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Duchenne Muscular Dystrophy (BMN 045)

Understanding Duchenne Muscular Dystrophy

Duchenne is an inheritable and fatal childhood disease affecting 1 in 3,500 newborn boys. In Duchenne, boys begin to show signs of muscle weakness as early as the age of 2. The disease gradually weakens the skeletal or voluntary muscles in the arms, legs, and trunk. Progressive muscle weakness often causes Duchenne patients to become wheelchair bound before the age of 12. As the disease worsens, the weakening respiratory muscles lead to respiratory failure. The cardiac muscle is also affected and recent figures estimate that around 15 percent of Duchenne patients die of disease of the heart muscle.

At present, there is no disease-modifying therapy for Duchenne available for the majority of boys. In addition to surgical and physical therapeutic measures, glucocorticosteroids are used in Duchenne. Clinical studies with glucocorticosteroids have shown a prolongation of the ability to walk of approximately 2 years, albeit accompanied with (sometimes severe) side effects. However, glucocorticosteroids are not able to induce the production of dystrophin-like proteins and therefore do not alter or impact the underlying cause of Duchenne. Other available treatment is mainly supportive, such as physiotherapy, wheelchair and other mechanical support (braces), scoliosis surgery, assisted ventilation and treatment of respiratory infections.

Program Overview

BMN 045 (formerly PRO045) is an investigational drug in clinical development to treat Duchenne Muscular Dystrophy patients with a specific genetic mutation underlying their disease. Duchenne is an inheritable and fatal childhood’s disease with an incidence of approximately 1 in 3,500 newborn boys. In Duchenne, boys begin to show signs of muscle weakness as early as the age of 2. The disease gradually weakens the skeletal or voluntary muscles in the arms, legs and trunk. Due to progressive muscle weakness, Duchenne patients are often wheelchair bound before the age of 12. At a later stage, the boys’ respiratory muscles are also affected and slowly the boys drift into respiratory failure. The cardiac muscle is also affected and recent figures estimate that around 15 percent of Duchenne patients die of a primary cardiomyopathy.

The severe and progressive deterioration of muscle fibers in Duchenne is caused by mutations in the gene that produces the dystrophin protein, an essential protein found in skeletal muscle. Deletions of RNA segments that code for the protein causes disruption of the synthesis of the dystrophin protein. Antisense oligonucleotides that are designed to skip one or more exon(s) in Duchenne patients, can allow restoration of the open reading frame, and induce production of novel shortened dystrophin, thereby potentially converting a severe Duchenne into a typically milder Becker Muscular Dystrophy phenotype. BioMarin’s RNA-modulating therapeutics can skip exons during pre-mRNA splicing and help restore dystrophin production.

BMN 045 induces exon 45 skipping in the dystrophin gene and is intended for approximately 8% of all Duchenne patients, including patients with deletions of exon 44, exon 46, exons 46-47, exons 46-48, exons 46-49, and exons 46-51. The underlying chemistry and mechanism of BMN 045 are similar to drisapersen. BMN 045 is highly sequence specific, minimizing the risk for off-target effects.

BMN 045 at a Glance

  • BMN 045 has been granted orphan drug status in the European Union and the United States
  • Currently in a Phase I/II dose-escalation study in Europe (PRO045-CLIN01), assessing different doses in a number of Duchenne patients
  • Extensively tested in a series of cultured muscle cells from patients with different relevant mutations and mouse models

Clinical Studies

BMN 045 is currently being evaluated in a Phase I/IIa dose-escalation study to assess the safety and efficacy of the medication for Duchenne Muscular Dystrophy patients with a mutation amenable to exon 45 skipping. Patients will be given the opportunity to continue into a treatment phase following dose selection. BMN 045 has been extensively tested in a series of cultured muscle cells from patients with different relevant mutations, and in the hDMD mouse model.

For additional information about the study, including details about participating centers, please click here.

BioMarin

Diseases

Lysosomal Storage Disorders (MPS I, MPS IVA, MPS VI) PKU, LEMS

Products

Vimizim®
Kuvan®
Naglazyme®
Aldurazyme®
Firdapse®

Patient/Physician Support Contact Information

BioMarin RareConnections
Tel: 866.906.6100
Fax: 888.863.3361
E-mail: support@biomarin-rareconnections.com

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