BridgeBio Reports Positive Data from High Dose Cohort of Gene Therapy Study for Canavan Disease at ESGCT 2024

BridgeBio Pharma, Inc., a commercial-stage biopharmaceutical company specializing in genetic diseases, has announced promising initial data from eleven participants in its CANaspire Phase 1/2 clinical trial. The trial is evaluating BBP-812, an investigational intravenous gene therapy intended for treating Canavan disease, using adeno-associated virus serotype 9 (AAV9). The study's preliminary findings were presented by Dr. Florian Eichler, an expert in rare neurological diseases, at the 31st Annual Congress of the European Society of Gene and Cell Therapy (ESGCT) in Rome.

Dr. Eichler expressed optimism about the results, noting that children in the CANaspire trial are achieving developmental milestones that are typically unattainable in the natural progression of Canavan disease. The encouraging developments include children being able to sit independently, take steps, and in some cases, walk – achievements that are remarkable compared to the disease's usual course, where most children do not develop beyond the capabilities of a six-month-old.

The CANaspire trial is designed as an open-label Phase 1/2 study to assess the safety, tolerability, and pharmacodynamic activity of BBP-812 in children with Canavan disease. The study is complemented by CANinform, an ongoing natural history study of more than 60 patients with Canavan disease, serving as a robust comparator for the CANaspire trial.

Key results presented at ESGCT 2024 highlighted significant and sustained reductions in N-acetylaspartate (NAA) levels in urine, cerebrospinal fluid (CSF), and brain after BBP-812 administration. Participants receiving the low dose showed an average urine NAA reduction of 64% 12 months post-treatment, while those given the high dose exhibited a 73% reduction three months post-treatment. NAA levels in CSF were reduced by an average of 70% after 12 months for the low dose group. These lower urine NAA levels have been maintained for nearly three years in the earliest dosed participants. Additionally, improved myelination was observed on T-2-weighted MRI in most participants treated with BBP-812.

Patients also showed continued and progressive improvements in gross motor function, as measured by the Gross Motor Function Measure (GMFM)-88, and in achieving motor milestones, as assessed by the Hammersmith Infant Neurological Examination (HINE)-2. This positive progression contrasts sharply with the natural history of Canavan disease, where developmental progression is generally stagnant. Notably, the low-dose cohort demonstrated statistically significant improvements in motor function and milestones 12 months post-treatment.

BBP-812 has been well-tolerated, with a safety profile consistent with other systemically administered AAV9 gene therapies. The therapy has received multiple designations from the FDA, including Regenerative Medicine Advanced Therapy (RMAT), Orphan Drug, Rare Pediatric Disease (RPDD), and Fast Track, as well as Orphan Drug Designation from the European Medicines Agency. With RPDD, if approved, BridgeBio may qualify for a priority review voucher.

Canavan disease is an ultra-rare, debilitating, and fatal neurodevelopmental disorder affecting approximately 1,000 children in the U.S. and the European Union. It results from a mutation in the ASPA gene, leading to the accumulation of NAA, which is toxic to myelin, the insulating sheath around nerve fibers. The current standard of care is limited to supportive therapy, as no approved treatments exist.

BridgeBio Pharma, founded in 2015, is dedicated to discovering, developing, and delivering innovative medicines for genetic diseases. The company has a diverse pipeline ranging from early scientific research to advanced clinical stages. The CANaspire trial represents a significant step in their mission to provide transformative treatments for patients with genetic disorders.

BBP-812 shows promise as a potential first therapeutic option for children with Canavan disease, offering hope for improved outcomes in this severe condition. The ongoing study will continue to evaluate the long-term efficacy and safety of the gene therapy.