FDA Speeds Up Testing Process for AIDS Drugs : Regulation: Instead of normal four-year minimum, AZT was whisked through in two. The agency is ready to do the same for any others that seem promising.
Responding to a national sense of urgency to find treatments to save the lives of AIDS victims, the Food and Drug Administration has speeded up the process it uses to determine whether a new drug is safe and effective enough to be sold in the United States.
The multistep clinical process that the FDA traditionally has required for gathering and analyzing data from human tests of a drug--which occurs only after that drug has passed animal tests--generally takes four to nine years, said FDA spokesman Bradford Stone. But AZT, the only AIDS-fighting drug yet to receive commercial approval by the FDA, whisked through the process in only two years.
The shortcut marketing approval that the FDA blazed for AZT set a precedent that the agency is willing to repeat for any other drug that shows particular promise for fighting AIDS and other life-threatening conditions, Stone said.
Currently, 85 to 90 new drugs are in clinical testing to prove they are useful in treating AIDS or AIDS-related diseases.
Most new drugs fail to survive the FDA’s rigorous approval process--only 20% of all drugs that begin the process make the final grade. But the stakes make the gamble worthwhile since FDA approval gives a company the right to sell its drug in the United States, by far the most lucrative pharmaceutical market in the world.
The process begins when the drug manufacturer applies to the federal agency for what is called an “investigational new drug application.” Within 30 days the FDA decides if the results of prior animal testing indicate that the drug is safe enough and has enough potential to warrant testing it on humans. Also, the agency determines if the manufacturer has a scientifically acceptable plan for such clinical tests.
If the FDA gives a go-ahead, the manufacturer starts treating a small group of people--between 20 and 100--to gather more information about the experimental drug’s toxicity and determine the maximum dose at which it can be tolerated.
About 70% of the drugs are given approval to go on to the next step, the first controlled test of a drug’s effectiveness. The group of patients involved is expanded, usually to between 200 and 300, some of whom are treated with the new drug and some of whom receive a placebo or an established remedy. This testing typically takes five months to two years to complete.
Only 33% of the drugs that begin the FDA approval process show enough promise to make the grade for the third testing phase. This step may involve 400 to 3,000 patients and take from one to four years. Its purpose is to more precisely determine the drug’s effectiveness and any harmful side effects that might develop from its long-term use.
For the survivors--about 25% to 30% of drugs entering the approval process--their manufacturers may make “a new drug application” to the FDA. The application is reviewed by a panel of medical experts, which makes a recommendation to allow marketing or not.
If rejected, the company may conduct additional tests in hopes that the results will persuade the panel to change its mind.
The whole process can be drastically shortened at the FDA’s discretion, as in the case of AZT.
Stone said Burroughs Wellcome, the drug’s manufacturer, submitted an investigative new drug application in May, 1985.
The company began its initial tests that July and moved on to the second round of tests in February, 1986.
He said phase-two clinical testing was cut short in September of 1986 by an FDA monitoring board that looked at the data gathered to date and concluded that the results were so promising that it was determined--because of the great public need--that the drug should be allowed on the market as further testing continued.
Within about a week, Stone said, the FDA gave Burroughs Wellcome permission to distribute the drug to patients dying from AIDS. The company obtained full marketing approval in March, 1987.
ANTI-AIDS DRUGS UNDER DEVELOPMENT
Dozens of compounds are being tested in the battle to find an effective treatment or cure for AIDS. The drugs listed below are in various stages of human clinical trials.
EXPERIMENTAL ANTI-VIRAL AGENTS
Company Headquarters GeneLabs Inc. Redwood City, Calif. G.D. Searle & Co. Chicago Elan Corp. Atlanta Carrington Laboratories Irving, Tex. Viratek/ICN Pharmaceuticals Costa Mesa Bristol-Myers Laboratories Wallingford, Conn. Hoffmann-La Roche Nutley, N.J. Matrix Laboratories Fort Lee, N.J. Ueno Fine Chemicals Industry New York, N.Y. Astra Pharmaceuticals Products Westboro, Mass. Triton Biosciences Alameda Wyeth-Ayerst Laboratories Philadelphia Bristol-Myers Laboratories Wallingford, Conn. Triton Biosciences Alameda
Company Drug GeneLabs Inc. GLQ223 G.D. Searle & Co. SC48334 Elan Corp. DHEA Carrington Laboratories Carrisyn Viratek/ICN Pharmaceuticals Ribavirin Bristol-Myers Laboratories DDI (Dideoxyinosine) Hoffmann-La Roche DDC (Dideoxycytidine) Matrix Laboratories AL 721 Ueno Fine Chemicals Industry Dextran sulfate (UAOO1) Astra Pharmaceuticals Products Foscornet Triton Biosciences R-beta-ser Interferon Wyeth-Ayerst Laboratories AS-101 Bristol-Myers Laboratories D4T (Didehydrode- oxymidine) Triton Biosciences Azdu (Azidouridine)
EXPERIMENTAL IMMUNOMODULATING AGENTS
Company Headquarters Drug MicroGeneSys Inc. West Haven, Conn. VaxSyn HIV-I Merieux Institute Miami DTC (Imuthiol) Immunobiology Research Inst. Annandale, N.J. Thymopentin National Inst. of Mental Health Bethesda, Md. Peptide-T Newport Pharmaceuticals Newport Beach Isoprinosine Hoffmann-La Roche Inc. Nutley, N.J. Alpha interferon Schering-Plough Corp. Kenilworth, N.J. Alpha interferon Genentech Inc. San Francisco Gamma interferon Genentech Inc. San Francisco CD4 Protein Biogen, Inc. Cambridge, Mass. CD4 Protein Hoffman-La Roche Inc. Nutley, N.J. Interleukin-II Sandoz Pharmaceuticals Corp. East Hanover, N.J. R-GM-Colony stimulating factor Schering-Plough Corp. Kenilworth, N.J. R-GM-Colony stimulating factor Amgen Thousand Oaks R-Granulocyte Colony stimulating factor Ortho Pharmaceutical Corp. Raritan, N.J. R-erythropoietin Amgen Thousand Oaks R-erythropoietin Immunization Products Ltd. Seattle Salk HIV Immunogen
Source: U.S. Food and Drug Administration
