BridgeBio encaleret hits ADH1 endpoints as NDA earns Priority Review
BridgeBio Pharma presented 24-week data from the Phase 3 CALIBRATE trial of encaleret in autosomal dominant hypocalcemia type 1 (ADH1) at the American Society for Bone and Mineral Research annual meeting in Boston, reporting that the oral calcium-sensing receptor modulator outperformed standard of care on both bone turnover and patient-reported outcome measures.
Encaleret stimulated endogenous parathyroid hormone (PTH) secretion to at or above the lower limit of normal in 91% of participants, compared with none in the standard-of-care arm. Bone formation and resorption markers increased in the encaleret group, a finding the investigators interpret as evidence of restored native bone physiology rather than simple correction of blood calcium levels.
Symptom burden and patient-reported outcomes
The patient-reported outcomes presentation, delivered by Steven Ing of Ohio State University, provided some of the most striking figures in the release. Every participant who received encaleret reported improvement in at least one ADH1 symptom, against 46% on standard of care. Symptom-by-symptom comparisons at 24 weeks showed encaleret ahead on fatigue (61% versus 27%), muscle cramps (58% versus 36%), muscle spasms (58% versus 18%), tingling (51% versus 9%) and brain fog (48% versus 9%). Functional impacts, covering mood, physical activities, daily life and work life, all showed a similar directional advantage.
"These findings suggest that encaleret is addressing the underlying biology of the disease, not just correcting blood calcium," said Erik Imel of Indiana University School of Medicine, who presented the bone turnover data.
In parallel, BridgeBio confirmed that the FDA has accepted its new drug application (NDA) for encaleret in ADH1 and granted Priority Review, with a PDUFA target action date of 8 May 2027. The company has also filed a marketing authorisation application with the EMA, meaning a near-simultaneous transatlantic review is now under way.
RECLAIM-HP and the hypoparathyroidism opportunity
Beyond ADH1, BridgeBio dosed the first participant in RECLAIM-HP, a global, randomised, double-blind, placebo-controlled Phase 3 study of encaleret in adults and adolescents with chronic hypoparathyroidism. The trial will enrol approximately 160 participants on a 3:1 active-to-placebo ratio, with the primary endpoint being normalisation of both blood and urine calcium at week 24. Key secondary endpoints include reduction in conventional therapy and long-term safety.
Chronic hypoparathyroidism affects an estimated 200,000 people across the US and EU, most commonly following damage to the parathyroid glands during neck surgery. Current management relies on calcium supplements and active vitamin D, which are associated with hypercalciuria, kidney stones and chronic kidney disease over time. A PTH-restoring oral agent that can regulate urine calcium independently would address a gap that existing therapies leave open.
Market and regulatory context
The hypoparathyroidism field has attracted meaningful attention following the approval of Shire's (now Takeda's) Natpara (PTH 1-84) in the US, though that product has faced supply constraints. BridgeBio's encaleret, as an oral small molecule targeting the upstream calcium-sensing receptor, would offer a distinct mechanism and administration route if approved. The FDA's Priority Review designation reflects the unmet need in ADH1, where no approved therapy exists, and Fast Track and Orphan Drug designations in multiple jurisdictions provide additional regulatory tailwinds.
For investors, the May 2027 PDUFA date and the RECLAIM-HP enrolment start create two near-term catalysts. The absence of a detailed safety summary in the CALIBRATE presentation is the main information gap; BridgeBio has said full data will be available through the conference proceedings, but prescribers and payers will scrutinise the renal endpoints closely given the known complications of hypercalciuria in this patient population.