The World Muscle Society (WMS) is hosting it’s 25th Annual Conference online. From September 28 – October 2, 2020, Our Director of Research and Advocacy, Nicola Worsfold, will be in attendance providing daily updates for our Duchenne community.

DAY ONE: MONDAY, SEPTEMBER 28

Today included six industry-sponsored symposia, two focusing on Duchenne muscular dystrophy.

Session One: Sponsored by PTC Therapeutics

This session focused on the role of real-world evidence in transforming the therapeutic outlook in Duchenne. Dr. Jean Mah (Calgary, Canada) discussed the impact of delaying milestones on disease progression; Professor Ros Quinlivan (London, UK) discussed the genetic diagnosis of Duchenne; and Professor Eugenio Mercuri (Rome, Italy) presented the real-world evidence for the treatment of nonsense mutation in Duchenne.

Key highlights included:

• Earlier diagnosis and earlier interventions (including corticosteroids and the standards of care management recommendations published 2018) are important in keeping our boys healthier for longer.
• Real-world data for ataluren in nonsense mutations (mutations that cause a premature stop codon in the dystrophin gene) continues to show a favourable safety profile and benefits in the clinical practice setting. Although it is not approved for use in Canada, there are opportunities to access through clinical trials or Health Canada Special Access Programs (SAP). Talk to your neuromuscular physician about how you can access these programs.

Click here to see PTC’s summary of this session.

Session Two: Sponsored by Sarepta Therapeutics

This session focused on the new era of gene transfer therapies and application to Duchene muscular dystrophy and limb-girdle muscular dystrophies. Professor Francesco Muntoni (London, UK) presented the clinical considerations for gene transfer therapy development; Dr. Krista Vanderborne (Florida, USA) discussed MRI imaging biomarkers to access the efficacy of new therapeutic strategies in Duchenne; Dr. Jerry Mendell (Columbus, Ohio) presented the clinical updates of micro-dystrophin gene transfer therapy in development for Duchenne; Dr. Louise Rodino-Klapac, (Sarepta Therapeutics Inc.) provided the clinical updates to Sarepta’s Limb-Girdle Muscular Dystrophy program.

Key highlights included:

• Gene therapy is a very promising therapeutic approach and is still under investigation.
• MRI appears to be a good biomarker for disease expression and will hopefully replace muscle biopsies in future clinical trials.
• Sarepta’s SRP-9001 micro-dystrophin gene therapy is showing good results in the early stages of their trials. We look forward to seeing more positive data from Phase 2 and Phase 3 trials in the near future. If you are interested in learning more about gene therapy and/or participation in a clinical trial, please speak to your neuromuscular team.

Click here to see the press release from Sarepta.

DAY TWO: TUESDAY, SEPTEMBER 29

Today’s focus was on the pre-congress teaching courses. Tomorrow starts the main plenary and panel discussions – stay tuned!

DAY THREE: WEDNESDAY, SEPTEMBER 30

The World Muscle Society (WMS) opened today with a welcome speech from its president Dr. Volker Straub’s (UK). An opening lecture on COVID-19 followed this, and two-panel discussions focused on considerations for pre-clinical work and new therapies for neuromuscular conditions.

Opening Lecture: COVID-19

Moderated by Dr. Jiri Vajsar (Toronto, Canada), this lecture focused on COVID-19 for NMD, telemedicine, changing practice in the pandemic situation, presented by Dr. Maxwell Damian (Cambridge, UK)

Key highlights included:

• WMS developed a position and advice document on COVID-19 for people living with NMDs.
• Avoiding infection is the best measure to minimize risk.
• Dr. Damian discussed changes to clinical practice, including telehealth and how this has impacted practice. He advised high-risk patients to maintain shielding measures.

If you would like to read more on the WMS advice, please refer to their document here.

As always, be sure to discuss any questions or concerns about you or your child’s/young adult’s health and safety with your neuromuscular team.

Panel Discussion 1: Pre-clinical requirements for novel neuromuscular therapies

Dr. Jim Dowling (Toronto, Canada) moderated this discussion with the following panellists: Dr. Annamarie De Luca (Italy), Dr. Kanneboyina Nagaraju (USA), Dr. Dominc Wells (UK), and Dr. Jennifer Morgan (UK).

