Washington Editor

The FDA approved Genzyme Corp.'s Myozyme (alglucosidase alfa), an enzyme-replacement therapy for Pompe disease, making it the first product cleared for the rare and often fatal muscle disorder.

Its label is broad, allowing for use in all patients with the inherited disorder, which is caused by a deficiency of the enzyme acid alpha-glucosidase.

While the approval was based largely on data from a pivotal trial that enrolled 18 infantile-onset Pompe disease patients, a fully enrolled study is further establishing Myozyme's profile in older patients, as well. And given the progressively degenerative nature of the disease, it's not surprising that the FDA granted the wide label.

"This is not so unusual," explained David Meeker, the president of Genzyme's therapeutics division, during a conference call. He noted Myozyme's broad indication "reflects a good level of cooperation between both Genzyme and the FDA."

The label, according to a research note from Robert W. Baird & Co. analyst Christopher Raymond, represents a "best-case scenario" for the company. In addition, he called Genzyme's valuation "compelling" and continued to recommend investments in its shares. On Friday, the stock (NASDAQ:GENZ) lost 3 cents to close at $61.16.

"It really is one disease," explained Genzyme spokesman Bo Piela. "It has different manifestations based on the age of onset, but the disease is caused by the same underlying enzyme deficiency."

He told BioWorld Today that the company, of Cambridge, Mass., first focused on Myozyme in younger patients, in whom efficacy would be more quickly proved. In the pivotal trial, 83 percent of those treated with the therapy were both alive and free of invasive ventilator support at 18 months of age, while comparatively 2 percent of similar patients were alive at that time in an untreated historical control population.

"The disease is rapidly fatal when it presents in infants," said Julie Beitz, the acting director of the Office of Drug Evaluation III in the FDA's Center of Drug Evaluation and Research, during the agency's conference call. Most die within a year of birth. She added that Pompe disease is "slowly progressive" in older patients, who often require mechanical ventilation to assist with breathing and wheelchairs to assist with mobility.

For those with late-onset disease, Genzyme recently completed enrollment in a 90-patient, placebo-controlled study that is evaluating Myozyme's ability to improve functional endurance and reduce respiratory muscle weakness. Data are expected in about a year.

"There has been relatively little research in this area," Piela said, "so all of the information that we are able to generate in these clinical trials is important."

Genzyme expects to launch Myozyme in about two weeks. Its cost will be in the same range with other treatments for lysosomal storage disorders, but will fluctuate from patient to patient, because its price is based on weight.

The product received European approval earlier this month and has been launched.

In addition to developing Myozyme to make up for the alpha-glucosidase shortfall, Genzyme also has come up with new diagnostic technology, an enzyme assay that evaluates blood samples to diagnose Pompe patients more rapidly and less invasively than in the past.

Before, muscle or skin biopsies were analyzed in a process that could take six weeks or more. The company will sell the new test through its Genzyme Genetics unit, and also it will be available through several clinical laboratories in the U.S. and elsewhere in the world.

The FDA has designated Myozyme an orphan drug, and at present, more than 280 patients in 30 countries receive treatment with it through clinical trials, expanded access programs or pre-approval regulatory mechanisms.

The product is delivered through an intravenous infusion every two weeks. Its label has a black box describing its association with the risk of hypersensitivity reactions such as anaphylactic shock during infusion, so the warning recommends appropriate medical support should be available during administration.

Genzyme is "supportive" of the warning, Meeker said, and the analyst Raymond said the black box would not be "an impediment to adoption." He estimated quarterly revenues growing from $6 million to $9.8 million and $13.6 million over the remainder of this year, followed by $102.9 million for next year and $199.7 million in 2008.

Myozyme is the fourth enzyme-replacement therapy developed by Genzyme for a rare genetic disease. Already on the market are Cerezyme (imiglucerase for injection) for Type I Gaucher's disease, Fabrazyme (agalsidase beta) for Fabry's disease and Aldurazyme (laronidase) for MPS I.

Genzyme filed its biologics license application last summer. (See BioWorld Today, Aug. 1, 2005.)