Innovative therapeutics

Products/
Pipeline

Duchenne Muscular Dystrophy (BMN 053)

Understanding Duchenne Muscular Dystrophy

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 053 (formerly PRO053) 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 053 induces exon 53 skipping in the dystrophin pre-mRNA and is intended for approximately 8% of all Duchenne patients, including patients with deletions of exon 52, exon 45-52, exons 47-52, exons 48-52, exons 49-52, and exons 50-52. The underlying chemistry and mechanism of BMN 053 are similar to drisapersen. BMN 053 is highly sequence specific, minimizing the risk for off-target effects.

BMN 053 at a Glance

  • BMN 053 has been granted orphan drug status in the European Union and the United States
  • Currently in a Phase I/II dose-escalation study to assess the safety and efficacy of the drug.
  • Extensively tested in a series of cultured muscle cells from patients with different relevant mutations, and in the hDMD mouse model

Clinical Studies

PRO053 is currently being evaluated in a Phase I/II dose-escalation study (PRO053-CLIN01) to assess the safety and efficacy of the drug. Patients in this study’s dose-finding phase will be given the opportunity to continue treatment following dose selection. PRO053 has been extensively tested in vitro in a series of cultured muscle cells from patients with different relevant mutations, and in the hDMD mouse model. Details of the clinical trial, such as inclusion/exclusion criteria and trial sites, are posted on the website www.clinicaltrials.gov. BMN 053 has been granted orphan drug status in the European Union and the United States.

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

Global Medical Information

Contact Global Medical Information

Top