BridgeBio's Encaleret Achieves Calcium Normalization in 80% of Post-Surgical Hypoparathyroidism Patients
核心洞察
BridgeBio's oral calcilytic encaleret demonstrated parathyroid hormone-independent normalization of blood and urine calcium in a Phase 2 proof-of-concept study for post-surgical hypoparathyroidism (搜索).
80% of participants achieved normal blood and urine calcium levels within 5 days of encaleret treatment, compared to 0% on conventional therapy at baseline.
The drug was well-tolerated with no serious adverse events, prompting BridgeBio to plan a registrational clinical study in chronic hypoparathyroidism (搜索) for 2026.
BridgeBio Pharma announced promising Phase 2 results for encaleret, an oral calcilytic drug that demonstrated parathyroid hormone-independent normalization of blood and urine calcium in patients with post-surgical hypoparathyroidism (搜索). The findings were presented at the American Society for Bone and Mineral Research (ASBMR) Annual Meeting 2025 in Seattle.
Study Results Show Rapid Calcium Normalization
The Phase 2 proof-of-concept study evaluated ten participants with post-surgical hypoparathyroidism (搜索) who received encaleret at 162 mg twice daily for up to five days. The results showed that 80% of participants achieved concomitant blood and 24-hour urine calcium in the normal reference range within five days of treatment initiation, compared to 0% of participants on conventional therapy at baseline.
"Chronic hypoparathyroidism (搜索) is a challenging condition to manage because treatment involves striking a balance between blood and urine calcium," said Iris Hartley, M.D., endocrinologist and clinician investigator at the National Institute of Dental and Cranial Facial Research of the National Institutes of Health. "With conventional therapy, using calcium and active vitamin D, we typically aim for a low or low-normal blood calcium to reduce the risk of high urinary calcium which can cause kidney calcifications and renal injury."
Mechanism and Safety Profile
Encaleret treatment resulted in a rapid and sustained reduction in fractional excretion of calcium in nine participants with post-surgical hypoparathyroidism (搜索). The drug works by affecting the calcium-sensing receptor (搜索) expressed in the kidney, allowing for calcium normalization without stimulating parathyroid hormone secretion.
The study protocol involved stopping calcitriol one day prior to the first encaleret dose, with subsequent titration of calcium and calcitriol based on blood calcium levels. Importantly, encaleret was well-tolerated with no serious adverse events reported over the study period.
Path to Registration
Based on these encouraging findings, BridgeBio intends to initiate a registrational clinical study of encaleret in chronic hypoparathyroidism (搜索) in 2026. "These Phase 2 results show that encaleret may help normalize blood and urine calcium in patients with chronic hypoparathyroidism, in the absence of stimulating PTH secretion, due to its effect on the calcium-sensing receptor (搜索) expressed in the kidney," said Scott Adler, M.D., Chief Medical Officer of Calcilytix (搜索), a BridgeBio affiliate focused on developing encaleret.
Additional Skeletal Dysplasia Research
During ASBMR 2025, BridgeBio also presented preclinical data from two studies of infigratinib, demonstrating that low-dose infigratinib significantly improved bone growth in a hypochondroplasia (搜索) mouse model and enhanced skull development in a Crouzon/Pfeiffer syndrome (搜索) model. The hypochondroplasia study was recently published in the Journal of Bone and Mineral Research, underscoring the therapy's broad potential for treating skeletal conditions.
The company's presentations at ASBMR 2025 included an oral session by Dr. Hartley titled "The Oral Calcilytic Encaleret Reduced Urinary Calcium While Maintaining Blood Calcium in Individuals with Post-Surgical Hypoparathyroidism (搜索)" and two poster sessions on skeletal dysplasia data presented by Bhavik Shah, Ph.D., Senior Vice President of Research, Genetic Medicine, Skeletal Dysplasia at BridgeBio.