Developments in international research and treatments

March 22nd, 2023


Researchers around the world are working very hard to find cures and treatments for neuromuscular conditions. Drug development takes years and at times studies that show promising results throughout the different clinical trial phases may fail at the last hurdle. Some promising studies on the horizon are described below and we will be watching them closely in the year ahead to see how they develop.  

If you have any questions or if you’d like to let us know about other developments in research and treatments so we can share news with members, please email our Research Officer, Dympna Mulroy at


Duchenne muscular dystrophy (DMD)

Approval sought for Vamorolone drug

DMD is usually managed with corticosteroids, anti-inflammatory medications, such as prednisone, however these often have several side effects that can reduce quality of life.

Santhera Pharmaceuticals has produced a drug called Vamorolone, that binds to the same receptors as corticosteroids and has shown to have good effect with fewer side effects over 48 weeks.

A 48-week Phase 2b trial called VISION-DMD demonstrated significantly improved Time to Stand (TTSTAND) after 24 weeks, meeting the trial’s main goal. TTSTAND measures the speed at which a person stands up from lying down. The drug also led to significant improvement in the six-minute walk test (6MWT), which assesses the distance walked in six minutes. Participants who took Vamorolone also scored significantly better in the North Star Ambulatory Assessment (standardised assessment used by physiotherapists) in comparison to the group that took a placebo. Placebo is made to look exactly like a real drug but is made of an inactive substance and has no therapeutic benefit.

The different phases of the trial combined have shown that Vamorolone didn’t stunt growth and had fewer side effects than those typical with corticosteroid use. Overall the drug was well tolerated in clinical studies. The most reported adverse events compared with placebo from the VISION-DMD study were cushingoid features (facial puffiness and weight gain), vomiting and vitamin D deficiency. Adverse events were generally of mild to moderate severity.

Due to these significant results of the study, Santhera Pharmaceuticals asked the European Medicines Agency (EMA) to approve Vamorolone to treat DMD in October 2022. The EMA assessments of new approval requests can take up to 210 days before a verdict is decided, therefore it is likely to be May/June 2023 before a decision is made.

Gene therapy and DMD

Gene therapy is a new type of medicine used to treat conditions caused by faulty genes, like DMD. In DMD, the faulty gene is the dystrophin gene. This gene is responsible for producing dystrophin, a protein which protects the muscles. The absence of dystrophin affects the stability and function of the muscle fibres, eventually leading to muscle wasting.

DMD gene therapy aims to deliver a working version of the dystrophin gene so that the body can produce functioning dystrophin. The potential benefits of gene therapy include protecting the muscles and preventing the progression of the condition. As all muscles in the body are affected by the lack of dystrophin, researchers expect that it could have muscle, heart, and breathing benefits.

However, gene therapy may not benefit people with advanced DMD. That’s because gene therapy will not be able to get into damaged muscle cells that have been replaced by fat or fibrotic tissue (scar tissue). Several gene therapies are currently being tested in clinical trials to assess whether they are effective and safe, and to understand benefits and risks.

Unfortunately gene therapy is not available to all people with DMD as recent findings from clinical trial have shown that people with some genetic mutations may be at risk of developing immune reaction to the gene therapy, which could cause severe side effects. In addition to the type of genetic mutation, trials may also include criteria such as age and whether the person is able to walk or not. To date no gene therapies have been approved for DMD across the world.

One gene therapy for DMD, called SRP-9001, was recently given priority review by the U.S. Food and Drug Administration (FDA). This means that the FDA can grant conditional marketing authorisation to treatments based on early clinical evidence of likely effectiveness. SRP-9001 is designed to deliver a copy of a shortened but functional version of the dystrophin protein to muscle cells using a lab-engineered, harmless virus as a vector. Early studies have shown it to have an improvement in motor function and walking. An FDA decision is expected on this treatment towards the end of May 2023. If this treatment is approved by the FDA, the developers, Sarepta Therapeutics and Roche, may file an application with the European Medicines Agency (EMA).

If you’d like to find out more about what gene therapy means for people living with DMD, click here to read Frequently Asked Questions from Duchenne UK.

Myotonic dystrophy


In myotonic dystrophy type 1 (DM1), defects in the DMPK gene lead to an abnormally long messenger ribonucleic acid (mRNA). mRNA is responsible for carrying the genetic information needed to make proteins. In DM1 the long mRNA form toxic clumps in muscle cells, which increase progression of the condition.

