Data is Promising for Parkinson’s and infantile Tay Sachs patients.

NYC-based Axovant Gene Therapies recently reported positive early results for two of its candidates, AXO-Lenti-PD for the treatment of Parkinson’s disease and AXO-AAV-GM2 for the treatment of advanced infantile Tay-Sachs disease, a rare and fatal pediatric neurodegenerative genetic disorder with no approved therapies.

AXO-Lenti-PD (and the predecessor product ProSavin) was licensed by Axovant from Oxford BioMedica in 2018 for $30 million up-front. This gene therapy delivers genes for tyrosine hydroxylase, cyclohydrolase 1, and aromatic l-amino acid decarboxylase via a lentiviral vector. The inserted genes code for enzymes that are necessary for dopamine synthesis, and the goal of the gene therapy is to restore steady levels of dopamine in the brain in one treatment. 

In its mid-stage SUNRISE-PD study, two patients that did not respond to oral levodopa therapy (the gold standard treatment for Parkinson’s) were given the gene therapy and then evaluated three months later according to a physician-rated scale (UPDRS) assessing motor function (the Part III score). One patient saw an improvement of 14 points, the other 36 points — an average of 25 points (a mean improvement of 42% from baseline). Improvement was also noted on other parts of the UPDRS scale, including in activities of daily living (Part II) – with an average improvement of 22 points. These results suggest that a lower dose might be more effective than the highest dose of ProSavin that was ever previously tested, according to the company. Axovant is planning to test a second dose of the therapy.

AXO-AAV-GM2, which is designed to restore β-hexosaminidase A enzyme activity in the central nervous system, was given to a 30-month-old patient. The treatment was generally well tolerated, and the clinical condition of the patient was observed to be stable three months following treatment. Notably, the β-hexosaminidase A activity in the cerebrospinal fluid was found to increase from 0.46% of normal to 1.44% of normal, surpassing the 0.5% threshold that could represent a clinically relevant effect.