Pulmozyme-the first new treatment approach for cystic fibrosis in 30 years-was developed through a collaborative effort by Genentech, the CF Foundation, CF centers in North America, and the FDA. It is a bioengineered drug: The human protein deoxyribonuclease was isolated and synthesized in the lab at the cost of "several hundred million dollars," according to Genentech's Senior Manager of Corporate Communications, James Weiss. Here are some of the most important milestones of the development process:
March, 1988: Genentech researcher Dr. Steven Shak was observing the blood-thinning drug TPA as it dissolved blood clots, and developed the idea to engineer an enzyme that would dissolve mucus plugs in the lungs of CF patients. Research from the 1950s suggested to him that DNase isolated from cows had been effective in breaking up mucus, though its use was discontinued because patients had allergic reactions.
October, 1988: Dr. Shak successfully isolated the human gene for DNase and cloned a small amount in the lab. Tests show that the cloned DNase did break down DNA accumulations in CF sputum. He assembled a team of 25 people to develop the drug.
1989: The DNase team began to purify large amounts of the enzyme. Dr. Shak spoke to CFRI about the development process and results to date.
1990: Genentech applied to the FDA for the approval of DNase. With FDA permission, Genentech began an accelerated campaign to test the drug, beginning Phase I testing (for safety in humans) in September and Phase II testing later in the year.
October, 1991: Phase II testing, conducted by Genentech with 181 CF patients at eight U.S. treatment facilities, successfully concluded. Genentech began the construction of a manufacturing facility to produce sufficient quantities of the drug once final approval was granted.
1992: Phase III testing began-over 900 CF patients participated at CF centers all over the U.S.-and took one year to complete. Although increases in lung function in CF patients during Phase III were lower than during the first two phases, the study provided conclusive evidence of an improvement in the incidence of lung infections.
1993: In March, Genentech filed it final product application for the approval of DNase, and in August the FDA unanimously approved it under the brand name Pulmozyme. The FDA did caution, however, that more research is needed on the effects of Pulmozyme on different populations of CF patients not represented during the clinical trials.
December, 1993: The FDA granted Genentech permission to sell Pulmozyme.
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