Canavan Disease Treatment Bringing Competition among Market Players


Canavan disease is a neurological disorder in which the brain degenerates into spongy tissue full of small fluid-filled spaces. It is caused by a mutation in the ASPA gene which makes an enzyme called aspartoacylase. This enzyme is primarily present in oligodendrocytes, contributes to the manufacture of myelin, and is responsible for breaking down (metabolizing) the brain chemical N-acetyl-L-aspartate or N-acetyl-L-aspartic acid. In Canavan disease, many oligodendrocytes do not mature and instead die, leaving nerve cell projections known as axons vulnerable and unable to function properly.

Currently, there is no cure, nor is there a standard course of treatment, and the treatment is symptomatic and supportive also the prognosis for Canavan disease is poor. Death usually occurs before age 10, although some children may survive into their teens and twenties.

“The emerging treatment for Canavan disease lies in the development of induced pluripotent stem cell (iPSC) technology, called hiPSC when human cells are used. Any cell from the body can be converted into iPSC which then, in the laboratory, the faulty gene is corrected, converted into relevant tissue type-specific cells, and infused back into the patient.”

Due to the efficacy of iPSC technology, the market players are focusing on developing drugs that could directly target the faulty gene and replace it with the working gene. AAV9 BBP-812 (Aspa Therapeutics) and rAAV-Olig001-ASPA (Myrtelle Inc.) are the two emerging biologics that could be the breakthrough for the Canavan disease treatment. AAV9 BBP-812 is an investigational AAV9 gene therapy for Canavan disease. Whereas, rAAV-Olig001 is a novel vector from a class of recombinant AAVs (rAAVs) that selectively target oligodendrocytes – the cells in the brain responsible for producing myelin, the insulating material that enables the proper function of neurons and makes up the brain’s white matter.

The rAAV-Olig001-ASPA (Myrtelle Inc.) phase 1/2 interim result showed that the first 8 patients in the clinical trial have reached at least 3 months of follow-up, and the results from this timepoint showed increases in white matter, grey matter, and total brain volumes, along with decreases in the volume of cerebrospinal fluid (CSF) in most patients, as measured by MRI. Furthermore, improvements across several domains were reported in clinical measurements of motor and cognitive function with the Gross Motor Function Measure (GMFM) and Mullen Scales of Early Learning (MSEL) tools. The first 3 patients treated in cohort 1, which includes those older than 36 months, are now at 18 months or more post-treatment. It was previously reported that at 6 months of follow-up, these patients improved on the GMFM and the MSEL and showed brain white matter and myelin content increases. In terms of safety, no serious adverse events related to gene therapy have been reported to date.

And, the AAV9 BBP-812 (Aspa Therapeutics) phase 1/2 interim data showed that, at Month 3 post-treatment, Participant 2 showed, an 89% reduction of NAA in CSF, 53% reduction in NAA in brain white matter by MRS imaging, and 81% reduction in urine NAA. At Month 6 post-treatment, Participant 1 showed a 77% reduction of NAA in CSF, a 15% reduction in NAA in brain white matter by MRS imaging, and a 45% reduction in urine NAA. Intravenous infusions of BBP-812 have been well-tolerated by all 3 participants with no reported treatment-related serious adverse events.

Conclusion:- Both the biologics are currently in phase 1/2 stage of development, and they are very well competing with each other. The phase 1/2 interim data of both drugs have shown good efficacy. But the rAAV-Olig001-ASPA (Myrtelle Inc.) have a little advantage over the AAV9 BBP-812 (Aspa Therapeutics), due to 2 main reason, firstly, the rAAV-Olig001-ASPA clinical trials have a more patient pool number which could show more efficacy and safety result, and secondly, the study completion date of rAAV-Olig001-ASPA is August 31, 2024, which is near to complete the phase 1/2 trial in compare to AAV9 BBP-812 drug.