BridgeBio Pharma’s Gene Therapy BBP-812 Effects Progressive Improvement in Motor Function in Patients With Canavan Disease
Furthermore, the majority of patients treated with the gene therapy showed improved myelination as measured by T-2-weighted MRI.
Florian Eichler, MD
BridgeBio Pharma’s BBP-812, an investigational adeno-associated virus serotype 9 (AAV9) vector-based gene therapy, has demonstrated the ability to improve motor function in patients with Canavan disease (CD) treated in the phase 1/2 CANaspire clinical trial (NCT04998396).1 The data were presented at the 31st Annual Congress of the European Society of Gene and Cell Therapy (ESGCT), held October 22 to 25 in Rome, Italy.
Patients treated in CANaspire received either a low dose or high dose of BBP-812. BridgeBio stated that patients treated in the low dose cohort showed trajectories of progressive improvement in gross motor function as measured by the Gross Motor Function Measure (GMFM)-88 and achievement of motor milestones as measured by the Hammersmith Infant Neurological Examination (HINE)-2), which at 12 months posttreatment constituted statistically significant improvements in comparison to CD natural history. The company noted that results for these metrics are not yet available for the high dose cohort.
Furthermore, the majority of patients treated with the gene therapy showed improved myelination as measured by T-2-weighted MRI. The study also measured levels of N-acetylaspartate (NAA) in the urine and central nervous system (CNS). For patients who received the low dose, an average decrease of 64%+/-14% in urine NAA was recorded at 12 months posttreatment. For patients who received the high dose, an average decrease of 73%+/-13% in urine NAA was recorded at 3 months posttreatment. These reductions brought the urine NAA levels to those associated with mild CD. In addition, BridgeBio noted that for the low dose cohort, an average decrease of 70%+/-10% in CSF NAA was recorded at 12 months posttreatment. In terms of safety, the company characterized BBP-812 as “generally well-tolerated”.
“We continue to be encouraged by the results children are achieving in the CANaspire trial of BBP-812,” principal investigator Florian Eichler, MD, director of the leukodystrophy service at Massachusetts General Hospital, said in a statement.1 “Compared to the natural course of CD, in which most children do not achieve developmental milestones beyond that of a 6-month old, the fact that some children are sitting independently, taking steps, or even walking post-dosing is truly remarkable.”
Notably, on September 10, 2024, BridgeBio announced that the FDA had granted BBP-812 regenerative medicine advanced therapy designation based on data from CANaspire.2 At the time, the company state that improvements in functional outcomes were observed in all patients who had 1 or more follow-up examinations. Given examples of functional outcomes included head control, sitting upright, reaching for and grasping objects, and visual tracking.
“CD is an extremely rare and rapidly progressive neurodegenerative disease that prevents most children from meeting basic developmental milestones, such as crawling, walking, speaking, and even holding their heads up,” Kathleen Flynn, BA, the chief executive officer of National Tay-Sachs & Allied Diseases Association, said in a statement at the time.1 “It is a terminal diagnosis with no approved treatment to date. The news of the RMAT designation, coupled with the preliminary results seen in the clinical trial, provides hope to children worldwide living with CD and their families.”
BBP-812 is not the only gene therapy product currently in development for the treatment of CD.3 Myrtelle’s rAAV-Olig001-ASPA (MYR-101), an investigational recombinant AAV vector-based gene therapy is currently being evaluated for CD in a phase 1/2 clinical trial (NCT04833907). Earlier this month, Myrtelle reported data including CSF analyses from 7 patients treated in the study, who had follow-up of up to 24 months posttreatment, that showed reductions of more than 80% in NAA levels from baseline in all 7 patients. In addition, functional improvements on validated functional scales were also recorded, in contradistinction to the deterioration that would be expected in untreated CD.
