BridgeBio Pharma has marked another significant milestone in rare disease research, announcing a second late-stage clinical trial success—this time with encaleret, a therapy for the uncommon endocrine disorder autosomal dominant hypocalcemia Type 1 (ADH1). This breakthrough, reported by BioPharma Dive, positions encaleret as a potential new standard for patients with this challenging condition.
ADH1 is a rare genetic disorder characterized by abnormally low blood calcium and excessive urinary calcium, caused by mutations in the CaSR gene. These mutations disrupt the regulation of calcium and parathyroid hormone, leading to neuromuscular symptoms and impaired kidney function. Current treatments primarily rely on calcium and vitamin D supplements, and in severe cases, surgical removal of the parathyroid glands. However, these approaches rarely normalize both blood and urine calcium levels, leaving patients at risk for ongoing complications.
BridgeBio’s late-stage study results for encaleret are striking. After 24 weeks of treatment, 76% of encaleret recipients achieved normalized calcium levels in both blood and urine, compared to just 4% of patients on standard therapy. Moreover, secondary analysis revealed that encaleret restored parathyroid hormone levels in 91% of treated participants—versus only 7% during an initial period on supplements. Notably, all patients who responded were able to discontinue supplemental therapy.
The company reported that encaleret was well tolerated and that its safety profile was consistent with what is known about ADH1. Based on these results, BridgeBio plans to file for regulatory approval next year, aiming to bring a much-needed therapy to the estimated 12,000 people in the U.S. with ADH1—3,000 to 5,000 of whom have uncontrolled or severe disease.
Encaleret works by binding to and inhibiting the overactive CaSR protein, directly addressing the underlying cause of ADH1 rather than simply managing symptoms. This disease-modifying approach could significantly improve quality of life for affected individuals and reduce the need for lifelong supplementation or invasive surgery.
The news comes as part of a banner year for BridgeBio, whose shares have more than doubled on the back of successful launches and late-stage trial results. Alongside encaleret, the company recently achieved pivotal study success for BB-418, a therapy for muscular dystrophy, with both drugs seen by analysts as potential billion-dollar opportunities.
Michael Mannstadt, Chief of the Endocrine Unit at Massachusetts General Hospital and a study investigator, called the findings “an important new standard of care for this patient community.” Analysts echoed this sentiment, with some describing the results as “paradigm shifting” and surpassing even optimistic expectations.
BridgeBio’s latest success not only cements its reputation as a leader in rare disease drug development, but also signals hope for patients with ADH1, offering the prospect of a targeted, more effective therapy on the horizon.