Avidity Biosciences is a biotechnology company that specialises in developing RNA therapies for rare conditions. They have developed a treatment, AOC 1001, that can target and reduce the levels of toxic mRNA in cells. A Phase 1/2 MARINA clinical trial found that treatment with AOC101 eased myotonic (when muscles are unable to relax after a contraction) in some participants. It also showed that the treatment reduced the activity of the DMPK gene, which is overactive in DM1, thereby addressing the underlying cause of the condition. Safety and tolerability, as assessed in all 38 participants, showed most adverse events were mild or moderate.

The company is now enrolling participants from the Phase 1/2 MARINA study into a Phase 2 open-label extension study (MARINA-OLE™) of AOC 1001 in adults with DM1. This is designed to evaluate the long-term safety and tolerability of AOC 1001 in people with DM1 who were previously enrolled in the MARINA Phase 1/2 study. Complete results from the phase 1/2 MARINA study are expected in 2023.

Facioscapulohumeral muscular dystrophy (FSHD)

Phase 3 Losmapimod clinical trial

FSHD is caused by an abnormal expression of the DUX4 gene, which leads to progressive muscle weakness and wasting. The condition gets its name from muscles that are affected in the face (facio), around the shoulder blades (scapulo), and in the upper arms (humeral). This progressive weakness can lead to functional difficulties for example in whistling, using a straw, communication using facial expression, use of upper limbs, and walking unassisted. To date there are no approved treatments for FSHD.

Fulcrum Therapeutics, Inc., a biopharmaceutical company is investigating the efficacy and safety of Losmapimod for the treatment of FSHD in a phase 3 clinical trial across multiple sites in Europe and USA. Results from a previous phase 2 clinical trial, demonstrated that Losmapimod was superior to placebo in slowing condition progression and maintaining upper limb function in adults with FSHD, despite no changes in DUX4 gene expression. As the larger phase 3 trial runs over 53 weeks, we will be keeping an eye on its progress towards the end of this year. If successful, this treatment could have the potential to be the first condition-modifying therapy for FSHD.

Report of Europe-wide survey of people living with FSHD

Last year we invited MDI members to take part in a Europe-wide survey of people living with FSHD on what they see as most important for any treatment to target. We are pleased to share the lay report of the survey published by FSHD Europe.

1,147 people living with FSHD across Europe responded to say what they see as most important for any treatment to target. These are:

· Stopping the progression of the condition – 100 per cent of all respondents wanted this

· Regaining strength – over 50 per cent of respondents said this was important

· Improving mobility – 40 per cent of respondents thought this was useful

· Reduction in fatigue – over 35 per cent of respondents wanted a treatment to address this.

People were also asked about what would encourage or discourage them from taking part in clinical trials and whether they were prepared to undertake invasive procedures such as providing blood samples or having an MRI scan. The survey found that generally people are keen to take part but they prefer trials where they are kept informed of the outcomes, and where travelling is reduced (either distance or the number of visits to the trial site). The report will be invaluable to any company planning clinical trials for FSHD in Europe and shows that patients are eager to take part in trials.

You can view the full lay report here

The survey was commissioned by FSHD Europe which represents FSHD patient organisations in Germany, France, Italy, the Netherlands, Spain and the UK. However, respondents came from 26 countries across Europe, including Ireland. It was carried out by the John Walton Muscular Dystrophy Research Centre (University of Newcastle) and received financial support from Facio-Therapies, Fulcrum Therapeutics and Roche.

Charcot-Marie-Tooth (CMT)


Charcot-Marie-Tooth (CMT) is a group of disorders that cause damage to the nerves that transmit information and signals from the brain and spinal cord to and from the rest of the body, as well as to sensory information such as touch back to the spinal cord and brain. This nerve damage causes progressive muscle wasting in the legs and arms, causing problems with walking, running and balance as well as hand functioning. People can also experience mild to moderate sensory symptoms. Charcot-Marie-Tooth type 1a (CMT1A) is the most common type of CMT. To date, no curative or symptomatic medications have been approved.

The biopharmaceutical company, Pharnext, is currently holding clinical studies for a treatment called PXT3003. This is a new fixed-dose combination of baclofen, naltrexone, and sorbitol, and is being evaluated in a phase 3 PREMIER study on people with mild-to-moderate CMT1A. This PREMIER trial has enrolled 387 people, to evaluate the efficacy and safety of PXT3003 compared with placebo in people over a 15-month period. Previous data, announced last year from a follow-up extension study of the first phase III study, showed a good safety profile and continuous treatment effect of PXT3003 after 5 years of total treatment. Publication of topline results from this trial is planned in Q4 2023.

