BridgeBio Submits NDA for Encaleret for Autosomal Dominant Hypocalcemia Type 1

BridgeBio has submitted its New Drug Application (NDA) for encaleret to the US Food and Drug Administration (FDA) for patients with autosomal dominant hypocalcemia type 1 (ADH1).1

Announced on May 12, 2026, this submission follows positive results from the CALIBRATE phase 3 trial, in which encaleret achieved all pre-specified primary and key secondary efficacy endpoints. Topline data were announced in October of 2025, while full data were presented at the European Congress of Endocrinology on May 12, 2026.1,2,3

“These phase 3 findings are a landmark moment for the autosomal dominant hypocalcemia type 1 community,” Filomena Cetani, MD, PhD, said in a statement. “Encaleret not only has the potential to become the first-ever approved therapy for this rare disease, but it does so by addressing the root cause, restoring normal calcium regulation and lowering the risk of renal complications that individuals on current treatment face every day.”1

CALIBRATE was a global phase 3 study comparing encaleret to standard of care (SOC) in ADH1 – the primary endpoint was the proportion of participants randomized to receive encaleret achieving both serum calcium (8.3-10.7 mg/dL) and urine calcium (<300 mg/day for men and <250 mg/day for women) within the respective target ranges. Secondary endpoints included the proportion of patients achieving intact parathyroid hormone (iPTH) above the lower limit of the reference range, bone turnover markers, renal ultrasound and renal function, among others.2,3

Patients were eligible for inclusion if they had a documented pathogenic activating variant of the calcium-sensing receptor, associated with biochemical findings of hypoparathyroidism, as well as ≥1 symptom of hypoparathyroidism at screening. Patients were also required to be on ADH1 treatment for ≥6 months prior to screening. Patients who had a history of thyroid or parathyroid surgery, renal transplantation, or cancer, among other criteria, were excluded.4

A total of 70 adults with ADH1 were enrolled in the study; of these, 67 were randomly assigned in a 2:1 ratio to either encaleret or SOC. Of these patients, the mean serum calcium was 2.05 mmol/L (standard deviation [SD], 0.19) and the mean 24-hour urine calcium was 9.39 mmol/day (SD, 4.62). 45 patients were assigned to receive encaleret, and 22 were assigned to SOC treatment.2,3

By day 3 following randomization, 71% of the encaleret arm (n = 32) had an albumin-corrected serum calcium within the reference range; by the end of the titration period at week 20, 98% of patients receiving encaleret (n = 44) were within range compared with 33% (n = 21) in the SOC arm. Additionally, by week 24, no encaleret recipients required conventional therapy. 91% of encaleret recipients also achieved restoration of endogenous iPTH.2

Encaleret ultimately achieved a mean increase in change from baseline of corrected calcium by 0.82 mg/dL between week 4 and week 24 (P <.0001), as well as a mean reduction in change from baseline of 200 mg/day in 24-hour urine calcium in the same period (P <.0001). Encaleret was also well-tolerated throughout the trial: safety findings were consistent with known ADH1 biology. Of the 67 patients randomized, 65 elected to continue into the long-term extension period.2

“The remarkable results of the landmark CALIBRATE study represent an important step forward for patients living with ADH1,” Michael Mannstadt, MD, chief of the endocrine unit at the Massachusetts General Hospital, said in an October 2025 press release detailing the topline results. “Unlike conventional therapy with calcium supplements and active vitamin D, encaleret not only increased and maintained both blood calcium and endogenous PTH but also decreased and maintained urine calcium in the normal range.”2

In the press release, BridgeBio announced anticipation of a US launch in early 2027. Additionally, the company is currently enrolling patients in CALIBRATE-PEDS, a global registrational phase 2/3 study of encaleret in pediatric ADH1.1

References

1. BridgeBio Pharma, Inc. BridgeBio Submits NDA to FDA for Encaleret for Individuals Living with ADH1. GlobeNewswire. May 12, 2026. Accessed May 12, 2026. https://www.globenewswire.com/news-release/2026/05/12/3292712/0/en/bridgebio-submits-nda-to-fda-for-encaleret-for-individuals-living-with-adh1.html

2. BridgeBio Pharma, Inc. BridgeBio Reports Positive Phase 3 Topline Results for Encaleret in Patients with Autosomal Dominant Hypocalcemia Type 1. October 29, 2025. Accessed May 12, 2026. https://investor.bridgebio.com/news/news-details/2025/BridgeBio-Reports-Positive-Phase-3-Topline-Results-for-Encaleret-in-Patients-with-Autosomal-Dominant-Hypocalcemia-Type-1/default.aspx

3. Kamenický P, Mannstadt M, Ing S, et al. Encaleret Restores Mineral Homeostasis in Autosomal Dominant Hypocalcemia Type 1 (ADH1): Primary Results from the Phase 3 CALIBRATE Trial. Presented at the 28th European Congress of Endocrinology, Prague. May 9-12, 2026.

4. Calcilytix Therapeutics, Inc. Efficacy and Safety of Encaleret Compared to Standard of Care in Participants With ADH1 (CALIBRATE). ClinicalTrials.gov Identifier: NCT05680818. Updated October 31, 2025. Accessed May 12, 2026. https://clinicaltrials.gov/study/NCT05680818#xd_co_f=ZDFlODdlNmUtNjdlMy00ZDIxLThlZTMtNzc3Y2YyNjcyMWM5~