BridgeBio reports results from Phase 1/2 open-label trial of BBP-631

BridgeBio Pharma announced topline results from the Phase 1/2 open-label ADventure study investigating BBP-631, the Company’s investigational adeno-associated virus 5 gene therapy, for the treatment of congenital adrenal hyperplasia. 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 undefined/dL and 6.6 undefined/dL was observed at the two highest dose levels, respectively, with cortisol levels as high as 11 undefined/dL achieved. Substantial and durable increases in 11-deoxycortisol, the product of 21-hydroxylase, and reductions in 17-hydroxyprogesterone, 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 greater than or equal to50%, 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.