Axovant’s gene therapies show promise for treating Tay-Sachs disease and Parkinson’sPublished: March 11, 2019
Three-month interim data obtained from two of Axovant’s gene therapy trials provide hope for patients with Tay-Sachs disease and Parkinson’s disease.
Tay-Sach’s disease is a rare and fatal pediatric neurodegenerative genetic disorder caused by defects in the HEXA gene that encode one of the two subunits of the β-hexosaminidase A (Hex A) enzyme. Impaired Hex A function leads to neurodegeneration and shortened life expectancy. Axovant’s gene therapy, AXO-AAV-GM2, is designed to restore Hex A enzyme activity by introducing a functional copy of the HEXA and HEXB genes via two co-administered AAV vectors.
Prof. Terence Flotte at the University of Massachusetts Medical School is the principal investigator of the study. This investigator-initiated trial administered a 1.0x 1014 vg dose of AXO-AAV-GM2 into the cisterna magna and lumbar spinal canal of a 30-month-old child with advanced infantile Tay-Sachs disease.
Results showed that the treatment was generally well-tolerated by the patient and no serious adverse events were reported within the three months. β-Hexosaminidase A activity in the cerebrospinal fluid increased from 0.46% of normal (at baseline) to 1.44% of normal (at three-month), implying a clinically relevant activity level.
Dr Gavin Corcoran, Axovant’s Executive VP of Research and Development commented: “This is the first time a gene therapy has been administered to a child with Tay-Sachs disease, and it is remarkable that we have not only seen good safety and tolerability to date, but also evidence of functional β-Hexosaminidase A enzyme activity. These encouraging early clinical results suggest that AXO-AAV-GM2 may offer a meaningful treatment option for patients who currently have no approved therapies.”
The company also reported 3-month data from the first dose cohort of its ongoing SUNRISE-PD Phase 2 trial of AXO-Lenti-PD for the treatment of Parkinson’s disease. The cohort consisted of two patients with advanced Parkinson’s disease who received a single dose (lowest dose of 4.2×106 TU) of AXO-Lenti-PD. The treatment was well-tolerated by both the patients. The Unified Parkinson’s Disease Rating Scale (UPDRS) Part III score (ranging from 0 to 108) was used to assess improvement in the patients, with lower scores indicating improvement. Patients in the first cohort experienced an average UPDRS Part III (motor) score improvement of 25 points at 3 months after administration of AXO-Lenti-PD, representing an average improvement of 42% from baseline.
Based on positive feedback received from members of the Data Monitoring Committee, Axovant intends to proceed to the planned second dose cohort of AXO-Lenti-PD. The first subject in this second cohort is expected to be dosed (dose-1.4×107 TU) in the second quarter of 2019.
In addition to Tay-Sachs disease and Parkinson’s, Axovant is developing gene therapies for additional debilitating neurological and neuromuscular diseases including GM2 gangliosidosis, oculopharyngeal muscular dystrophy, amyotrophic lateral sclerosis and frontotemporal dementia.
Source: AXOVANT REPORTS POSITIVE INTERIM RESULTS FROM FIRST COHORT OF SUNRISE-PD PHASE 2 TRIAL OF AXO-LENTI-PD GENE THERAPY IN PARKINSON’S DISEASE; PRESS RELEASE
AXOVANT ANNOUNCES CLINICAL UPDATE FROM FIRST TAY-SACHS DISEASE PATIENT DOSED WITH AXO-AAV-GM2 GENE THERAPY; PRESS RELEASE