Encaleret Showed Parathyroid Hormone-Independent Normalization of Blood and Urine Calcium in Phase 2 Proof-of-Concept Study in Post-Surgical Hypoparathyroidism

Rhea-AI Summary

BridgeBio Pharma (Nasdaq: BBIO) announced positive Phase 2 proof-of-concept results for encaleret in treating post-surgical hypoparathyroidism. The study showed that 80% of participants achieved normal blood and urine calcium levels within 5 days of treatment, compared to 0% on conventional therapy.

The oral therapy demonstrated PTH-independent normalization of calcium levels, with nine participants showing rapid and sustained reduction in fractional excretion of calcium. The drug was well-tolerated with no serious adverse events reported. Based on these promising results, BridgeBio plans to initiate a registrational clinical study in 2026.

Positive

• 80% of participants achieved normalized blood and urine calcium levels within 5 days
• No serious adverse events reported during the study period
• Treatment showed rapid and sustained reduction in calcium excretion in 90% of participants
• Potential for improved treatment option in convenient pill form

Negative

• Small study size with only 10 participants
• Registrational study not starting until 2026

Insights

Biomedical Researcher

BridgeBio's encaleret shows promising Phase 2 results for hypoparathyroidism, normalizing calcium levels in 80% of patients within 5 days.

BridgeBio's encaleret has demonstrated remarkable efficacy in a Phase 2 proof-of-concept study for post-surgical hypoparathyroidism, addressing a critical therapeutic challenge. The data revealed that 80% of participants achieved normalized blood and urine calcium levels within just 5 days of treatment initiation, compared to 0% on conventional therapy at baseline. This represents a significant breakthrough for a condition that typically requires a difficult balancing act between maintaining blood and urine calcium levels.

The mechanism of action is particularly noteworthy—encaleret works through PTH-independent normalization by targeting the calcium-sensing receptor in the kidney. This resulted in rapid and sustained reduction in fractional excretion of calcium in 90% of participants. Current standard treatments using calcium and active vitamin D often force clinicians to target low or low-normal blood calcium to reduce risks of high urinary calcium, which can lead to kidney calcifications and renal injury.

The safety profile appears favorable with no serious adverse events reported during the study period. As an orally-administered therapy, encaleret offers considerable convenience compared to existing options. This positions BridgeBio's treatment as potentially transformative for chronic hypoparathyroidism management. The company's plan to advance to a registrational clinical study in 2026 suggests confidence in these results and a clear regulatory pathway. Given the unmet need in this patient population and the compelling efficacy data, these results represent a significant advancement in the treatment landscape for hypoparathyroidism.

- 80% of post-surgical hypoparathyroidism participants achieved concomitant blood and 24-hour urine calcium in the normal reference range within 5 days of encaleret treatment initiation compared to 0% of participants on conventional therapy at baseline

- Encaleret was well-tolerated with no serious adverse events reported over the study period

- Based on these findings, BridgeBio intends to initiate a registrational clinical study of encaleret, an orally-administered investigational therapy, in chronic hypoparathyroidism in 2026

PALO ALTO, Calif., Sept. 06, 2025 (GLOBE NEWSWIRE) -- BridgeBio Pharma, Inc. (Nasdaq: BBIO) (“BridgeBio” or the “Company”), a new type of biopharmaceutical company focused on genetic diseases, announced today that encaleret showed parathyroid hormone (PTH)-independent normalization of blood and urine calcium in post-surgical hypoparathyroidism. The Phase 2 results were shared in an oral presentation at the American Society for Bone and Mineral Research (ASBMR) Annual Meeting 2025.

“Chronic hypoparathyroidism is a challenging condition to manage because treatment involves striking a balance between blood and urine calcium. With conventional therapy, using calcium and active vitamin D, we typically aim for a low or low-normal blood calcium to reduce the risk of high urinary calcium which can cause kidney calcifications and renal injury. Unfortunately, not all patients are able to achieve this balance, and many still struggle – some with the disruptive symptoms of low blood calcium, and others with persistently high urine calcium,” said Iris Hartley, M.D., endocrinologist and clinician investigator at the National Institute of Dental and Cranial Facial Research of the National Institutes of Health. “There is a clear need for better options. New results from this study are very promising, suggesting a potential path for improved calcium control in a convenient pill form.”

