May 26, 2011
Table of Contents
Ah, there's nothing like the smell of a fresh antiretroviral in the morning. It's been more than three years since we've gotten a whiff of that lovely scent here on the HIV treatment ranch: The last HIV medication approved in the U.S. was the non-nucleoside reverse transcriptase inhibitor (NNRTI) Intelence (etravirine, TMC125), back in January 2008.
Now we have another NNRTI: The U.S. Food and Drug Administration (FDA) approved Edurant (rilpivirine, originally known as TMC278) on May 20, and it should hit U.S. pharmacies sometime next month, according to the drug's manufacturer, Tibotec.
Unlike Intelence, which was approved for use in people who had developed resistance to other HIV medications -- particularly those within the NNRTI class, such as Sustiva [efavirenz, Stocrin] and Viramune [nevirapine] -- Edurant was approved as a first-line treatment option. (This AIDSinfo fact sheet provides much more info on the basics of Edurant, including dosing and side effects.)
We wanted to delve more deeply into Edurant's approval, what makes the drug unique, what side effects and other concerns people should watch out for, and how the introduction of Edurant may change the answer to the question, "What should I start HIV treatment with?" So we spoke to one of the people most qualified to answer those questions: Cal Cohen, M.D., a prominent HIV clinician-researcher who was the lead investigator for the clinical trials that led to Edurant's approval.
Incidentally, as Dr. Cohen and a Tibotec representative both confirmed, the correct pronunciation of Edurant is EE-der-int, and the generic name, rilpivirine, is pronounced rill-PIHV-er-in.
[Disclosure: Dr. Cohen conducts research on behalf of and consults on the advisory board for Tibotec Therapeutics, as well as for Bristol-Myers Squibb Company, Gilead Sciences Inc., and Roche. However, Dr. Cohen notes he has not received compensation from Tibotec for his role as lead investigator of the ECHO and THRIVE studies that led to Edurant's FDA approval.]
What makes Edurant different from the other 30 HIV pills and combo drugs that have been approved by the FDA?
One reason this drug is distinct is that it went up head-to-head against efavirenz, which is amongst the drugs that have always performed the best in terms of establishing virologic suppression. Edurant, in combination with two nucleosides, allowed patients to get their viral load controlled at a rate that, looking at the entire population, was similar to patients on efavirenz -- and it did so with fewer side effects.
That, of course, is the combination we all want: a simple, once-daily combination that will get your viral load controlled with as few side effects as possible. That's the constant search; that's why we look for new drugs. And Edurant provided many of these attributes in these studies.
What are we talking about in terms of the efficacy numbers when they were comparing Edurant against Sustiva?
In the overall analysis, in terms of getting the viral load controlled, the percentage of volunteers who reached an undetectable viral load on Edurant was 83 percent, versus 80 percent for those taking Sustiva.
You mentioned that Edurant appears to be more tolerable than Sustiva. In what way? How do the side effects compare?
For me, one of the easiest ways to summarize the fact that there were fewer side effects is to look at how often people stopped participating in the study due to adverse events, due to side effects, at the end of one year. Because, I think, while people might have a side effect for a week or two and then it goes away, it's a bigger deal for somebody to say, "I've tried this, I've tried it a while more, and it's just not good enough. I can't do this. I have to leave your study." That's a bigger thing.
One of the more striking findings in the study is that only 2 percent of people on Edurant stopped study participation. But in contrast, 8 percent on efavirenz did so, if I have the numbers exact. To me, that's an important thing, because I think what we're all looking for is a combination that allows me to say to somebody, "If you take this, the odds that you're gonna tell me you don't want to stay on this medicine anymore due to side effects is amongst the lowest we have in our field." And that's a pretty reassuring start.
Is that one of the reasons why this was approved for first-line therapy, because of the low toxicity, as opposed to an attempt to develop it as a more treatment-experienced option?
The studies were only done in treatment-naive patients, or patients just starting therapy for their first time, so the label is limited to that because those are the only populations that were studied for this drug. I think there are many reasons for that, including: These days, most people -- though not everybody, most people -- who start on a combination can, with either the first or second combination, stay on that regimen for hopefully the rest of their lives, and certainly our studies are pretty reassuring [that this can be the case].
As a result, there really aren't a lot of people in search of rescue regimens. And as a result [of that], a lot of the emphasis in clinical trials these days is to find the best way to start, because if you do that, odds are good you'll be able to stay on that from now on.