Encaleret Shows Promising Results in ADH1 Phase 3 Trial

BridgeBio Pharma, Inc. announced positive results from its Phase 3 CALIBRATE trial of encaleret in autosomal dominant hypocalcemia type 1 (ADH1), a genetic condition that affects blood calcium levels and can lead to muscle cramps, tingling, and brain fog. The trial demonstrated that encaleret administration increased bone turnover, as evidenced by the recovery of endogenous parathyroid hormone (PTH) secretion in 91% of participants, compared to 0% on standard of care (SoC).

The company also reported that 100% of participants who received encaleret reported improvements in at least one ADH1 symptom, compared to 46% of those who received SoC. The improvements in daily functioning were also more pronounced among the encaleret group, with 61.3% of participants reporting reduced fatigue, 58.1% experiencing fewer muscle cramps, 58.1% noting less muscle spasms, 51.6% feeling less tingling, and 48.4% experiencing a reduction in brain fog. Additionally, improvements in daily activities, mood and emotions, physical activities, daily life, and work life were more frequently reported among the encaleret group.

Encaleret, an investigational, orally administered small molecule, is designed to selectively negatively modulate the calcium-sensing receptor. The FDA has accepted BridgeBio’s New Drug Application (NDA) for encaleret in ADH1 and granted Priority Review, with a Prescription Drug User Fee Act (PDUFA) target action date of May 8, 2027. The company has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA).

In partnership with the HypoPARAthyroidism Association (HPA), BridgeBio shared findings from a proband-initiated model that evaluated the effectiveness of bringing no-cost genetic testing and counseling directly to at-risk relatives in their home regions. The study found that 44% of participants (N=27) were symptomatic at the time of testing, and 77% of those individuals had exhibited symptoms for more than two years.

BridgeBio also dosed the first participant in RECLAIM-HP (NCT07805356), a global, randomized, double-blind, placebo-controlled Phase 3 study designed to evaluate the efficacy and safety of oral encaleret in adults and adolescents with chronic hypoparathyroidism. Approximately 160 participants will be enrolled and randomized 3:1 to receive encaleret or placebo during the 24-week double-blind treatment period. The primary endpoint is the proportion of participants achieving both blood and urine calcium within the target range at Week 24.

Chronic hypoparathyroidism, a rare endocrine condition affecting more than 200,000 people across the U.S. and EU, is characterized by insufficient production of parathyroid hormone, leading to hypocalcemia and a range of symptoms and complications. The condition is often managed with calcium supplements and active vitamin D, which can be associated with long-term complications such as excess calcium excretion in the urine, kidney stones, and chronic kidney disease.

BridgeBio’s encaleret program is advancing rapidly, with the first participant dosed in RECLAIM-HP marking an important step toward addressing the needs of individuals living with chronic hypoparathyroidism.