Accelerated approval for Etravirine granted by FDA

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Dear Forum,

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 s- 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.

Based on News from FDA

Dr Diwakar Tejaswi

Patna

+91-9835078298

e-mail: <diwakartejaswi@...>