The Food and Drug Administration
(FDA), on January 18, 2007, granted accelerated approval for
etravirine 100 mg tablets, a
non-nucleoside reverse transcriptase inhibitor (NNRTI), an
antiviral drug that helps to block reverse transcriptase, an
enzyme necessary for HIV virus replication. It is the first
NNRTI to demonstrate antiviral activity in patients with
NNRTI-resistant virus. Etravirine will be sold under the trade
name Intelence.
Etravirine is indicated for use in combination with other
antiretroviral agents for the treatment of human
immunodeficiency virus type 1 (HIV -1) infection in
antiretroviral treatment-experienced adult patients who have
evidence of viral replication and HIV-1 strains resistant to a
non-nucleoside reverse transcriptase inhibitor (NNRTI) and other
antiretroviral agents.
Accelerated approval is a regulatory mechanism that allows
earlier approval of drugs used to treat serious or
life-threatening conditions, based on surrogate endpoints that
demonstrate meaningful therapeutic advantage over existing
treatment. Accelerated approval is based on evidence of a
drug's effect on a surrogate endpoint that reasonably suggests
clinical benefit. Accelerated approval requires any necessary
studies to establish and define the degree of clinical benefit
to patients be completed before traditional approval can be
granted.
FDA granted this accelerated approval based on 24 week viral load and CD4
data from 1,203 adults in two randomized, double-blind,
placebo-controlled trials (DUET-1 and -2 studies) conducted in
clinically advanced, antiretroviral treatment-experienced adults
with evidence of resistance to NNRTI(s) and protease inhibitors
(PIs). The studies compared 599 patients receiving etravirine
200 mg twice daily plus optimized background regimen with 604
patients receiving optimized background regimen plus placebo.
All patients received darunavir/rtv (DRV/rtv) as part of their
optimized background regimen.
The 24 week pooled analysis of the DUET studies showed
significantly more patients in the etravirine arm as compared to
the placebo arm achieved undetectable viral load (less than 50
copies/mL); 59.8 percent vs. 40.2 percent (p<0.0001), and
significantly greater mean increase in CD4+ cell count from
baseline of 81 vs. 64 cells/mm3 (p<0.0022).
The most common adverse events reported were rash (16.9 percent)
and nausea (13.9 percent).
In general, rash was mild to moderate, occurred primarily in the
second week of therapy, and was infrequent after Week 4. Rash
generally resolved within 1-2 weeks on continued therapy.
Patients developing a rash while taking etravirine should
contact their doctor.
Rare cases of serious skin reactions such as Stevens-Johnson
syndrome and erythema multiforme have been reported. Treatment
with etravirine should be discontinued if severe rash develops.
Elevations in total cholesterol and low density lipoprotein (LDL)
and initiation of lipid lowering therapy were more common in
etravirine-treated subjects compared with those in the placebo
arm.
Etravirine should be used with caution in patients with severe
hepatic impairment (Child-Pugh class C) as pharmacokinetics of
etravirine have not been studied in these patients.
To avoid drug interactions, patients starting etravirine
treatment should tell their doctors about all the medications
they take. Information about drug interactions is contained in
the etravirine package insert.
The long-term effects of etravirine are not known, and its
safety and effectiveness in children ages 16 years and younger
has not been studied.
Etravirine also has not been studied in pregnant women. Women who are
taking HIV medications when they get pregnant are advised to
consult their physician or other health care professional about
use of etravirine during pregnancy and about registering with
the Antiviral Pregnancy Registry.
Etravirine is distributed by Tibotec Therapeutics, Bridgewater,
N.J., a division of Ortho Biotech Products, L.P.
Richard Klein
HIV/AIDS Program Director
Food and Drug Administration
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