BridgeBio Pharma, Inc. (Nasdaq: BBIO), a commercial-stage biopharmaceutical company founded to discover, create, test and deliver meaningful medicines for patients with genetic diseases and cancers with clear genetic drivers, today announced updated results from its ongoing Phase 2b proof-of-concept, open-label study of encaleret for the treatment of Autosomal Dominant Hypocalcemia Type 1 (ADH1). Within five days of individualized dose titration in 13 participants, encaleret normalized mean blood calcium levels and 24 hour urine calcium excretion. The results are featured in an oral presentation titled ‘The Effects of Encaleret (CLTX-305) on Mineral Physiology in Autosomal Dominant Hypocalcemia Type 1 (ADH1) Demonstrate Proof-of-Concept: Early Results from an Ongoing Phase 2B, Open-Label, Dose-Ranging Study’ at the American Society for Bone and Mineral Research (ASBMR) 2021 Annual Meeting, taking place in San Diego, California on October 1 – 4, 2021.
“Autosomal dominant hypocalcemia type 1 is a rare genetic form of hypoparathyroidism caused by gain-of-function variants of the calcium-sensing receptor (CASR) gene. The current standard of care consists of calcium and active vitamin D supplements, which do not address the root cause of ADH1,” said Rachel Gafni, M.D., Senior Research Physician and Head, Mineral Homeostasis Studies Group of the National Institute of Dental and Craniofacial Research, National Institutes of Health (NIH). “These updated results from the ongoing Phase 2b study of encaleret demonstrate consistent improvements in mineral homeostasis and support further study.”
In this update from the ongoing Phase 2b open-label, dose-ranging study, 13 adults with ADH1 with nine distinct CASR variants were administered encaleret. Calcitriol (active Vitamin D) and extra-dietary calcium supplementation beyond the recommended daily intake (current standard of care) were discontinued during the study.
Through the inpatient observation periods of defined dose escalation and individualized dose titration, encaleret was well-tolerated with no serious adverse events, no adverse events of severe intensity, or treatment discontinuation due to adverse events reported. Across 13 trial participants, encaleret normalized mean blood calcium levels and 24-hour urine calcium excretion during Periods 1 and 2. Parathyroid hormone levels increased in all participants and mean blood phosphate decreased into the normal range during Periods 1 and 2. The tolerability and consistent mineral responses following encaleret administration demonstrate that encaleret may become an efficacious therapy option for patients with ADH1.
“As a direct modulator of the calcium-sensing receptor’s (CaSR) sensitivity to calcium, encaleret is designed to target this genetic disease at its source, which is gain-of-function (increased sensitivity to calcium) variants in the receptor. The results we are achieving with encaleret for autosomal dominant hypocalcemia type 1 in the current clinical trial are remarkable, as both blood and urine calcium normalize within five days of dosing. Given the consistent improvements seen in mineral homeostasis, we are excited about encaleret’s potential to help patients with ADH1 who currently have no approved therapy indicated to treat this disease,” said Jonathan Fox, M.D., Ph.D., Chief Medical Officer of the cardiorenal companies at BridgeBio. “We recognize the magnitude of the unmet need for these patients and are working collaboratively with regulators to define a path forward for registration. We look forward to sharing complete results next year from this ongoing study which is currently in an outpatient treatment phase.”
BridgeBio plans to engage with regulatory health authorities to discuss the design of a Phase 3 registrational study in patients with ADH1. If the development program is successful, encaleret could be the first approved therapy indicated specifically for the treatment of ADH1.
At ASBMR 2021, BridgeBio will also present a retrospective systematic literature review of ADH1 and clinical study designs for its PROPEL and PROPEL2 studies of low-dose infigratinib in people with achondroplasia, which is the most common form of genetic short stature with a prevalence of greater than 55,000 cases in the United States and European Union. Low-dose infigratinib is the only known product candidate in clinical development for achondroplasia that is designed to target the disease at its genetic source and the only orally administered product candidate in clinical-stage development.
BridgeBio’s investigational therapies for ADH1 and achondroplasia are two of the company’s 14 programs that are being advanced in the clinic or commercial setting for patients living with genetic diseases and genetically driven cancers.
BridgeBio’s first wave of programs are the now-approved drugs for Molybdenum Cofactor Deficiency (MoCD) Type A and previously-treated locally advanced or metastatic cholangiocarcinoma (CCA) harboring an FGFR2 fusion or rearrangement. The second wave of programs includes the Company’s four major near-term catalysts for its product candidates for the treatment of ADH1 and achondroplasia, as well as transthyretin (TTR) amyloidosis (ATTR) and congenital adrenal hyperplasia (CAH).
BridgeBio’s ongoing third wave in development includes a variety of programs in the cancer and mendelian space already in the clinic.
Learn more about the updated data for encaleret, low-dose infigratinib and the BridgeBio pipeline at the Company’s upcoming virtual R&D Day on Tuesday, October 12, 2021, from 8:30 – 11:30 am ET. The event will be webcast and registration information can be found here.
The ASBMR presentation for the updated Phase 2b data in encaleret can be found here.
Encaleret is an investigational, orally-administered small molecule that selectively antagonizes the CaSR, targeting ADH1 at its source. The current standard-of-care for ADH1 patients consists of oral calcium and/or vitamin D supplements that are typically administered to manage signs and symptoms associated with hypocalcemia. Encaleret has received Fast Track and Orphan Drug Designations from the U.S. FDA.
About Autosomal Dominant Hypocalcemia Type 1 (ADH1)