– These results are the first reported demonstration of rapid and robust treatment changes in key disease markers associated with the severity of disease
– Initial pharmacodynamic results for two participants show unprecedented decreases in N-acetylaspartate (NAA) in the brain and urine, suggesting the therapy is producing functional ASPA enzyme
– If successful, BridgeBio’s gene therapy could be the first therapeutic option for children born with Canavan disease, a devastating and fatal neurodevelopmental disorder
PALO ALTO, Calif., June 22, 2022 (GLOBE NEWSWIRE) — BridgeBio Pharma, Inc. (NASDAQ:BBIO), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, today announced promising pharmacodynamic data from the first two participants dosed in CANaspire, its Phase 1/2 clinical trial of BBP-812, an investigational intravenous (IV) adeno-associated virus serotype 9 (AAV9) gene therapy for the treatment of Canavan disease. Canavan disease is an ultra-rare and fatal disease with no approved therapies.
“Taken together, these robust decreases in urine, cerebrospinal fluid (CSF) and brain N-acetylaspartate (NAA), along with MRI signs of new myelination reported by the principal investigator are exciting and suggest we are on the right track when it comes to potentially making a difference for patients with this disease, and we look forward to gathering more data as the trial progresses,” said Genevieve Laforet, M.D., Ph.D., vice president of clinical development at Aspa Therapeutics, the BridgeBio Gene Therapy affiliate company developing the gene therapy for Canavan disease. “We are continuing to recruit and dose new participants for CANaspire and we are grateful to be able to collaborate with the advocacy organizations in the Canavan community in the pursuit of potential meaningful therapeutic advances for children with this cruel and fatal disorder.”
Data from the first two CANaspire participants show rapid and robust post-treatment decreases in NAA in urine, and importantly, in CSF and brain tissue as shown by magnetic resonance spectroscopy (MRS), to a degree not seen in available natural history data. Reduction in brain NAA is an early signal suggesting that BBP-812 administered IV has reached its intended target behind the blood-brain-barrier and is expressing functional aspartoacylase (ASPA) enzyme. There is evidence in the scientific literature that lower NAA levels are associated with milder disease. More time will be needed to see how these reductions in NAA translate to clinical outcomes.
From a safety standpoint, IV infusions of BBP-812 have been well-tolerated, and to date, no participants have experienced a treatment-related serious adverse event. BridgeBio reported:
- At Month 6 post-treatment, Participant 1 showed:
- 77% lowering of NAA in the CSF
- 15% reduction in NAA in brain white matter by magnetic resonance spectroscopy (MRS) imaging
- ~50% decrease in urine NAA
- At Month 3 post-treatment, Participant 2 showed:
- 89% reduction of NAA in CSF
- >50% decrease in NAA in brain white matter by MRS imaging
- 81% drop in urine NAA
“To see this biochemical change suggests that we are reaching cells critical to the disease process, a milestone in this disease. The ongoing myelination seen on MRI and the new interactions witnessed between children and their parents are both encouraging,” said Florian Eichler, M.D., director of the Leukodystrophy Service and principal investigator at Massachusetts General Hospital and lead investigator of the CANaspire trial.
While the data reported here are still early and the final safety and efficacy profile of the investigational gene therapy remains to be fully established, BridgeBio believes these data show the potential of BBP-812.
“BridgeBio’s early trial results are deeply encouraging for the Canavan community,” said Orren Alperstein, president of the Canavan Foundation, whose daughter Morgan died in 1997 of Canavan disease. “These preliminary but unprecedented decreases in brain and urine NAA suggest that meaningful progress is underway for patients and their families. The thoughtful and careful approach BridgeBio is taking in this trial continues to impress me.”
Data on the first two CANaspire participants will be presented on Friday, July 8, 2022, during Research Day at the National Tay Sachs & Allied Diseases Association Annual Family Conference in Denver, Colorado. A broader Phase 1/2 data readout, including safety and efficacy data and updates on the pharmacodynamic data, for Canavan disease is expected later in 2022.
