By Mary Welch
Results from a recently concluded pivotal trial showed that patients with the fatal genetic disorder mucopolysaccharidosis 1 (MPS-1) showed substantial improvement when treated with the enzyme alpha-L-iduronidase. The drug is being developed by Genzyme General, of Cambridge, Mass., and BioMarin Pharmaceutical Inc., of Novato, Calif. Both companies presented the data at the American Society of Human Genetics meeting in Denver.
The companies expect to submit the data from this clinical trial in a biologics license application (BLA) during the first quarter of 1999. The FDA has designated a-L-iduronidase a fast-track product. BioMarin, a privately held company, received an orphan drug designation for the enzyme in September 1997, potentially giving the product market exclusivity for seven years following FDA approval.
MPS-1 encompasses three syndromes — Hurler, Hurler-Schele, and Schele syndromes. It is caused by a deficiency in an active enzyme, a-L-iduronidase, which results in a build-up of carbohydrate materials called glycosaminoglycans in all tissues of the body. This leads to cell, tissue and organ dysfunction. MPS-1 can lead to an early death — often before the age of 10. It is estimated that between 2,000 to 3,000 patients in the developed world have been diagnosed with MPS-1. There is no known treatment.
Symptoms include the enlargement of the liver and spleen, joint pain and immobility, skeletal deformity, vision impairment, stunted growth, hearing loss, obstruction of airways, severe headaches and cardiomyopahy.
Data from the trial showed that a-L-iduronidase replacement therapy reduced clinical measurements of the disease and improved patients' ability to perform normal functions. The trial, which was started in 1997, involved 10 patients in a 26-week treatment protocol. Ages ranged from 5 to 22 years.
A clinical baseline was first established and then patients were given a weekly intravaenous infusion of 125,000 units of a-L-iduronidase per kilogram of body weight. Quantitative magnetic resonance imaging studies showed that there was a rapid 20 percent or more reduction in liver size after six to 12 weekly doses in almost all patients, and that liver size returned to normal in the majority of patients by 26 weeks.
Patients also showed a decrease in the excretion of urinary glycosaminoglycans, indicating that a-L-iduronidase broke down these complex carbohydrate materials that otherwise are accumulated in patients.
In addition, patients reported improvements in physical abilities and qualify of life. Joint pain was reduced and mobility improved, for instance. Patients also had improvements in endurance and in breathing. Hearing and vision improved in some patients and the severe headaches suffered by some patients stopped after several weeks of therapy.
Adverse effects such as hives were noted in a minority of patients but were manageable. All enrolled patients are continuing to receive therapy and will be evaluated at 12- and 18-month intervals.
Genzyme General's stock (NASDAQ:GENZ) closed Friday at $$42.062, down $.50. *