Enzon Corp. is about to obtain a partially exclusive license fromthe National Institutes of Health to produce a longer-livedversion of Ceredase, Genzyme Corp.'s treatment for Gaucher'sdisease.

Ceredase, which is a chemically remodeled-carbohydratereplacement for the enzyme glucocerebrosidase (GC), receivedFDA marketing and use approval in April 1991 as an OrphanDrug.

NIH's technology was developed by Edward I. Ginns, who headsthe neurogenetics section in the National Institute of MentalHealth. It covers a cDNA that, Ginns stated, can synthesize 10times as much GC as the placental version, using a baculovirus(insect) expression system.

Enzon of South Plainfield, N.J., will wrap the recombinantprotein in PEG (polyethylene glycol) to shield the GC cells'surface from immune degradation. This technique increases theenzyme's survival in the bloodstream "from six minutes toalmost a week," Enzon spokeswoman Donna Chappina toldBioWorld.

On the heels of this NIH-to-industry technology transfer,another federal agency, the Office of Technology Transfer(OTA), issued a 34-page report last week that stronglyreproaches Genzyme of Framingham, Mass., for pricingCeredase "at $71,000 at least, and as much as half a milliondollars per year per patient."

Henri A. Termeer, Genzyme's chairman, president and chiefexecutive officer, promptly contested OTA's data andconclusions.

"The range of costs for most patients will be between $20,000and $60,000 per year for maintenance," Termeer said. Headded that Ceredase costs $2.74 per unit to produce -- notOTA's estimate of $1.90. Termeer also declared that "Genzymerisked the investment of $70 million prior to FDA approval todevelop the product."

Chappina said it is "too early to comment on pricing issues" forEnzon's drug.

"In the next month or two," Genzyme spokeswoman Donna L.LaVoie told BioWorld, Genzyme will complete Phase IIImulticenter clinical trials of a recombinant glucocerebrosidase.FDA approved these studies on November 27, 1991.

This genetically engineered glucocerebrosidase is intended tobreak out of the limited supply of Ceredase, which is extractedonly from human placental tissue. However, LaVoie added, theprice of the new product "will absolutely not be significantlyless than that of Ceredase because of its very manymanufacturing steps."

She expects the new drug to reach the market "presumably bythe end of 1993," and noted that some 800 patients worldwideare currently on Ceredase replacement therapy, most of themin the U.S.

In the offing, which they define as "within the next six monthsto a year," several investigators will attempt somatic genetherapy to cure rather than relieve the symptoms of Gaucher'sdisease, the second-largest genetic disease after cystic fibrosis.

Three molecular geneticists described their cell-transducingstrategies to the recent Gene Therapy meeting at Cold SpringHarbor Laboratory:

-- Ginns, in partnership with Richard C. Mulligan of theMassachusetts Institute of Technology's Whitehead Institute,hopes to transfect the GC gene into human macrophages, whichin Gaucher's patients fail to break down the perpetual build-upof lipids.

-- John Barranger of the University of Pittsburgh is pursuing asimilar transduced macrophage plan. It was in his laboratory atNIH that Ginns discovered the GC gene eight years ago.

-- Jan A. Nolta, research immunologist at Los Angeles Children'sHospital, intends to insert a normal GC gene into human bonemarrow cells, and return these to the patient. She hopes theywill correct the Gaucher's mutation in enough stem cells tomitigate the horrendous spleen, liver and bone devastation thedisease causes.

Ginns and Barranger are also preparing bone-marrowalternative gene therapies.

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.

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