BridgeBio Pharma Announces Phase 1/2 Trial Results for CAH Gene Therapy

BridgeBio Pharma, Inc., a company focused on genetic diseases, has announced significant results from its Phase 1/2 ADventure study. This study examined BBP-631, an adeno-associated virus 5 gene therapy aimed at treating congenital adrenal hyperplasia (CAH).

The ADventure study sought to evaluate the safety, tolerability, and pharmacodynamic activity of BBP-631 in adults suffering from classic CAH. The topline findings from the study are notable:

Firstly, increased endogenous cortisol production was achieved in all patients in the higher dose cohorts. The two highest dose levels showed a maximum change from baseline post-ACTH stimulation test of 4.7 μg/dL and 6.6 μg/dL, with cortisol levels reaching up to 11 μg/dL. This is a milestone, as it indicates the potential of BBP-631 in enabling CAH patients to produce their own cortisol.

Additionally, the study reported substantial and durable increases in 11-deoxycortisol, which is a product of the enzyme 21-hydroxylase, and reductions in 17-hydroxyprogesterone (17-OHP), a substrate of 21-hydroxylase. These changes substantiate the sustained activity of the BBP-631 transgene. At the highest doses, the levels of 11-deoxycortisol experienced an average 55-fold increase from baseline, with a peak increase of 99-fold. These figures represent an average maximum of 23 times the upper limit of normal levels.

A significant reduction in 17-hydroxyprogesterone levels was also observed, with most patients achieving a reduction of 50% or more and the maximum reduction being 95%. This is a promising result indicating the gene therapy's potential impact on biochemical markers of CAH.

BBP-631 was well tolerated by the participants. The study reported only mild to moderate treatment-emergent adverse events, with no treatment-related serious adverse events recorded.

Despite these scientific advancements, the data does not justify further capital investment at this time. Consequently, BridgeBio Pharma will significantly reduce its gene therapy budget. The company will now seek partnership opportunities to continue the development of BBP-631 or other next-generation gene therapies for CAH.

BBP-631 is a gene therapy developed to combat CAH caused by 21-hydroxylase deficiency. It aims to deliver a functional copy of the 21-hydroxylase gene to restore normal hormone and steroid balance in patients. The therapy could potentially alleviate or substantially reduce the need for daily glucocorticoid or mineralocorticoid doses, which are the current standard treatments.

Congenital adrenal hyperplasia is a group of genetic conditions affecting approximately 75,000 individuals in the United States and European Union. These conditions stem from mutations in the gene for 21-hydroxylase, an enzyme needed for producing cortisol and aldosterone, hormones critical for various physiological functions. People with classic CAH cannot produce these hormones, which can result in life-threatening adrenal crises, especially in young children.

BridgeBio Pharma, established in 2015, is dedicated to discovering, creating, and delivering transformative medicines for genetic diseases. The company has a broad pipeline of development programs, ranging from early-stage research to advanced clinical trials.