The FDA approves new drug for Pompe disease

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The Food and Drug Administration on Tuesday approved a new drug called Lumizyme for the treatment of Pompe disease, a disabling genetic disorder that is often fatal. A drug called Myozyme is available to treat the disease, but supplies have been severely restricted and it is reserved for use in children and infants with the most severe form of the disorder. Approval of Lumizyme, which is closely related to Myozyme, will make treatment available to much larger numbers of people.

Pompe disease, which affects about one in 40,000 Americans, is caused by mutations in the gene that is the blueprint for an enzyme called acid alpha-glucosidase, which is used by tissues to convert a form of sugar called glycogen into energy. If the enzyme is not working properly, glycogen builds up in tissues, especially in the heart and muscles, weakening them severely. Many different mutations have been discovered, and they vary in severity. Some mutations produce only a partial impairment in activity and the disease does not become a problem until adolescence or adulthood. In other cases, however, the enzyme does not work at all, and the disorder can be fatal at a very young age unless treated. In infants, symptoms include respiratory problems that often lead to infections, feeding problems, poor weight gain, muscle weakness, floppiness, head lag and an enlarged heart. More than half of victims also suffer enlarged tongues. In the late onset form, the primary symptom is muscle weakness leading to respiratory problems that can be fatal. The heart is usually involved, but it does not become grossly enlarged.

Myozyme, produced by Genzyme Corp. of Cambridge, Mass., is a synthetic form of alfa-glucosidase that breaks down the glycogen, easing Pompe symptoms. The company originally produced the drug in 160-liter batches, which limited the available supply so that its use had to be restricted to infants and children who were most severely affected. The company applied to the FDA to manufacture the drug in 2,000-liter batches, but the agency determined that the synthetic enzyme produced in the larger batches was slightly different from the original product. Apparently, more sugar molecules are attached to its surface. The company was thus forced to conduct clinical trials of the new form, which it chose to call Lumizyme. The safety and efficacy of the drug was demonstrated in a trial on 90 late-onset patients ages 10 to 70, and the FDA granted approval. An estimated 200 adult patients in this country are already receiving the drug on a compassionate basis, and it has already been approved in several other countries.

Because it is a protein, the drug has to be administered by infusion. The primary side effects are allergic reactions to the drug, which include hives, diarrhea, vomiting, itchy skin, skin rash and chest discomfort. The drug will carry a so-called black box warning cautioning about the possibility of severe allergic reactions. The company will undertake a post-marketing surveillance program to monitor for side effects, and the drug will be available only through a restricted distribution system to ensure that it reaches the proper patients, the FDA said.

-- Thomas H. Maugh II