Hepatitis C is an inflammatory liver disease caused by infection with the hepatitis C virus (HCV). There are currently 130-150 million people living with chronic Hepatitis C infection (HCV), of which 85% live in low- and middle-income countries (LMICs). The newest drugs, which are called Direct Acting Antivirals (DAAs), include molecules that directly interfere with replication of the virus in cells. Using different drugs with different targets is needed to fully block replication of the virus. There are six genotypes of HCV, and the efficacy of drugs can vary according to the genotype.

The majority of global research and development (R&D) efforts are focused on genotypes that are prevalent in high-income countries, neglecting other genotypes which infect the majority of patients in low and middle-income countries (LMICs). Market competition between companies to advance their own pipelines has stalled innovation and hindered the development of optimal pan-genotypic drug combinations for public health use. In addition, approved treatments are very expensive and nearly half of the world’s HCV patients live in LMICs that are excluded from current licensing agreements.

Map of the global prevalence of chronic hepatitis C virus infection (Averhoff FM, et al. Clinical Infectious Diseases, 2012; 55: S10–S15.)

The hepatitis C virus (HCV) causes a liver disease which ranges in severity from a mild illness lasting a few weeks to a serious, lifelong condition. 15-45% of those infected spontaneously clear the virus within six months; this acute infection is usually asymptomatic and is only very rarely associated with life-threatening manifestations. The remaining 55-85% develop chronic HCV infection; for these people there is a 15-30% risk of cirrhosis of the liver within 20 years.

Since acute HCV infection is usually asymptomatic, early diagnosis is rare. The infection generally remains undiagnosed in people who go on to develop chronic HCV, often until serious liver damage has developed. HCV infection is diagnosed firstly by detecting anti-HCV antibodies with a serological test. The presence of antibodies shows that the organism has been in contact with the virus and that there has been an immunological reaction to it. However, the virus may have been cleared or could be still multiplying in the body. Therefore, a second test that demonstrates the presence or absence of the virus must be performed: the nucleic acid test for HCV RNA. In order to decide which treatment to use, the degree of liver damage is assessed by a liver biopsy or through a variety of non-invasive tests and the genotype of HCV responsible for the infection is determined.

According to the World Health Organization, 130-150 million people are infected with HCV and 2.3 million are HIV/HCV co-infected. [1] New direct-acting antivirals (DAAs) demonstrate cure rates of >95% in clinical trials, including in previously hard-to-treat populations, and have revolutionized HCV therapy.. The HCV drug pipeline continues to be extremely robust and promising. However, pricing of DAAs on the market is exorbitant, making them inaccessible to the vast majority of HCV patients. In addition, much of the R&D is focused on meeting the needs of patients in high-income markets where genotype 1 (GT1) is prevalent, instead of middle and low-income regions where other genotypes of HCV are prominent, in particular genotype 3 (GT3) which accounts for 30% of Global HCV infection (54 million people). While many promising drugs are in late-stage development or even on the market, competition between companies in a race to advance their own pipelines has prevented timely development of combinations for public health use.

Access programmes designed by pharmaceutical companies focus on least-developed or low-income countries and the most recent voluntary licenses granted to generic companies systematically exclude the middle-income countries that bear the greatest burden of disease.

 

[1] WHO Media Centre – http://www.who.int/hiv/mediacentre/news/hep-hiv-coinfected/en/