Key highlights included:

• The panel discussed areas for consideration when conducting animal models for investigational treatments. Emphases was placed on the importance of pre-clinical experiments to mimic clinical trial as best as possible.
• It is important to establish potential safety concerns and benefits before moving to human trials. However, it is not always predictive what happens in an animal model will translate to human trials, and there is always some risk for patients when participating in clinical trials.
• If you consider participating in a clinical trial, it is especially important to discuss and understand all the risks and benefits with your neuromuscular team and/or clinical investigator before consenting to participate.

Panel Discussion 2: Gene/advanced/new therapies

Dr. Kathryn Wagner (USA) moderated this discussion with the following panellists: Dr. Carsten Bonnemamm (USA), Dr. Francesco Muntoni (UK), Dr. Barry Byrne (USA), Dr. Chris Weihl (USA) and Dr. Ana Buj Bello (France).

Key highlights included:

• Panellist began their discussion on appropriated dosing for gene therapies. It was concluded the optimal dose to administer still needs to be established.
• Next, they discussed the window of opportunity and durability for treating. Muscle tissue regenerates, and it is best to treat cells that are still viable and can be rescued. Re-dosing may also be necessary, and there is still much to understand here.
• Disease dynamics within an individual varies and a teenage DMD individual, for example, could have as much to benefit from a gene therapy as a younger individual.
• The panellist discussed immunological consideration and challenges to redosing AAV gene therapy. There are ways to block an immune response before a first dose that may prove beneficial and allow for redosing. Dr. Muntoni discussed the long-term toxicology and off-target effects of gene therapy.
• AAV-based therapy has been around for some time in hemophilia; however, the doses used in neuromuscular disease are much higher. It is, therefore, particularly important to closely monitor safety. Pre-treatment with corticosteroids is a good practice to dampen the immune response.
• The session ended with each of the panellists describing what they were most excited about for future treatments. All the panellists were enthusiastic about the advances in gene therapies, including gene-editing technology.

DAY FOUR: THURSDAY, OCTOBER 1

Today’s oral sessions covered topics related to new genes in neuromuscular diseases; artificial intelligence approaches to muscle diseases, from the spinal cord to muscle, and highlights across Myology. Not a lot of focus on Duchenne, so today’s focus was on the poster presentations. There was a total of 97 posters related to Duchenne muscular dystrophy organized into four different sessions. I have summarized the first two sessions below and will be reviewing the final two sessions tomorrow.

Poster Session 1:

Clinical key highlights for Duchenne and Becker muscular dystrophy

• Data gathering on the natural history of Becker muscular dystrophy (BMD) on respiratory function, cardiomyopathy and loss of ambulation was a focus.
• A study on the prophylactic use of cardiac medications adds to the growing evidence supporting the use of cardiac medicine before symptoms to delay the onset of cardiac functional loss.
• Research in bone health supports the importance of vitamin D and following the standards of care to maintain bone health in Duchenne.
• Another study exploring BMI during disease progression, nutrition, corticosteroid use and ambulation concluded there is a need for attention to and intervention during the transition to non-ambulation to prevent obesity.
• PTC presented data from their STRIDE registry, an important study collecting real-world data in boys taking ataluren with nonsense mutations. This data is important to establish long-term data on the safety and effectiveness of ataluren.
• Finally, there were a few posters on affected siblings with Duchenne. Younger effected Duchenne siblings tend to experience better outcomes as they are typically diagnosed earlier, and intervention occurs sooner.

Late-Breaking Posters:

• Capricor’s HOPE-2 study results were presented during the late-breaking poster session. Results in CAP-1002 molecule, currently under investigation, showed this therapy to be safe and effective in treating upper limb and cardiac function deterioration in non-ambulant Duchenne boys.

Poster Session 2:

Biomarkers and outcome measures in Duchenne

• There were several posters presenting data on different types of biomarkers and their correlation to functional outcomes and disease severity in Duchenne, to establish and validate these as possible outcome measures in clinical trials.

