FDA accepts BridgeBio’s NDA for encaleret in autosomal dominant hypocalcemia type 1 (ADH1). PDUFA decision set for May 8, 2027, after positive Phase 3 results.
Written By: Rishabh Sonawane, BPharm
Reviewed By: Pharmacally Editorial Team
BridgeBio Pharma has announced that the U.S. Food and Drug Administration (FDA) has accepted the New Drug Application for encaleret, an investigational oral therapy for autosomal dominant hypocalcemia type 1 (ADH1). The application is supported by positive results from the pivotal Phase 3 CALIBRATE trial, in which encaleret met all pre-specified primary and key secondary efficacy endpoints. The therapy normalized blood and urinary calcium levels, restored physiological parathyroid hormone (PTH) secretion, and demonstrated a favorable safety and tolerability profile.
The FDA has assigned a Prescription Drug User Fee Act target action date of May 8, 2027, and has informed the company that it is not currently planning to convene an Advisory Committee meeting to review the application. If approved, encaleret would become the first and only therapy specifically indicated for ADH1, addressing a major unmet need in this rare endocrine disorder.
Phase 3 CALIBRATE Trial Demonstrated Positive Results
The NDA is supported by findings from the Phase 3 CALIBRATE trial (NCT05680818), which achieved all pre-specified primary and key secondary efficacy endpoints. The study demonstrated normalization of blood calcium and urinary calcium levels while restoring physiological PTH secretion, enabling normalization of calcium homeostasis without the need for chronic calcium and active vitamin D supplementation in many participants. These findings support encaleret’s potential as a disease-modifying therapy by correcting the underlying calcium-sensing receptor dysfunction rather than simply treating the consequences of hypocalcemia. The therapy also maintained a favorable safety and tolerability profile throughout the study.
Clinical data presented at the European Congress of Endocrinology (ECE) 2026 and the Endocrine Society Annual Meeting (ENDO) 2026 further confirmed simultaneous restoration of blood and urinary calcium levels together with physiological PTH production.
Targeting the Underlying Cause of ADH1
ADH1 is a rare inherited form of hypoparathyroidism caused by gain-of-function mutations in the calcium-sensing receptor (CASR) gene. Excessive activation of the receptor suppresses PTH secretion and increases urinary calcium loss, resulting in hypocalcemia, hypercalciuria, kidney complications, muscle spasms, fatigue, paresthesia, brain fog, and seizures. Current treatment relies primarily on calcium and active vitamin D supplementation, which helps manage symptoms but does not correct the underlying disease mechanism and may increase the risk of long-term renal complications.
Encaleret is a selective negative allosteric modulator of the calcium-sensing receptor (CaSR) that restores physiological calcium homeostasis by targeting the genetic cause of ADH1 rather than providing symptomatic calcium replacement.
According to BridgeBio, more than 2,100 individuals in the United States had been diagnosed with autosomal dominant hypocalcemia as of April 2026, reflecting growing disease recognition and improved diagnosis of this rare disorder.
Ongoing Development Program
BridgeBio continues to expand the clinical development of encaleret beyond the current NDA. The company is enrolling patients in CALIBRATE-PEDS (NCT07080385), a global Phase 2/3 registrational study evaluating encaleret in pediatric patients with ADH1.
In addition, BridgeBio plans to initiate the RECLAIM-HP global Phase 3 trial in chronic hypoparathyroidism later this summer. The study follows encouraging Phase 2 proof-of-concept findings demonstrating PTH-independent improvements in renal calcium handling and will evaluate the broader therapeutic potential of encaleret in disorders of calcium regulation.
Regulatory Path
Encaleret has received FDA Fast Track designation and Orphan Drug designation in the United States, European Union, and Japan. BridgeBio also plans to submit a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) during the second half of 2026.
If approved, encaleret would become the first disease-specific therapy for ADH1 and the first treatment approved specifically for this rare genetic disorder. By correcting the underlying calcium-sensing receptor dysfunction rather than relying on lifelong calcium replacement.
Reference
BridgeBio Pharma Inc.-BridgeBio Announces FDA Acceptance of NDA for Encaleret for ADH1
About the Writer
Rishabha Sonawane, B.Pharm (LinkedIn) is healthcare writer with a strong interest in medical writing, regulatory affairs, clinical research, and AI-driven drug discovery. He has completed specialized training from the NIH and ICMR in clinical pharmacology, clinical research, and scientific writing. Passionate about evidence-based healthcare communication, he focuses on translating complex scientific research into clear, accurate, and engaging medical content.