Kidney Week

Abstract: SA-PO0551

Encaleret Normalizes Mineral Homeostasis and Is Associated with an Increase in eGFR in Patients with Autosomal Dominant Hypocalcemia Type 1 (ADH1): 24-Week Phase 3 CALIBRATE Results

Session Information

• Bones, Stones, and Mineral Metabolism: Research and Cases
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

• 502 Bone and Mineral Metabolism: Clinical

Authors

• Sayer, John Andrew, Newcastle University, Newcastle upon Tyne, United Kingdom

John Andrew Sayer, MBChB, PhD

• Palermo, Andrea, Policlinico Universitario Campus Bio-Medico, Rome, Italy

Andrea Palermo, MD, PhD

• Gafni, Rachel, National Institutes of Health, Bethesda, Maryland, United States

Rachel Gafni, MD

• Ing, Steven, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Steven Ing, MD

• Khan, Aliya Aziz, McMaster University, Hamilton, Ontario, Canada

Aliya Aziz Khan, MD

• Levine, Michael Alan, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States

Michael Alan Levine, MD

• Ito, Nobuaki, The University of Tokyo, Graduate School of Medicine and Faculty of Medicine, Tokyo, Japan

Nobuaki Ito, MD, PhD

• Imel, Erik, Indiana University School of Medicine, Indianapolis, Indiana, United States

Erik Imel, MD, MS

• Kamenicky, Peter, Université Paris-Saclay, AP-HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France

Peter Kamenicky

• Rejnmark, Lars, Aarhus Universitetshospital, Aarhus, Denmark

Lars Rejnmark, MD, DrMed, PhD

• Warren, Mark L., Physicians East PA, Greenville, North Carolina, United States

Mark L. Warren, MD

• Wermers, Robert A., Mayo Clinic, Department of Medicine, Rochester, Minnesota, United States

Robert A. Wermers, MD

• Cetani, Filomena, University of Pisa, Department of Clinical and Experimental Medicine, Pisa, Italy

Filomena Cetani, MD, PhD

• Kansara, Abhishek, Houston Methodist, Department of Medicine, Houston, Texas, United States

Abhishek Kansara, MBBS, MPH

• Lemoine, Sandrine, Edouard Herriot Hospital, Department of Nephrology and Physiology, Lyon, France

Sandrine Lemoine, MD, PhD

• Zikan, Vit, Charles University, General University Hospital and Faculty of Medicine 1, Prague, Czechia

Vit Zikan, MD, PhD

• Clifton-Bligh, Roderick John, Royal North Shore Hospital, Sydney, New South Wales, Australia

Roderick John Clifton-Bligh, MBBS, PhD

• Ma, Nina S., University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, United States

Nina S. Ma, MD

• Rubin, Mishaela, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, United States

Mishaela Rubin, MD, MS

• van Velsen, Evert F.S., Erasmus University Medical Center, Rotterdam, Netherlands

Evert F.S. van Velsen, MD, MSc, PhD

• Chen, Jessica, Bridgebio Pharma Inc, San Francisco, California, United States

Jessica Chen, PhD

• Singh, Ajay, Bridgebio Pharma Inc, San Francisco, California, United States

Ajay Singh

• Roberts, Mary Scott, Bridgebio Pharma Inc, San Francisco, California, United States

Mary Scott Roberts, MD

• Adler, Scott H., Bridgebio Pharma Inc, San Francisco, California, United States

Scott H. Adler, MD

• Mannstadt, Michael, Massachusetts General Hospital, Boston, Massachusetts, United States

Michael Mannstadt, MD

Background

ADH1 is caused by gain-of-function CASR variants. Standard-of-care (SoC) with calcium and/or active vitamin D can worsen hypercalciuria and lead to renal morbidity.

Methods

CALIBRATE (NCT05680818) is a global, randomized, open-label trial evaluating encaleret, an investigational oral calcilytic, in ADH1. After a 4-wk (W) SoC maintenance period, participants were randomized 2:1 (in Period 2) to receive encaleret or SoC in a 20-wk dose titration period, followed by a 4-wk maintenance period (ending at W24). SoC was discontinued prior to encaleret initiation, and encaleret dosing was titrated to achieve target albumin-corrected calcium (cCa).

Results

Sixty-seven participants with ADH1 (16-76y, 52% female) were randomized and 66 completed W24. Data are presented in the Table. At baseline, participants exhibited signs of ADH1. By W24, encaleret restored mineral homeostasis with normalized mean cCa and 24-hour uCa. PTH secretion increased with normalization of phosphate and magnesium. eGFR increased on encaleret arm and remained stable on SoC. While there were numeric changes in both arms for nephrocalcinosis and nephrolithiasis, there was no clear change in associated calcifications over this short follow-up.
Treatment-emergent adverse events (TEAEs) occurred in 63.6% (14) of those randomized to SoC vs 88.9% (40) of encaleret-treated participants and were mostly mild or moderate in severity. At least 1 serious TEAE occurred in 13.6% (3) and 8.9% (4), respectively. No deaths or discontinuations due to TEAEs occurred.

Conclusion

Encaleret safely and effectively normalizes blood and urine calcium and is associated with an increase in eGFR in individuals with ADH1. Further follow-up is needed to assess its impact on renal calcifications and function.

Funding

• Commercial Support – BridgeBio Pharma/Calcilytix Therapeutics