MRI for muscle imaging

• This poster session focused on muscle MRI imaging as a potential diagnostic tool and a way to monitor disease progression in clinical trials. Whether this becomes a part of clinical practice stands to be determined and can be limited by access to MRI and resourcing in centers.

DAY FIVE: FRIDAY, OCTOBER 2

Today marked the final day of the 2020 WMS Congress and sessions covered key highlights on both the oral and poster sessions throughout the week.

Poster Session 3:

Duchenne-animal models and preclinical treatment

• Studies here focused on animal models and preclinical studies. Data was presented on a novel exon skipping therapies, gene therapy and CRISPR/Cas9 candidates. Still early stages but encouraging to see proof of concepts and advancement of work.
• Catabasis presented early preclinical work on their investigational therapy, CAT-1004, demonstrating the prevention of cardiac dysfunction in a mouse model. Studies are ongoing – please see more from Catabasis under the “Duchenne therapy” section below.

Outcome measures

• This session presented several posters focused on different types of outcome measures ranging from functional outcomes to wearable devices. These studies will help inform clinical trial design.

Poster Session 4:

Duchenne therapy: This is by far the most extensive section of posters to report on. To make it easy, we have decided to categorize them by industry name or non-industry sponsored.

• Sarepta Therapeutics by far had the largest presence with many poster presentations. They reported 2-year data with their micro-dystrophin gene therapy (SRP-9001) in 4 patients. Results showed a favourable safety profile and improvements in motor function compared to baseline. They also presented data on golodirsen (exon 53 skipping therapy), casimersen (exon 45 skipping therapy), golodirsen (exon 53 skipping therapy), and eteplirsen (exon 51 skipping therapy). All show favourable safety profiles, and they continue to collect clinical data to demonstrate benefits.To see a full list of Sarepta’s data presentations, click here.
• Catabasis presented four posters on their investigational therapy edasalonexent. This molecule has the potential to be a disease-modifying in Duchenne without the associated effects of high-dose steroids. The Phase 3 PolarisDMD trial is fully enrolled, and underway, results are expected in Q4 2020.Click here to read Catabasis announcement on this data.
• Antisense Therapeutics presented their poster on ATL1102, a molecule currently under investigation in multiple sclerosis (MS) with a mechanism of action that may work in Duchenne. Early studies showed ATL1102 in Duchenne to have a statistically significant meaningful improvement on upper limb function compared to natural history data and maybe an exciting prospect for non-ambulatory Duchenne patients.To read more about this program, click here.
• Santhera presented the long-term effects of idebenone therapy on respiratory function in non-ambulant boys with Duchenne. They were able to extrapolate long-term data to show idebenone delays time to assisted ventilation by three years. Idebenone data is currently under review by the European drug approval agency. Santhera recently obtained rights to vamorolone and recently announced its long-term clinical data. To read more about this, click here.
• PTC Therapeutics presented two posters; their STRIDE real-world data (described earlier on “Day 1”) and a study looking at a long-term data analysis. This analysis was performed on a data set that was already unblinded and demonstrated treatment with ataluren, in addition to standards of care, delayed loss of ambulation. It may delay pulmonary decline in patients with a nonsense mutation.See full details here.
• Two independent non-industry sponsored posters were presented; the first investigated teriparatide as a potential treatment of severe osteoporosis. Early results show good safety data and warrants further study. The second focused on steroid use after the loss of ambulation. It was concluded that the continuation of steroid use after the loss of ambulation might be beneficial for delaying respiratory function decline and the onset of or progression of scoliosis.

Registries, care, quality of life, management of neuromuscular disorders

• Several posters focused on identifying criteria for cardiac and respiratory decline, raising awareness about neuromuscular disorders in schools, evaluating the quality of life measure in clinical trials, and finally, describing the newly formed neuromuscular disease network in Canada (NMD4C).

Overall, the conference was a great success and we want to thank the World Muscle Society (WMS) for hosting a wonderful virtual conference.

If you would like more information about the conference or the content discussed above, please feel free to reach out to:

Nicola Worsfold

Defeat Duchenne Canada

Director of Advocacy and Research

[email protected]