NIAID's clinical trial ACTG 241 was central to Nevirapine FDA approval

[James Love <love@cptech.org>]

According to a 1996 NIH press release, Nevirapine's approval was based
upon NIAID funded research.


        "Central to the FDA's approval 
        of nevirapine was the NIAID clinical 
        trial ACTG 241, a study of nearly 400 
        patients with advanced HIV infection 
        who had received extensive treatment 
        with nucleoside analogs."

<------------------NIAID's 1996 release-------------------->

http://www.niaid.nih.gov/publications/agenda/0996/page9.htm


    September 1996 

Nevirapine Approved by FDA
First non-nucleoside reverse transcriptase inhibitor

  In June, nevirapine became the ninth drug approved by the Food and
Drug Administration (FDA) for the treatment of people with HIV
infection. The first in a new class of antiretroviral drugs known as
non-nucleoside reverse transcriptase inhibitors (NNRTIs), nevirapine
will be marketed under the name Viramune by Boehringer Ingleheim
Pharmaceuticals, Inc. As their name implies, NNRTIs inactivate reverse
transcriptase, the same HIV enzyme targeted by the nucleoside analog
drugs AZT, ddI, ddC, d4T
and 3TC. NNRTIs and nucleoside analogs attack the enzyme at different
locations, however. 

Central to the FDA's approval of nevirapine was the NIAID clinical trial
ACTG 241, a study of nearly 400 patients with advanced HIV infection who
had received extensive treatment with nucleoside analogs. ACTG 241
showed that nevirapine, combined with AZT and ddI, was significantly
better than the combination of AZT and ddI at reducing viral load and
increasing CD4+ T cell counts in these patients. A second study
conducted by the drug's manufacturer showed that the same three-drug
combination also was significantly better than AZT and ddI for
HIV-infected patients who had received no prior treatment. 

The new drug further expands the treatment options available to
individuals infected with HIV. In combination with nucleoside analogs,
nevirapine could be used as a first-line therapy or as an alternative
treatment for patients who either show no improvement with other drugs
or experience adverse reactions to them, says Steven M. Schnittman,
M.D., assistant director for clinical research in NIAID's Division of
AIDS. 

"Some individuals, for example, can't tolerate the new protease
inhibitors," says Dr. Schnittman. "For those patients, it may turn out
that a regimen of two nucleosides combined with nevirapine provides
anti-HIV activity reasonably close to that seen with protease
inhibitors." Dr. Schnittman adds that the additional combination therapy
regimens made possible by nevirapine could help physicians devise better
strategies for avoiding drug resistance. 

Another attractive aspect of nevirapine is its long half-life--the time
it takes for half of a given dose to be eliminated from the body.
Nevirapine remains active much longer than other antiretrovirals and
thus can be administered less frequently. Dr. Schnittman says
nevirapine's long half-life suggests that it might be useful in
strategies for preventing mother-to-infant HIV transmission by reducing
the amount of virus in a womans blood before she gives birth.
NIAID-supported clinical trials are under way in which HIV-infected
pregnant women are given a dose of nevirapine when they arrive at the
hospital in labor. 

"The drug is highly active and should remain in the woman's blood, and
hopefully the infant's as well, throughout the perinatal period," says
Dr. Schnittman. "Although HIV quickly develops resistance to nevirapine
when it is administered alone, that should not be a concern in perinatal
settings, where the drug will only be given for a day or two." 

--John Bowersox
--