By Mary Welch
BioMarin Pharmaceutical Inc. closed a $26 million private placement that will be used to fund the worldwide development and commercialization of alpha-L-iduronidase, an enzyme replacement therapy for Maroteaux-Lamy Syndrome, or mucopolysaccharidosis I (MPS-I).
The money also will be used to build a commercial manufacturing facility for MPS-I outside of Los Angeles, and will support the company¿s second genetic-therapy program, an enzyme replacement therapy for MPS-VI, as well as the company¿s carbohydrate enzyme therapeutics.
¿We have had success in our clinical trials, and now we are moving ahead expeditiously,¿ said Grant Denison, chairman and CEO. ¿That¿s the good news. The bad news is that it costs more ¿ production scale-up, marketing costs and other things.¿
The placement was managed by LaMont Asset Management SA, of Zurich, Switzerland. Participants included A and A Actienbank GmbH, and SMS Securities (Sigg-Merkli-Schrodel AG), both of Zurich, as well as several other European investors; and Glyko Biomedical Ltd., a founder of BioMarin. Glyko, of Toronto, invested about $4.5 million in this round.
The development and commercialization of a-L-iduronidase is part of a 50-50 joint venture with Genzyme Corp., of Cambridge, Mass., called BioMarin/Genzyme LLC. Pivotal trials were finished last October and a rolling biologics license application (BLA) should be completed by June or July. Given the drug¿s fast-track status, the BLA might be approved by year¿s end.
¿The FDA certainly seems motivated, and has been very cooperative and helpful with our filing,¿ he said.
As part of the joint-venture partnership, Genzyme made an $8 million equity investment in the Novato, Calif., company and will pay another $12.1 million upon FDA approval. When BioMarin completes an initial public offering, it will make a $10 million purchase. The companies believe the drug could turn into a $300 million to $400 million product. (See BioWorld Today, Sept. 16, 1998, p. 1.)
The two companies are splitting costs and revenues equally. ¿It¿s a partnership, in substance as well as in spirit,¿ he said. ¿Plus, Genzyme was a natural partner for us because of their success in marketing Cerezyme and Ceredase.¿ Cerezyme (recombinant glucocerebrosidase) and Ceredase, the natural version of the enzyme, which is derived from human placenta, are enzyme treatments for Gaucher¿s disease.
So far a-L-iduronidase has not been given a brand name, Denison said. ¿We have three names floating around and all are in the registration process of being checked to see if anyone owns the names,¿ he added.
MPS I is a lysosomal storage disease that is one of seven similar genetic conditions. The disease, of which the most serious form is Hurler¿s syndrome, afflicts 2,000 to 3,000 patients, mainly children, in the developed world. The expense of maintaining children with MPS I is astronomical, about $800,000 to $1.5 million per patient, the company said
The disease, characterized by a halt in physical development, causes carbohydrate materials to build up in all parts of the body, leading to enlargement of the liver and spleen, skeletal deformity, vision impairment, stunted growth, hearing loss and fluid on the brain. Although there is a wide spectrum of severity and complications, the average patient¿s life is around 12 years, and about 80 percent of those afflicted die.
The trial, done with 10 patients, ages 5 to 22, showed that weekly intravenous infusions of a-L-iduronidase returned the size of the liver to normal in the majority of patients within 26 weeks and also showed a decrease in the excretion of urinary glycosaminoglycans. The latter indicates that the compound was successful in breaking down the complex carbohydrate materials that would otherwise accumulate in patients.
All the patients are still taking the drug, and BioMarin is collecting data on their progress after 18 months on therapy.
¿Almost even more relevant than the clinical data was the quality of life issues,¿ Denison said. One patient, who had previously seen only shadows because of his cataracts, was able after treatment to read. ¿We had several patients with cataracts, all in remission,¿ he said. ¿Those with problems in moving are showing an improvement in their range of motion. Some who couldn¿t walk are now walking. Patients and their parents are telling us how this changed their lives. That¿s the really gratifying piece of the story.¿
The company expects to file an investigational new drug (IND) application before the third quarter for N-acetylgalactosamine 4-sulfatase for enzyme-replacement therapy in MPS-VI, a disease similar to MPS-I. MPS-VI is a fatal genetic disorder that afflicts children with a broad spectrum of debilitating clinical manifestations, including extremely short stature.
¿We are having success in developing enzymes for our genetic area of research, and we will be bringing them into the clinic soon,¿ Denison said.
In addition, the company is working on non-genetic applications of its technology, particularly in the areas of burn and wound care, fungal infections, pro-fertility and inflammation.
The company plans to file an IND and start human trials in the second half of this year for its burn program, which involves using enzymes to accelerate the debriding of wounds in preparation for skin grafting.
BioMarin is also developing a new class of anti-fungal enzyme drugs for severe systemic fungal infections, with the first product targeting Aspergillus infections. Aspergillus, an airborne fungus, causes fatal fungal infections in immune-compromised patients, such as transplant recipients and AIDS patients. Preclinical trials are ongoing, and an IND application is expected to be filed this year.