BridgeBio Reports Positive Phase 3 Topline Results for ADH1 Therapy

Rare Daily Staff

BridgeBio reported that phase 3 topline results for its experimental therapy, encaleret, for autosomal dominant hypocalcemia type 1—a rare genetic form of hypoparathyroidism—met all pre-specified primary and key secondary efficacy endpoints.

The primary endpoint, defined as the proportion of participants randomized to receive encaleret who achieved both serum calcium and urine calcium in the respective target ranges, was achieved by 76 percent of encaleret-treated participants, compared to 4 percent for these same participants while on conventional therapy.

Encaleret was well tolerated, with no discontinuations related to the study drug.

BridgeBio plans to submit a New Drug Application to the U.S. Food and Drug Administration in the first half of 2026, and also plans to study encaleret in chronic hypoparathyroidism and pediatric ADH1 next year. If approved, encaleret could become the first targeted oral therapy for ADH1—directly addressing the underlying cause, rather than just managing calcium levels with supplements and active vitamin D.

Autosomal dominant hypocalcemia type 1 (ADH1) is caused by pathogenic variants in the calcium-sensing receptor gene (CASR), which senses the level of calcium in the body and regulates the amount of calcium in the blood through its effects on the parathyroid glands, the kidney, and bone. Patients with ADH1 have low blood calcium (hypocalcemia), low or low-normal parathyroid hormone levels, and excess urinary excretion of calcium (hypercalciuria). Hypocalcemia can cause severe muscle cramping and seizures, while hypercalciuria can lead to impaired kidney function and kidney stone formation. The current standard of care for ADH1 patients consists of oral calcium supplements in excess of typical dietary requirements for people with normal CaSR function, and activated vitamin D, which can partially correct hypocalcemia but typically worsens both hypoparathyroidism and hypercalciuria.

Encaleret is an experimental, orally administered small molecule under investigation to treat ADH1. It is designed to selectively and negatively modulate the calcium-sensing receptor, targeting ADH1 at its source. Encaleret has received Fast Track designation from the U.S. FDA, and Orphan Drug Designation in the United States, European Union, and Japan.

“The remarkable results of the landmark CALIBRATE study represent an important step forward for patients living with ADH1,” said Michael Mannstadt, chief of the Endocrine Unit at Massachusetts General Hospital. “Unlike conventional therapy with calcium supplements and active vitamin D, encaleret not only increased and maintained both blood calcium and endogenous parathyroid hormone (PTH), but also decreased and maintained urine calcium in the normal range. The consistent and clinically meaningful improvements in calcium and mineral homeostasis indicate its potential to become an important new standard of care for this patient community.”