BridgeBio Pharma submits FDA NDA for Encaleret in ADH1 backed by positive Phase 3 CALIBRATE trial results.
Written By: Mahathi Palivela, PharmD
Reviewed By: Pharmacally Editorial Team
BridgeBio Pharma has announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration seeking approval of encaleret for the treatment of individuals suffering from Autosomal Dominant Hypocalcemia Type 1 (ADH1), a rare inherited endocrine disorder associated with significant unmet medical need.
ADH1 is caused by activating mutations in the calcium-sensing receptor (CaSR), leading to suppressed parathyroid hormone secretion, chronic hypocalcemia, neuromuscular symptoms, and renal complications including nephrocalcinosis and kidney stones. Conventional treatment with calcium and vitamin D supplementation may help manage symptoms but does not address the underlying disease mechanism and can increase the risk of kidney-related complications.
The NDA submission is supported by results from the Phase 3 registrational CALIBRATE trial (NCT05680818), which achieved all pre-specified primary and key secondary efficacy endpoints. Data presented at the European Congress of Endocrinology (ECE) 2026 demonstrated comprehensive normalization of mineral homeostasis in participants treated with encaleret.
In the study, 76% of participants randomized to encaleret achieved both target serum calcium and urine calcium levels compared with 4.4% of the same individuals while on standard of care (p<0.0001). Improvements in calcium metabolism were observed rapidly, with serum calcium increases seen by Day 3 and reductions in urine calcium by Week 3, maintained through Week 24. At Week 24, 91.1% of participants receiving encaleret demonstrated restoration of endogenous parathyroid hormone secretion compared with 0% in the standard-of-care arm.
Encaleret also demonstrated a favorable safety and tolerability profile, with no discontinuations reported in the treatment arm. Rates of serious adverse events were low and comparable between encaleret and standard-of-care arms.
According to BridgeBio Pharma, encaleret has the potential to become the first therapy to directly address the underlying genetic mechanism of ADH1 rather than only managing symptoms.
Encaleret is an investigational oral small-molecule calcilytic therapy designed to selectively modulate the calcium-sensing receptor and restore physiologic calcium regulation by increasing endogenous parathyroid hormone secretion.
The therapy has received Fast Track Designation from the U.S. FDA and Orphan Drug Designation in the United States, European Union, and Japan. The company anticipates a potential U.S. launch in early 2027 and plans to submit a Marketing Authorization Application (MAA) to the European Medicines Agency in the second half of 2026.
BridgeBio is also currently enrolling CALIBRATE-PEDS (NCT07080385), a global registrational Phase 2/3 study evaluating encaleret in pediatric ADH1 patients. In addition, the company plans to initiate the Phase 3 RECLAIM-HP study in chronic hypoparathyroidism in Summer 2026. Beyond ADH1, BridgeBio is positioning encaleret as a potential therapy for chronic hypoparathyroidism, further expanding its role in calcium regulation disorders.
References
BridgeBio Pharma Inc. – BridgeBio Submits NDA to FDA for Encaleret for Individuals Living with ADH1
About the Writer
Mahathi Palivela (LinkedIn) is pursuing PharmD and has a strong interest in Clinical Pharmacy and Patient safety. She is passionate about handling and analyzing patient data, and translating clinical insights into clear, meaningful summaries. She aims to apply this interest in Medical Writing and Pharmacovigilance, focusing on improving patient outcomes through careful data interpretation and communication.