BridgeBio Pharma Announces New England Journal of Medicine Publication of Positive Encaleret Proof-of-Concept Phase 2b Results in Patients with Autosomal Dominant Hypocalcemia Type 1 (ADH1)

– In our study, encaleret restored physiologic mineral homeostasis in 13 participants with ADH1, specifically correcting hypocalcemia and reducing hypercalciuria

– Rapid and sustained impact of encaleret on mineral homeostasis was observed, specifically in the normalization of blood calcium, urine calcium and parathyroid hormone (PTH)

 No serious adverse events were reported with encaleret and no treatment discontinuations or study withdrawals occurred during the trial

 The Phase 3 CALIBRATE trial of encaleret in patients with ADH1 is ongoing in six countries with topline data expected in the first half of 2024

– If approved, encaleret could be the first therapy specifically indicated for the treatment of ADH1

PALO ALTO, Calif., Oct. 10, 2023 (GLOBE NEWSWIRE) — BridgeBio Pharma, Inc. (Nasdaq: BBIO) (“BridgeBio” or the “Company”), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, announced that the proof-of-concept Phase 2b data evaluating the effects of orally-administered encaleret on mineral homeostasis in patients with ADH1 were published in the New England Journal of Medicine in partnership with the National Institutes of Health (NIH).

“Conventional therapy for ADH1 includes raising the blood calcium levels with calcium supplements and activated vitamin D, taken in multiple doses throughout day. But this burdensome regimen may also increase urine calcium levels above normal, which can damage the kidney, leading to kidney failure in worst-case scenarios. People with ADH1 need better treatments, so they are not constantly walking on a tightrope. It’s been rewarding to observe the robust response in our study participants, some of whom I’ve known for almost 20 years, to this investigational medication that directly targets the underlying cause and appears to restore the calcium balance back towards normal,” said Rachel Gafni, M.D., the principal investigator of the study and a senior research physician in the National Institute of Dental and Craniofacial Research at the NIH.

As part of the Phase 2b study, participants completed one or two 5-day inpatient dose-ranging periods, followed by a 24-week outpatient period. Encaleret was administered twice daily with doses adjusted to achieve normal albumin-corrected blood calcium levels and participants stopped taking calcium and vitamin D supplements, the standard of care for ADH1. The results showed that:

  • Encaleret corrected hypocalcemia and reduced hypercalciuria within a few days of treatment initiation with sustained effect during the 24-week outpatient period
  • As expected with elevated PTH levels, levels of bone turnover markers increased during the outpatient period, with levels in nine of 13 participants remaining normal. Long-term study will continue to assess skeletal effects
  • Kidney function and preexisting renal calcifications did not worsen and will continue to be monitored in longer-term studies. No serious adverse events were reported with encaleret. Treatment-related adverse events were limited to infrequent mild, transient, asymptomatic hypophosphatemia, or hypercalcemia that resolved either spontaneously or with dose adjustment
  • No treatment discontinuations or study withdrawals occurred

“The profound impact we’ve seen on mineral homeostasis in the ADH1 participants to date is deeply encouraging. Encaleret appeared to restore physiologic mineral homeostasis in 13 participants with ADH1 within days of undergoing treatment and the results continue to be sustained 18 months out from the trial’s start date. We hope to see similar results in our Phase 3 trial and are excited about what this means for a patient population in need of targeted therapeutic options,” Scott Adler, M.D., chief medical officer of Calcilytix, a BridgeBio affiliate that is focused on developing encaleret for ADH1.

BridgeBio recently shared data from 18 months of outpatient treatment in the long-term extension of its Phase 2b trial in an oral presentation at the Endocrine Society Meeting 2023. Additionally, the Company plans additional presentations related to the program at the upcoming American Society for Bone and Mineral Research (ASBMR) 2023 Annual Meeting.

CALIBRATE, BridgeBio’s Phase 3 trial (NCT05680818) of encaleret for the treatment of ADH1 is ongoing in six countries with topline data expected in the first half of 2024. The design of the CALIBRATE study incorporates feedback from global regulatory authorities and patients, with a primary composite endpoint of blood and urine calcium concentrations within target ranges in participants treated with encaleret compared to standard of care and secondary endpoints evaluating other measures of mineral homeostasis, quality of life and kidney function.

