encaleret, a negative allosteric modulator of the calcium-sensing receptor for ADH1
Encaleret is an investigational small molecule that targets low calcium levels in the blood (hypocalcemia) and high levels of calcium in the urine (hypercalciuria) by selectively modulating the calcium-sensing receptor protein (CaSR).1 BridgeBio is investigating encaleret as a potential therapeutic for autosomal dominant hypocalcemia type 1 (ADH1).2
Now enrolling for our Phase 3 CALIBRATE study
We are currently enrolling people ages 16 years and older in the US and 18 years and older in the EU who have a documented CASR gene variant and exhibit signs or symptoms of ADH1. This study will assess the efficacy and safety of encaleret compared with standard of care.
our approach
The calcium-sensing receptor (CaSR) maintains blood calcium (Ca2+) levels by regulating the release of parathyroid hormone (PTH). People with ADH1 carry an activating variant in the CASR gene that causes the protein to become too sensitive, leading to hypocalcemia, hypercalciuria, and low levels of PTH.1
Encaleret is an investigational, orally administered, negative allosteric modulator of the CaSR designed to restore normal levels of PTH, blood calcium, and urine calcium, with the goal of resolving key symptoms of ADH1.1,3
In a Phase 2b clinical study, encaleret was well-tolerated and demonstrated rapid and sustained normalization of calcium (blood and urine) and PTH levels.4 CALIBRATE, the registrational Phase 3 clinical study of encaleret, is ongoing.2 If successful, encaleret has the potential to be the first targeted therapeutic for ADH1. Learn more about CALIBRATE at www.adhstudies.com >
clinical program
The global Phase 3 clinical study CALIBRATE (NCT05680818) is currently enrolling people with ADH1 who are at least 16 years of age. CALIBRATE will evaluate the efficacy and safety of encaleret in people with ADH1 compared with standard of care.2
If you have potential patients to refer, or if you are interested in study participation, please email [email protected]
Click here > to learn more about CALIBRATE.
CLARIFY (NCT05227287) is a long-term, disease-monitoring study to better understand ADH1 progression in people who continue their existing treatment plan as directed by their physician. CLARIFY is also investigating autosomal dominant hypocalcemia type 2 (ADH2), a form of hypoparathyroidism caused by genetic variants in GNA11.5
Click here > to learn more about CLARIFY.
References
- Roszko KL, et al. Autosomal Dominant Hypocalcemia Type 1: A Systematic Review. J Bone Miner Res. 2022;37(10):1926 – 1935.
- Efficacy and Safety of Encaleret Compared to Standard of Care in Participants With ADH1 (CALIBRATE). ClinicalTrials.gov identifier: NCT05680818. Updated September 26, 2023. Accessed October 24, 2023. https://clinicaltrials.gov/study/NCT05680818.
- Mannstadt M, et al. Hypoparathyroidism: Genetics and Diagnosis. J Bone Miner Res. 2022;37(12):2615 – 2629.
- Gafni RI, et al. Efficacy and Safety of Encaleret in Autosomal Dominant Hypocalcemia Type 1. N Engl J Med. 2023;389(13):1245 – 1247.
- CLARIFY: ADH1 and ADH2 Disease Monitoring Study (DMS). ClinicalTrials.gov identifier: NCT05227287. Updated September 1, 2023. Accessed October 24, 2023. https://clinicaltrials.gov/study/NCT05227287.
presentations and publications
asbmr 2023 – calibrate phase 3 study design
10.14.2023
encaleret – endo 2023 18 month phase 2b data
06.17.2023
ese 2023 –12 month phase 2b data
05.17.2023
asbmr 2022 – 6 month phase 2 data
12.14.2022
asn 2022 – mineral homeostasis phase 2b data
12.14.2022
endo 2022 – complete phase 2b data
06.13.2022
ects 2022 – phase 2b period 2 data
05.20.2022