FDA Accepts NDA for Encaleret for Autosomal Dominant Hypocalcemia Type 1

The US Food and Drug Administration (FDA) has accepted a New Drug Application (NDA) for encaleret for the treatment of autosomal dominant hypocalcemia type 1 (ADH1).¹

Announced on July 22, 2026, by parent company BridgeBio, the acceptance was accompanied by a Prescription Drug User Fee Act (PDUFA) date of May 8, 2027. If approved, encaleret will be the only therapy indicated specifically for patients with ADH1. The orally administered small molecule designed to selectively negatively modulate the calcium sensing receptor has previously received Fast Track Designation from the FDA and Orphan Drug Designation in the US, European Union, and Japan.¹

“The FDA’s acceptance of our NDA is a powerful validation of encaleret’s differentiated clinical profile and enables a major step forward for the ADH1 community,” Ananth Sridhar, chief executive officer of BridgeBio Endocrinology, said in a statement. “We believe encaleret has the potential to transform care for patients who currently have no indicated treatment options, and we’re moving with urgency to bring it to them.”¹

The NDA submission was based on data from CALIBRATE, a phase 3 randomized, open-label study investigating encaleret’s efficacy and safety compared to standard of care (SoC) in patients with ADH1. Conducted across 25 locations worldwide, the study included patients 16-<18 years old with a documented history of ADH1 symptoms or signs and a documented or likely pathogenic activating variant of the calcium sensing receptor (CASR) gene associated with biochemical findings of hypoparathyroidism.²

The study’s primary endpoint was the number of responders achieving both albumin-corrected blood calcium (cCa) and 24-hour urinary calcium (UCa) within the target range, which was defined as 8.3-10.7 mg/dL and 300 mg/day for men or 250 mg/day for women, respectively. Secondary outcomes included the number of patients with blood magnesium within the reference range and intact parathyroid hormone within or above the reference range, as well as change in blood vitamin D from baseline.³

After a 4-week SoC maintenance period, a total of 67 patients were randomly assigned in a 2:1 ratio to receive encaleret or SoC for 20 weeks. After this, both groups entered a 4-week dose maintenance period, which lasted until week 24 of the study.³

Ultimately, 75.6% of patients receiving encaleret achieved both target cCa and UCa by week 24 versus 4.4% of patients at week 4 (P <.0001). Additionally, 91.1% of encaleret patients had a PTH ≥15 pg/mL at week 24, compared to only 6.7% at week 4 of the SoC period. 91.1% had also achieved normal serum phosphate compared to 55.6% at week 4 of the SoC period.³

“For too long, ADH1 has been an invisible condition that disrupts several systems in the body, from the kidneys to the nervous system to the muscles, and often goes unrecognized for years,” Patty Keating, executive director of the HypoPARAthyroidism Association, said in a statement. “The FDA’s acceptance of this NDA is a moment of real hope for ADH1 patients and a signal that the medical and regulatory community understands the seriousness of this condition and that an orally administered option may finally be on the horizon for those in need.”¹

References

1. BridgeBio. BridgeBio Announces FDA Acceptance of NDA for Encaleret for ADH1. GlobeNewswire. July 22, 2026. Accessed July 22, 2026. https://www.globenewswire.com/news-release/2026/07/22/3331254/0/en/BridgeBio-Announces-FDA-Acceptance-of-NDA-for-Encaleret-for-ADH1.html

2. Calcilytix Therapeutics. Efficacy and Safety of Encaleret Compared to Standard of Care in Participants With ADH1 (CALIBRATE). ClinicalTrials.gov Identifier: NCT05680818. Updated June 11, 2026. Accessed July 22, 2026. https://clinicaltrials.gov/study/NCT05680818

3. Livingston R. CALIBRATE: Encaleret Achieves Mineral Homeostasis in Patients With ADH1, With Rachel Gafni, MD. HCPLive. June 18, 2026. Accessed July 22, 2026. https://www.hcplive.com/view/calibrate-encaleret-achieves-mineral-homeostasis-in-patients-with-adh1-with-rachel-gafni-md