Genentech Inc.'s next product has performed well inpreliminary clinical testing, with cystic fibrosis patientsshowing significant improvements in lung function while theywere taking DNase.

As reported today in the New England Journal of Medicine, thePhase I trials at the National Institutes of Health showed that,as predicted, the DNA-digesting enzyme appeared to improvelung function, presumably because it thins the mucus.

Cystic fibrosis is associated with difficulty in clearing thickmucus from the lungs and air passages. The patients typicallyhave reduced lung volume and air flow. Infections becomedifficult to eradicate, and the chronic lung disease usually killspatients by their third decade.

The lung secretions in the inherited disease have high amountsof DNA from disintegrating white blood cells, and DNA in highconcentrations is known to form thick gels. Reasoning that theDNA-digesting enzyme DNase might help, the South SanFrancisco, Calif., company (NYSE:GNE) has engineered the genefor human DNase into hamster cells to make the enzymeavailable for clinical testing.

Two studies were reported. One trial enrolled 16 patientswhose lung function was compared with their pre-studymeasures. A second, crossover trial, had 16 patients receive theDNase for six days and then a placebo or the two treatments inreverse order. The enzyme was inhaled in an aerosol.

The studies demonstrated 10 percent to 20 percentimprovement in lung function. The short-term therapy testedwas well-tolerated and easily administered, the investigatorssaid.

Because of its probable mechanism of action, to thin secretions,the investigators concluded that the treatment may benefitpatients with lung infections, such as bronchitis, that alsoinvolve infected mucus. If studies show that DNase works inbronchitis, study investigator Ronald C. Crystal of the NIH toldBioWorld, "there would be a market for it" in that indication aswell.

Phase II studies of DNase in chronic bronchitis are under way,said Dr. Steven Shak, Genentech director of immunobiology,who cloned the enzyme.

Genentech has not yet calculated a market size for its product,but Phase III trials are under way for DNase in cystic fibrosis,and the agent has orphan drug designation for that indication,said spokesman Jim Weiss. Phase II testing has ended, and thedata should be presented in the next few months, Weiss said.

The enzyme is only available through the clinical trials, Weisssaid. He estimated that the company would seek permission tomarket DNase in the United States in early 1993.

On March 3, Genentech and F. Hoffmann-La Roche ofSwitzerland announced an agreement to develop DNase. Thecompanies will establish Genentech Europe, a Europeansubsidiary that will have DNase as its first product.

Other strategies to treat the genetic disease, which affects50,000 Americans, include a variety of drugs to treat the thickmucus and to slow lung damage, and gene therapy to correctthe mutated gene.

Genentech shares closed Wednesday at $28.50, up 13 cents.

-- Roberta Friedman, Ph.D. Special to BioWorld

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