BridgeBio two for two as rare disease drug aces ph3 trial

BridgeBio's week just went from great to superb, as it reports a second positive topline result in a pivotal trial of a late-stage pipeline drug.

Today's readout comes from the CALIBRATE study of encaleret in patients with autosomal dominant hypocalcaemia type 1 (ADH1), a rare disease caused by a mutation in a gene that regulates thyroid hormones, leading to hypoparathyroidism and low blood calcium. That in turn leads to symptoms like muscle cramps, numbness, and sometimes seizures and memory problems.

In CALIBRATE, encaleret – which targets the calcium-sensing receptor gene (CaSR) that is mutated in ADH1 – was shown to restore blood and urine calcium to normal levels in around three-quarters (76%) of patients within 24 weeks, compared to just 4% of a control group getting standard care.

Study investigator Michael Mannstadt, who is chief of the endocrine unit at the Massachusetts General Hospital, said the result is "remarkable" and a step forward for people living with ADH1, who currently rely on treatment with calcium supplements and active vitamin D.

"Unlike conventional therapy […] encaleret not only increased and maintained both blood calcium and endogenous parathyroid hormone (PTH), but also decreased and maintained urine calcium in the normal range," he added.

"The consistent and clinically meaningful improvements in calcium and mineral homeostasis indicate its potential to become an important new standard of care for this patient community."

BridgeBio said it intends to file for approval of encaleret for adults with ADH1 in the first half of 2026 on the strength of the CALIBRATE data. The news comes just a couple of days after the company also cued up marketing applications for BBP-418 as a treatment for limb-girdle muscular dystrophy (LGMD) type 2I/R9 in the same timeframe.

BBP-418 hit the mark in the phase 3 FORTIFY trial by achieving a significant increase in glycosylated alpha-dystroglycan (αDG), which is impaired in LGMD and causes muscle wasting, initially in the limbs and ultimately in the lungs and heart, typically leading to death before the age of 30.

If both of those candidates reach the market, they will join BridgeBio's transthyretin amyloidosis cardiomyopathy (ATTR-CM) therapy Attruby (acoramidis), which was approved last year as a rival to Pfizer's blockbuster Vyndamax/Vyndaqel/Vynmac (tafamidis).

"We are extremely encouraged by the robust and positive findings of this registrational study, which underscore the potential for encaleret to meaningfully improve the lives of people living with ADH1," said Scott Adler, chief medical officer of Calcilytix, a BridgeBio affiliate that is focused on developing encaleret.

The company said it intends to file for approval of encaleret in adult ADH1 patients in Europe shortly after the FDA filing, and will also start studies of the drug in paediatric ADH1 patients and adults with chronic hypoparathyroidism next year.