Taysha Granted European Orphan Drug Designation for Giant Axonal Neuropathy Gene Therapy
The AAV9 gene therapy is currently being evaluated in a clinical trial conducted by NINDS.
The European Commission has granted orphan drug designation to TSHA-120, an investigational AAV9 gene therapy currently being evaluated for the treatment of giant axonal neuropathy.1
The intrathecal therapy, developed by Taysha Gene Therapies, is the subject of an ongoing phase 1 clinical trial (NCT02362438) being conducted by the National Institute of Neurological Disorders and Stroke (NINDS), which is being led by Carsten Bonneman, MD. The therapy has previously received orphan drug and rare pediatric disease designations from the FDA.
Caused by a loss of function mutation, TSHA-120 intrathecally delivers a replacement of the gene gigaxonin. The trial, which is enrolling patients age 3 and older with giant axonal neuropathy, is exploring safety and efficacy end points of 4 escalating doses over 12 months. Beyond safety, the study will assess for motor and sensory disease symptoms compared with baseline; neuropathology in peripheral nerve biopsy post-treatment; cerebrospinal fluid assessment; vector shedding; and safety and tolerability of gene transfer in CRIM-negative patients.
Earlier this year, Taysha announced interim data1 from the 3.5x1014 total vg high-dose cohort, which demonstrated clinically meaningful and statistically significant slowing of disease progression in the form of a 5-point improvement in the change in rate of decline on the 32-item Motor Function Measure (MFM32) compared with natural history (8 point decline; P =.04). Among all dose cohorts, a 7-point improvement in change in rate of decline on the MFM32 was recorded compared with an 8-point decline in natural history cohort over 12 months (n=12; P <.001).
In 5 patients, a 10-point improvement from baseline on the MFM32 was recorded over 3 years, with 1 patient reaching 5-year follow-up who demonstrated a 26-point improvement from baseline and disease stabilization.
In addition, nerve biopsy in 5 of 6 patient samples confirmed active axon regeneration with an increase in regenerative nerve clusters; preserved visual acuity in all dose cohorts; and stabilization of retinal nerve fiber layer thickness and prevention of axonal nerve degeneration compared with natural history.
The therapy also showed good safety and tolerability based on 53 patient-years of data.
“The totality of data generated by TSHA-120 to date support our plans to engage with major regulatory agencies in order to discuss pathways for registration and we look forward to providing a regulatory update later this year,” RA Session II, president, founder, and CEO of Taysha, said in a statement at the time.2 “In the interim, we are finalizing our commercial strategy with a focus on patient identification, disease awareness, and payor engagement for the estimated 5000 affected patients in addressable markets.”
“These data also provide new evidence of TSHA-120’s ability to regenerate nerve fibers, demonstrating an improvement in disease pathology, and to preserve visual acuity, which should significantly benefit patients’ and families’ quality-of-life,” added Taysha chief medical officer and head of R&D, Suyash Prasad, MBBS, MSc, MRCP, MRCPCH, FFPM.2
Notably, Taysha has partnered with GeneDx to include the genetic marker for giant axonal neuropathy on the company’s hereditary neuropathy panel at no cost to patients at risk of or suspected of having the disease. In turn, Taysha is also working with the Hereditary Neuropathy Foundation and Charcot-Marie-Tooth Association Centers of Excellence to boost disease awareness and access to genetic testing.
