Gene Therapy for Adrenal Disorders: Early but Encouraging Results
BridgeBio Pharma, Inc. (Nasdaq: BBIO) has reported notable progress on a gene therapy approach for congenital adrenal hyperplasia (CAH). The company shared topline findings from its Phase 1/2 open-label ADventure study of BBP-631, an investigational therapy designed for people with classic CAH. The early data suggest meaningful biologic activity and a potential path toward restoring hormone production that CAH disrupts.
Inside the ADventure Study
The ADventure study evaluates the safety and efficacy of BBP-631 in adults with classic CAH, a genetic condition that impairs adrenal hormone production. A central outcome stood out: participants in the higher dose cohorts showed increases in their own cortisol production. For the first time, patients living with CAH in this study were able to produce cortisol independently—an essential step toward more stable disease control and day-to-day resilience.
Key Findings
Highlights from the trial include:
- Participants in the higher dose groups experienced clear gains in endogenous cortisol, measured after an ACTH stimulation test. From baseline, some individuals showed changes ranging from 4.7 µg/dL to 6.6 µg/dL, with maximum levels reaching up to 11 µg/dL.
- There was a substantial and sustained rise in 11-deoxycortisol—produced by the enzyme 21-hydroxylase—pointing to active expression of the delivered gene. At higher dose levels, some participants saw up to a 55-fold increase from baseline, with peak increases approaching 99-fold.
- Tolerability was favorable. Reported treatment-emergent side effects were mild to moderate, and there were no severe adverse events attributed to BBP-631.
Company Perspective and Next Steps
Neil Kumar, Ph.D., CEO and Founder of BridgeBio, noted that while the results are encouraging, they don’t yet meet the company’s internal threshold for additional investment at this time. As a result, BridgeBio plans to significantly scale back its gene therapy budget, with reductions exceeding $50 million.
Chief Financial Officer Dr. Brian Stephenson emphasized that BridgeBio will allocate resources to programs addressing high-priority conditions with no available alternatives. The company underscored its continued commitment to running rigorous gene therapy studies where the unmet need remains high.
Program Pause and Partnership Exploration
Following the Phase 1/2 readout, BridgeBio intends to pause further development of BBP-631 for CAH. At the same time, the company is exploring partnerships that could support future progress in this area. The need is substantial: CAH affects more than 75,000 people across the U.S. and EU, underscoring the urgency for treatments that address the underlying biology rather than only managing symptoms.
What CAH Means for Patients
CAH stems from mutations that limit the adrenal glands’ ability to produce hormones like cortisol and aldosterone. These hormones help the body respond to stress and maintain fluid and electrolyte balance. When cortisol is low or absent, everyday stressors can overwhelm the body’s response, and in severe cases this can lead to life-threatening adrenal crises, particularly in young children.
Where BBP-631 Fits
BBP-631 is designed to deliver a working copy of the 21-hydroxylase gene directly to the adrenal glands. If successful, it could help people with CAH make their own cortisol and aldosterone. That, in turn, may decrease reliance on daily hormone replacement therapies that serve as the current standard of care, and it could offer steadier control over day-to-day hormone needs.
About BridgeBio Pharma, Inc.
BridgeBio develops medicines for genetic diseases, from discovery through clinical trials. Founded in 2015, the company works with experts across biopharma to advance programs with clear biological rationale and strong patient need. Its portfolio spans early research to late-stage studies, with a focus on translating genetics into potential treatments.
Frequently Asked Questions
What did the ADventure study show about BBP-631?
The study showed that adults with classic CAH receiving higher doses of BBP-631 increased their own cortisol production, alongside strong signals such as rises in 11-deoxycortisol. The therapy was generally well tolerated, with only mild to moderate side effects reported and no severe events attributed to treatment.
Does BridgeBio plan to continue developing BBP-631 for CAH?
No. After reviewing the Phase 1/2 data and internal investment criteria, BridgeBio plans to halt development of BBP-631 for CAH while it looks for potential partners who could help advance future work.
Why is restoring endogenous cortisol important for people with CAH?
Cortisol helps the body respond to daily stressors. Restoring a person’s own cortisol production can support steadier hormone levels and may reduce the need for intensive daily replacement regimens used to manage CAH.
What are the key safety and efficacy signals seen so far?
Increases in cortisol after stimulation testing were observed in higher dose groups, and 11-deoxycortisol rose markedly, suggesting transgene activity. Safety findings to date showed only mild to moderate side effects, with no severe adverse events attributed to the therapy.
How is BridgeBio adjusting its overall strategy?
The company is reducing its gene therapy budget by more than $50 million and concentrating on programs where no alternatives exist today, while maintaining its commitment to carefully designed trials that address significant unmet needs.
