Actelion Ltd. and partner Celltech Group plc received FDA clearance to market Zavesca to Type I Gaucher's disease patients who are not candidates for Cerezyme, an orphan product made by Genzyme Corp.

Zavesca (once called Vevesca), an oral treatment, is expected to be launched by Actelion, of Basel, Switzerland, later this year. Developed by Oxford GlycoSciences Group plc (now part of Celltech, of Slough, UK), Zavesca is a first-in-class substrate reduction therapy that reduces the amount of glycosphingolipid production to a level that can be effectively cleared by the naturally occurring glucocerebrosidase in the cells.

Approval of Zavesca means that people suffering from Gaucher's disease, a rare genetic lipid storage disorder, will have another treatment option, said Roland Haefeli, Actelion's vice president of corporate communications. For Actelion, approval of the capsule is a testament to the strength of the company, he said.

"We have been able to prove that our regulatory abilities and capabilities are really at the top of the industry standard and that we are able to get drugs registered on a global basis even when there has been a non-approvable letter," he said. "We were able to resolve outstanding issues with Zavesca in only a few months to get the drug approved."

The FDA rejected the Zavesca new drug application filed by Oxford GlycoSciences (OGS) in August 2001. The agency cited the company's failure to provide sufficient evidence of safety and efficacy.

The rejection came about a year ago, around the same time OGS signed a five-year marketing partnership with Actelion.

"[OGS]called us to help them get through the European Union [regulatory process]," Haefeli said. "We decided to go to the FDA together to determine what was lacking, and we found out, beyond formal details, the application lacked clinical data that had already been submitted to the EU," Haefeli said. "Basically, we filed an amendment to the existing NDA where we resolved technical matters as well as clinical data that were included in the EU dossier."

The amendment was filed in February. Meanwhile, Celltech purchased OGS, inheriting Zavesca.

Neither Haefeli nor Richard Bungay, Celltech's director of corporate communications, would discuss specific financial arrangements between the companies, but Haefeli characterized the deal as a 60-40 split under which Celltech will receive undisclosed royalties on U.S. and European sales. U.S. approval does not trigger a milestone, Bungay said. Actelion is responsible for all regulatory and marketing activities.

The companies said an estimated 10,000 people worldwide are affected by Gaucher's disease. In the U.S. it is classified as an orphan disease that has been served by Genzyme's Cerezyme, an enzyme replacement therapy delivered via intravenous infusion twice monthly.

U.S. patients pay about $180,000 a year to get Cerezyme. Genzyme, of Cambridge, Mass., estimates 2003 sales could approach $700 million.

Zavesca's U.S. price will be determined at launch. However, Bungay said the product costs about 190,000 a year in Europe. While the product has received EU approval, it has been launched only in Germany and the UK. It also has been approved in Israel, where Jerusalem-based Teva Pharmaceutical Industries Ltd. owns marketing and distribution rights.

Meanwhile, Zavesca is undergoing pilot studies in other indications, including Type III Gaucher's disease, Niemann-Pick Type C and late-onset Tay-Sachs disease.

Gaucher's disease is a progressive condition caused by a deficiency of glucocerebrosidase, an enzyme used in the metabolism of lipids in the body. The deficiency of the enzyme results in accumulation of excess amounts of glycosphingolipids in specific cells primary in the liver, spleen and bone marrow. Such accumulation leads to liver and spleen enlargement/dysfunction, anemia, bone disease and pain.

The FDA specifically approved Zavesca for adults with mild to moderate Type I Gaucher's disease for whom enzyme replacement therapy is not a therapeutic option, possibly due to allergy, hypersensitivity or poor venous access.