BridgeBio Pharma reports symptom gains in Phase 3 encaleret trial
The FDA has accepted the ADH1 application for priority review, with a May 8, 2027 target decision date.
Adrian Kessler
Symptom improvements were reported by all encaleret recipients versus 46 per cent on standard care as BridgeBio Pharma, Inc. NASDAQBBIO presented new Phase 3 rare-disease results on Sunday.
The Oct. 11 release adds patient-reported symptoms and bone turnover findings to CALIBRATE, which studied autosomal dominant hypocalcemia type 1, or ADH1. BridgeBio says the FDA has accepted its encaleret application for priority review, with a May 8, 2027 target action date, and a European application has also been submitted.
BridgeBio is a commercial-stage drug developer focused on genetic conditions, with multiple products and specialized research teams. Encaleret is an investigational oral medicine designed to modulate the calcium-sensing receptor, which regulates parathyroid hormone secretion and calcium handling in the kidneys.
Shares closed at US$65.35, up 0.48 per cent, on Nasdaq at 4 p.m. Eastern on Oct. 9, according to the Google Finance quote for NASDAQBBIO. That close preceded Sunday's presentation and does not measure a response to the new data.
Symptom Findings Add To The Calcium Results
At 24 weeks, fatigue improved in 61.3 per cent of encaleret recipients versus 27.3 per cent on standard care, according to the Oct. 11 release. Muscle spasms improved in 58.1 per cent versus 18.2 per cent, while tingling improved in 51.6 per cent versus 9.1 per cent.
Participants also reported changes in daily functioning: physical activities improved in 45.2 per cent on encaleret versus 9.1 per cent on standard care. Conventional treatment consisted of calcium supplementation and/or active vitamin D.
The release does not give the symptom-analysis sample sizes, p values or confidence intervals. Its bone turnover account reports increases in markers of bone formation and resorption without numerical effect sizes, limiting assessment of those changes.
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The symptom findings supplement a previously successful calcium endpoint. In its May 12 SEC-filed announcement, BridgeBio reported that 76 per cent of encaleret recipients achieved target blood and urine calcium at week 24, versus 4.4 per cent of those same participants during standard care at week four.
That primary comparison had a p value below 0.0001. The separate randomized comparison at week 24 showed 76 per cent reaching both calcium targets on encaleret versus 19 per cent among participants remaining on standard care, also with p below 0.0001.
BridgeBio's May report described no treatment discontinuations in the encaleret arm and low rates of serious adverse events, with similar frequency between the treatment arms. The Oct. 11 release says encaleret restored parathyroid hormone secretion to at least the lower normal limit in 91 per cent of participants, versus none on standard care.
"The observed increases in bone turnover markers following encaleret administration are consistent with the effects of restored endogenous PTH secretion," CALIBRATE presenter Erik Imel said in BridgeBio's release.
A Broader Trial Has Started Dosing
The new findings arrive during regulatory review rather than ahead of an initial U.S. filing. The Oct. 11 release reports application acceptance and priority review, but does not describe an FDA assessment of the new symptom results or give a decision date for Europe.
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BridgeBio also reported the first participant dosed in RECLAIM-HP, a separate Phase 3 trial in chronic hypoparathyroidism. The study plans approximately 160 participants randomized three to one to encaleret or placebo during a 24-week double-blind period.
RECLAIM-HP's primary endpoint is the proportion achieving both blood and urine calcium within target ranges at week 24. BridgeBio's Oct. 11 release estimates chronic hypoparathyroidism affects more than 200,000 people in the U.S. and European Union. The study extends development beyond ADH1, whose genetic variants can suppress hormone secretion and disrupt calcium regulation.
The next dated U.S. milestone for encaleret is the FDA's May 8, 2027 target action date, when the agency is expected to decide on encaleret's application for ADH1.
