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Audentes Therapeutics Presents 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

- Significant continued improvements in neuromuscular and respiratory function observed in all treated patients, with follow-up assessments ranging from 4 to 48 weeks
- Three patients have achieved complete ventilator independence
- Encouraging initial safety and efficacy results observed in Cohort 2 sentinel patient at 4-week timepoint
- No new treatment-related serious adverse events (SAEs) reported since the May 2018 interim update

SAN FRANCISCO, Oct. 5, 2018 /PRNewswire/ --

Conference call and webcast Friday, October 5, 2018 at 8:30 am ET
Webcast may be accessed via the Investor and Media page of the Audentes website
Call may be accessed by dialing (833) 659-8620 (U.S.) or (409) 767-9247 (international) and using conference ID# 8458939

Audentes Therapeutics, Inc. (Nasdaq: BOLD), a biotechnology company focused on developing and commercializing innovative gene therapy products for patients living with serious, life-threatening rare diseases, today announced new positive interim data from ASPIRO, the Phase 1/2 clinical trial of AT132 for the treatment of X-linked Myotubular Myopathy (XLMTM).  The data will be presented at the 23rd International Annual Congress of the World Muscle Society by Nancy Kuntz, MD, Principal Investigator at Ann & Robert H. Lurie Children's Hospital of Chicago, Medical Director of Mazza Foundation Neuromuscular Program and Professor of Pediatrics and Neurology at Northwestern University Feinberg School of Medicine.  The oral presentation by Dr. Kuntz will be held during a session on new therapeutic modalities scheduled to begin at 9:30 a.m. ET on October 5, 2018. 

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 (MIP) 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.

"The encouraging safety and efficacy trends we've seen throughout the ASPIRO trial of AT132 are further strengthened by this latest update, with continued and durable improvements seen in all treated patients," stated Dr. Kuntz.  "The dramatic reductions in required respiratory support, with three patients achieving ventilator independence post-treatment, is an unprecedented outcome in children with a congenital myopathy who have been ventilated from birth."

"We are thrilled with the continued progress in ASPIRO, including the promising early data for the Cohort 2 sentinel patient, and plan to continue enrollment at the 3x1014 vg/kg dose in the coming weeks," stated Matthew R. Patterson, Co-Founder and Chief Executive Officer of Audentes.  "With the recently awarded RMAT and PRIME designations, we look forward to collaborating closely with the FDA and EMA to advance AT132 toward our goal of making AT132 available to patients living with XLMTM as rapidly as possible."

Data Summary
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.

Today's 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 localization.


Summary Table of Key Baseline and Follow-up Assessments 




Neuromuscular Assessment


Respiratory Assessments




Age at Baseline


at Baseline

at Last Report
(Max Score=64)

Δ  From Baseline


MIP at
(cm H2O) 2

MIP at
Last Report
(cm H2O) 2

Δ  From Baseline


Ventilator Status at Baseline

Use at
(hrs per day)

Use at Last
(hrs per day)

Δ  From
(hrs per day)


per diploid genome

Normal 4


Cohort 1


Patient 1




56 (Wk 48)

+27 (93%)



89 (Wk 24)3

+56 (170%)



12 hrs.

0 (Wk 48)

-12 hrs.


6.2 (Wk 24)


Patient 2




64 (Wk 48)

+19 (42%)



112 (Wk 48)

+68 (155%)



22 hrs.

6 (Wk 48)

-16 hrs.


7.1 (Wk 24)


Patient 3




34 (Wk 36)

0 (0%)1



70 (Wk 24)

+44 (170%)



24 hrs.

0 (Wk 40)

-24 hrs.


2.7 (Wk 24)


P. 4 (Control)




47 (Wk 36)

-2 (-4%)



46 (Wk 24)

-12 (-21%)



12 hrs.

12 (Wk 36)

0 hrs.


NA 5

NA 5


Cohort 1


Patient 5




53 (Wk 24)

+17 (47%)



78 (Wk 24)

+64 (457%)



24 hrs.

12 (Wk 24)

-12 hrs.


2.2 (Wk 24)


Patient 6




52 (Wk 16)

+13 (33%)



87 (Wk 12)

+52 (149%)



24 hrs.

0 (Wk 20)

-24 hrs.


NA 6

NA 6

Patient 7




53 (Wk 16)

+10 (23%)



68 (Wk 12)

+39 (134%)



23.5 hrs.

