In May Audentes released new data at the American Society for Gene and Cell Therapy (ASGCT) to include more positive feedback about their AT132 gene therapy trial programme (ASPIRO), which is aimed at patients with x-linked myotubular myopathy (MTM1) aged up to five years.
Outcomes from nine patients in total were shared at the meeting. Chairman and Chief Executive Officer of Audentes, Matthew R Patterson said “We are excited to share today’s results and are working hard toward our goal of making AT132 available to patients living with XLMTM globally as rapidly as possible. We look forward to important next steps for the program, including selection of the optimal dose and further discussions with regulators in the U.S. and Europe regarding possible pathways to license applications.”
In October Audentes presented new positive data from ASPIRO, the clinical trial evaluating AT132 in patients with X-Linked myotubular myopathy, at the 24th International Annual Congress of the World Muscle Society. The data was presented by Dr James J Dowling from the Toronto Hospital for Sick Children. Dr Dowling said “The new ASPIRO data shared today builds upon the encouraging efficacy and safety profile seen to date with AT132. Treated patients across both dose cohorts show significant reductions in ventilator dependence and the progressive attainment of developmental motor milestones, suggesting that AT132 has the potential to deliver transformative benefit to patients and families living with XLMTM.”
Natalie Holles, President and Chief Operating Officer of Audentes said “We remain focused on our goal of rapidly progressing AT132 toward global regulatory approvals. Importantly, we have fully enrolled 14 patients into the ASPIRO dose escalation cohorts, and plan to complete enrolment of the ASPIRO pivotal expansion cohort imminently. ”
In November the organisation reported its third quarter 2019 financial results and provided a corporate update. Matthew R Patterson, Chairman and Chief Executive Officer stated “AT132 continues to show a promising safety and efficacy profile in patients with XLMTM, with the first seven treated patients now ventilator independent. Beyond AT132, we are excited about the significant momentum building across our entire pipeline of development candidates.”
Share your experience with x linked myotubular myopathy (xlmtm): a survey for the US X linked myotubular myopathy community
Also in November, Audentes Therapeutics launched the xlmtm parent and caregiver community survey in the US. Initially the survey is live for US based families, with UK and German versions coming in early 2020.
The survey aims to gather important data related to the quality of life and economic impacts of xlmtm and to create a more thorough understanding of the quality of life and economic impact of xlmtm on families and caregivers. The results of this survey will be published and shared with the xlmtm community and may be shared with health policy makers and insurance companies to support patient access to future treatments.
More detailed information about the study is available below.
Share your experience
The second RECENSUS manuscript entitled ‘Mortality and Respiratory Support in X-linked Myotubular Myopathy: A RECENSUS Retrospective Analysis’ was recently accepted by the journal Archives of Disease in Childhood and the full text published online as an open access article. Below Kimberly Trant, Senior Director of Patient Advocacy and Engagement at Audentes Therapeutics writes about the study.
RECENSUS is one of the largest natural history studies of patients with XLMTM. This means that, with approval from patients and their families, researchers have collected medical records on 145 patients and reviewed them as a group to help understand their symptoms, their medical treatment, and the course of their disease.
From prior studies, we know that nearly half of children with XLMTM do not survive past 18 months due to respiratory failure, and those who survive typically require respiratory and feeding support, and never sit without support or walk on their own. To ensure that patients get the best care possible, it is important that they obtain a timely diagnosis. This can be more difficult in rare diseases, like XLMTM. Data from studies like RECENSUS help medical professionals recognize the signs and symptoms, request the appropriate diagnostic tests, and then provide patients with the best options possible.
The first analysis from RECENSUS (Beggs and colleagues, 2017) looked at patients’ burden of disease and their medical treatment. Here’s what we learned.
- The average age at diagnosis was at three years old (36 months), which is decreasing over time.
- Nearly all (90%) XLMTM patients required respiratory support at birth.
- 60% of patients had a tracheostomy.
- 48% of patients were dependent on ventilator support 24 hours per day.
- In their first year of life, affected children had an average of 3.7 surgeries and spent 35% of the year in the hospital.
- A substantial number of mothers reported signs of XLMTM during pregnancy, including decreased fetal movement (53%), polyhydramnios (excess amniotic fluid; 52%), and premature birth (31%).
The second analysis from RECENSUS (Graham and colleagues, 2019) looked at how respiratory support relates to survival, especially for younger patients. Here’s what we learned.
- The most common cause of death was respiratory failure (67%), despite nearly all patients having respiratory support from birth.
- Patients with a tracheostomy lived much longer than those without a tracheostomy (22.8 years vs 1.8 years) on average.
