TWO NEW TRIALS AND BIOTECH MERGER MAY SPEED POMPE'S TREATMENT PROGRAM

The results of two new clinical trials of a potential therapy for Pompe's disease, also known as acid maltase deficiency and glycogen storage disease type 2, will soon reveal which of two types of "designer enzymes" should be brought before the U.S. Food and Drug Administration, say spokesmen for two biotech companies that have recently merged. One trial is under way, and the other is slated to begin this year.

A laboratory-engineered version of the acid maltase enzyme called Pompase was developed by the Genzyme Corp. of Cambridge, Mass. Its structure is based on research conducted in the 1990s at Duke University by MDA-supported Yuan-Tsong Chen. The other enzyme, known as NZ-1001, was developed by Novazyme Pharmaceuticals of Princeton, N.J.

Each designer enzyme mimics the actions of natural acid maltase, a lack of which is the underlying problem in Pompe's disease. Modifications of the natural enzyme are needed to move the injected enzyme from the bloodstream into the body's cells and then to direct it to the right place in the cells. (In nature, acid maltase is produced inside cells.)

Without acid maltase, glycogen (the storage form of sugar) builds up in muscle cells, including those involved in heart function and breathing. Death in early childhood is the result if the enzyme deficiency is severe.

This month, Genzyme announced it would purchase Novazyme and that the companies would join forces to produce a treatment for Pompe's. Until now, the two biotech firms have been arch rivals in the race to build the best enzyme.

Genzyme has recently begun a one-year clinical trial of Pompase at three centers, in Durham, N.C.; Essen, Germany; and Lyon, France. Results are expected in late 2002. The study builds on encouraging results in three babies treated with Pompase, all of whom are still alive past age 2, contrary to what was expected without treatment.

The data from that and an earlier study are "very encouraging," Paul Kaplan, senior director of program management at Genzyme, said, and "give us the scientific confidence to move forward with the program."

Novazyme will begin testing its NZ-1001 enzyme (which has more phosphate groups and may be better at getting into muscle cells) by the end of the year. The trial is likely to involve fewer than 20 patients.

John Crowley, president and chief executive officer of Novazyme and soon to be senior vice president of Genzyme Therapeutics, said the Novazyme enzyme's results in mice with Pompe's disease give him "great hope" for the human trials.

After just two injections of NZ-1001 over two weeks, Crowley said, normal enzyme activity in mice lacking acid maltase was restored; significant amounts of glycogen were cleared; and -- most important -- the Pompe's-affected mice quickly acquired normal muscle strength. Crowley considers the last point a "huge finding."

Crowley said the new Genzyme-Novazyme firm "will put the [two] drugs up against each other and see which one to take to the FDA." He said he couldn't recall other examples of a company taking two competing products this far in clinical trials. "This is a huge commitment on Genzyme's part to assure that the best drug gets to as many patients as quickly as possible," he said.

For more information or to express an interest in the NZ-1001 trial (not yet officially recruiting participants), families can call the Genzyme medical information line at (617) 252-7832, or visit Genzyme (www.genzyme.com) or Novazyme (www.novazyme.com).