10 (Wk 20)

-13.5 hrs.


NA 6

NA 6


Cohort 2


Patient 8




55 (Wk 4)

+19 (53%)



67 (Wk 4)

+36 (116%)



22.5 hrs.

23.3 (Wk 4)

+0.8 hrs.


NA 6

NA 6


MIP = Maximal Inspiratory Pressure; Ventilator Use = Ventilator Dependence Over Prior 24 hours; VCN = Vector Copy Number

1. Patient 3 was fitted with a temporary halo traction device for treatment of preexisting scoliosis at the time of his week 36 visit, impeding his ability to complete the full CHOP INTEND assessment. As of the 24-week assessment, Patient 3 had achieved a 41% improvement in CHOP INTEND from baseline.

2. >80 cmH20 is considered in the normal range for healthy children less than five years of age.

3. Unable to collect data at week 48 due to lack of cooperation by the patient.

4. Protein expression numbers may change in future presentations as Audentes is currently titrating the standard and extending the linear range of the assay.

5. Control patients are not treated until the optimal dose has been selected. Once treated, biopsies are conducted at baseline, week 24 and week 48 post treatment.

6. The longest duration of follow-up for Patients 6, 7 and 8 is 16 weeks. Post treatment biopsies will be conducted at week 24 and week 48.

The independent Data Monitoring Committee (DMC) 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 U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) on the potential registration pathway for AT132 under its Regenerative Medicine Advanced Therapy (RMAT) 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 percent increase over earlier reports.  The Vandersmissen publication confirms previous literature estimates of two-year mortality of approximately 50 percent but shows that for boys who survive this critical period, subsequent 10-year survival is between 75 and 80 percent.  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.

Conference Call
At 8:30 a.m. Eastern Time today, October 5, 2018, Audentes management will host a conference call and a simultaneous webcast to discuss the new interim data from ASPIRO that will be presented at the 23rd International Annual Congress of the World Muscle Society.  To access a live webcast of the conference call, please visit the Investor and Media page of the Audentes website at  Alternatively, please call (833) 659-8620 (U.S.) or (409) 767-9247 (international) and dial the conference ID# 8458939 to access the call.  A replay of the webcast will be available on the Audentes website for approximately 30 days.

About AT132 for X-linked Myotubular Myopathy
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 (RMAT), 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 (EMA).

About Audentes Therapeutics, Inc.
Audentes Therapeutics (Nasdaq: BOLD) is a biotechnology company focused on developing and commercializing innovative gene therapy products for patients living with serious, life-threatening rare diseases.  We are currently conducting Phase 1/2 clinical studies of our lead product candidates, AT132 for the treatment of X-linked Myotubular Myopathy (XLMTM), and AT342 for the treatment of Crigler-Najjar syndrome.  We have two additional product candidates in development, including AT982 for the treatment of Pompe disease, and AT307 for the treatment of the CASQ2 subtype of catecholaminergic polymorphic ventricular tachycardia (CASQ2-CPVT).  We are a focused, experienced and passionate team committed to forging strong, global relationships with the patient, research and medical communities.

For more information regarding Audentes, please visit

Forward Looking Statements
This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, anticipated clinical milestones, the timing and nature of clinical development activities, the nature of the results of clinical data, the timing of regulatory filings, the potential market size and market opportunity for AT132 and the expected benefits of the company's product candidates.  All statements other than statements of historical fact are statements that could be deemed forward-looking statements.  Although the company believes that the expectations reflected in such forward-looking statements are reasonable, the company cannot guarantee future events, results, actions, levels of activity, performance or achievements, and the timing and results of biotechnology development and potential regulatory approval is inherently uncertain.  Forward-looking statements are subject to risks and uncertainties that may cause the company's actual activities or results to differ significantly from those expressed in any forward-looking statement, including risks and uncertainties related to the company's ability to advance its product candidates, obtain regulatory approval of and ultimately commercial its product candidates, the timing and results of preclinical and clinical trials, the company's ability to fund development activities and achieve development goals, the company's ability to protect intellectual property and other risks and uncertainties described under the heading "Risk Factors" in documents the company files from time to time with the Securities and Exchange Commission.  These forward-looking statements speak only as of the date of this press release, and the company undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof.

Audentes Contacts:

Investor Contact:
Andrew Chang

Media Contact:
Katie Hogan

Audentes Therapeutics, Inc. (PRNewsfoto/Audentes Therapeutics, Inc.)



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