To understand why there is so much buzz in the pharmaceutical world for a better Hepatitis C virus (HCV) treatment, as with most things, you have to start with history. This article will highlight the history, why there is a growing need for better HCV treatment and a sample of what is in the clinical pipeline.
Starting in the 1970s, there was an increase in people infected with HCV. This increased rate of infection continued and then peaked in the 1990s. We know that HCV is primarily spread by: sharing infected needles with a carrier, from receiving infected blood, and from accidental exposure to infected blood. Estimates show that there are around 3.4 – 4.9 million people in the United States diagnosed with HCV and 170 million worldwide.
Hepatitis C is classified as a major global public health problem and that HCV infection is one of the main causes of liver cirrhosis and hepatocellular carcinoma (HCC). Most persons who develop acute and chronic HCV have no symptoms however they become chronic carriers that develop chronic liver disease that leads to cirrhosis of the liver. The rate of progression to cirrhosis is usually slow, with 20 or more years elapsing between infection and the development of serious complications.
This brings us to why there is a rush to find a new treatment. Since the disease progression is slow, we are currently seeing an increase in patients with liver cirrhosis and HCC because of the large population infected between the 1970s and 1990s. It is predicted that the cases of liver cirrhosis will peak around 2020 with >145,000/cases/year and HCC cases will peak around 2019 with around 14,000/cases/year.
There is currently no vaccination against hepatitis C as they have for Hepatitis A and B. The rationales for treatment of chronic hepatitis are to reduce inflammation, to prevent progression to fibrosis, cirrhosis, and HCC through the eradication of the virus in chronically infected patients, and to decrease infectivity and control the spread of the disease.
For many years, pegylated interferon in combination with ribavirin was the only treatment and considered the standard of care. However about 50% of patients respond to interferon but half of these relapse within the six months after interferon withdrawal after twenty-four months of treatment.
On 13-May-2011, the FDA approved Vertex’s compound Victrelis (Boceprevir) which was the newest treatment in twenty years. On 23-May-2011, the FDA also approved Merck’s compound Incivek (Telaprevir). Both of these medications are used as combination therapy with pegylated interferon and ribavirin.
What’s in the pipeline?
Currently there are several companies in the pharmaceutical headlines racing to FDA approval with new treatment options and the number of compounds in the development cycle numbers somewhere around one hundred. The landscape changes daily with data (both positive and negative) that is merging and companies buying compounds to boost their pipeline. Some of these therapies are intended as combination therapy with pegylated interferon/ribavirin and some are interferon sparing regimens. According to ClinicalTrials.gov, there are currently three hundred and seven studies active regarding HCV. Below is just a small sample of companies and compound in this competitive landscape.
|Medivir||GS 7977 + TMC435|
|Abbott Laboratories||ABT-450; ABT-267; ABT-333|
|Bristol-Myers Squibb||Daclatasvir + Asunaprevir + BMS-791325|
|Achillion||Sovaprevir; ACH-3102; ACH-2684;|
As with the approvals in 2011, getting to the market first is crucial. However, this is not easy, it is necessary when millions if not billions of research and development dollars are at stake. Company management is looking internally and externally to “out of the box” strategies to optimize clinical trial protocol designs and clinical operations procedures to ensure speedy results for their compound.
Project Director - Clinical Research
SGS Life Science Services
Houghton M. Hepatitis C viruses. In: Fields BN, Knipe DM, Howley PM, eds. Fields Virology, 3rd ed. Philadelphia, Lippincott - Raven, 1996:1035-1058.
Hsu HH, Greenberg HB. Hepatitis C. In: Hoeprich PD, Jordan MC, Ronald AR, eds. Infectious Diseases. A treatise of infectious processes., 5th ed. JB Lippincott Co, Philadelphia, 1994:820-825.
Lemon SM, Brown EA. Hepatitis C virus. In: Mandell GL, Bennett JE, Dolin R, eds. Principle and Practice of Infectious Disease, Fourth. New York, Churchill Livingstone, 1995:1474-1486.
World Health Organization. Global surveillance and control of hepatitis C. Report of a WHO Consultation organized in Collaboration with the Viral Hepatitis Prevention Board, Antwerp, Belgium. Journal of Viral Hepatology, 1999, 6:35-47.
World Health Organization. Hepatitis C - global prevalence (update). Weekly Epidemiological Record, 1999, 74:425-427.
EASL International Consensus Conference on Hepatitis C. Consensus Statement. Journal of Hepatology, 1999, 31:3-8.
Projects in Knowledge. DAA Treatment: A Guide for Managing the HCV Epidemic satellite symposium, 2012