FDA Approval of Stavudine (d4T)

Date: June 27, 1994
Source: Food and Drug Administration (FDA)

The Food and Drug Administration today announced the approval of stavudine, or d4T -- the fourth drug approved for the treatment of AIDS and HIV infection.

Stavudine is an antiviral agent of the nucleoside analog class, which includes zidovudine (AZT), didanosine (ddi) and zalcitabine (ddC). Nucleoside analogs are thought to slow the progression of AIDS by inhibiting HIV replication. Data indicate that this class of drugs may delay the onset of AIDS symptoms in HIV-infected individuals, and may extend survival in some.

Stavudine is specifically approved for the treatment of adults with advanced HIV infection who no longer respond to or are intolerant of other antiviral drugs.

This is another sign of our commitment to act quickly on treatments for life threatening diseases," said FDA Commissioner David A. Kessler, M.D. "Stavudine is an important drug because it gives people with AIDS -- and their doctors -- another treatment option, when currently available drugs become less effective."

Data supporting the approval were obtained in an ongoing trial of stavudine versus continued AZT in HIV-infected adults with CD4 cell counts between 50 and 500 and at least 24 weeks of prior AZT treatment. CD4 cell counts reflect the strength of the immune system, and counts in healthy individuals are normally 1,000 or higher. Twelve weeks into the trial with 359 patients, the mean CD4 cell count in patients receiving stavudine increased by 22 cells per milliliter of blood, while the mean count in patients continuing on AZT declined by 22.

Stavudine's major side effect is peripheral neuropathy -- characterized by pain and tingling or numbness in the hands and feet. Between 15 and 21 percent of patients in stavudine trials reported the condition, which appears to be dose-related and can usually be reversed by withdrawal from treatment.

Stavudine was the first drug granted parallel track status by FDA. The parallel track policy allows the agency to make available promising new drugs to patients before approval. Since October 1992, when the drug was granted parallel track status, about 11,000 patients have been enrolled for treatment with stavudine.

The application for stavudine was submitted under FDA's accelerated approval mechanism. Under this mechanism, drug effectiveness is assessed by surrogate rather than clinical endpoints. The major surrogate endpoint in the stavudine trials is CD4 cell counts. In approving stavudine, the agency concluded that the increase in CD4 counts is a likely indicator of a meaningful clinical benefit.

In addition, the rules of accelerated approval require applicants to continue studies to evaluate the true clinical benefit of the drug. If the data fail to verify a clinical benefit, the accelerated approval may be withdrawn.

FDA's Antiviral Drugs Advisory Committee reviewed the stavudine application on May 20, 1994. Based on the data presented the committee felt that the drug is likely to provide clinical benefits to adult AIDS patients with advanced HIV infection who are intolerant of or who deteriorate clinically or immunologically on the other approved antiviral therapies.

Stavudine is manufactured by Bristol-Myers Squibb Co. of New York, N.Y., under the trade name Zerit.

FDA is one of eight Public Health Services agencies in HHS.