BridgeBio encaleret ADH1 三期 CALIBRATE 阳性补充数据在 ASBMR 披露，但核心结果早已读出且 NDA 已获受理，新增预期差有限

BridgeBio Pharma ( BBIO ) reported positive results from a late-stage clinical trial of its experimental drug encaleret, showing improvements in symptoms and bone health among patients with a rare genetic disorder that affects the body's ability to regulate calcium. The company said Sunday that all patients treated with the drug in its Phase 3 CALIBRATE trial reported improvement in at least one symptom of autosomal dominant hypocalcemia type 1 (ADH1), compared with 46% of patients receiving standard treatment. BridgeBio shares have fallen 15% since the beginning of the year, underperforming the broader biotechnology sector. The State Street SPDR S&P Biotech ETF ( XBI ) has gained 26% during the same period. Drug targets underlying cause ADH1 is an inherited disorder that causes abnormally low calcium levels in the blood. Patients can experience muscle cramps, spasms, fatigue, tingling sensations and difficulty concentrating. The condition can also lead to kidney stones and other serious kidney complications. Current treatment generally involves calcium supplements and active vitamin D. BridgeBio's therapy is designed to address the underlying cause of the disorder by helping the body restore its natural production of parathyroid hormone, which regulates calcium levels. After 24 weeks of treatment, 91% of patients receiving the experimental therapy had parathyroid hormone levels at or above the lower limit of normal, compared with none of those receiving standard care. Researchers also observed increased markers of bone formation and breakdown, suggesting that the drug may help restore more normal bone activity. "These findings suggest that encaleret is addressing the underlying biology of the disease, not just correcting blood calcium," said Dr. Erik Imel of Indiana University School of Medicine, who presented the findings at the American Society for Bone and Mineral Research annual meeting in Boston. Patients report less fatigue, muscle pain The trial also showed improvements in symptoms that affect patients' everyday lives. About 61% of patients receiving the drug reported reduced fatigue, compared with 27% of those receiving standard care. Muscle cramps improved in 58% of treated patients, compared with 36% in the comparison group. Other reported improvements included muscle spasms, tingling sensations and brain fog. Nearly half of patients taking the experimental treatment reported less brain fog, compared with 9% of patients receiving conventional care. Patients were also more likely to report improvements in their mood, physical activities and ability to work. The findings provide additional evidence of the therapy's potential benefits, although the results are based on patient-reported outcomes and changes in biological markers. The drug remains investigational and has not yet received regulatory approval. FDA decision expected in May 2027 For investors, the next major milestone is a decision by the U.S. Food and Drug Administration on whether to approve the treatment for ADH1. The FDA has accepted BridgeBio's new drug application and granted it priority review, setting a target decision date of May 8, 2027. Priority review shortens the agency's review timetable but does not guarantee approval. BridgeBio ( BBIO ) has also submitted an application seeking approval from European regulators. The company is pursuing a potentially larger market through a separate Phase 3 trial involving patients with chronic hypoparathyroidism, a condition in which the body produces insufficient parathyroid hormone. BridgeBio ( BBIO ) said the first participant has received treatment in that study, called RECLAIM-HP, which plans to enroll approximately 160 adults and adolescents. The trial will compare the drug with a placebo over 24 weeks, measuring whether patients can achieve target calcium levels in both their blood and urine. Researchers will also evaluate whether treatment reduces patients' dependence on conventional therapies. Chronic hypoparathyroidism affects an estimated 200,000 or more people in the United States and European Union, according to BridgeBio. Expansion into this broader condition could increase the drug's commercial opportunity beyond ADH1, although success in the larger patient population remains unproven. The latest findings strengthen BridgeBio's ( BBIO ) clinical case as it approaches a regulatory decision next year. Investors will be watching whether the FDA agrees that the drug's benefits and safety profile support approval, and whether the separate trial can establish its usefulness in a larger market.