BridgeBio Pharma Reports Topline Results from Phase 1/2 Trial of Investigational Gene Therapy for Congenital Adrenal Hyperplasia (CAH)
– Increase in endogenous cortisol production achieved in all patients in higher dose cohorts of BBP-631, a result seen for the first time ever in CAH patients
– The gene therapy was well tolerated with no treatment-related serious adverse events (SAEs) reported
– Despite novel scientific advancements achieved with this program, the data do not warrant additional capital investment at this time and the gene therapy budget is being significantly reduced
PALO ALTO, Calif., Sept. 10, 2024 (GLOBE NEWSWIRE) — BridgeBio Pharma, Inc. (Nasdaq: BBIO) (“BridgeBio” or the “Company”), a commercial-stage biopharmaceutical company focused on genetic diseases, today announced topline results from the Phase 1/2 open-label ADventure study investigating BBP-631, the Company’s investigational adeno-associated virus (AAV) 5 gene therapy, for the treatment of congenital adrenal hyperplasia (CAH).
The Phase 1/2 open-label ADventure study was designed to evaluate the safety, tolerability and pharmacodynamic activity of BBP-631 in adults with classic CAH. To date, key results from the study include:
- Increased endogenous cortisol production was achieved in all patients at higher doses. A maximum change from baseline post-ACTH stimulation test of 4.7 μg/dL and 6.6 μg/dL was observed at the two highest dose levels, respectively, with cortisol levels as high as 11 μg/dL achieved.
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Substantial and durable increases in 11-deoxycortisol, the
product of 21-hydroxylase, and reductions in
17-hydroxyprogesterone (17-OHP), the substrate of
21-hydroxylase, provide compelling evidence of durable BBP-631
transgene activity.
- At the highest dose levels, sustained 11-deoxycortisol averaged a 55-fold increase from baseline with a maximum of 99-fold increase from baseline. These represent an average maximum of 23-fold the upper-limit of normal.
- Robust reduction in 17-hydroxyprogesterone, with the majority of patients reaching a reduction of ≥50%, with a max reduction of 95%.
- BBP-631 has been well tolerated with only mild to moderate treatment-emergent adverse events (TEAEs) and no treatment-related SAEs reported.
“While the data to date are not yet transformational, the study showed for the first time that people living with CAH can indeed make their own cortisol, and that gene therapy can be safely administered in this patient population. We remain committed to finding the right partner for those in the CAH community and are grateful to the participants and those who expressed interest in both the pre-screening study and the ADventure study. We also want to thank the ADventure study investigators and staff, the CAH patient advocacy organizations and the broader CAH community,” said Neil Kumar, Ph.D., CEO and Founder of BridgeBio.
“Given that the results of the trial did not meet the threshold to warrant additional capital investment at this time, BridgeBio will be reducing the gene therapy budget more than $50M, consistent with our capital allocation principles, and reserving gene therapy for priority targets that we cannot treat any other way,” said Brian Stephenson, Ph.D., CFA, Chief Financial Officer of BridgeBio. “We believe that gene therapies have the potential to fulfill a significant unmet need and are eager to work closely with the FDA and the Canavan community with the goal of bringing our therapy to families living with Canavan disease as fast as possible.”
BridgeBio will no longer be pursuing development of BBP-631 for CAH and the Company is actively seeking partnership opportunities to support future development of BBP-631 or next-generation gene therapies for the treatment of CAH, a very prevalent genetic disease that still has significant unmet need, with more than 75,000 cases estimated in the United States and European Union.
About BBP-631
BBP-631 is an AAV5 gene therapy developed to treat CAH due to
21-hydroxylase deficiency at its source. BBP-631 is designed to
deliver a functional copy of the 21-hydroxylase gene and has
been shown through multiple preclinical studies to result in
efficient and persistent delivery to the adrenal gland, where
hormones are naturally made. If successful, BBP-631 may restore
the body’s hormone and steroid balance by enabling people with
CAH to naturally make their own cortisol and aldosterone. It
could also allow for people with CAH to eliminate or
significantly reduce their daily glucocorticoid or
mineralocorticoid doses, which is the current standard of care
for patients.
About Congenital Adrenal Hyperplasia (CAH)
Affecting approximately 75,000 people in the United States and
European Union, CAH is a group of genetic disorders that affect
the adrenal glands, which is caused by a mutation in the gene
encoding for 21-hydroxylase, an enzyme essential for making the
hormones cortisol and aldosterone which are critical for various
physiologic functions. Cortisol is necessary for the body to
respond to injury, stress or illness, and aldosterone is
required to maintain proper blood pressure and sodium levels.
Unable to produce cortisol and aldosterone, people with classic
CAH cannot mount the healthy physiological response to
stressors, such as illnesses, that allows their heart, lungs,
kidneys and other organs to compensate for the stress, which can
be life-threatening. These adrenal crises can be particularly
dangerous for young children.
About BridgeBio Pharma, Inc.
BridgeBio Pharma, Inc. (BridgeBio) is a commercial-stage
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 bridgebiodev.wpengine.com and follow us on LinkedIn, Twitter and Facebook.
BridgeBio Pharma, Inc. 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,” “continues,”
“estimates,” “expects,” “hopes,” “intends,” “may,” “plans,”
“projects,” “remains,” “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 in Dr.
Kumar’s quote relating to the expectations, plans and prospects
regarding BBP-631, the statements in Dr. Stephenson’s quote
relating to the Company’s financial performance, capitalization
status, strategy, business plans and goals and the potential for
gene therapy and future partnership opportunities for BBP-631,
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, risks inherent in developing therapeutic
products, the success, cost, and timing of the Company’s product
candidate research and development activities and ongoing and
planned preclinical studies and clinical trials, the success and
timing of preclinical study and clinical trial results, the
success of its clinical trial designs, the fact that successful
preliminary preclinical study or clinical trial results may not
result in future clinical trial successes and/or product
approvals, trends in the industry, the legal and regulatory
framework for the industry, the accuracy of the Company’s
estimates regarding expenses, future revenue, future
expenditures and needs for and ability to obtain additional
financing, the Company’s ability to be a sustainable genetic
medicine innovation engine and to build the next great genetic
medicine company, the Company’s ability to obtain and maintain
intellectual property protection for its product candidates and
approved products, the competitive environment and clinical and
therapeutic potential of the Company’s product candidates and
FDA-approved products, potential adverse impacts due to global
health emergencies, including delays in regulatory review,
manufacturing and supply chain interruptions, adverse effects on
healthcare systems and disruption of the global economy, the
impacts of current macroeconomic and geopolitical events,
including changing conditions from 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 BridgeBio’s most recent Annual Report on Form
10-K, and BridgeBio’s other filings with the U.S. Securities and
Exchange Commission. 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.
BridgeBio Contact:
Vikram Bali
[email protected]
(650)-789-8220