In my latest article I wrote about the three newest drugs we have been blessed with: Intelence, Isentress, and Selzentry. All were approved by the Food and Drug Administration based on 24-week data from clinical trials, which means that enough patients had their viralload reduced to less than 50 after six months that the FDA was willing to approve the drug while more long-term results were collected. So it was reassuring to hear at this year's Conference on Retroviruses and Opportunistic Infections that the 48-week data confirmed their effectiveness.
Selzentry and Isentress were approved in the second half of 2007, and each was the first drug in a totally new class of antiretrovirals. Intelence, approved in January, is a nonnucleoside reverse transcriptase inhibitor, like Sustiva and Viramune, but because it has resistance mutations different from the other nonnukes, it has the potential to have an impact on treatment options that are nearly the same as having another new drug class available.
With Sustiva and Viramune, one single mutation at location K103N causes complete loss of anti-HIV activity by both drugs. Needless to say, K103N is now a common mutation. Intelence, on the other hand, is not affected by K103N. In fact, of the 12 nonnuke-resistant mutations defined by the International AIDS Society, it takes three or more mutations to reduce the effectiveness of this drug. In essence, it can resurrect the nonnucleoside class.
As with Selzentry and Isentress, Intelence was approved based on a trial of three-class-resistant patients who were given an optimized salvage regimen with either Intelence or a placebo. At 48 weeks 61% of the patients on Intelence had undetectable viral loads compared to 40% who were given a placebo. Interestingly, in patients whose salvage regimen contained no other active drug, Intelence by itself got 45% of them to undetectability.
Intelence is dosed as two tablets to be taken twice a day with food. A rash occurred in 17% of patients, mostly between weeks two and four, but only 2% of patients stopped the drug due to the rash. Nausea occurred in 14% of patients versus 11% of patients who were on a placebo (remember these were multidrug salvage regimens that they were being given).
The one issue with this drug is its somewhat complicated metabolism pathways, which limit its combining options. While Intelence can be combined with any nucleoside reverse transcriptase inhibitor, the only protease inhibitors that it can be used with are Invirase or Prezista (each boosted) or with Kaletra. And it cannot be combined with any of the other nonnucleosides.
Despite theses restrictions, we can extend a warm welcome to this newest kid on the block.