POSITIVELY AWARE MARCH/APRIL 2011
rilpivirine (TMC 278)
(brand name not yet established)
common name: unavailable at press time
class: Non-nucleoside reverse transcriptase inhibitor
(non-nucleoside, NNRTI, or non-nuke)
manufacturer: Tibotec Therapeutics | (877) REACH-TT (732-2488),
www.tibotectherapeutics.com
Standard dose: 25 mg once daily with food has been selected in the Phase 3 trials. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose.
AWP: pricing unavailable at press time
Potential side effects and toxicity
When looking at pooled data of the two Phase 3 studies (ECHO and THRIVE), rilpivirine had significant tolerability advantages when compared to Sustiva (efavirenz). There were lower rates of discontinuation due to side effects. The most common side effects of rilpivirine and Sustiva compared in these studies were central nervous system symptoms (17% vs. 38%), psychiatric symptoms (15% vs. 23%), dizziness (8% vs. 26%), abnormal dreams or nightmares (8% vs. 13%), skin rash (3% vs. 14%), and lab abnormalities (11% vs. 18%). Rilpivirine also has a favorable lipid profile when compared to Sustiva. There were minimal increases in LDL (“bad” cholesterol), total cholesterol, and triglycerides. Available data are limited due to experimental drug status.
Potential drug interactions
Can decrease levels of methadone; however, no dosage adjustments are necessary. Careful monitoring is recommended to avoid methadone withdrawal symptoms. Again, available data is limited due to experimental drug status.
More information
Expected to be approved by the FDA in May, 2011, either as a stand-alone medication or in a fixed dose regimen with Truvada (one pill, once-a-day regimen—see rilpivirine/Truvada) as well. On July 23, 2010, Tibotec Therapeutics filed a NDA (new drug application) for rilpivirine to the U.S. FDA based on 48-week data from two Phase 3, double blind, randomized studies called ECHO and THRIVE. The main objective of these studies is to show safety and efficacy in treatment-naïve (first time on treatment) adults. Pooled data from the two studies showed that 1,368 adults were randomized 1:1 into two arms, a rilpivirine arm and a Sustiva arm. Both studies mostly used Truvada as the backbone (100% in ECHO and 60% in THRIVE), but the backbone made no impact in response. The data show that rilpivirine is non-inferior (a term used in scientific research that means the drug is no worse nor better than those it’s compared to) to Sustiva in efficacy—84% vs. 82% of patients achieved viral load of less than 50 copies/ml (undetectable) and CD4 count increases of 190 vs. 172 when comparing rilpivirine and Sustiva arms, respectively. Although individuals were less likely to stop treatment due to side effects, their HIV was more likely to develop drug resistance mutations when compared to Sustiva. A new NRTI resistance mutation was developed by 68% vs. 32% and 63% vs. 54% developed a new NNRTI resistance mutation. Pooled data from the two studies showed 9% virologic failure in the rilpivirine arm when compared to 4.8% in the Sustiva arm. This can be explained by looking at an individual’s baseline viral load and their adherence to medication. With the combination of high viral load and poor adherence, individuals in the study were three times more likely to experience virological failure with rilpivirine when compared to Sustiva. The 25 mg rilpivirine dose was selected because the 75 mg and 150 mg doses studied were associated with a risk of abnormal heart rhythm (prolonged QT interval). Perhaps a 50 mg dose would have been more successful at avoiding the development of drug resistance, including cross-resistance to other medications in this drug class, without increasing toxicity. The greater potential for cross-resistance compared to Sustiva puts rilpivirine at a disadvantage for first-time treatment with an NNRTI, since people may be less likely to switch to another NNRTI if their HIV develops NNRTI resistance mutations with rilpivirine. See package insert, once approved, for complete information on potential side effects and drug interactions.
Doctor’s comments
Rilpivirine is an investigational NNRTI that will be approved this spring if all goes well at the FDA. Although it has activity against NNRTI-resistant virus, it will be approved only for initial therapy. The combination of rilpivirine plus two NRTIs was shown to be better tolerated than Atripla in two large clinical trials. Overall results were similar, but Atripla looked better in people with high viral loads, and there was more virologic failure and resistance in subjects taking rilpivirine. In addition, rilpivirine resistance caused cross-resistance to Intelence, which wasn’t the case with Atripla. Rilpivirine will have clear advantages over Sustiva in terms of side effects, but it may not be the complete replacement we were hoping for. Rilpivirine must be taken with a meal and should not be taken with drugs that reduce stomach acid. —Joel Gallant, MD, MPH
Activist’s comments
Expected to be approved in 2011 for people starting meds for the first time, this non-nuke has proven to be comparable to Sustiva, without the mind-warping side effects. The downside is that it may not be as effective as Sustiva in those with higher viral loads (over 100,000). In addition to not making you crazy, it also doesn’t raise cholesterol and triglycerides like Sustiva can. It’s a small pill, so look to see it used in fixed dose combos with other drugs like Truvada. —Jeff Taylor