Friedreich’s ataxia

US approval of first treatment for Friedreich’s ataxia 

On 28 February, the first medication to treat Friedreich’s ataxia (FA) was approved by the US Food and Drug Administration. Reata Pharmaceuticals’ drug SKYCLARYS™ (omaveloxolone), was approved for the treatment of people in the US who have FA and are 16 years of age or older.

This approval comes after a series of clinical trials and an open-label extension study examining the safety, efficacy, and tolerability of the drug. The key outcomes from these trials include:

  • Clinical trial data showed that, after one year, individuals on treatment with SKYCLARYS compared to placebo had an improvement in neurological symptoms.
  • The longer-term open-label extension study, where individuals with FA were taking SKYCLARYS for three years, showed a greater than 50 per cent slowing of progression compared to closely-matched individuals with the condition.
  • SKYCLARYS is supported by the efficacy and safety data from the clinical trials and extension study.

The European Medicines Agency (EMA) is also reviewing Reata’s marketing authorisation application (MAA) for SKYCLARYS in Europe. MDI is committed to advocating for orphan drugs approved by the EMA to be made available in a timely manner for our community in Ireland.

2023 may be a pivotal year for Friedreich’s ataxia drug development. In addition to the recent approval of SKYCLARYS, a phase II/III trial of PTC’s vatiquinone, a phase I/II trial of Stealth Bio’s elamipretide, and a phase II study of Larimar’s CI-1601 all have key results expected this year.

In the US there have been nearly 20 clinical trials for Friedreich’s ataxia that failed to meet their primary endpoints despite strong preclinical data and trial designs. This is often due to the complexity of the condition. We will therefore be keeping an eye on the developments of these other studies over the coming months. Read more about the FDA approval of SKYCLARYS™ here.

Disclaimer: Please note that MDI shares information about neuromuscular conditions. We do not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition.

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Categories: Research

1. Muscular Dystrophies

  • Becker muscular dystrophy
  • Duchenne muscular dystrophy
  • Manifesting carrier of Duchenne
  • Congenital muscular dystrophy
  •     •  General
  •     •  MDC1A (merosin-deficient congenital muscular dystrophy)
  •     •  Rigid spine syndrome (RSS)
  •     •  Ullrich congenital muscular dystrophies
  •     •  Bethlem myopathy
  • Emery-Dreifuss muscular dystrophy
  • Facioscapulohumeral muscular dystrophy
  • Limb-girdle types of muscular dystrophy (LGMD)
  •     •  General
  •     •  LGMD 1B (also known as Laminopathy)
  •     •  LGMD 1C (also known as Caveolinopathy)
  •     •  LGMD 2A (also known as Calpainopathy)
  •     •  LGMD 2B (also known as Dysferlinopathy)
  •     •  LGMD 2I
  • Ocular myopathies including ocularopharangeal muscular dystrophy

2. Myotonic Disorders

  • Congenital Myotonic Dystrophy
  • Myotonia
  • Myotonic Dystrophy

3. Congenital Myopathies

  • Central Core Myopathy
  • Congenital Fibre-type Disproportion Myopathy
  • Minicore (Multicore) myopathy
  • Myotubular or Centronuclear myopathy
  • Nemaline myopathy

4. Mitochondrial Myopathies

  • Mitochondrial Myopathies

5. Metabolic Disorders

  • Metabolic disorders (general)
  • McArdle’s Disease
  • Pompe’s Disease

6. Periodic Paralyses

  • Periodic Paralyses

7. Autoimmune Myositis

  • Polymyositis, Dermatomyositis and Sarcoid myopathy
  • Juvenile dermatomyositis
  • Inclusion body myositis

8. Spinal Muscular Atrophies

  • Severe (Type I)
  • Intermediate (Type II)
  • Mild (Type III)
  • Adult spinal muscular atrophy

9. Hereditary Motor and Sensory Neuropathies

  • (Also known as Charcot-Marie-Tooth or Peroneal muscular atrophy)

10. Disorders of the Neuromuscular Junction

  • Congenital myasthenic syndromes
  • Myasthenia Gravis

11. Friedreich’s Ataxia

  • Friedreich’s Ataxia

12. Other (Please Specify)

13. Unspecified