BridgeBio Pharma's BBP-812, an investigational adeno-associated virus serotype 9 (AAV9) gene therapy for Canavan disease, has been granted Regenerative Medicine Advanced Therapy (RMAT) designation by the FDA. This designation aims to expedite the development and review of regenerative medicine therapies for serious conditions, potentially accelerating BBP-812's path to market. The decision was based on promising clinical evidence from the ongoing CAN aspire Phase 1/2 trial (NCT04998396).
Clinical Trial Data and Functional Improvements
The RMAT designation was supported by 12-month safety and efficacy data from the first eight patients treated in the CAN aspire trial. According to BridgeBio, all patients with at least one follow-up assessment showed improvements in key functional outcomes, including head control, sitting upright, reaching for and grasping objects, and visual tracking. Furthermore, a reduction in N-acetylaspartate (NAA) levels in both urine and the central nervous system was observed, bringing levels closer to those seen in milder forms of the disease.
Safety Profile and Tolerability
BBP-812 has demonstrated a favorable safety profile in the clinical trial, generally consistent with other AAV9 gene therapy programs. This is a critical factor for gene therapies, where safety is a paramount concern.
RMAT Designation Benefits
The RMAT designation provides several benefits, including increased interaction with the FDA to align on critical aspects of the development program. This can lead to a more efficient development process and potentially faster approval timelines. Eric David, MD, JD, CEO at BridgeBio Gene Therapy, expressed the company's eagerness to work closely with the FDA and the Canavan community to bring the therapy to families as quickly as possible.
Canavan Disease: An Unmet Need
Canavan disease is an ultra-rare, rapidly progressive neurodegenerative disorder affecting approximately 1,000 children in the U.S. and European Union. It is caused by a mutation in the ASPA gene, leading to a deficiency in aspartoacylase, an enzyme that breaks down NAA. The resulting accumulation of NAA damages myelin, the protective sheath around nerve fibers, leading to severe developmental delays and a shortened lifespan. Currently, there are no approved therapies for Canavan disease, and treatment is limited to supportive care.
Kathleen Flynn, CEO of the National Tay-Sachs & Allied Diseases Association, emphasized the hope that this designation and the preliminary trial results bring to children and families affected by Canavan disease.
Regulatory Landscape and Future Prospects
In addition to the RMAT designation, BBP-812 has been granted Orphan Drug, Rare Pediatric Disease, and Fast Track Designations by the FDA, as well as Orphan Drug Designation from the European Medicines Agency. If approved, the Rare Pediatric Disease designation could qualify BridgeBio for a Priority Review Voucher, further incentivizing the development of this therapy.
The CAN aspire trial is ongoing, evaluating the safety, tolerability, and pharmacodynamic activity of BBP-812 in pediatric patients with Canavan disease. The primary outcomes include safety and changes in NAA levels, with motor function and development also being assessed.
