Innovative therapeutics


Duchenne Muscular Dystrophy (BMN 044)

Understanding Duchenne Muscular Dystrophy

Duchenne muscular dystrophy 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 044 (formerly PRO044) is an investigational drug in clinical development to treat Duchenne Muscular Dystrophy patients with a specific genetic mutation underlying their disease. The severe and progressive deterioration of muscle fibers in Duchenne is caused by mutations in the dystrophin protein gene, mostly deletions of one or more exons that disrupt the open reading frame of the transcript and prematurely abort the synthesis of the dystrophin protein. Using BioMarin’s RNA-modulating therapeutics, specific exon skipping can be induced during pre-mRNA splicing by disturbing specific exon inclusion signals. 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.

BMN 044, induces exon 44 skipping in the dystrophin pre-mRNA and is intended for approximately 6 percent of all Duchenne patients, including those with deletions of exon 43, exon 45, exons 38-43, exons 40-43, exons 42-43, and exons 45-54. The underlying chemistry and mechanism of BMN 044 are similar to drisapersen but exhibits higher skipping efficiency at lower concentrations when compared to drisapersen. BMN 044 is highly sequence specific, minimizing the risk for off-target effects.

BMN 044 at a Glance

  • BMN 044 has been granted orphan drug status in the European Union and the United States
  • Completed a Phase I/II dose-escalation study in Europe (PRO044-CLIN01), assessing six doses in 18 Duchenne patients
  • No drug related serious adverse events were reported

Clinical Studies

BMN 044 addresses a separate sub-population of Duchenne patients with a mutation amenable to exon 44 skipping. BMN 044 has recently completed a phase I/II dose-escalation study in Europe, assessing six doses in 18 Duchenne patients. BMN 044 was generally well tolerated up to dose levels of 12mg/kg for five weeks by subcutaneous or intravenous administration. Safety findings of the study are consistent with the known class safety profile and no drug related serious adverse events were reported. The extension study for participants of this dose-escalation study (PRO044-CLIN02) is underway and planning for future studies is ongoing.

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



Lysosomal Storage Disorders (MPS I, MPS IVA, MPS VI, CLN2 disease) PKU, LEMS



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