Merck’s novel HIV drug Isentress has impressed again in clinical trials by demonstrating its ability to maintain viral suppression and increase CD4 cell counts when combined with other anti-HIV drugs at 48 weeks of therapy.

Forty-eight week data from the Phase III Benchmrk-1 trial, presented at the 15th Conference on Retroviruses and Opportunistic Infections in Boston, USA, showed that a combination of Isentress (raltegravir) and optimised background therapy was able to suppress HIV viral load to under 400 copies/mL in 74% of patients, compared to 36% in the placebo/OBT arm. Furthermore, the drug/OBT regimen boosted CD4 cell counts from baseline by 120 cells/mm3 versus 49 cells/mm3 in the control group.

Commenting on the results, Dr Mark Nelson, Director of HIV Services, Chelsea and Westminster Hospital, London, said: “The 48 week efficacy data are consistent with, if not better than, what we observed at week 24 [and] clearly show that there is a very important place for this integrase inhibitor.”

Isentress is the first in a new class called integrase inhibitors to hit the market on both sides of the Atlantic, and has been cleared for use in combination with other antiretrovirals against HIV-1 infection in adults who continue to exhibit viral replication despite prior therapy.

Unique mode of action
The drug has a unique mode of action in that it targets integrase, one of three enzymes essential for HIV replication. By preventing the action of integrase, which basically inserts the viral DNA into that of the host cell, Isentress affects the ability of the virus to replicate, thereby preventing the infection of other cells.

Analysts believe that Isentress could get its blockbuster badge in a couple of years’ time, and the drug joins Pfizer’s Selzentry (maraviroc), which was also approved last year, on the market. Selzentry is also a first-in-class HIV treatment, which prevents entry of the virus into white blood cells through the CCR5 co-receptor.

Settles drug rebate claims
Meanwhile, Merck has agreed to pay more than $670 million to lay to rest claims that it artificially inflated prices for some of its drugs in the USA, including Mevacor (lovastatin), Vioxx (rofecoxib) and Zocor (simvastatin).

The group said it had reached civil settlements with federal and state authorities to resolve longstanding investigations related to disputes over the proper calculation of Medicaid rebates, as well as improper sales and marketing activities that ended in 2001.

Merck insists that the settlements “do not constitute an admission” of any liability or wrongdoing, but has agreed to pay $250 million plus interest to settle the case in Louisiana, and $399 million plus interest in Pennsylvania, totaling $671 million and marking one of the largest healthcare fraud settlements in history, according to media reports.