GAITHERSBURG, Md. _ An advisory panel has recommended thatthe FDA allow Genentech Inc. to market its cystic fibrosis (CF) drug,Pulmozyme, to the sickest of CF patients in a vote of eight to three.
"Clearly it's these tremendously ill patients who won today," saidPaul Laland, associate director of communications for Genentech, ofSouth San Francisco.
Pulmozyme originally was approved by the FDA in December 1993as a treatment to help CF patients clear the sticky mucous from theirlungs. Because the initial study was limited to patients suffering frommild to moderate disease, the drug label currently states that safetyand efficacy has not been established for patients with severe disease.Nevertheless, according to Cystic Fibrosis Foundation registries, 80percent of severely ill patients currently use Pulmozyme.
CF, an autosomal recessive disease, affects 25,000 Americans. Thegene that causes CF occurs in 3 percent to 4 percent of allCaucasians.
Studies of the drug in patients with mild to moderate disease _defined as better than 40 percent of healthy, or predicted, lungfunction _ showed that Pulmozyme reduced the risk of respiratoryinfection by about 30 percent and increased lung function by 5.8percent over the 12-month study period. Side effects includedhoarseness, laryngitis and conjunctivitis.
In order to get approval for the drug in severely ill patients _ thosewith less than 40 percent of predicted lung function _ Genentechsubmitted the results of a three-month trial of 320 patients who tookPulmozyme or placebo once a day.
Severely ill patients on Pulmozyme experienced on average a 9.4percent improvement in lung function compared to those takingplacebo. In contrast to the study in less affected people with CF, therewas no difference in the number of infections the between the drugand placebo groups. And, both groups suffered similar degrees ofshortness of breath.
Because the study results appeared to show no clinical benefit forthese severely ill patients, the FDA took the unusual step of puttingthis labeling change to an advisory committee.
The Pulmonary Allergy Drug Advisory Committee expressedconcerns that the only measure of improvement was lung function,and questioned its reliability as a marker if the patients weren'tfeeling better.
"We wish that we could show a clinical benefit for these patients,"Charles Johnson, clinical scientist at Genentech, told BioWorldToday. "But, with this patient population we can't. And we can't dothis study again."
Robert Beall, president and CEO of the Cystic Fibrosis Foundation,warned the panel that a refusal of Genentech's supplemental drugapplication could open the door for insurance companies to denyPulmozyme to patients on the drug when their lung function slipsbelow 40 percent of predicted.
"I am actually astounded that they were able to show significantdifferences in lung function," said committee chair Shirley Murphy,of the University of New Mexico.
Sally Wenzel, of the National Jewish Center for Immunology andRespiratory Medicine in Denver, was less impressed by the study.She opposed the approval based upon questions about the long termsafety and efficacy of Pulmozyme: "It is a very expensive drug totake if there is little patient benefit. And, we don't have theinformation about which patients will benefit. We need additionalstudies."
Committee members proposed additional studies ranging frommortality studies to exercise studies, but did not recommend specificstudies the FDA should require of Genentech in order to gainapproval.
Genentech's stock (NYSE:GNE) closed Wednesday unchanged at$52.75. n
-- Lisa Seachrist Washington Editor
(c) 1997 American Health Consultants. All rights reserved.