BioMarin positive about Aryplase
BioMarin Pharmaceutical of Novato, CA, US, has seen 'positive results' from its Phase II open-label study of Aryplase, recombinant human arylsulfatase B (rhASB), an investigational enzyme replacement therapy for the treatment of mucopolysaccharidosis VI (MPS VI). MPS VI (also known as Maroteaux-Lamy Syndrome) is a debilitating, life-threatening genetic disease for which no drug therapies are currently available, that is caused by a deficiency of the enzyme arylsulfatase B.
The open-label, 10 patient, clinical study of Ary-plase was conducted at two sites, one in the US, and one in Australia. The study evaluated clinical and biochemical measures of safety and efficacy in male and female subjects between the ages of 6 and 22, for a duration of 24 weeks. During the study, subjects received weekly 1.0 mg/kg infusions of Aryplase, a dose selected based on results from both a Phase I study, and the feline MPS VI model.
Results from this Phase II study indicate that Aryplase is well tolerated and is associated with improvements in several clinical endpoints. On average, subjects experienced improvements in endurance as measured by the distance walked at the 6 and 12 minutes time points of a 12-minute walk test, and the number of stairs climbed in three minutes. Functional improvements were also observed in joint pain and stiffness, and in shoulder flexion, extension, and rotation in subjects who exhibited less than 90 degrees shoulder flexion at baseline.
In addition to the clinical improvements observed, study participants also demonstrated an average decrease in urinary glycosaminoglycan (GAG) excretion of 71% in 24 weeks, indicating Aryplase reduced carbohydrate storage in MPS VI subjects. As part of the Phase II trial, several other exploratory endpoints were evaluated, but on average did not indicate meaningful changes in the 24- week study period. These include pulmonary function as measured by forced vital capacity, a pinch and grip strength test, physical activity, oxygenation level during sleep, expanded time to get up and go test, and a set of tasks reflecting quality of life. Improvement in these clinical endpoints may be observed with continued infusions over a longer period of time. Results of the study demonstrated that Aryplase was generally well tolerated.
BioMarin has received orphan drug and fast track designations for Aryplase from the FDA. In addition, the European Commission has designated Aryplase for the treatment of MPS VI as an orphan medicinal product within the EC. BioMarin plans to initiate a multi-national, placebo-controlled, double-blind Phase III trial of Aryplase in MPS VI subjects in 2003.
Maroteaux-Lamy Syndrome
MPS VI (also known as Maroteaux-Lamy Syndrome) is a debilitating, life threatening genetic disease for which no drug therapies are currently available. It is caused by a deficiency of the enzyme arylsulfatase B. The deficiency leads to the accumulation of GAGs in the lysosomes, the digestive organelles of the cell. This accumulation in the lysosomes leads to progressive cellular, tissue and organ system dysfunction. Debilitating symptoms can include impaired cardiac and pulmonary function, delayed physical development, skeletal and joint deformities, impaired vision and hearing, sleep apnea, and reduced endurance. The majority of subjects die from disease-related complications between childhood and early adulthood, depending on the severity of the disease.