BridgeBio Announces Positive Phase 3 CALIBRATE Trial Results for Encaleret in Autosomal Dominant Hypocalcemia Type 1 (ADH1)

BridgeBio Pharma announced on October 29, 2025, positive topline results from CALIBRATE, the global Phase 3 study of Encaleret in adults with autosomal dominant hypocalcemia type 1 (ADH1). The company reported that Encaleret met all primary and key secondary endpoints, demonstrating statistical and clinically meaningful improvements in calcium and parathyroid hormone (PTH) homeostasis compared to conventional therapy. The Phase 3 results reinforce Encaleret potential as a novel oral treatment targeting the underlying cause of ADH1, a rare genetic disorder characterized by disrupted calcium sensing. This announcement marks a major milestone as BridgeBio plans to submit a New Drug Application (NDA) to the FDA in the first half of 2026, with further registrational studies planned in pediatric ADH1 and chronic hypoparathyroidism in 2026.

Clinical Evidence: CALIBRATE Phase 3 Trial

Study Design

The CALIBRATE Phase 3 trial was a multicenter, international, randomized, open-label, two-arm, three-period study designed to evaluate the efficacy and safety of Encaleret compared to conventional therapy in adult patients with autosomal dominant hypocalcemia type 1 (ADH1). The study enrolled approximately 70 participants aged 16 years or older, all with genetically confirmed ADH1 and biochemical evidence of hypocalcemia (low serum calcium), low parathyroid hormone (PTH), and hypercalciuria (high urinary calcium). After an initial standard-of-care (SoC) maintenance period, participants were randomized in a 2:1 ratio to receive either Encaleret or SoC for 20 weeks during a titration phase, followed by a 4-week maintenance period with doses adjusted only for safety concerns such as hypo- or hypercalcemia.

Endpoints

The primary composite endpoint assessed the proportion of participants achieving normalization of both albumin-corrected serum calcium within 8.3-10.7 mg/dL and 24-hour urine calcium excretion within sex-specific normal reference ranges (men <300 mg/day; women <250 mg/day). Key secondary endpoints included comparisons of intact PTH levels above the lower limit of normal and other measures of mineral homeostasis, renal health, bone health, and patient-reported outcomes.

Results

CALIBRATE met its primary composite endpoint: 76% (34 of 45) of participants treated with encaleret achieved both target serum calcium and sex-specific 24-hour urine calcium ranges at Week 24, compared with 4% of those same participants while they were on conventional therapy (p<0.0001). Additionally, 91% of Encaleret-treated participants reached intact PTH levels above the lower limit of normal at Week 24 versus 7% on SoC (p<0.0001), indicating restored parathyroid function. Encaleret treatment rapidly normalized serum calcium, with 71% of participants achieving target serum calcium by Day 3 and 98% by Week 20, compared to 33% on SoC. Throughout the study, Encaleret showed sustained improvements in mineral homeostasis without the need for calcium or active vitamin D supplements. The drug was well tolerated, with no study drug discontinuations due to adverse events.

Safety Profile

Encaleret was generally well tolerated throughout the study. There were no study drug-related discontinuations reported. Mild, transient, and manageable adverse events such as asymptomatic hypophosphatemia or hypercalcemia were infrequent and resolved spontaneously or after dose adjustments.