Raltegravir (Isentress) Demonstrates Sustained Viral Suppression through 48 Weeks in Treatment-experienced Patients

By Liz Highleyman

Merck's experimental integrase inhibitor raltegravir (Isentress, formerly MK-0518) continues to demonstrate sustained viral suppression in treatment-experienced HIV patients through 48 weeks, according to a presentation this week at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy in Chicago.

At the 14th Conference on Retroviruses and Opportunistic Infections this past February, researchers presented 24-week data from the BENCHMRK-1 and BENCHMRK-2 studies, identical Phase 3 trials involving highly-treatment experienced patients.

Prior to the BENCHMRK studies, researchers conducted a double-blind Phase 2 dose-ranging trial in which participants were randomly assigned to receive raltegravir at doses of 200, 400, or 600 mg twice daily, or else placebo, plus an optimized background regimen. After the 400 mg dose was chosen for the BENCHMRK studies, all participants in the Phase 2 study were offered open-label raltegravir 400 mg twice-daily after 24 weeks of follow-up.

The data presented in Chicago this week are the 48-week results from 100 participants in the Phase 2 study (including 6 in the original placebo arm) who elected to continue on raltegravir. The 24-week results were published in the April 14, 2007 issue of The Lancet in the April 14, 2007 issue of The Lancet.* In these 2 studies, 65% of patients in the raltegravir arms achieved a viral load below 50 copies/mL, compared with about 35% of those receiving placebo along with an optimized background regimen.

Results

• After 48 weeks, 46%-64% of patients who took raltegravir (depending on the original dose) achieved a viral load below 50 copies/mL.

• 64%-71% had a viral load below 400 copies/mL.

• Among a subset of patients followed for up to 72 weeks, about 70% maintained a viral load below 400 copies/mL.

• CD4 counts increased by a mean 64-110 cells/mm3.

• Treatment outcomes were better among patients who had other active drugs besides raltegravir in their background regimen.

• Overall, at all doses studied, raltegravir was generally well tolerated.

• The most common side effects were nausea, diarrhea, headache, fatigue, and itching.

• 5% of patients discontinued therapy due to adverse events.

• 38% of patients experienced viral rebound during follow-up.

• All but 3 of these patients developed raltegravir resistance mutations.

Discussion

"The findings at 48 weeks are consistent with the 24 week results and what we know to date about the drug's efficacy and tolerability profile," said Jose M. Gatell, MD, PhD, from the University of Barcelona in a press release issued by Merck. "These results reinforce the drug's potential as the first in a promising new class of antiretroviral agents."

Earlier this month, an advisory committee of the US Food and Drug Administration (FDA) unanimously voted in favor of approval of raltegravir. Merck said it anticipates a decision from the full FDA by mid-October.

In the meantime, raltegravir is available through an expanded access program called EARMRK. Currently the program includes more than 5000 patients worldwide. For further information, see www.benchmrk.com.

Isentress articles on HIV and Hepatitis.com


09/21/07

Sources

B Grinsztejn, B Nguyen, C Katlama, and others. 48 week efficacy and safety of MK-0518, a novel HIV-1 integrase inhibitor, in patients with triple-class resistant virus. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, September 17-20, 2007. Abstract H-713.

Merck and Company. ISENTRESS (raltegravir), in Combination with Optimized Background Therapy (OBT), Provided Sustained Viral Suppression in Highly Treatment-Experienced Patients Infected with HIV, through 48 Weeks. Press release. September 18, 2007.

*B Grinsztejn, N Bach-Yen, C Katlama, and others. Safety and efficacy of the HIV-1 integrase inhibitor raltegravir (MK-0518) in treatment-experienced patients with multidrug-resistant virus: a phase II randomized controlled trial. The Lancet 369(9569): 1261-1269. April 14, 2007.