The Phase 2 proof-of-concept study evaluated the PTH-independent effects of encaleret on renal calcium handling in patients with post-surgical hypoparathyroidism. Ten participants with post-surgical hypoparathyroidism were administered encaleret at 162 mg twice daily for up to 5 days. Calcitriol was stopped one day prior to the first dose. After starting encaleret, calcium and calcitriol were titrated based on blood calcium. The findings from the study include:

• Encaleret treatment resulted in a rapid and sustained reduction in fractional excretion of calcium in nine participants with post-surgical hypoparathyroidism
• 80% of post-surgical hypoparathyroidism participants achieved concomitant blood and urine calcium in the normal reference range within 5 days of treatment initiation compared to 0% of participants on conventional therapy at baseline
• These results support the continued evaluation of encaleret as an orally-administered treatment option for patients with chronic hypoparathyroidism
  

“These Phase 2 results show that encaleret may help normalize blood and urine calcium in patients with chronic hypoparathyroidism, in the absence of stimulating PTH secretion, due to its effect on the calcium-sensing receptor expressed in the kidney. Based on these encouraging findings, we intend to initiate a registrational clinical study of encaleret in chronic hypoparathyroidism in 2026,” said Scott Adler, M.D., Chief Medical Officer of Calcilytix, a BridgeBio affiliate that is focused on developing encaleret.

During ASBMR 2025, we also presented data from two preclinical studies of infigratinib, which demonstrated that low-dose infigratinib significantly improved bone growth in a hypochondroplasia mouse model as well as enhanced skull development in a Crouzon/Pfeiffer syndrome model. These data underscore the therapy’s broad potential for treating skeletal conditions. Additionally, the study of infigratinib in the hypochondroplasia mouse model was recently published in the Journal of Bone and Mineral Research.

About BridgeBio Pharma, Inc.
BridgeBio Pharma, Inc. (BridgeBio) is a new type of biopharmaceutical company founded to discover, create, test, and deliver transformative medicines to treat patients who suffer from genetic diseases. 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 bridgebio.com and follow us on LinkedIn, Twitter, Facebook, Instagram, and YouTube.

BridgeBio Forward-Looking Statements
This press release contains forward-looking statements. Statements 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,” “continues,” “estimates,” “expects,” “hopes,” “intends,” “may,” “plans,” “projects,” “remains,” “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. These forward-looking statements, including statements relating to the clinical, therapeutic and market potential of our programs and product candidates, the progress of our ongoing and planned clinical trials of encaleret in chronic hypoparathyroidism and other indications, our plans to initiate a registrational clinical study of encaleret in 2026, and the statements regarding the potential clinical benefits of encaleret for patients in the quotes of Dr. Hartley and Dr. Adler, reflect our current views about our plans, intentions, expectations and strategies, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations and strategies as reflected in or suggested by those forward-looking statements are reasonable, we 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, initial and ongoing data from our clinical trials not being indicative of final data, the design and success of ongoing and planned clinical trials, difficulties with enrollment in our clinical trials, adverse events that may be encountered in our clinical trials, the FDA or other regulatory agencies not agreeing with our regulatory approval strategies, components of our filings, such as clinical trial designs, conduct and methodologies, or the sufficiency of data submitted, the potential inability to obtain regulatory approvals in a timely manner or at all, potential manufacturing and supply chain interruptions, adverse effects on healthcare systems, disruption of the global economy, the impacts of current macroeconomic and geopolitical events, including hostilities in Ukraine and in Israel and the Gaza Strip, increasing rates of inflation and rising interest rates, on our business operations and expectations, as well as those risks set forth in the Risk Factors section of our most recent Annual Report on Form 10-K and our other filings with the U.S. Securities and Exchange Commission. Moreover, we operate 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 our 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.

BridgeBio Media Contact:
Bubba Murarka, Executive Vice President, Corporate Development
contact@bridgebio.com  
(650)-789-8220

BridgeBio Investor Contact:
Chinmay Shukla, Senior Vice President, Strategic Finance
ir@bridgebio

FAQ

What were the key results of BridgeBio's (BBIO) Phase 2 encaleret study?

The study showed that 80% of participants achieved normal blood and urine calcium levels within 5 days of treatment, with no serious adverse events reported. The drug demonstrated PTH-independent normalization of calcium levels.

How does encaleret work in treating hypoparathyroidism?

Encaleret works by affecting the calcium-sensing receptor in the kidney, allowing normalization of blood and urine calcium levels without stimulating PTH secretion.

When will BridgeBio (BBIO) start the registrational trial for encaleret?

BridgeBio plans to initiate the registrational clinical study for encaleret in chronic hypoparathyroidism in 2026.

What advantages does encaleret offer over conventional hypoparathyroidism therapy?

Encaleret offers potential advantages as an oral treatment that can normalize both blood and urine calcium levels, while conventional therapy with calcium and vitamin D often struggles to achieve this balance.

How many patients participated in BBIO's Phase 2 encaleret study?

The Phase 2 proof-of-concept study included 10 participants with post-surgical hypoparathyroidism who received encaleret at 162 mg twice daily for up to 5 days.