Encaleret for hypoparathyroidism

Last updated June 26, 2025, by Margarida Maia, PhD
Fact-checked by Jose Lopes, PhD

What is encaleret for hypoparathyroidism?

Encaleret is an orally administered small molecule being developed by Bridgebio for the treatment of autosomal dominant hypocalcemia type 1 (ADH1) — a rare type of hypoparathyroidism caused by mutations in the CASR gene — and chronic hypoparathyroidism. It has received fast track designation in the U.S., in addition to orphan drug status in the U.S., the European Union, and Japan.

Symptoms of hypoparathyroidism occur when the body does not produce enough parathyroid hormone (PTH), which helps maintain balanced levels of calcium and phosphorus in circulation. In ADH1, the condition is caused by genetic mutations that result in an overly sensitive calcium-sensing receptor, or CaSR. This protein works to detects levels of calcium outside cells. As a result of being overly sensitive, it wrongly signals the parathyroid gland to stop releasing PTH.

Known as a calcilytic, encaleret works by blocking CaSR, decreasing its sensitivity to extracellular calcium. This is expected to signal the parathyroid gland to release more PTH, helping to restore calcium to normal levels in the blood and urine, and easing symptoms of hypoparathyroidism. Unlike standard treatment with oral supplements of calcium and vitamin D, encaleret uses the body’s own mechanisms to normalize levels of calcium.

Therapy snapshot

How will encaleret be administered?

In clinical trials, encaleret is being tested as tablets taken once or twice daily by mouth.

Encaleret in clinical trials

Encaleret is being tested for both ADH1 and chronic hypoparathyroidism.

• In an open-label Phase 2 clinical trial (NCT04581629) involving 13 adults with ADH1, encaleret was given twice daily for 24 weeks, or about six months. The treatment brought blood levels of calcium into the normal range and reduced the excessive levels of calcium in urine. The dose needed to maintain calcium within normal levels ranged widely across participants — from 5 to 190 mg — but remained mostly stable for each patient over time.
• A larger, fully enrolled Phase 3 clinical trial, called CALIBRATE (NCT05680818), is testing encaleret against standard of care treatment with oral calcium and/or an active form of vitamin D for ADH1. This study involves 71 adults and adolescents, ages 16 and older, and is being conducted at 25 locations globally. Its main goal is to compare the number of patients who achieve normal levels of calcium in blood and urine within 24 weeks.
• In a small proof-of-concept clinical trial involving nine adults with chronic hypoparathyroidism, most (78%) achieved normal levels of calcium in both blood and urine within five days.
• An ongoing investigator-initiated Phase 2 clinical trial (NCT05735015) is testing encaleret — given twice daily for five days — in as many as 30 adults with postoperative hypoparathyroidism, which develops after a surgical procedure that removes or accidentally damages the parathyroid glands. The main goal is to watch for a reduction in fractional excretion of calcium, a measure of how much calcium is cleared in urine relative to the amount filtered by the kidneys. Early data from four patients showed that encaleret reduced the fractional excretion of calcium by 52%. On average, blood calcium increased from 8.4 to 9.3 mg/dL, while urinary calcium excretion normalized in three participants and decreased in the fourth.

Encaleret side effects

The most common side effects reported with encaleret in clinical trials were:

• transient hypercalcemia, or elevated blood calcium
• transient hypophosphatemia, or reduced blood phosphorus.

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