Research & Development
Audentes Therapeutics Touts New Positive Interim Data from ASPIRO, the Phase 1/2 Clinical Trial of AT132 in Patients with X-linked Myotubular Myopathy, at 23rd International Annual Congress of the World Muscle Society
8 October 2018 - - US-based biotechnology company Audentes Therapeutics, Inc. (NASDAQ: BOLD) has received new positive interim data from ASPIRO, the Phase 1/2 clinical trial of AT132 for the treatment of X-linked Myotubular Myopathy (XLMTM), the company said.

The newly reported data include follow-up assessments ranging from 4 to 48 weeks for the eight patients enrolled in ASPIRO to date, including the seven patients enrolled in Cohort 1 (1x1014 vg/kg; six treated and one untreated control) and one patient enrolled to date in Cohort 2 (3x1014 vg/kg).

Key assessments include neuromuscular function as measured by CHOP INTEND; respiratory function as measured by maximal inspiratory pressure and ventilator dependence; and vector transduction, transgene expression and histological improvement as assessed via muscle biopsy.

All treated patients continue to show meaningful improvements in neuromuscular and respiratory function, with no new treatment-related SAEs reported since the last scientific update in May 2018.

AT132 has been well tolerated with a manageable safety profile to date at doses up to 3x1014 vg/kg. There have been no treatment-related SAEs reported since the last scientific update in May 2018.

This presentation provides incremental new CHOP INTEND and ventilator dependence data for all patients; MIP data for Patients 2, 5, 6, 7, and 8; and week 24 biopsy data for Patient 5.

Data continue to show significant improvements in neuromuscular and respiratory function as assessed via CHOP INTEND and MIP in all treated patients, including the Cohort 2 sentinel patient.

All treated patients in Cohort 1 have shown significant reductions in ventilator use, and three patients have now achieved ventilator independence.

Week 24 muscle biopsies show evidence of highly efficient tissue transduction as indicated by vector copy number and robust myotubularin protein expression as assessed by Western blot. Histological analyses also show significant improvements in myofiber size, nuclear peripheralization and organelle localisation.

The independent Data Monitoring Committee has reviewed the preliminary safety and efficacy data from the Cohort 2 sentinel patient and has recommended continuing with enrollment of the remaining three patients in Cohort 2, which is expected to commence in the coming weeks.

In addition, with the goal of gaining alignment with the US Food and Drug Administration and the European Medicines Agency on the potential registration pathway for AT132 under its Regenerative Medicine Advanced Therapy and Priority Medicines (PRIME) designations, Audentes plans to hold initial discussions with both regulatory bodies beginning in the fourth quarter of 2018.

XLMTM is a rare monogenic disease characterized by extreme muscle weakness, respiratory failure and early death. The XLMTM patient population may be larger than previously reported, potentially increasing the future market opportunity for AT132.

A recent publication by Vandersmissen et al. in Neuromuscular Disorders indicated that incidence of XLMTM may be up to 1 in 40,000 live male births, a 20% increase over earlier reports.

The Vandersmissen publication confirms previous literature estimates of two-year mortality of approximately 50% but shows that for boys who survive this critical period, subsequent 10-year survival is between 75% and 80%.

A recent mortality analysis of the RECENSUS retrospective chart review corroborates this finding, suggesting that while severely functionally impaired, there exists a larger prevalent population of older boys who may benefit from treatment with AT132.

AT132 is the Audentes product candidate being developed to treat XLMTM, a disease caused by mutations in the MTM1 gene, which encodes the protein myotubularin. Myotubularin plays an important role in the development, maintenance and function of skeletal muscle cells.

AT132 is comprised of an AAV8 vector containing a functional copy of the MTM1 gene.

Over the course of 2018, Audentes has reported promising safety, efficacy and muscle biopsy data from ASPIRO, a multicenter, ascending dose Phase 1/2 clinical study to evaluate the safety and preliminary efficacy of AT132 in approximately 12 XLMTM patients less than five years of age.

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

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

Audentes Therapeutics is a biotechnology company focused on developing and commercialising innovative gene therapy products for patients living with serious, life-threatening rare diseases.


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