AEGiS-LT: 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.

Important note: Information in this article was accurate in 1990. The state of the art may have changed since the publication date.

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.

Los Angeles Times (LT) - SUNDAY July 8, 1990 Edition: Orange County Edition Section: Business Page: 9 Pt. D Col. 1 Story Type: Sidebar Word Count: 698
Leslie Berkman; Times Staff Writer

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 Drug

GeneLabs Inc. Redwood City, Calif. GLQ223

G.D. Searle & Co. Chicago SC48334

Elan Corp. Atlanta DHEA

Carrington Laboratories Irving, Tex. Carrisyn

Viratek/ICN Pharmaceuticals Costa Mesa Ribavirin

Bristol-Myers Laboratories Wallingford, Conn. DDI (Dideoxyinosine)

Hoffmann-La Roche Nutley, N.J. DDC (Dideoxycytidine)

Matrix Laboratories Fort Lee, N.J. AL 721

Ueno Fine Chemicals Industry New York, N.Y. Dextran sulfate (UAOO1)

Astra Pharmaceuticals Products Westboro, Mass. Foscornet

Triton Biosciences Alameda R-beta-ser Interferon

Wyeth-Ayerst Laboratories Philadelphia AS-101

Bristol-Myers Laboratories Wallingford, Conn. D4T (Didehydrode- oxymidine)

Triton Biosciences Alameda 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

CAPTION: Table: ANTI-AIDS DRUGS UNDER DEVELOPMENT: EXPERIMENTAL ANTI-VIRAL AGENTS Table: ANTI-AIDS DRUGS UNDER DEVELOPMENT: EXPERIMENTAL IMMUNOMODULATING

AGENTS Photo: Ribavirin, marketed as Virazole by ICN Pharmaceuticals, has not yet been approved for treating AIDS patients in the United States. GLENN KOENIG / Los Angeles Times

Keywords: PHARMACEUTICAL INDUSTRY; MEDICAL TREATMENTS; ACQUIRED IMMUNE DEFICIENCY SYNDROME; ICN PHARMACEUTICALS INC; RIBAVIRIN (DRUG); DRUG CERTIFICATION; FOOD AND DRUG ADMINISTRATION (U.S.)

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