BridgeBio shares promising Canavan disease gene therapy trial results

BridgeBio reported new findings on Thursday from its Phase 1/2 trial evaluating a gene therapy for Canavan disease, a rare and severe genetic disorder that deteriorates the brain's white matter. Canavan disease is caused by mutations in the ASPA gene, which is responsible for producing an essential enzyme that breaks down N-acetyl-L-aspartic acid (NAA). The mutation leads to white matter damage in the brain. The disorder affects approximately 1 in 100,000 births, with a higher prevalence observed in the Ashkenazi Jewish population. In cases of infantile-onset Canavan disease, survival into the teenage years is uncommon.

BridgeBio has administered its gene therapy, BBP-812, to eight children at the lowest dose and three children at a higher dose. Post-treatment results indicate a significant reduction in NAA levels in both urine and cerebrospinal fluid. Children receiving the lower dose exhibited an average 64% decrease in urinary NAA levels, while those on the higher dose showed an average 73% reduction. In the cerebrospinal fluid, a 70% average decrease in NAA was observed among children at the lower dose, though changes in the higher dose group were not disclosed.

These findings were shared at the European Society of Gene and Cell Therapy. The participants, aged 0 to 30 months at the time of dosing, demonstrated notable improvements in motor skills, contrasting sharply with the typically stagnant progression of the disease. BridgeBio highlighted these outcomes in their results announcement.

The progress of BridgeBio's program is noteworthy, especially in the face of challenges encountered by other gene therapy initiatives for rare diseases. Many such programs, often developed in academic settings and later transferred to pharmaceutical companies, have faced delays or cancellations. BridgeBio's gene therapy was licensed from UMass Chan Medical School, where it was developed under the leadership of professor Guangping Gao.

BridgeBio has not yet finalized a dosing strategy for Canavan disease, stated Eric David, CEO of gene therapy at BridgeBio. The next phase of the study will involve a 15-patient expansion cohort, which the company intends to use to seek accelerated approval from the FDA. BridgeBio plans to utilize NAA levels as a surrogate biomarker for the accelerated approval process and will compare their trial outcomes to a natural history study of Canavan disease.

In a related development, BridgeBio had previously decided in September not to proceed with its gene therapy for congenital adrenal hyperplasia. The decision followed data results that were described as "not yet transformational" by CEO Neil Kumar. Consequently, the company reduced its gene therapy budget by $50 million.