Washington Editor

As expected, Genzyme Corp. filed for FDA approval of Myozyme (alglucosidase alfa) concurrent with a report that the enzyme-replacement therapy met its primary endpoint in a pivotal study of infantile-onset Pompe disease patients.

"It's a very important milestone for Genzyme," said Bo Piela, company spokesman, "and also for the patients and families who are dealing with Pompe disease, because it means that a potential treatment is on the horizon."

The Cambridge, Mass.-based company could get a decision early next year if the biologics license application receives priority review from the FDA, which is expected. If approved, Myozyme would represent the first treatment developed for patients with the debilitating and often fatal muscle disorder that results from an inherited deficiency of the enzyme acid alpha-glucosidase.

The submission, seeking approval for the product's use as a long-term enzyme-replacement therapy for all patients with a confirmed diagnosis, is based on data from several clinical trials. Included is study AGLU01602, the aforementioned pivotal trial that enrolled 18 patients who began receiving Myozyme by 6 months of age. All of them were alive at 18 months, compared with 2 percent of patients who were alive at that age in a historical cohort. (Outcomes were compared to that historical cohort rather than a placebo group because of the disease's rapidly progressive and fatal nature in infantile-onset patients, most of whom die from cardiac or respiratory complications by 1 year of age.) Also, 83 percent of Myozyme patients were both alive and free of invasive ventilator support at that age, compared with 2 percent in the control group, the study's primary endpoint.

"The strategy was to design a trial that could demonstrate the efficacy of Myozyme as quickly as possible, given the urgent medical need," Piela told BioWorld Today. "We have clearly done that in this study; the results are very strong."

Genzyme said it would submit results to European regulatory authorities who already are reviewing an application for Myozyme filed last December. A decision in that territory also is expected early next year, Piela said. Later this year, the company plans to file for Japanese approval. In both Europe and Japan, the product has been designated an orphan drug, a status it also has in the U.S.

The Myozyme program represents Genzyme's largest research and development initiative to date, and it has advanced quickly. Its development began in 2001, clinical studies began in 2003, "and here we are at the point of having applications before the FDA," Piela said. The company's efforts are partly attributable to past clinical development and manufacturing experience with other enzyme-replacement products.

"And we've also made a tremendous financial investment," Piela said, Genzyme having spent $500 million on the program thus far. "And we will invest several hundred million more dollars in the next few years as we expand the manufacturing capacity so that we can supply a worldwide market and work to get the drug approved outside the major markets."

The muscle disease, a lysosomal storage disorder, affects less than 10,000 people worldwide, and the company plans to make Myozyme available through its international network of global operations. Already that formula has worked for Cerezyme (imiglucerase), the Gaucher's disease treatment that is approved in almost 80 countries, and Fabrazyme (agalsidase beta), the Fabry's disease therapy licensed in more than 40 countries.

"Operating as a global company has been an important part of the way we've worked," Piela said.

At present, more than 130 patients continue to receive Myozyme in clinical studies, through Genzyme's expanded access program or through pre-approval mechanisms sponsored by governments in several European countries. Also, the company is planning to soon begin a study in patients with late-onset Pompe disease, a group in which the product has not been largely studied. In late-onset Pompe disease, muscle or respiratory weakness can occur anytime during childhood or adulthood, and its progression is less rapid.

The trial will enroll about 70 patients in the U.S. and Europe. Going forward, the product will be manufactured in a Boston-area facility, as well as at a site in Geel, Belgium.

Beyond the latest Myozyme milestone, upcoming product development highlights from Genzyme include plans to begin a Phase III study of DX-88 in hereditary angioedema. That drug is partnered with Dyax Corp., also of Cambridge. The company also continues to enroll patients in a Phase III trial of tolevamer, a non-absorbed polymer therapy to treat Clostridium difficile-associated diarrhea.

On Friday, Genzyme's shares (NASDAQ:GENZ) lost 79 cents to close at $74.41.