Gaucher disease is a rare metabolic disorder with less than 20,000 sufferers worldwide. It is caused by lack of an enzyme (glucocerebrosidase) that metabolizes the glycosphingolipid (GSL) class of fats. Patients suffer spleen and liver enlargement, bone disease, and anemia. OGS began clinical work on miglustat as an orphan drug—until recently known as Vevesca and now called Zavesca—for Gaucher's in 1998. It is now OGS's main product, with peak sales estimated by ING Barings (London) at £55 million per year. The small-molecule, oral-formulation drug acts by so-called “substrate reduction” to inhibit the synthesis of GSL itself—unlike its main rival, Genzyme's (Cambridge, MA) Cerezyme, a direct enzyme-replacement therapy that has been on the US market since 1994.
The FDA's outright rejection seems to follow mainly from symptoms of peripheral neuropathy shown by some miglustat users. Of the 24 patients in the main Phase-3 one-year trial, 5 developed some neuropathy symptoms, although OGS chief finance officer Stephen Parker asserts that neurological symptoms are associated with the disease, as opposed to the drug. “You find neurological impairment in people who have never had Vevesca,” he says. OGS is now conducting a further trial to measure patients' baseline neurological behavior, the results of which will be compared with levels at the end of the trial in March 2003.
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