- By six months old, only 50% of patients were living without a tracheostomy; by two years old, this number fell to 28%.
Audentes Therapeutics sponsors and runs the RECENSUS study. Audentes thanks the patients and families with XLMTM who allowed their data to be collected for the RECENSUS study. We are also grateful for support from the XLMTM patient advocacy community: The Joshua Frase Foundation; MTM-CNM Family Connection; the Myotubular Trust; Where There’s a Will There’s A Cure Foundation for Myotubular Myopathy; and ZNM – Zusammen Stark!
- NCT02231697 – A Medical Chart Review of Patients With X-Linked Myotubular Myopathy (RECENSUS). Available at https://clinicaltrials.gov/ct2/show/NCT02231697. Accessed October 14, 2019.
- BeggsAH, Byrne BJ, De Chastonay S, et al. A multicenter, retrospective medical record review of X-linked myotubular myopathy: the recensus study. Muscle Nerve. 2018;57:550. Available at https://doi.org/10.1002/mus.26018. Accessed October 14, 2019.
- GrahamRJ, Muntoni F, Hughes I, et al. Mortality and respiratory support in X-linked myotubular myopathy: a RECENSUS retrospective analysis Archives of Disease in Childhood. Sep 4 [Epub ahead of print]. Available at http://dx.doi.org/10.1136/archdischild-2019-317910. Accessed October 14, 2019.
This article first appeared in The Information Point newsletter Our World in 2018.
Audentes Therapeutics recently released their first quarter 2018 results, in which they confirmed they had “Completed dosing of three additional patients as an expansion of the first dose cohort of ASPIRO, the Phase 1 / 2 clinical study of AT132, their gene therapy product.” They confirmed there were no significant adverse safety events in these three extra patients.
And during a presentation at the 21st annual meeting of the American Society of Gene and Cell Therapies in Chicago Dr. Suyash Prasad, Senior Vice President and Chief Medical Officer of Audentes stated “We continue to be highly encouraged by the profile of AT132 observed to date in the ASPIRO study. Patients treated in the initial cohort continue to make advancements in neuromuscular and respiratory function, highlighted by the fact that our earliest treated patient has now been ventilator independent for over eight weeks.”
Dr. Prasad continued, “We are pleased to see the encouraging trends in safety and efficacy continue in the recently enrolled Cohort 1 expansion patients, with early gains in CHOP-INTEND and MIP observed by the four-week timepoint and no significant treatment-related adverse events reported to date. We remain inspired by our patients and their families, and we look forward to continuing our work with the XLMTM community to advance this important work as rapidly as possible.”
This story first appeared in the Information Point newsletter Our World in 2013, when Andy C Villon, a 19 year old freelance artist, diagnosed with X-linked myotubular myopathy, who lives in Greenville, South Carolina told us about four watercolours he had produce for Audentes Therapeutics in San Francisco, a biotechnology company developing new treatments for people with serious rare diseases, through the application of gene therapy technology and currently working to develop a treatment for myotubular myopathy.
Andy says: I am diagnosed with X-linked myotubular myopathy however I do not let this disability stop me from enjoying life. I have been painting and drawing as a hobby all of my life. When I graduated from high school, I knew I wanted to do something with art. Around this time, I painted my first watercolor of the Grand Canyon and seeing how it came out, I knew I was on the right track. This painting won in the youth category in the 2014 RareArtist.org art competition.
For the past three years I have been instructed by Bruce L Bunch who is a professional artist. Mr Bunch has guided me and given me advice on how to improve my painting skills, I have learned a lot about art history, digital art and traditional art from watching videos on YouTube and I learned about design when I read the biography of Steve Jobs by Walter Isaacson.
My watercolors tend to look much more realistic than my acrylic paintings. My acrylics are very impressionistic and vibrant. After watching a girl on YouTube draw photorealistic portraits using colored pencils, I was inspired to try that medium too. When I paint with watercolors and acrylics I enjoy painting broad landscapes.
I love powerful scenes where you can see an entire city or valley and earlier this year was contacted by Tristen Moors of Audentes Therapeutics. She wanted me to paint four watercolors of scenes from around San Francisco, California, to go in their new office. These were the first large (18″ x 24″) and realistic watercolors I had ever done and I truly appreciated what I was painting due to the fact that I had traveled to San Francisco in 2013 and the paintings helped me learn so much about working with watercolors.
The four watercolours painted by Andy are now showcased on the walls of the Audentes offices in San Fransciso and as the photos here show, the team are very happy with his work.