BOSTON -- A controversial drug appears to delay the onset of AIDS in those infected with the disease-causing virus, scientists said, but federal regulators said there is not enough evidence to support the claim.
A study conducted in Denmark and Sweden found that only two of 429 people infected with the human immunodeficiency virus (HIV) who were given the drug Isoprinosine daily showed AIDS symptoms after 24 weeks, compared wit 17 of 437 given a worthless substitute.
Researchers at the University of Copenhagen who conducted the study said it suggests that the drug, manufactured by Newport Pharmaceuticals International Inc. and known generically as inosine pranobex, can delay the development of fully developed AIDS in those with HIV.
The results of the study were to be published Wednesday in the New England Journal of Medicine. In an accompanying editorial, officials of the Food and Drug Administration sharply criticized the study, saying that more research is needed before claims for the drug can be accepted by the scientific or medical communities or the FDA.
Judy Archbold, a spokeswoman for Newport Pharmaceuticals in Laguna Hills, Calif., said the drug enhances the body's natural immune response to infections. It is approved and marketed outside the United States to treat a variety of non-AIDS disorders, such as herpes simplex, genital warts and viral hepatitis, but has not been approved by the FDA for these diseases or for AIDS.
Currently, the only FDA-approved drug for AIDS is AZT or zidovudine, manufactured by the Burroughs-Wellcome Co. of Research Triangle Park, N.C.
Newport officials said in 1986 that in studies involving a small number of HIV patients, Isoprinosine treatment had restored their basic immune deficiency and slowed their progression to AIDS. Company officials implied at that time that the FDA was not moving fast enough to approve the drug for AIDS treatment.
The FDA responded by accusing the company of making 'public misstatements' and suggesting that promotion of unfounded 'therapeutic' claims could violate federal law.
Since then, the company has not submitted data based on clinical studies that the agency requires to consider licensing the drug for use against AIDS or other disorders, FDA spokesman Brad Stone said.
In the new Swedish-Danish study, researchers speculated that Isoprinosine slowed the development of AIDS in some of the HIV patients in the study by bolstering their immune systems through enhanced production of key disease-fighting cells known as T4 helper cells.
But in an aspect of the study that critics found puzzling, the Copenhagen researchers said they found no evidence that Isoprinosine was able to increase the number of CD4 cells in the patients. CD4 cells are the most abundant of T-cells, and their numbers are a key indicator of the comparative strength of a person's immune system.
In the editorial, Dr. Ellen Cooper, director of the FDA's Division of Antiviral Drug Products, and FDA researchers Dr. Sandra Kweder and Dr. Robert Schnur, cited the lack of increased CD4 cell production as one of the question marks surrounding the study.
They said although it is possible that Isoprinosine may delay the development of AIDS without affecting 'other clinical manifestations or laboratory markers of disease progression, the lack of additional evidence of the drug's activity is disconcerting' in light of what is known about the natural history of HIV infection.
The editorial also noted that a multicenter trial of the drug sponsored by Newport Pharmaceuticals and involving 696 male HIV patients in Great Britain and the United States showed no benefit for those who received Isoprinosine daily for six months compared with those who were given an inactive substitute.
Archbold said the company is now 'trying to figure out why the results of the two studies were different.' She also said that the firm now has 'a good relationship with the FDA. We understand that they are raising provocative questions and that they need to see more studies.'
She said the company cannot afford to do the extensive further research required by the FDA unless it gets funding from the National Institutes of Health, or some other source.
Dr. Paul Skolnik, director of the AIDS laboratory at the New England Medical Center in Boston, said from a treatment standpoint, 'it is hard to know whatto make' of the new study. He said that past reports on Isoprinosine as an AIDS treatment 'really have not been impressive. It is surprising that this large study did show an effect.'
Nevertheless, Skolnik called the results 'statistically significant.' But he said additional confirmatory studies now need to be done. Until such research is carried out, the FDA officials said, the drug 'will remain in scientific and regulatory limbo.'
