Bioengineered cystic fibrosis drug approved

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    22-Feb-2017

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  • Bioengineered cystic fibrosis drug approved Genentech has received Food & Drug Administration and Canadian Health Protection Branch approval to market a new, genetically engineered drug for treatment of cystic fibrosiswhich the South San Francisco-based biopharma-ceutical firm will sell under the tradename Pulmozyme.

    A recombinant form of the human enzyme deoxyribonuclease (DNase) 1, Pulmozyme is the first new treatment for cystic fibrosis in 30 years. Affecting about 33,000 Americans and Canadians, the disease is the most common fatal genetic condition in Caucasians, with a median survival age of 29 years. The drug is not a cure for cystic fibrosis, FDA notes, but its use will improve lung function and quality-of-life in many patients.

    Cystic fibrosis is characterized in part by buildup of secretions in the lungs. A faulty gene is believed to cause flawed production of a protein that regulates the flow of chloride ions across cell membranes. These secretions contribute to frequent bacterial infections and life-threatening lung damage.

    In the 1950s and 1960s, cystic fibro-sis-related secretions in the lungs were found to contain large amounts of mucus-thickening DNA, the result of dead white blood cells that accumulate to fight infections. Genentech's DNase enzyme, which is inhaled through a nebulizer, breaks up such lung secretions. Naturally occurring bovine DNase, isolated from cow pancreas, had previously been shown to be effective, but

    Cystic fibrosis patient inhales Pulmozyme.

    allergic reactions to the animal protein limited its use, and it is no longer available. The most common treatments for cystic fibrosis, which still will be used in conjunction with Pulmozyme, include clearing lung secretions and controlling infections with antibiotics.

    Genentech's development of DNase ranks among the fastest for biotech drugs, taking about half the average industry time. DNase moved from lab to market in about five yearshelped, Genentech says, by the collaborative efforts and cooperation of regulatory agencies, the Cystic Fibrosis Foundation, and clinical centers, among others. FDA approved the drug for marketing in only nine months under its expedited review procedures.

    The company says its DNase program team, led by Steven Shak, director of Genetech's department of pulmonary research, was the first to clone and express the human gene for DNase. Genentech has a collaborative R&D program with GenVec, a young Rockville, Md.-based company, to develop gene therapies for cystic fibrosis.

    Pulmozyme is Genentech's first new product approval in three years. (Its most recent approval was -interferon, which has a small market for chronic granulomatous disease.) Because of the low incidence of cystic fibrosis, FDA also has granted "orphan drug" status to Pulmozyme, giving Genentech a seven-year exclusive market. Analysts estimate an annual per-patient cost for Pulmozyme of as much as $10,000, yielding a potential U.S. market of as much as $300 million. The drug is already sold in a few countries in Europe, which has some 20,000 cystic fibrosis patients.

    Genentech will market it exclusively in the U.S. and Canada. Hoffmann-La Roche, which holds a 63% interest in Genentech, will share marketing in Europe and have exclusive marketing rights elsewhere. Genentech will produce the drug at a plant completed a year ago in South San Francisco. The company says it is making enough Pulmozyme to meet current demand, and will begin shipping it in the U.S. by mid-January.

    jme. Ann Thayer

    CFC substitutes proven safe for ozone layer A comprehensive study by National Oceanic & Atmospheric Administration (NOAA) researchers has laid to rest suspicions that hydrofluorocarbon (HFC) substitutes for ozone-depleting chloro-fluorocarbons (CFCs) might themselves contribute to depletion of the stratospheric ozone layer. The new laboratory measurements and computer modeling calculationspublished in last week's Science [263, 71 (1994)]confirm that HFCs do not destroy ozone.

    Because HFCs contain no chlorine or bromine that can catalyze destruction of ozone, they had been assumed to have zero potential for depleting the ozone layer. However, at a workshop held last March, several scientists raised the possibility that molecules containing the tri-fluoromethyl (CF3) group might pose a risk when they are oxidatively degraded in the atmosphere. The unusually stable trifluoromethyl fragments, they feared, could destroy ozone through reaction cycles involving alkoxy (CFsO) and peroxy (CF302) radicals.

    If validated, this hypothesis would have triggered a major upheaval in the transition away from CFCs. In 1992, the countries that are party to the Montreal Protocol on Substances That Deplete the Ozone Layer decided to move up the deadline for phasing out CFCs to 1996 from 2000. That decision was based in part on the availability of environmentally safe alternatives, several of which contain the trifluoromethyl group. For example, chemical companies have invested heavily in development of HFC-134a (CH2FCF3), which is fast becoming the substitute of choice for numerous refrigeration and air-conditioning applications (C&EN, Nov. 15,1993, page 12).

    "We considered this a critical issue; HFC-134a is already in use," says Du-Pont scientist Mack McFarland, who is vice chairman of an industry consortium that sponsors research on CFC substitutes. "Most scientists believed it was unlikely that HFCs could contribute to ozone depletion, but we needed hard data. Our customers were raising questions, and there were indications their concern could be slowing the transition out of CFCs."

    The NOAA study has provided the hard data that were missing. "The rate

    JANUARY 10,1994 C&EN 5

    Bioengineered cystic fibrosis drug approved

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