Specialty Pharmaceuticals: Hepatitis C Update

Researchers assess new study models and investigate triple drug therapies to fight hepatitis C infection.

Todd Cooperman, PharmD,

Russel Allinson, RPh, MS

RPh, PAHM

Incidence^1,2

Hepatitis C infection is a major public health problem in the United States. Approximately 4.1 million individuals (1.6% of the US population) have a positive hepatitis C virus (HCV) antibody, and 80% of those people are viremic. There are about 36,000 new infections annually. Cirrhosis will occur in 20% of those newly infected patients within 20 years. The mortality rate for patients who develop cirrhosis is 2% to 5%, accounting for 8000 to 10,000 deaths per year. Hepatocellular carcinoma occurs in 3% to 7% of patients with cirrhosis, and 35% to 40% of all liver transplants are for patients whose livers have been damaged by HCV.

Current Treatment ^3-5

Since 2001, the standard approach to treating HCV has been the combination of pegylated interferon and ribavirin. The development of pegylated interferon was a significant advance in treatment, as it achieved higher blood levels of interferon for a longer period of time and afforded more patient convenience by reducing the number of weekly injections from 3 to 1. Still, even in patients who maintain optimal adherence to therapy, the chance of achieving a sustained viral response (SVR) is 50% for genotype 1 and 80% for genotypes 2 and 3 (the most common genotypes in the United States).

New Approaches to Therapy HCV is an area of intense research, and 2011 is expected to yield significant advances in the treatment and success of therapy. HCV therapy is expected to evolve toward multidrug therapy consisting of drugs with complementary mechanisms of action. To that end, 2 protease inhibitors are expected to be approved in 2011.

Boceprevir (Schering/Merck) has been studied in combination with pegylated interferon and ribavirin in both treatment- naïve patients and in patients who previously failed on standard therapy. In the HCV SPRINT-2 study, boceprevir demonstrated improved success for treatment-naïve patients when it was added to the standard pegylated interferon/ ribavirin combination. Overall, 66% of genotype 1 patients in the boceprevir 48-week treatment group achieved SVR, whereas 63% had an SVR following 4 weeks of standard therapy and 44 weeks of boceprevir plus standard treatment. In the HCV RESPOND-2 study, conducted with patients who had previously failed on HCV therapy, 66% of patients had an SVR with boceprevir plus standard treatment for 48 weeks and 59% had an SVR after 4 weeks of standard therapy and 44 weeks of boceprevir plus standard treatment. ³

Results of research with another protease inhibitor, telaprevir (Vertex Pharmaceuticals), have demonstrated similar success when it was added to the standard HCV regimen. The results of the PROVE1 study suggest that the addition of telaprevir to current standard therapy can significantly improve the rate of SVR in treatment-naïve patients infected with HCV genotype 1 compared with the standard therapy. Sixty-one percent of patients who received telaprevir for 12 weeks and standard therapy for 24 weeks achieved SVR, while 67% of patients who received telaprevir for 12 weeks and standard therapy for 48 weeks achieved SVR. Similar results were seen in patients who had previously failed on standard therapy. The PROVE3 study of telaprevir combined with standard therapy for patients previously treated achieved SVR rates between 51% and 53%, depending on the duration of treatment.^4,5

Each of these studies also investigated different schedules of therapy. In the PROVE1 and PROVE3 studies, telaprevir was given for the first 12 weeks of therapy only and the duration of therapy was tested at 24 and 48 weeks. In the HCV SPRINT and the HCV RESPOND studies, there was a lead-in period of 4 weeks of standard therapy followed by triple drug therapy for 44 or 48 weeks.

Viral Kinetics

Another area of research within the HCV treatment is viral kinetics, which measures the impact of drug therapy on viral levels. Standard therapy has required an evaluation of viral response following 12 weeks of therapy and is referred to as the “early viral response” (EVR). Researchers are investigating the usefulness of measuring viral response following 4 weeks of therapy (“rapid viral response” or RVR), and using that outcome to suggest a shorter duration of therapy if the patient exhibits a viral response at 4 weeks. At the same time, researchers are studying the outcomes of a longer duration of therapy for SVR patients.

Future for Pharmacists

Given this brief introduction to the results of research with new agents and the investigation of different HCV therapy schedules, doses, and durations, it is evident that new regimens are achieving significant improvements in outcomes but are also becoming much more complicated. Furthermore, researchers report significantly greater side effects when a third drug is added to the standard regimen. For all these reasons, there is going to be even greater need for the pharmacist to provide in-depth assessment, education, and support to the patient on triple drug HCV therapy.

The pharmacist will also have the opportunity to closely monitor the patient’s response to therapy (RVR, EVR, and SVR) and intervene when appropriate. With a therapy that has such clearly defined end points, the pharmacist has a wonderful opportunity to demonstrate the impact of pharmacy care on clinical outcomes. PT

Dr. Cooperman is director of research and development and Mr. Allinson is chief executive officer and chief clinical officer of Therigy, LLC.

References

1. CDC Hepatitis C Fact Sheet. www.cdc.gov/hepatitis. Accessed 1/30/11.

2. CDC Hepatitis C at a Glance Toolkit for Physicians. www.cdc.gov/ncidod/diseases/hepatitis/c/hcv_physician_booklet.pdf. Accessed January 30, 2010.

3. WebMD Web site. www.webmd.com/hepatitis/news/20100809/boceprevir. Accessed August 17, 2010.

4. McHutchison JG, Everson GT, Gordon SC, et al; for the PROVE1 Study Team. Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. NEMJ. 2009;360(18):1827-1838.

5. McHutchison JG, et al; for the PROVE3 Study Team. Telaprevir for previously treated chronic HCV infection. NEMJ. 2010;362(14):1292-1303.