GAITHERSBURG, Md. _ An FDA advisory committee was dividedFriday on whether to recommend Pharmacia & Upjohn's anti-HIVdrug Rescriptor (delavirdine) for expedited approval. The panel splittheir vote 4-4 based on equivocal results from clinical trials.
The FDA usually relies on the recommendations of its advisorypanels to guide its final decisions. However, Rescriptor's fate willnow rely entirely on the judgment of FDA reviewers. "We only bringyou the difficult cases," David Feigal Jr., of the FDA's division ofantiviral drug products told the advisory committee.
For their part, the Kalamazoo, Mich., company remains confidentthat the agency will ultimately grant expedited approval for the drugby the Jan. 15 user fee deadline. "We are disappointed by the factthat the committee came to a split decision," said Donald Batts,Pharmacia & Upjohn's director of infectious diseases. "But, we areconfident in our data and we are confident that Rescriptor will begranted expedited approval."
Rescriptor is one of a new class of drugs that inhibit the reversetranscriptase enzyme. Unlike drugs such as AZT and ddI whichsimply mimic the normal components of DNA and stop reversetranscriptase from making copies of the HIV RNA, Rescriptorstymies the enzyme itself.
The company presented interim results from a trial showing thatRescriptor in combination with AZT and ddI significantly increasedthe numbers of CD4 cells in the blood of trial participants comparedto AZT and ddI alone. And, the major side effect was non-seriousrash.
However, the same trial failed to confirm the results of a previoustrial which showed an increase in CD4 counts when just AZT andRescriptor were used in combination. That caused committeemember Henry Masur, chief of critical care medicine at the NationalInstitutes of Health, in Bethesda, Md., to note that inconsistencies inthe data make it impossible to know how to use the drug.
However, Mary Dianne Murphy, chief of the ambulatory pediatricservices at the University of Florida Health Science Center inJacksonville argued that the "drug needs to be evaluated in terms ofsafety and that the drug is safe."
This approval application also highlighted a new focus in thedecisions of the Antiviral Drugs Advisory Committee: pediatricusage. Panel chair Scott Hammer, associate professor of medicine atHarvard Medical School, in Cambridge, Mass., said the panel"preferred not to see another proposal for expedited approval for anAIDS drug without at the very least preliminary data in children."
The panel noted that should the FDA choose to grant expeditedapproval for Rescriptor, the agency should require postmarketingevaluations of triple and 4-drug therapy as well as a study in children.
"We plan to work with the FDA to get Rescriptor approved," Battssaid. "And, we have every confidence that will happen."
Pharmacia & Upjohn may have good reason for their optimism. InJune, the FDA granted Boehringer Ingelheim Pharmaceuticals Inc.'sexpedited approval for Viramune (nevirapine), another non-nucleoside inhibitor of reverse transcriptase despite a no-vote fromthe committee as a result of concerns over toxicity. (See BioWorldToday, June 25, 1996, p. 1.) Ingelheim, of Ridgefield, Conn., wasthe first company to seek clearance of a non-nucleoside compound.
Non-voting panel member Gary Blick, of the Southern New EnglandCommunity Consortium, in Greenwich, Conn., noted "As a clinician,I am terrified of the side effects of nevirapine. This drug is leaps andbounds safer than a drug that has already been approved." n
-- Lisa Seachrist Washington Editor
(c) 1997 American Health Consultants. All rights reserved.