Registrational trial of encaleret in chronic hypoparathyroidism sought
Bridgebio Pharma hopes to launch study of investigational therapy in 2026
Treatment with the investigational therapy encaleret normalized calcium levels for most people with chronic hypoparathyroidism in a small proof-of-principle study.
That’s according to data announced by Bridgebio Pharma, which is developing encaleret with its affiliate Calcilytix Therapeutics. The company said it hopes to launch a clinical trial that could serve as a basis for encaleret’s approval for chronic hypoparathyroidism in 2026.
Hypoparathyroidism is marked by abnormally low levels of parathyroid hormone (PTH), a signaling molecule made by the parathyroid glands. One of the most important roles of PTH is to help regulate calcium in the body, so people with chronic hypoparathyroidism often have abnormally low calcium levels (hypocalcemia).
Encaleret is an oral therapy that’s designed to block the activity of a sensor protein that normally helps measure how much calcium is in the body. By blocking the protein, the therapy essentially signals that calcium levels are too low, activating biological mechanisms to increase them.
A proof-of-principle study tested encaleret in nine people with chronic hypoparathyroidism. After five days, seven participants had normal calcium levels in their blood and urine, according to Bridgebio.
Testing encaleret
The National Institute of Dental and Craniofacial Research (NIDCR) — part of the National Institutes of Health (NIH) — is sponsoring a Phase 2 study (NCT05735015) testing encaleret in adults with hypoparathyroidism due to surgery that damaged or removed the parathyroid glands. The study seeks to enroll 30 participants and recruitment is ongoing at a site in Maryland. All the participants will be treated with encaleret, with the main goal being to evaluate how it affects calcium after about a week.
Bridgebio is also developing encaleret for autosomal dominant hypocalcemia type 1 (ADH1), a rare genetic form of hypoparathyroidism caused by mutations that interfere with how the body senses calcium. There are no approved therapies for ADH1. The U.S. Food and Drug Administration (FDA) has granted encaleret fast track status for ADH1, a designation that’s intended to speed up the development of potentially important new therapies for conditions with unmet medical needs.
The company is also sponsoring a Phase 3 clinical trial called CALIBRATE (NCT05680818) that’s testing encaleret against standard of care with calcium supplements and/or active vitamin D in people with ADH1, with the main goal being to evaluate its effects on calcium after about six months. The study is fully enrolled with 71 participants, which according to Bridgebio makes it “the largest prospective interventional study to ever be conducted in ADH1.” Results are expected this year, the company said.
About the Author
