BridgeBio’s Calcilytix Reports Proof-Of-Concept for ADH1 Therapy

BridgeBio Pharma announced early results from an ongoing phase 2b proof-of-concept, open-label study of encaleret for the treatment of autosomal dominant hypocalcemia type 1 (ADH1).

Photo: Rachel Gafni, senior research physician and head of the Mineral Homeostasis Studies Group of the National Institute of Dental and Craniofacial Research at the National Institutes of Health

The data are featured in an ePoster presentation at the Endocrine Society’s 2021 Annual Meeting (ENDO 2021).

ADH1 is a rare genetic form of hypoparathyroidism caused by pathogenic variants in the calcium-sensing receptor (CASR) gene that are estimated to be harbored by 12,000 individuals in the United States. Patients with ADH1 experience a range of symptoms associated with low blood calcium and high urine calcium, which cannot be adequately addressed with current standard of care therapies.

Encaleret is an investigational small molecule antagonist of the calcium sensing receptor (CaSR) and is being studied as a potential treatment for ADH1.

“In these initial results from the phase 2b study of encaleret in ADH1, blood and urine calcium levels were normalized in all trial participants within five days of treatment,” said Rachel Gafni, senior research physician and head of the Mineral Homeostasis Studies Group of the National Institute of Dental and Craniofacial Research at the National Institutes of Health.

In these data from the ongoing phase 2b open-label, dose-ranging study, six adults with ADH1 with four distinct CaSR genotypes were administered encaleret. Calcitriol (active Vitamin D) therapy (current standard of care) was discontinued prior to and throughout the study. Non-dietary calcium supplements were withheld in five participants with adequate dietary calcium intake.

Participants received sequential, increasing daily doses of encaleret starting at 30 mg while undergoing intensive safety monitoring and frequent blood and urine sampling for biochemical measures. Following five days of dosing with encaleret, blood calcium, parathyroid hormone, phosphorus, and magnesium were within the normal range on average. Urinary calcium excretion was normal or undetectable in all participants.

Throughout this initial period of dose escalation, encaleret was well-tolerated with no serious adverse events and no adverse events of moderate or severe intensity reported. Two participants experienced transient, asymptomatic hypophosphatemia which was the only treatment-related adverse event. The tolerability and consistent mineral responses following encaleret administration in all six ADH1 trial participants demonstrates proof of concept that encaleret may be an efficacious therapy option for ADH1.

The company said it intends to meet with regulatory health authorities in 2021 to discuss potential paths to registration prior to initiation of a phase 3 registrational study in patients with ADH1. If the development program is successful, encaleret could be the first approved therapy option indicated specifically for the treatment of ADH1.

Author: Rare Daily Staff