Canavan Disease (Passage Bio)

BridgeBio disclosed results Thursday from a Phase 1/2 study of its gene therapy for Canavan disease, an extremely rare and devastating genetic disorder that causes the brain’s white matter to break down. The body needs a gene called ASPA to code for a key enzyme that breaks down an amino acid called N-acetyl-L-aspartic acid — or NAA. In people with Canavan, that gene is mutated, leading to damage of the white matter in the brain. It’s estimated to impact roughly 1 in 100,000 births, more frequently in the Ashkenazi Jewish population. With the infantile-onset form of the disease, most patients don’t live into their teens. Thus far, BridgeBio has treated eight children with the lowest dose of its virus-based gene therapy, called BBP-812, as well as three children at a higher dose. After treatment, children who got the lower dose saw the levels of NAA in their urine go down by 64% on average, and those who received the higher dose saw an average 73% decrease. In the cerebrospinal fluid, children who got the lower dose saw an average 70% decrease in NAA measures. (Fluid changes in the three who received the higher dose weren’t reported.) The data were presented at the European Society of Gene and Cell Therapy. Participants, who were dosed at 0 to 30 months of age, also saw “clinically meaningful” improvements in motor skills. That “stands in stark contrast to the characterized natural history of the disease, where the trajectory over this time period is essentially flat,” BridgeBio said in its announcement of the results. The program stands out against an increasingly challenging backdrop for rare disease gene therapies, where other academic-developed programs that were handed off to drug companies have been shelved or stalled, as Endpoints News has previously reported . In this case, BridgeBio’s subsidiary licensed the gene therapy from UMass Chan Medical School, where it was developed by researchers led by professor Guangping Gao. For Canavan disease, the company hasn’t yet selected a dose, according to BridgeBio’s CEO of gene therapy Eric David. It expects to use the next part of the study — a 15-patient expansion cohort — to apply for accelerated approval with the FDA. BridgeBio plans to use NAA as a surrogate biomarker for accelerated approval. It will also compare the results of its trial to a natural history study of the disease. In September, BridgeBio announced that it wasn’t moving forward with its other gene therapy for congenital adrenal hyperplasia following data that were “not yet transformational,” according to CEO Neil Kumar, cutting its gene therapy budget by $50 million as a result.