An NDA submission for a first-in-indication oral therapy positions encaleret as a potential alternative to a standard of care that has remained unchanged for decades in autosomal dominant hypocalcemia type 1. BridgeBio Pharma (Nasdaq: BBIO), based in Palo Alto, California, has submitted a New Drug Application (NDA) to the US FDA for encaleret, an investigational oral calcilytic, seeking approval in adults with autosomal dominant hypocalcemia type 1 (ADH1). The filing represents the first NDA submission for a therapy specifically indicated for ADH1, a rare genetic condition for which no approved treatment currently exists.
The company said encaleret may be eligible for priority review, and it anticipates a US launch in early 2027 if approved. BridgeBio also intends to submit a Marketing Authorization Application (MAA) to the European Medicines Agency in the second half of 2026.
CALIBRATE trial results underpin the submission
The NDA is supported by data from the Phase III CALIBRATE trial, a randomized study evaluating encaleret against conventional therapy in patients with ADH1. The trial met all pre-specified primary and key secondary efficacy endpoints.
The primary result showed that 76% of participants randomized to encaleret achieved both target serum calcium and urine calcium levels at Week 24, compared with 4% of the same individuals while on standard of care at Week 4 (p<0.0001). At Week 24, the comparison against those remaining on standard of care showed 76% versus 19% achieving dual calcium targets (p<0.0001).
The data also indicated that encaleret restored endogenous parathyroid hormone (PTH) secretion in 91.1% of participants in the encaleret arm, compared with 0% in the standard-of-care group at Week 24. Improvements in serum calcium were observed as early as Day 3, with reductions in urinary calcium by Week 3, both maintained through Week 24. The safety profile showed no discontinuations in the encaleret arm, with rates of serious adverse events similar between treatment groups.
Primary results from CALIBRATE were presented in an oral session at the European Congress of Endocrinology (ECE) 2026, with the company describing comprehensive normalization of mineral homeostasis across the study population.
The unmet need in ADH1 treatment
ADH1 is caused by gain-of-function mutations in the calcium-sensing receptor (CaSR) gene, which render the receptor hypersensitive to calcium. This suppresses PTH secretion and drives chronic hypocalcemia alongside paradoxically elevated urinary calcium excretion. The condition creates a therapeutic paradox that has defined its management for decades: raising serum calcium through conventional means worsens hypercalciuria, accelerating renal complications including nephrolithiasis and nephrocalcinosis.
Current ADH1 treatment relies on oral calcium supplementation and active vitamin D analogues such as calcitriol, used off-label and targeting symptom management rather than the underlying mechanism. Clinicians typically set a conservative serum calcium target — deliberately below the normal range — to limit renal damage, leaving patients with ongoing neuromuscular symptoms including tetany, muscle cramps, and in some cases seizures.