FDA delays approval of Genzyme drug

By Robert Weisman, Globe Staff

Genzyme Corp. today said US regulators are delaying approval of Lumizyme, its drug to treat the rare genetic disorder Pompe disease in adults, until the Cambridge biotechnology company solves persistent problems at its cell-culture manufacturing plant in Allston.

Genzyme officials said they are moving aggressively to correct "deficiencies" that were spelled out by the Food and Drug Administration during a meeting with company officials late Friday night. The session came as the FDA wrapped up a five-week inspection at the Allston Landing plant where Genzyme detected a virus last June.

The company, which decontaminated production equipment during a plant shutdown over the summer, now is tightening internal controls and temporarily closing a "fill finishing" area of the plant -- where its enzyme replacement drugs are put in vials for shipment to patients -- to update machinery and parts. FDA inspectors warned doctors last week about "foreign particle contamination," tiny bits of steel, rubber, and fiber found in five Genzyme drugs during the finishing process.

In perhaps the most significant new steps, Genzyme said it is transferring some finishing operations from Allston to outside contractors, at least temporarily, and flying more drums of Cerezyme -- which treats Gaucher disease, another genetic disorder -- to its state-of-the-art fill finishing plant in Waterford, Ireland. That plant already handles the finishing for most Cerezyme shipped to patients in Europe and the United States.

Genzyme chief executive Henri A. Termeer said the company is aware of its responsibility to quickly resolve its production problems. He said the FDA is conscious of the importance of approving the company's application for Lumizyme, a drug allowed for use by adults in more than 40 countries, but not in the US. It treats Pompe disease, a muscular disorder.

"We are very determined to work with the FDA to get Lumizyme approved," Termeer said in a conference call with investors.

FDA spokesman Karen Riley said the agency doesn't comment on drug approval deliberations. Riley confirmed the agency completed its Allston inspection Friday night and said it presented Genzyme will a list of deficiencies to be corrected. The FDA is expected to post the list on its website as early as this week.

Before its inspection of the Allston plant, the FDA had set Nov. 14 as its "action day" for ruling on Genzyme's application to produce Lumizyme in 2,000-liter bioreactors.

The company produces a similar drug, Myozyme, with a slightly different carbohydrate structure, in 160-liter batches in Framingham to treat children under 18 years old who suffer from Pompe disease. It also treats about 170 adults in the US through a temporary access program while it awaits the FDA ruling on Lumizyme.

The transfer of fill finishing work to Ireland, and the shutdown of the Allston fill finishing operation as Genzyme installs new metal components that are less likely to shed particles, will not result in the loss of jobs, said company spokeswoman Lori Gorski. But the complications could further slow efforts to resume full-scale shipment of Fabrazyme, one of the drugs that has been rationed in recent months because of last summer's viral contamination at the Allston plant.

Company officials said they can't yet say how long the additional delay might be. Genzyme already has resumed production of Fabrazyme and Cerezyme, the two drugs made in Allston, and has said it expects to rebuild its inventories and fully resume shipments of both treatments by the first quarter of next year.

"Any delay is a concern to the patients," said Jack Johnson, founder and executive director of the Fabry Support and Information Group in Concordia, Missouri. Johnson said some Fabry patients have reported experiencing fatigue during the rationing, but many remain free of symptoms as they await resumption of the drugs. "Most of them seem to be taking it in stride," he said.