Immune Response Corp., whose stock was pummeled after aFood and Drug Administration advisory committeerecommended against use of CD4 cell counts as a primary endpoint in clinical studies of AIDS vaccines, on Wednesday saidthe recommendation wouldn't slow its pace of clinicaldevelopment.
The stock (NASDAQ:IMNR) lost $15.75 -- 25 percent of its value-- to close at $46 on Wednesday. Shares of other companiesdeveloping AIDS vaccines also declined slightly. Speculationthat the committee on Tuesday would favor the CD4 surrogatemarker had driven the stock up last week.
Perhaps ironically, the FDA on Wednesday said it wouldimplement a White House-led program that commits theagency to pursuing the development of surrogate markers toexpedite drug approvals. (See related stories above.)
Immune spokesman Steven Basta said the company anticipatesno change in its trial schedule. Current Phase II/III trials areexpected to end in late 1992, after which the company willdecide whether to do a Phase III trial or file for marketingapproval.
The San Diego company's vaccine uses a whole killed virusdepleted of the gp120 outer envelope. The company is usingviral burden as its principal end point. The company is alsolooking at changes in T cell counts, antibody levels and othermarkers, as well as changes in clinical outcomes such asopportunistic infections.
Standard clinical end points can include opportunisticinfections, development of AIDS, and patient death or survival.
Surrogate markers have been used as biological/functionalmeasures that anticipate clinical events such as death oropportunistic infections, said Franklin Volvovitz, president ofMicroGeneSys Inc.
Volvovitz on Tuesday told the committee that privately heldMicroGeneSys is considering using CD4 counts as a primary endpoint in its trials. But the Meriden, Conn., company is designingits studies to look at other markers and end points.MicroGeneSys is conducting Phase I and Phase II trials of itsgp160 vaccine. Its p24 vaccine is in Phase I trials.
"We think CD4 is an extraordinarily relevant end point,especially in a Phase I study, where you're not looking forefficacy," said Vincent Simmon, president of Viral TechnologiesInc. Viral, a joint venture of Alpha 1 Biomedicals Inc.(NASDAQ:ALBM) and CelSci Corp. (NASDAQ:CELI), is developinga vaccine based on the p17 core protein. That vaccine is inPhase I trials with HIV-negative individuals.
But Robert Abbott, president of Viagene Inc., applauded thecommittee's recommendation. He told BioWorld that CD4 countwas inappropriate because immunotherapeutics causeproliferation of CD4 cells. He said CD4 is an appropriate markerfor anti-viral drugs such as AZT, which don't stimulate CD4cells.
"There probably were half a dozen products that could havegotten approval based on CD4 counts," Abbott said. "Thecommittee was saying there are only two acceptable endpoints: survival and incidence of opportunistic infections.Ultimately, you need to show a correlation between a clinicalend point and a proposed surrogate marker. It's a leap of faithto assume reducing viral load matters. If you show a reductionof viral load, but the patients all still die, so what?"
San Diego-based Viagene, which is privately held, is using agenetically engineered non-human virus to deliver genes fromthe HIV virus into human cells. Viagene plans to begin Phase Itrials in 1992.
-- Karen Bernstein BioWorld Staff
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