Palopegteriparatide

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. Thiazide diuretics are used as adjuncts to reduce urinary calcium excretion, and PTH analogues have been explored off-label, but no agent has been approved specifically for ADH1. Palopegteriparatide (Yorvipath), approved by the US FDA in August 2024, addresses hypoparathyroidism in adults through PTH replacement — a distinct condition and mechanism from ADH1, and one for which the label does not cover ADH1 patients. Mechanism and broader development context Encaleret is a small molecule designed to selectively reduce CaSR sensitivity, thereby restoring normal PTH secretion and correcting both hypocalcemia and hypercalciuria simultaneously. This mechanism targets the root cause of ADH1 rather than managing downstream calcium levels, a distinction that differentiates it from all current approaches. The drug carries Fast Track Designation from the US FDA and Orphan Drug Designation in the US, EU, and Japan. BridgeBio is also enrolling CALIBRATE-PEDS (NCT07080385), a global registrational Phase II/III study of encaleret in pediatric ADH1, reflecting the recognized absence of approved options in younger patients. The company plans to initiate RECLAIM-HP, a Phase III study of encaleret in chronic hypoparathyroidism, in summer 2026, building on Phase II proof-of-concept data showing PTH-independent effects on renal calcium handling. The company cited claims data indicating that nearly 2,000 individuals have been diagnosed with autosomal dominant hypocalcemia in the US since October 2023, which it described as suggestive of elevated diagnostic activity in the condition. If approved, encaleret would enter a rare-disease endocrinology space where disease-modifying oral therapies remain absent, and where the standard of care has required patients and clinicians to accept an unresolvable trade-off between symptom control and renal risk. This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: https://allsci.com/news/ Your email address will not be published. Required fields are marked * Comment * Name * Email * Website Copyright © 2026. AllSci Corp. All rights reserved.