The potential development of inexpensive, low-tech, newtreatments for diseases like cystic fibrosis won't preclude theuse of biotechnology products, according to CF experts. Butgene therapy might.
A report in last week's New England Journal of Medicine holdsthe promise of a cheap new treatment for CF. Researchers atthe University of North Carolina, Chapel Hill, showed that thenucleotides ATP and UTP can stimulate chloride secretionindependently of the ion pathway that is damaged in thedisease.
The lungs of CF patients are easily infected, kicking off acycle of inflammation that eventually causes death. The initialcause is defective control of chloride ion secretion acrossmucosal tissues. That, coupled with excess sodium uptake,dries out the mucus, which can't be properly cleared from thelungs and invites bacterial infection.
The researchers suggest a combination of aerosolizedamiloride, which corrects the sodium ion defect, and eitherUTP or a form of ATP that resists metabolism. The group hasshown positive results in a six-month pilot study of amiloride.
All three products are inexpensive. "Twenty-five dollars'worth did all of the studies I did in the paper," Dr. MichaelKnowles, one of the study's authors, told BioWorld.
Another inexpensive treatment, in Phase III clinicals, is highdoses of ibuprofin to treat the inflammatory cascade. TheCystic Fibrosis Foundation is running those trials.
But unlike the case of tissue plasminogen activator, whereclinical comparisons of thrombolytics showed that an older,cheaper drug works at least as well as the biotech drug for anarrowly defined purpose, diseases like CF offer numerouspoints of intervention.
At least four biotech companies are targeting CF, which is themost common fatal genetic disease in the United States,affecting about 30,000 people. The companies see synergiesbetween the various products.
Genentech Inc.'s drug, DNase, "may help open up clogged mucusso patients could inhale other drugs," said Jack Murphy, aspokesman for the South San Francisco, Calif., company.Genentech is running Phase II trials of DNase, a recombinantform of an enzyme that breaks down the excess DNA thatcontributes to thickened mucus.
Boulder, Colo.-based Synergen Inc. began Phase I/II trials inDecember of a protein called secretory leukocyte proteaseinhibitor. SLPI is a natural inhibitor of elastase, an enzymefound in lung mucus. Elastase strips a vital receptor proteinfrom white blood cells, preventing them from recognizing anddestroying infection-causing bacteria.
SLPI and DNase are complementary products that hit differentparts of the cascade of symptoms, according to analyst MarkSimon of Robertson, Stephens & Co. SLPI will also work wellwith amiloride, said Synergen spokeswoman Debra Bannister.
Potential competition for SLPI is a leukocyte elastaseinhibitor, ICI 200,880, being developed by ICI Americas Inc. ofWilmington, Del. That drug, which is in Phase I/II trials, wouldalso work with DNase, amiloride or ibuprofin, said Dr. MitchellGlass, director of pulmonary therapeutics at ICI.
But Genzyme Corp. of Cambridge, Mass., is developing a drugthat might shrink the market for other drugs. Genzyme hopes toreplace the CFTR protein, which malfunctions in CF patients.That product is in the research stage, with a 1997 productlaunch target.
It would be the next best thing to gene therapy, said Dr. RobertBeall, medical director of the Cystic Fibrosis Foundation inBethesda, Md. If it works in rebuilding defective ion channels,it might preclude other therapies in younger, healthier patients,said ICI's Glass.
The wild card is gene therapy, which could wipe out the marketfor drug treatments. Companies taking this route includeGenzyme and Gene Therapy Inc. of Gaithersburg, Md. Beall saidgene replacement trials using CFTR will begin by the end of1992.
"Twenty years from now, I expect all other therapies will beobsolete except in older patients," said Glass.
But that leaves plenty of time for biotech companies to recouptheir investments. Successful products will make back theircosts in a couple of years, said Synergen's Bannister.
SLPI and ICI 200,880 will also be useful for much largerpatient populations, such as those with chronic bronchitis oreven gingivitis and acute myocardial ischemia, in which whiteblood cells are out of control, said Glass.
-- Karen Bernstein BioWorld Staff
(c) 1997 American Health Consultants. All rights reserved.