About Encaleret
Encaleret is an investigational, orally administered small molecule that selectively antagonizes the calcium sensing receptor (CaSR), targeting ADH1 at its source. The current standard of care for patients with ADH1 includes oral calcium and/or active vitamin D supplements that are typically administered to manage signs and symptoms associated with hypocalcemia. Encaleret has received Fast Track Designation by the U.S. Food and Drug Administration (FDA) and Orphan Drug designation in the United States and the European Union.

About Autosomal Dominant Hypocalcemia Type 1 (ADH1)
ADH1 is caused by gain-of-function variants of the CASR gene encoding the CaSR. The calcium-sensing receptor regulates the extracellular calcium concentration in the body primarily through its activity in the parathyroid glands and the kidney. Due to increased sensitivity of the variant CaSR to extracellular calcium, patients with ADH1 have low blood calcium (hypocalcemia), inappropriately low parathyroid hormone levels, and excess excretion of calcium in the urine (hypercalciuria). Hypocalcemia can cause neuromuscular symptoms, which can include severe muscle cramping and seizures, while hypercalciuria can lead to kidney calcifications and impaired kidney function.

Studies estimate that there are 25,000 carriers of gain-of-function variants of the calcium-sensing receptor (CaSR) gene, the underlying cause of ADH1, in the US and EU. This estimate is based on analyses of independent general population genetic datasets, including Geisinger Health System, UK Biobank, gnomAD, and TopMed.1,2

About BridgeBio
BridgeBio is a commercial-stage biopharmaceutical company founded to discover, create, test and deliver transformative medicines to treat patients who suffer from genetic diseases and cancers with clear genetic drivers. BridgeBio’s pipeline of development programs ranges from early science to advanced clinical trials. BridgeBio was founded in 2015 and its team of experienced drug discoverers, developers, and innovators are committed to applying advances in genetic medicine to help patients as quickly as possible. For more information visit and follow us on LinkedIn and Twitter.

BridgeBio Forward-Looking Statements
This press release contains forward-looking statements. Statements BridgeBio makes 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. BridgeBio intends 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. 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 continuation of the Phase 3 CALIBRATE trial of encaleret in patients with ADH1 in six countries; the timeline of expected topline data of the Phase 3 CALIBRATE trial; the statement regarding the expectation of data from the Phase 3 trial in Dr. Adler’s quote; the timing and success of our interactions with regulatory health authorities, including the FDA, in connection with Phase 3 CALIBRATE trial; and the timing of these events, reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Although BridgeBio believes that its plans, intentions, expectations, strategies and prospects as reflected in or suggested by those forward-looking statements are reasonable, BridgeBio can give no assurance that the plans, intentions, expectations or strategies will be attained or achieved. Furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a number of risks, uncertainties and assumptions, including, but not limited to, BridgeBio’s ability to continue and complete its ongoing and planned clinical trials of Phase 3 CALIBRATE trial of encaleret in patients with ADH1, the design and success of BridgeBio’s ongoing and planned clinical trials, difficulties with enrollment in BridgeBio’s clinical trials, adverse events that may be encountered in BridgeBio’s clinical trials, the FDA or other regulatory agencies not agreeing with BridgeBio’s regulatory approval strategies, components of BridgeBio’s filings, such as clinical trial designs, conduct and methodologies, or the sufficiency of data submitted, as well as those risks set forth in the Risk Factors section of BridgeBio’s Annual Report on Form 10-K for the year ended December 31, 2022, and BridgeBio’s other SEC filings. Moreover, BridgeBio operates in a very competitive and rapidly changing environment in which new risks emerge from time to time. These forward-looking statements are based upon the current expectations and beliefs of BridgeBio’s management as of the date of this press release and are subject to certain risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. Except as required by applicable law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise.


  1. Dershem et al., Am. J. Hum. Genet., 2020.
  2. Data obtained from the gnomAD, TopMed, and UK Biobank databases as of 2022.

BridgeBio Media Contact:
Vikram Bali
[email protected]



Hope through rigorous science - medicines with transformative potential for patients with unmet needs.

Our Mission