On May 22, 2023 BridgeBio Pharma, Inc. (Nasdaq: BBIO) ("BridgeBio" or the "Company"), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, reported promising positive data from six 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 (Press release, BridgeBio, MAY 22, 2023, View Source [SID1234631910]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"Canavan disease is a rapidly progressive, rare neurological disease that affects children from birth and has no treatment options beyond supportive care. The changes in key biomarkers, brain myelination and – critically – clinical function observed in children receiving BBP-812 in our study are compelling, and as we continue to advance our program we are hopeful that we will see outcomes that make a meaningful difference in the lives of children with Canavan disease and their families," said Genevieve Laforet, M.D., Ph.D., vice president of clinical development at Aspa Therapeutics, the BridgeBio affiliate that is developing BBP-812 for Canavan disease. "We are beyond grateful to the children and their families who are participating in CANaspire as well as the study investigators, who together are making it possible to explore the potential of BBP-812 as a therapy for Canavan disease. We intend to work with the FDA to move our program forward as rapidly as possible, including exploring available expedited programs such as accelerated approval."
As of March 23, 2023, findings from the trial include:
All participants showed a rapid and lasting decrease in levels of NAA, a key chemical marker elevated in children with Canavan disease, after dosing with BBP-812
The duration of individual participant follow-up ranged from 1 to 15 months post-treatment
The most recent data continue to show reductions in NAA in all participants and all compartments tested. Across individual participants, percent decreases in NAA from baseline ranged between 70% and 95% in cerebrospinal fluid (CSF), 29% and 88% in urine, and 8% and 75% in brain (by magnetic resonance spectroscopy)
All participants in the CANaspire trial had urine NAA levels consistent with typical Canavan disease prior to receiving BBP-812. After receiving BBP-812, urine NAA levels in all participants fell to what can be considered less severe Canavan disease as reported in the scientific literature and observed in the Company’s natural history study
MRI scans indicated the presence of improved myelination, which is essential for brain development, in the brainstem and cerebellum of all participants
These findings have been noted as early as 3 months after BBP-812 administration and were present at post-dosing Month 12 in the participant who has been followed the longest in the trial
In contrast to the natural history of typical Canavan patients in which already-limited functional abilities are lost over time, no trial participants have lost function and there have been incremental improvements in achievement of developmental milestones
Improvement in the GMFM-88 sitting dimension (measuring upright head control and sitting ability) has been shown to varying degrees in all participants who have been evaluated post-treatment, including one participant who has developed the ability to walk with a mobility aid and has a score on the GMFM-88 sitting dimension consistent with that of unaffected children
BBP-812 has been shown to be generally well-tolerated to date, with a safety profile consistent with other systemically administered AAV9 gene therapies
The Data and Safety Monitoring Committee (DSMC), an independent panel of expert physicians and clinical trial experts, has conducted a thorough evaluation of the CANaspire trial safety data and have endorsed the Company’s plan for advancement to the next dosing level
Florian Eichler, M.D., director of the leukodystrophy service at Massachusetts General Hospital, Center for Rare Neurological Disease and principal investigator of the CANaspire gene therapy clinical trial for Canavan disease, reflects on the progress of the trial: "The reduction in NAA to levels consistent with less severe Canavan disease, MRIs indicating potential improvement of myelin in the brainstem, and the measurable functional gains observed among participants, together are unlike any findings I have seen in children with Canavan disease."
About CANaspire
CANaspire is a Phase 1/2 open-label study designed to evaluate the safety, tolerability, and pharmacodynamic activity of BridgeBio’s AAV9 gene therapy candidate, BBP-812, in pediatric patients with Canavan disease. Each eligible patient will receive a single intravenous (IV) infusion of BBP-812. The primary outcomes of the study are safety, as well as change from baseline of urine and central nervous system N-acetylaspartate (NAA) levels. Motor function and development will also be assessed.
For more information about the CANaspire trial, visit TreatCanavan.com or ClinicalTrials.gov (NCT04998396).
About BBP-812
BBP-812 is an investigational AAV9 gene therapy for Canavan disease. Using AAV gene therapy, BridgeBio seeks to deliver functional copies of the ASPA gene throughout the body and into the brain, potentially correcting the disease at its source. Preclinical proof-of-concept results have shown the approach restores survival and normal motor function in Canavan disease models. BBP-812 was granted Fast Track Designation, Rare Pediatric Drug Designation, and Orphan Drug Designation by the U.S. Food and Drug Administration. BBP-812 was also granted Orphan Drug Designation by the European Medicines Agency.