TMC278 (Rilpivirine) Stands Up to Efavirenz in Battle of First-Line NNRTIs; FDA Approval May Be Drawing Near
Myles is the editorial director of TheBody.com and TheBodyPRO.com.
The NNRTI efavirenz (EFV, Sustiva, Stocrin) is one of the most popular first-line HIV medications, but its risk of associated neurological side effects sometimes leaves people seeking other options. An NNRTI in late-stage development, TMC278 (rilpivirine), appears firmly set on offering treatment-naive people a viable alternative.
It's too soon to predict whether TMC278 will succeed in that goal. But research presented at AIDS 2010 appears to support this young upstart's progress toward U.S. Food and Drug Administration (FDA) approval, perhaps within the next several months.
- A pair of nearly identical studies (ECHO and THRIVE) found that TMC278, when taken as part of a first-line treatment regimen that also included two nucleoside reverse transcriptase inhibitors (NRTIs), was "non-inferior" to (i.e., at least as effective as) efavirenz plus two NRTIs.
- The percentage of people who reached an undetectable viral load was similarly high between the two regimens (82% to 84%) through 48 weeks of study.
- TMC278 was more likely to fail to suppress HIV replication than efavirenz (9% versus 4.8%). The reasons for this were unclear at the time of the presentation, though it was noted that TMC278 appeared to lose some of its effectiveness among people with a viral load above 100,000 copies/mL.
- On the flip side, TMC278 was significantly less likely to cause some of the mind-warping side effects that are sometimes associated with efavirenz. It appeared to be more lipid-friendly as well, causing fewer increases in cholesterol, triglycerides and alanine aminotransferase (ALT) levels than efavirenz.
- Taken together, the viral suppression and side-effect issues appeared to pretty much balance out. People were more likely to stop taking TMC278 because it wasn't effective enough, but people were more likely to stop taking efavirenz because of the side effects. Taken together, the number of treatment discontinuations was very similar for each of the two antiretrovirals.
- Late-stage clinical study will continue on TMC278; the studies presented at AIDS 2010 will ultimately follow volunteers for 96 weeks.
- TMC278 is also being developed as part of a one-pill, once-a-day regimen in which it's combined with Truvada (TDF/FTC, tenofovir/emtricitabine). That puts Atripla (EFV/TDF/FTC, efavirenz/tenofovir/emtricitabine) -- the only one-pill, once-a-day option currently on the market -- squarely in its crosshairs. In fact, the TMC278-plus-Truvada combination is commonly referred to as "Btripla."
- Within days of the AIDS 2010 presentation, the company developing TMC278 submitted a formal "new drug application" to the FDA seeking the agency's approval to sell the drug as part of an antiretroviral regimen in HIV treatment-naive people. The last new HIV medication approved by the FDA, the NNRTI etravirine (TMC125, Intelence), was approved six months after its new drug application was submitted in mid-2007. FDA approvals for new HIV medications generally come anywhere from a few months to a year after a new drug application is submitted -- assuming the drug actually gets approved, that is.
For a more detailed breakdown of the ECHO and THRIVE 48-week results, take a look at the abstract of the AIDS 2010 presentation by Cal Cohen, M.D., or read Mark Mascolini's lovely recap of the study details at NATAP.org. We also hope to add the slides from Cohen's presentation to this page soon.
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