BridgeBio Pharma is slashing its gene therapy budget and pulling back from the modality after seeing the results of a phase 1/2 clinical trial. CEO Neil Kumar, Ph.D., said the data “are not yet transformational,” driving BridgeBio to shift its focus to other drug candidates and ways to treat disease.
Kumar set the go/no-go criteria for BBP-631, BridgeBio’s gene therapy for congenital adrenal hyperplasia (CAH), at the 2024 J.P. Morgan Healthcare Conference in January. The candidate is designed to provide a working copy of a gene for an enzyme, enabling people to make their own cortisol. Kumar said BridgeBio would only advance the asset if it was more effective, not just more convenient, than the competition.
BBP-631 fell short of the bar for further development. Kumar said he was looking to get cortisol levels up to 10 μg/dL or more. Cortisol levels got as high as 11 μg/dL in the phase 1/2 trial, BridgeBio said, and a maximum change from baseline of 4.7 μg/dL and 6.6 μg/dL was seen at the two highest doses.
Normal cortisol levels vary between people and throughout the day, with 5 μg/dL to 25 mcg/dL being a typical range when the sample is taken at 8 a.m. Glucocorticoids, the current standard of care, treat CAH by replacing deficient cortisol and suppressing a hormone. Neurocrine Biosciences’ near-approval CRF1 antagonist can reduce the glucocorticoid dose but didn’t increase cortisol levels in a phase 2 trial.
BridgeBio generated evidence of durable transgene activity, but the data set failed to compel the biotech to pump more money into BBP-631. While BridgeBio is stopping development of BBP-631 in CAH, it is actively seeking partnerships to support development of the asset and next-generation gene therapies in the indication.
The discontinuation is part of a broader rethink of investment in gene therapy. Brian Stephenson, Ph.D., chief financial officer at BridgeBio, said in a statement that the company will be cutting its gene therapy budget more than $50 million and reserving the modality “for priority targets that we cannot treat any other way.” The biotech spent $458 million on R&D last year.
BridgeBio’s other clinical-phase gene therapy is a phase 1/2 treatment of Canavan disease, a condition that is much rarer than CAH. Stephenson said BridgeBio will work closely with the FDA and the Canavan community to try to bring the therapy to patients as fast as possible. BridgeBio reported improvements in functional outcomes such as head control and sitting upfront in patients who received the therapy.