By Kim Coghill
BioMarin Pharmaceutical Inc. and Genzyme General aim to file regulatory applications early next year in the U.S., Canada and Europe for Aldurazyme, an enzyme replacement therapy for people with mucopolysaccharidosis I (MPS I).
They said Friday that preliminary data from a 45-patient, randomized, double-blind, placebo-controlled Phase III pivotal trial were positive.
The companies signed a 50-50 collaboration deal to develop and market Aldurazyme (laronidase) in 1998. FDA approval of the drug would trigger a $12 million milestone payment to BioMarin.
BioMarin¿s stock (NASDAQ:BMRN) closed Friday at $12.87, up $2.86, or 28.6 percent. Genzyme¿s stock (NASDAQ:GENZ) closed at $54.38, up 69 cents.
¿We think this is an extraordinary result and it validates our enzyme approach,¿ Fredric Price, chairman and CEO of Novato, Calif.-based BioMarin, told BioWorld Today. ¿We have a good methodology for determining how to create these enzymes and how to get them to work. If all goes well, these kids are going to get drugs next year and I think this is strong validation of the technology platform of the company.¿
Dan Quinn, a spokesman for Cambridge, Mass.-based Genzyme General, a division of Genzyme Corp., said the company is extremely pleased with the data and intends to rapidly set up a meeting with the FDA to discuss the filing of a BLA.
In the pivotal Phase III study, Aldurazyme was given intravenously once weekly to each of the 45 participating children affected by MPS I, also known as Hurler, Hurler-Scheie or Scheie syndromes. Most patients die before reaching adulthood due to complications of this genetic disease caused by a deficiency of the enzyme alpha-L-iduronidase.
¿These kids don¿t have this enzyme or they have so little that it is hardly expressed,¿ Price said. ¿You give them the enzyme, and it starts to do its job, then they approach normalcy. We¿ve only had the kids [in the trials] on the drug for three years and the theory is as long as they keep getting the enzyme, and it is doing its job, they will be able to live fairly normal lives. That is, if you get the kids early.¿
According to the companies, all patients who participated in the trial have elected to receive Aldurazyme in an open-label extension study. The FDA granted Aldurazyme fast-track and orphan status. Price said about 3,000 to 4,000 people in the Western world suffer from MPS I.
Preliminary data from the study showed a statistically significant increase in pulmonary capacity (p=0.028), and demonstrated a positive trend in endurance as measured by a 6-minute walk test (p=0.066). And data show evidence of reduction in liver size and a reduction in excretion of urinary glycosaminoglycans (the carbohydrate substance that accumulates in patients with MPS I). The companies reported no Aldurazyme-related serious adverse events, with the most common reactions being fever, headache, rhinitis and rash.
The pivotal trial follows an earlier 10-patient preliminary trial that ended two years ago. The endpoints were a normalization of liver size and a decrease in the excretion of urinary glycosaminoglycans. (See BioWorld Today, Nov. 19, 1999.)
¿That was an open-label trial and the safety and efficacy data were exquisite,¿ Price said. ¿The FDA said the data was superb and told the companies to do a double-blind, placebo-controlled trial.¿
BioMarin also has completed an enzyme replacement Phase I study for MPS VI and will begin an MPS IVA trial.