Approval of stavudine(D4T)

NEWS 06/27/1994 Approval of stavudine(D4T)
P94-13                            Food and Drug Administration 
FOR IMMEDIATE RELEASE              Arthur Whitmore (301) 443-3285 
 

      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 
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                                      Page 2,  P94-13, Stavudine
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 
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                                Page 3, P94-13, Stavudine
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 Service agencies in HHS.
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