BioMarin Pharmaceutical Inc. will start a late-stage study by the end of this year for patients with the rare and fatal muscular disorder Pompe disease. The decision to move into a Phase II/III program follows a Phase I/II study that showed that patients who received BioMarin’s drug, called BMN-701, were able to walk a longer distance and breathe more strongly. Pompe disease is a lysosomal storage disorder in which cells accumulate glycogen in the lysosome due to deficiency of the lysosomal acid alpha-glucosidase enzyme. The build-up of glycogen causes progressive muscle weakness throughout the body and affects various body tissues, particularly in the heart, skeletal muscles, liver and nervous system. The disease is caused by mutations in a gene that makes an enzyme called acid alpha-glucosidase, or GAA. Normally, the enzyme breaks down glycogen, a stored form of sugar used for energy, but the mutated GAA gene reduces or completely eliminates the enzyme, allowing glycogen to accumulate everywhere in the body. BioMarin’s drug targets late-onset Pompe disease, which means the disease shows itself as early as the first decade of childhood or in adults as old as 60. That subset of patients has a partial deficiency of GAA. Late-onset Pompe starts with muscle weakness and ultimately leads to respiratory failure. BioMarin’s 22-patient, 24-week Phase I/II study found that 16 patients injected with the highest dose of BMN-701 averaged a 6.3 percent improvement in the distance of a six-minute walk. Side effects in the trial included drug reactions, which made one patient withdraw from the trial, and hypoglycaemia. BioMarin said both side effects are associated with drug infusions. The new 24-week trial targets late-onset Pompe patients who have been treated with Myozome or Lumizyme, the current treatment options for Pompe disease. It will look primarily at improvement in inhalation strength, but better exhalation and longer six-minute walks are secondary goals.
