Incivek (Telaprevir) in HIV/HCV-Coinfected Patients: A Look at Recent Research
What a great year 2011 was for news about hepatitis C virus treatment! The last major meeting of the year featuring hepatitis research, the American Association for the Study of Liver Diseases (AASLD) meeting (referred to as the "Liver Meeting"), was filled with breathtaking data on what promises to be an amazing pipeline of new HCV drugs.
When I think back to the development of drugs for HIV, several years would pass between the release of one drug and the next. Also, in the beginning of the HIV treatment era, we had several drugs for HIV, but they were all within the same class (like the nucleoside analogs) until other drug classes came along. That is why it is truly stunning to see so many new drugs being developed for HCV -- and multiple new drugs within a variety of classes, such as polymerase inhibitors, protease inhibitors, cyclophillin inhibitors and others. More than two dozen drugs are in various stages of development.
These new developments deserve some special attention. I'll present new data on these medications, as well as other research and important developments in hepatitis, in this blog. Each time I post a new blog entry, I'll also explain some of the clinical terms researchers use when discussing these new treatments and developments.
I'll start in this blog entry with the latest data on Incivek (telaprevir), one of two new drugs which were approved in 2011 by U.S. and European agencies for the treatment of patients with HCV alone. (The other is Victrelis, or boceprevir; I'll discuss that in my next blog entry.) Incivek is a protease inhibitor that specifically targets one part of the virus's life cycle. Incivek is used in combination with pegylated interferon (PEG) and ribavirin (RBV), the current "backbone" of HCV treatment.
Incivek is not used by itself because HCV rapidly becomes resistant to it. However, triple-class therapy is very effective against HCV. Does this concept sound familiar to you? HIV has very striking similarities to HCV: We must always use combination therapy, or else HIV becomes resistant, and a similar story is true for HCV as well.
Incivek plus PEG/RBV is much more effective than PEG/RBV dual therapy in patients with HCV infection. In the large treatment trials involving Incivek, about 75 percent of the patients were cured of their HCV infection, which is a great improvement over PEG/RBV dual therapy, which only led to cure in about 44 percent of patients. In addition, those patients who had no detectable virus in their blood as early as 4 weeks after starting treatment were cured of their HCV infection about 90 percent of the time.
The big question is whether Incivek can also improve cure rates of HCV infection in patients with HIV and HCV coinfection. The 24-week results from an Incivek phase 2 trial in HIV/HCV coinfected patients were presented at the Liver Meeting, and the results are very encouraging.
"Phase 2 trials" are early studies to determine the safety and efficacy of a particular drug in a small population of patients. If the results look promising, then a larger, phase 3 trial follows.
These experimental trials compare the experimental drug to a placebo. A placebo is similar to a sugar pill, which will obviously have no effect on HCV. When patients are taking a placebo, no one knows who is getting the real drug. This strategy can help determine the true benefit of a new drug.
In this phase 2 trial, 60 HIV-infected patients with HCV genotype 1 infection were randomly assigned to Incivek plus PEG/RBV (the triple-therapy arm) or to placebo plus PEG/RBV (the control arm). Patients took Incivek (or placebo) for the first 12 weeks. Once the drug (or placebo) was discontinued, the patient continued PEG/RBV for an additional 36 weeks of therapy to complete a total of 48 weeks of treatment.
Thirteen of the patients participating in this trial were not taking HIV medications, but the rest were. The patients who were taking HIV medications were either taking tenofovir/emtricitabine/efavirenz (Atripla) or tenofovir/emtricitabine/boosted atazanavir (Truvada plus boosted Reyataz).
After four weeks of treatment, the proportion of patients who had suppression of their HCV virus on the triple-therapy arm was 70 percent, while none of the patients on the control arm had viral suppression. At 24 weeks, the proportion of persons with viral suppression was higher among the patients in the Incivek arm compared to the placebo arm (74 percent versus 55 percent).
These results are encouraging because we know that the faster your virus is suppressed to non-detectable levels, the higher your chance of cure. What is more encouraging is that the level of suppression has been maintained for most patients through 24 weeks of treatment.
Side effects were similar to those seen among HCV-infected patients. They included rash, itching (pruritis), abdominal pain, nausea, vomiting and dizziness. Many have also developed anemia, a side effect of ribavirin and Incivek. However, most patients continued on without stopping their HCV medications.
This small trial is not yet completed; the final results will be available in 2012. Let's hope they continue to be as good as they look today. A larger, phase 3 trial is already being planned, which will try to determine whether the optimal duration of treatment is 24 weeks or 48 weeks.
It is important to know that Incivek has drug interactions with certain HIV medications, so patients will need to take Incivek with the HIV medications studied in the trial -- or with Isentress (raltegravir)-containing HIV regimens, since this drug doesn't seem to interact with Incivek. In addition, Incivek must be taken three times a day with a fatty snack, like mixed nuts, cheese or peanut butter. As with HIV treatment, adherence really counts!
In my next blog, I'll provide a similar summary of exciting new research on the other protease inhibitor approved in 2011 for HCV treatment, Victrelis (boceprevir).
|Glossary of Terms|
Direct-acting antivirals (DAA).
Telaprevir, an HCV protease inhibitor (PI).
Pegylated interferon (PEG) and ribavirin (RBV) are the "backbone" drugs for HCV treatment in 2011.
A "phase 2 trial" is an early trial to determine the safety and efficacy of a particular drug in a small population of patients.
A placebo can be compared to a sugar pill, which will obviously have no drug effect. When patients are taking a placebo, no one knows who is getting the real drug. This approach can help determine the true benefit of the real drug.