FDA Grants Accelerated Approval for 3TC with AZT to Treat AIDS

Date: November 20, 1995
Source: Food and Drug Administration (FDA)

The Food and Drug Administration today announced its accelerated approval for the drug lamivudine, or 3TC, for use in combination with AZT (zidovudine) in treating AIDS and HIV infection.

AZT and 3TC are members of the nucleoside analogue class of drug compounds, and both interfere with the replication of HIV, the virus that causes AIDS.

Food and Drug Commissioner David A. Kessler, M.D., said the 3TC/AZT approval is the latest example of the agency's accelerated review of drugs for HIV infection. All currently marketed drugs for treating HIV underwent such fast-track review and approval. The 3TC review was accomplished in four-and-a-half months.

Of the five drugs now approved for the treatment of AIDS, three were first approved for use in the United States," Kessler said. "We remain committed to accelerated approval as seen by the review of 3TC. At he same time, we have much to learn about the most effective combination therapies and we are equally committed to getting the answers through the required post-marketing studies."

Accelerated approval is a regulatory mechanisms which allows FDA to grant early marketing status for a product based on laboratory markers such as CD4 cell counts (a reflection of immune system strength) rather than on clinical endpoints such as delay in death or reduction in opportunistic infections. Clinical benefit must eventually be demonstrated the clinical benefit of the 3TC/AZT treatment regimen are currently ongoing.

The 3TC/AZT approval was based on data form four clinical trials enrolling approximately 1,000 HIV-infected adults who received either the combined 3TC/AZT therapy, 3TC as a single therapy, AZT as a single therapy, or AZT and ddC (Roche Co.'s anti-AIDS nucleoside analogue, which received accelerated approval in 1992).

The trials showed that patients treated with the 3TC/AZT combination sustained higher increases of CD4 cells than patients on the other three regimens. On average, CD4 cell counts in patients on the 3TC/AZT combination increased by 30 to 50 cells above the levels at the start of the 24-week trials.

Adverse events were similar to those associated with other nucleoside analogue drugs: nausea, diarrhea, anemia, low white blood cells, pancreatitis (especially in children who had received prior nucleoside analogue therapy) and neuropathy. Some of the more severe adverse reactions required withdrawal from therapy.

3TC has been studied in humans since April 1991. Since October 1993, the drug has been available to patients outside of controlled clinical trials under an open-labeled protocol. More than 35,000 patients have received the drug under this expanded program, which allows access to promising drugs for serious diseases prior to marketing approval.

3TC and AZT are manufactured by Glaxo-Wellcome Inc. of Research Triangle Park, N.C. The registered trade name for 3TC is Epivir; for AZT, Retrovir.

Information on ongoing clinical trials on drugs for HIV infection may be obtained from the Public Health Service's AIDS Clinical Trial Information Service (ACTIS) at 1-800- TRIALS-A.