Duchenne Muscular Dystrophy (DMD) is a severe inherited neuromuscular disorder caused by mutations in the dystrophin gene. It leads to progressive muscle wasting and irreversible functional decline. Primarily affecting males due to X-linked recessive inheritance, DMD can also rarely affect females. Symptoms include gradual muscle atrophy and fibrous tissue replacement in skeletal and cardiac muscles. Patients typically show initial signs of muscle weakness and difficulty walking around ages 2 to 3, often demonstrated by the Gower’s sign.

With fewer than 50,000 cases reported in the US, current management of DMD focuses on symptomatic and palliative care to slow disease progression. There are no curative treatments available, and clinical practice guidelines for comprehensive management in the US are limited. This article reviews recent guidelines on DMD and discusses six new FDA-approved medications. It aims to examine changes since guideline publication and speculate on future treatment and management options in light of these medications.

Part 1 – Current DMD Guidelines

To start, here is a listing of some of the most recent DMD treatment and management guidelines published in the US:

Part 2 – FDA Approvals Since the Most Recent Guidelines

The medications/therapies that have been approved by the FDA since the last DMD Clinical Guideline:

ELEVIDYS® (delandistrogene moxeparvovec-rokl)

  • Sarepta Therapeutics, Inc.
  • ELEVIDYS is an adeno-associated virus vector-based gene therapy indicated in individuals at least 4 years of age for the treatment of Duchenne muscular dystrophy (DMD) in patients who are ambulatory or non-ambulatory and have a confirmed mutation in the DMD gene. 

AGAMREE® (vamorolone)

  • Catalyst Pharmaceuticals, Inc.
  • AGAMREE is a corticosteroid indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients 2 years of age and older.

DUVYZAT (givinostat)

  • ITF Therapeutics, LLC.
  • DUVYZAT is a histone deacetylase inhibitor indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients 6 years of age and older.

VYONDYS 53® (golodirsen)

  • Sarepta Therapeutics, Inc.
  • VYONDYS 53 is an antisense oligonucleotide indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 53 skipping. This indication is approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with VYONDYS 53. Continued approval for this indication may be contingent upon verification of a clinical benefit in confirmatory trials.ics.

VILTEPSO® (viltolarsen)

  • NS Pharma
  • VILTEPSO is an antisense oligonucleotide indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 53 skipping.

AMONDYS 45 (casimersen)

  • Sarepta Therapeutics, Inc.
  • AMONDYS 45 is an antisense oligonucleotide indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 45 skipping.

Part 3 – Predictions

Now that we’ve covered the current available DMD guidelines, the “what’s changed” and new FDA approvals since the most recent 2018 publication, we can jump into our predictions for future DMD guidelines. As a reminder, this is a list of predictions focused specifically on treatment of DMD, and including pharmacological treatments. These predictions are not based on specific guidelines or a specific organization, but instead provide broad, high-level predictions covering potential next guideline(s) on the topic of DMD, regardless of which organization produces them.

Prediction 1 – Gene Therapies: Dystrophin gene mutations

It is anticipated that the drugs mentioned above, which belong to a class of therapies known as exon-skipping oligonucleotides, will be included in future guidelines. These novel drugs aim to restore the reading frame of the dystrophin gene in patients with specific mutations, representing significant advancements in the treatment of DMD. They offer potential benefits in slowing disease progression and improving functional outcomes for eligible patients.

Prediction 2 – Gene Therapies: Exon Skipping & Gene Editing

We predict the further development and approval of gene therapies and other genetic-based treatments are expected to progress and included in future guidelines. Approaches such as exon skipping (e.g., eteplirsen) and gene editing techniques (e.g., CRISPR/Cas9) hold promise for modifying disease progression by addressing the underlying genetic mutations.

Prediction 3 – Targeted Therapies: Muscle Function & Inflammation

Moreover, ongoing research into pharmacological treatments, including steroids and newer compounds targeting muscle function and inflammation, is likely to lead to refinements in treatment protocols and guidelines. This research may provide valuable insights into improving the management of DMD and enhancing patient outcomes.

There you have it – an overview of the current DMD guidelines, updates on recent major changes and FDA approvals have happened since publication, and our informal, but evidence-based, predictions for what the next guidelines on Duchenne muscular dystrophy may include. Once the next DMD guideline update happens, we will compare our predictions to reality to see how we measured up. Do you agree with our predictions? Do you think we missed anything? We’d love to hear your input!

Do you agree with our predictions? Do you think we missed anything? And is there another topic you would like to see covered in a future guideline predictions series article? Contact us today and let us know!

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