612 is an oral tablet formulation of long-acting parathyroid hormone being developed by Entera Bio and OPKO Health for the treatment of hypoparathyroidism. Hypoparathyroidism is a chronic endocrine condition in which the parathyroid glands fail to produce sufficient PTH, leading to hypocalcemia, hyperphosphatemia, and a constellation of neuromuscular and cognitive symptoms that calcium and active vitamin D supplementation often fail to control. Approved PTH replacement options are limited: Natpara (recombinant human PTH 1-84, injectable) was withdrawn from the U.S. market in 2024 due to manufacturing issues, and palopegteriparatide (Yorvipath, injectable) was FDA-approved in 2024. EB612 would, if approved, be the first oral PTH replacement therapy in this orphan indication. As of May 2026 the program is preclinical-to-IND, with Entera planning to file an Investigational New Drug application in late 2026 under an expanded 50/50 partnership with OPKO. Tissue-protective TPTX and PK data have been submitted to ENDO 2026.
Mechanism of Action
PTH replacement therapy in hypoparathyroidism works by restoring physiological PTH signaling at PTH receptor 1 in kidney and bone. In the kidney, PTH increases distal tubule calcium reabsorption, decreases proximal tubule phosphate reabsorption, and activates 1-alpha-hydroxylase to increase active vitamin D synthesis. In bone, intermittent or continuous PTH signaling regulates remodeling. The therapeutic challenge in hypoparathyroidism is matching physiological exposure — too brief and the drug fails to control serum calcium; too sustained and the drug shifts the balance toward bone resorption. EB612 is engineered as a long-acting oral formulation to flatten the exposure curve relative to short-acting PTH and approximate the constant low-level PTH tone of a healthy patient.
Potential Benefits
- Oral administration in an orphan indication where current options require injection
- Long-acting profile designed to approximate physiological PTH tone
- Potential first-line oral alternative to injectable PTH replacement
- OPKO partnership brings hormone biologics development infrastructure
Dosage Protocols
The following reflects doses used in published research studies. This is not medical advice. Consult a qualified healthcare professional.
| Beginner | Investigational only — not available outside trial |
| Intermediate | Investigational only — not available outside trial |
| Advanced | Investigational only — not available outside trial |
| Cycle Duration | Chronic replacement therapy if approved (hypoparathyroidism is a lifelong condition) |
EB612 is not commercially available. Patients with hypoparathyroidism should consult their endocrinologist about approved options (palopegteriparatide/Yorvipath) and standard supportive care.
Use our Reconstitution Calculator to determine exact syringe units for your protocol.
Routes of Administration
Oral (tablet) Not publicly disclosed
Long-acting oral PTH formulation based on the Entera tablet platform that underpins EB613.
Read our full Routes of Administration Guide for detailed comparison of all delivery methods.
Reconstitution
| Storage | Per trial protocol |
|---|
No reconstitution required.
Need exact syringe measurements?
Amino Acid Sequence
Long-acting PTH analog; full sequence not publicly disclosed in current Entera filings
Side Effects & Safety
- Preclinical only — human safety profile not characterized
- PTH-class effects expected: potential for transient hypercalcemia, hypocalcemia between doses, headache, nausea
Safety & Contraindications
This information is for educational purposes only. Consult a qualified healthcare provider before using any peptide.
Investigational only
FDA Safety Information
Investigational. No human safety data publicly available as of May 2026.
Pharmacokinetics
| Half-Life | Long-acting profile by design; specific PK parameters not publicly disclosed |
|---|---|
| Storage | Per clinical trial protocol |
Synergistic Compounds
The following compounds have been studied alongside EB612 (Oral Long-Acting PTH Tablet) for potential complementary or synergistic effects:
Learn More
References & Further Reading
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