In the news ... 2007

FDA committee recommends first integrase inhibitor

September 7, 2007

An anti-viral advisory committee of the Food and Drug Administration (FDA) has recommended accelerated approval of Isentress (raltegravir)—the first-ever integrase inhibitor (II)—for people with extensive experience taking HIV drugs. Although the FDA isn’t required to follow the recommendations of the advisory panel, it almost always does.

This recommendation was expected. The results from two pivotal trials, named BENCHMRK 1 and 2, were impressive. These studies used a common design for drugs studied in highly treatment experienced people who had developed resistance to three classes of anti-HIV drugs. Everyone in the study was given optimized background therapy (OBT)—the best available combination of anti-HIV drugs based on resistance testing, treatment history and other factors. People were randomly chosen to add either Isentress or a placebo to their OBT.

In one study, after 48 weeks, 54% of people taking Isentress had HIV levels below 50 copies, compared to just 9% of people taking the placebo. HIV levels were reduced an average of over 1.5 logs (97%) for people taking Isentress vs. .28 log (47%) for people taking the placebo.

With any new drug, safety is of utmost importance. More people taking Isentress experienced a rash than those taking placebo. Other side affects associated with Isentress were headache, diarrhea and nausea, which were generally mild to moderate and rarely led people to stop taking their treatment.

There was some concern in the early months of the study about higher rates of cancer seen in people taking Isentress compared to placebo. The FDA found this was likely due to people taking Isentress for longer than the placebo (people were able to switch from placebo to open-label Isentress after 24 weeks). Others believed that it was due to a temporary, unusually low incidence of cancer in the placebo group, which changed in longer term follow-up. No advisors to the company or the FDA believed that there was evidence suggesting the effect was due to the drug. Still, activists and regulators will watch carefully for this when the drug becomes more widely available.

Isentress is the first successfully developed drug to target the integrase enzyme, which allows HIV to combine its genetic code with human DNA. The studies used for the approval of Isentress were in heavily treatment experienced people, with documented resistance to many HIV drugs. Studies continue in people taking HIV drugs for the first time.

It is critical to recognize that Isentress works best when combined with at least one, and even better with two, new active drugs. This should be possible for a great majority of people, due to the recent approval of Selzentry (maraviroc), last year’s introduction of Prezista (darunavir), and the anticipated approval of etravirine (TMC-125) in early 2008. This represents a moment of great hope and opportunity for people with drug-resistant HIV. The importance of combining Isentress with other active drugs cannot be overemphasized. It would be a horrible mistake for people with highly resistant virus to waste this opportunity by using Isentress alone or merely adding it to a failing regimen. The proper way to use the drug is to combine it in a new regimen with other active drugs.

Project Inform welcomes the FDA advisory committee’s recommendation for accelerated approval of Isentress, and calls for the FDA to quickly follow the recommendations of the committee. The FDA is expected to issue a formal ruling on Isentress sometime in October, though an earlier ruling is also possible.

Along with our partners in the Fair Pricing Coalition, Project Inform is working on the price of this drug with Merck (the developer of Isentress) to ensure the widest possible access to this vitally important new option for treating drug-resistant HIV.