Research & Development
Audentes Therapeutics Presents New Positive Data from ASPIRO, the Clinical Trial Evaluating AT132 in Patients with X-Linked Myotubular Myopathy (XLMTM), at the 24th International Annual Congress of the World Muscle Society
9 October 2019 - - US-based AAV-based genetic medicines company Audentes Therapeutics, Inc. (NASDAQ: BOLD) has presented new positive data from ASPIRO, the clinical trial evaluating AT132 in patients with X-Linked Myotubular Myopathy (XLMTM), the company said.

The data were presented at the 24th International Annual Congress of the World Muscle Society by Dr. James J. Dowling, Hospital for Sick Children, Toronto, Canada.

The newly reported data include safety and efficacy assessments as of the August 7, 2019 data cut-off date for 12 patients enrolled in the ASPIRO dose escalation cohorts.

The data includes 48 weeks or more of follow-up for seven patients enrolled in Cohort 1 (1x1014 vector genomes per kilogram (vg/kg); six treated and one untreated control) and 24-48 weeks of follow-up for five patients in Cohort 2 (3x1014 vg/kg; four treated and one untreated control).

Key assessments include neuromuscular function as assessed by the achievement of motor milestones and improvement in CHOP INTEND score, and respiratory function as assessed by reduction in ventilator dependence and improvement in maximal inspiratory pressure.

Today's presentation does not include new muscle biopsy data.

Patients receiving AT132 have achieved significant and durable reductions in ventilator dependence, an endpoint considered to be closely correlated with morbidity and mortality in XLMTM patients.

To date, the first seven patients treated (all six treated patients in Cohort 1 and the first patient treated in Cohort 2) have achieved ventilator independence.

All treated patients continue to show gains in neuromuscular function, with the first seven patients treated achieving the ability to rise to a standing position, or walk.

AT132 has been generally well-tolerated and has shown a manageable safety profile across both dose groups. Since the last data update in May 2019, there has been one new serious adverse event in Cohort 2, an episode of joint swelling that resolved without treatment.

Results to date indicate no clinically meaningful differences in the safety and tolerability profile of AT132 between the 1x1014 vg/kg and 3x1014 vg/kg dose cohorts.

Next steps in the AT132 development program include the completion of enrollment and follow-up of patients in the ASPIRO pivotal expansion cohort, designed to confirm the safety and efficacy profile of AT132 at a dose of 3x1014 vg/kg, and preparations for filing of a Biologics License Application for AT132 in the United States planned in mid-2020 and filing of a Marketing Authorization Application in Europe planned for the second half of 2020.

XLMTM is a serious, life-threatening, rare neuromuscular disease that is characterized by extreme muscle weakness, respiratory failure, and early death.

Mortality rates are estimated to be 50% in the first 18 months of life, and for those patients who survive past infancy, there is an estimated additional 25% mortality by the age of 10.

XLMTM is caused by mutations in the MTM1 gene that lead to a lack or dysfunction of myotubularin, a protein that is needed for normal development, maturation, and function of skeletal muscle cells.

The disease affects approximately one in 40,000 to 50,0000 newborn males.

XLMTM places a substantial burden of care on patients, families and the healthcare system, including high rates of healthcare utilization, hospitalization and surgical intervention.

More than 80% of XLMTM patients require ventilator support, and the majority of patients require a gastrostomy tube for nutritional support.

In most patients, normal developmental motor milestones are delayed or never achieved.

Currently, only supportive treatment options, such as ventilator use or a feeding tube, are available.

Audentes is developing AT132, an AAV8 vector containing a functional copy of the MTM1 gene, for the treatment of XLMTM.

AT132 may provide patients with significantly improved outcomes based on the ability of AAV8 to target skeletal muscle and increase myotubularin expression in targeted tissues following a single intravenous administration.

The preclinical development of AT132 was conducted in collaboration with Genethon.

AT132 has been granted Regenerative Medicine and Advanced Therapy, Rare Pediatric Disease, Fast Track, and Orphan Drug designations by the US Food and Drug Administration, and Priority Medicines (PRIME) and Orphan Drug designations by the European Medicines Agency.

Audentes Therapeutics is an AAV-based genetic medicines company focused on developing and commercialising innovative products for serious rare neuromuscular diseases.
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