Coverage of 2007 ICAAC
(Interscience Conference on Antimicrobial Agents and Chemotherapy)

September 17–20, 2007, Chicago, Illinois

Early study results of etravirine showing promise

September 18, 2007

Results from a pivotal study of the experimental non-nucleoside reverse transcriptase inhibitor (NNRTI) etravirine (TMC-125) were presented at the 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) being held in Chicago. The study found etravirine to be effective and well tolerated. Etravirine is being developed by Tibotec Therapeutics as a second generation NNRTI for people with resistance to the other NNRTIs, like Sustiva (efavirenz) and Viramune (nevirapine).

The combined results from two studies, called DUET 1 and 2, were presented. In these studies, people with documented resistance to the current NNRTIs, as well as 3 or more mutations from protease inhibitors (PI) were randomly assigned to take either etravirine or placebo. Everyone also took an optimized background therapy of the PI Prezista (darunavir) boosted with Norvir (ritonavir) and the best available NRTIs. Volunteers were able to use Fuzeon (enfuvirtide, T20) if they chose to.

The people who enrolled in the study (over 1,200 in all) were highly treatment experienced. Two-thirds of them had taken 10–15 anti-HIV drugs before the study. Nearly half had no more than one active drug available to them, as determined by phenotypic resistance testing. The participants were mostly male (90%) and Caucasian (70%).

After 24 weeks of the study which will last 48 weeks, 59% of people taking etravirine had HIV levels below 50 copies compared to 41% on placebo. The difference was larger for people with fewer available drugs. When one drug was available, 60% of people on etravirine had viral loads below 50 vs. 30% on placebo. When resistance testing showed no active drugs, 45% of people on etravirine had undetectable HIV levels, compared to only 8% on placebo. CD4 cell counts increased more (86 vs. 67 cells/mL) for people taking etravirine as well.

People taking etravirine averaged a drop in HIV levels of 2.4 logs (over 99%) vs. 1.7 logs (around 96%) reduction for placebo. Viral loads were reduced the most in people with fewer NNRTI mutations. Between 60–75% of people with two or fewer NNRTI mutations had HIV levels below 50 copies, compared to 25–48% for placebo. A significant drop-off occurred for people with 3 or more mutations, with 25–41% of people taking etravirine reaching HIV levels below 50 copies vs. 17–25% on placebo.

The major side effect for etravirine was rash, which occurred in 17% of people. The rash most often started within the first two weeks of treatment and lasted about 11 days. Most rashes were mild to moderate, with only 1.3% considered serious. Only 2.2% of people stopped treatment due to rash. Rash was more common in women (although the number of women was small), and there was no connection seen between pre-treatment CD4 cell counts or history of NNRTI rash.

Etravirine is currently available to people who need it to construct a viable regimen through an expanded access program. Physicians can find out more by calling 1-866-889-2074 or by emailing the program. The drug is likely to be approved early in 2008.

These are encouraging results for a much needed drug. The NNRTI class has been hampered by the high degree of cross resistance among the drugs. In most cases, when someone develops resistance to one NNRTI, their HIV is also resistant to the others. Etravirine was designed to overcome this resistance. It could provide an important option for people who don’t have any options for NNRTIs.