Audentes Doses First patient in Gene Therapy Trial for Rare Muscle Disease

September 21, 2017

Rare Daily Staff

Audentes Therapeutics said it initiated a phase 1/2 trial of AT132, its gene therapy for a rare muscle disease that is fatal.

X-Linked myotubular myopathy is characterized by extreme muscle weakness, respiratory failure and early death. About half of those with the condition will die by 18 months of age. The disease is caused by mutations in the MTM1 gene, which encode myotubularin, a protein that plays a critical role in the development, maintenance and function of skeletal muscle cells.

Audentes gene therapy known as AT132 is an AAV8 vector containing a functional copy of the MTM1 gene. Multiple studies in animal models of X-Linked myotubular myopathy have demonstrated that a single administration of AT132 improved disease symptoms and survival rates, with no significant AT132-related adverse events or safety findings.

The clinical trial is a multicenter, multinational, open-label, ascending dose study to evaluate the safety and preliminary efficacy of AT132 in approximately 12 patients with X-Linked myotubular myopathy patients less than five years of age. The study is expected to include nine AT132 treated subjects and three delayed-treatment concurrent control subjects. Primary endpoints include safety (adverse events and certain laboratory measures) and efficacy (assessments of neuromuscular and respiratory function).

Secondary endpoints include the burden of disease and health related quality-of-life, and muscle tissue histology and biomarkers. The primary efficacy analysis is expected to be conducted at 12 months, with interim evaluations expected to be conducted at earlier time points. After the primary 12-month assessment, investigators will follow subjects for another four years to assess long term safety, durability of effect, and developmental progression.

Audentes is developing AT132 in collaboration with Genethon, a non-profit R&D organization based in Evry, France.

September 21, 2017

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