BETHESDA, Md. -- The Vaccines and Related Biological Productsadvisory committee unanimously recommended Tuesday thatthe Food and Drug Administration not use CD4 cell counts as aprimary end point in clinical studies of AIDS therapeutics.
CD4 receptors on T cells are the primary target of HIV 1, and adecrease in the number of T cells with CD4 receptors gives anearly indication that a patient may develop AIDS.
The committee unanimously recommended that some clinicalend point be made primary studies of therapeutic vaccines totreat patients with early HIV infection, rather than acceptchanges in the CD4 count as a surrogate marker.
Clinical end points can include opportunistic infections,development of AIDS, and patient death or survival.
Investor anticipation that the committee would recommend infavor of surrogates last week helped push up the stock ofImmune Response Corp. (NASDAQ:IMNR), one of the companiesthat participated in the meeting here. The FDA recentlyexpedited approval of the AIDS drug ddI, basing the decisionon an increase in the number of T cells.
However, Dr. Herbert Slade, clinical project director ofImmunization Products Ltd., a joint venture of ImmuneResponse and Rhone-Poulenc Rorer Inc., told the committeethat "you shouldn't rely on surrogate markers" to prove theefficacy of a vaccine.
"Exactly what those end points would be is something thatwould require more careful thought than we could give it now,"said acting chairman Dr. Richard Johnston Jr., professor ofpediatrics at the University of Pennsylvania's school ofmedicine.
Committee members stressed that more study is neededbecause CD4 surrogate markers are a "novel biologic concept"and a therapeutic HIV vaccine is a "novel mechanism."
Members called for shorter clinical trials to speed thedevelopment of a vaccine. They said that this could beaccomplished by a variety of methods, including increasing thenumber of patients in trials and studying children afflicted bythe virus.
If Genentech Inc. were allowed to use CD4 counts as a primaryend point, Phase II/III study of its rgp120 HIV1 vaccine inthree groups of 300 patients could be completed within threeyears, said Dr. Arthur Armman, company director of clinicalresearch. Otherwise, Genentech could complete a study usingclinical end points in just three years, instead of the normalseven, by increasing the study size to three groups of between2,275 and 4,200 patients.
MicroGeneSys Inc., which is in Phase I trials of a therapeuticHIV vaccine, presented plans for a Phase II/III trial that wouldinclude CD4 count as a marker.
The committee members also suggested that candidatesurrogate markers continue to be used with clinical end pointsto increase the chances of discovery of surrogates that could beused as a primary end point.111391CD4
-- Kris Herbst BioWorld Washington Bureau
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