BridgeBio Pharma, Inc. has released the topline results from the phase 1/2 open-label adventure study investigating BBP-631, an investigational gene therapy for congenital adrenal hyperplasia (CAH). The study aimed to evaluate the safety, tolerability, and pharmacodynamic activity of BBP-631 in adults with classic CAH.
The key results from the study revealed that increased endogenous cortisol production was achieved in all patients at higher doses. At the two highest dose levels, a maximum change from baseline post-ACTH stimulation test of 4.7 μg/dl and 6.6 μg/dl was observed, with cortisol levels reaching as high as 11 μg/dl.
Moreover, 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, representing an average maximum of 23-fold the upper-limit of normal. There was also a robust reduction in 17-OHP, with the majority of patients reaching a reduction of ≥50%, with a maximum reduction of 95%.
The gene therapy, BBP-631, was well tolerated with only mild to moderate treatment-emergent adverse events (TEAEs) and no treatment-related serious adverse events (SAEs) reported.
As a result of the trial's outcomes, BridgeBio Pharma, Inc. has announced a significant reduction in the gene therapy budget by more than $50 million and will no longer be pursuing the development of BBP-631 for CAH. The company is actively seeking partnership opportunities to support future development of BBP-631 or next-generation gene therapies for the treatment of CAH.
BridgeBio's CEO and founder, Neil Kumar, expressed gratitude to the participants and those who expressed interest in the study, as well as the investigators, staff, patient advocacy organizations, and the broader CAH community. However, the company will be redirecting its focus and resources toward priority targets that cannot be treated in any other way.
It's noteworthy that despite the novel scientific advancements achieved with the program, the data did not meet the threshold to warrant additional capital investment at this time. The company remains committed to finding the right partner for the CAH community and is eager to work closely with the FDA and the Canavan community with the goal of bringing the therapy to families living with Canavan disease as fast as possible. The market has reacted to these announcements by moving the company's shares -5.0% to a price of $28.5. For the full picture, make sure to review BridgeBio Pharma's 8-K report.
