BridgeBio Pharma Announces Updated Phase 2B Data for Encaleret in Autosomal Dominant Hypocalcemia Type 1 (ADH1) Demonstrating Blood and Urine Calcium Normalization in Trial Participants
"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
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
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
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
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
About Autosomal Dominant Hypocalcemia Type 1 (ADH1)
ADH1 is caused by gain-of-function variants of CASR, which are estimated to be harbored by 12,000 individuals in
This press release contains forward-looking statements. Statements we make in this press release may include statements that are not historical facts and are considered forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended (the Securities Act), and Section 21E of the Securities Exchange Act of 1934, as amended (the Exchange Act), which are usually identified by the use of words such as "anticipates," "believes," "estimates," "expects," "intends," "may," "plans," "projects," "seeks," "should," "will," and variations of such words or similar expressions. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Exchange Act and are making this statement for purposes of complying with those safe harbor provisions. These forward-looking statements, including statements relating to expectations, plans and prospects regarding the preclinical and clinical development plans, clinical trial designs, clinical and therapeutic potential, and strategy of our product candidates, including, but not limited to: the unknown future impact of the COVID-19 pandemic delay on our ongoing clinical trials and/or our operations or operating expenses; updated results from our ongoing Phase 2b proof-of-concept, open-label study of encaleret for the treatment of Autosomal Dominant Hypocalcemia Type 1 (ADH1) not being indicative of final data from our Phase 2b study of encaleret; the potential size of the target patient population with a rare genetic form of hypoparathyroidism caused by pathogenic variants in the calcium-sensing receptor (CASR) gene; the inability of current standard of care therapies to treat ADH1; encaleret continuing to be well-tolerated with no serious adverse events and no adverse events of moderate or severe intensity reported in our ongoing Phase 2b proof-of concept, open-label study; tolerability and consistent mineral responses following encaleret administration in all 13 ADH1 trial participants continuing to demonstrate proof-of-concept that encaleret may be an efficacious therapy option for ADH1; the timing and success of our planned meetings with regulatory health authorities, including the
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