Being a person living with HIV/AIDS, hepatitis C, and an injection drug user, I look at my body. People want to treat my virus -- my immune system -- people want to treat my chest -- my TB -- but no one wants to treat my liver, so we have to find someone who wants to treat our livers. WHO calls this a viral time bomb. No one is acting on this time bomb. It is going to explode. Donors are waiting, the governments are waiting are they waiting for us to die?
-- Loon Gangte, President, Delhi Network of Positive People
AIDS activists have set precedent for demanding -- and securing -- access to lifesaving antiretroviral therapy (ART) for millions of people around the world. Many people think of hepatitis C virus (HCV) as a common, potentially deadly coinfection of HIV, but hepatitis C itself is a global health threat. Like HIV, HCV is highly prevalent among current and former injection drug users. The mode of transmission is often used as a reason to withhold treatment, which is a violation of human rights and a disastrous public health strategy.
For several years, a few activists have been pushing for global access to treatment for HCV. Although HCV treatment remains unaffordable, momentum for global access to such treatment is building. In June 2010, activists from Southeast Asia met to share their resources, goals, and progress, and develop advocacy strategies. In July 2010, the XVIII International AIDS Conference included its first session on access to HCV treatment, with speakers from Brazil, India, and Ukraine, and Treatment Action Group's Tracy Swan, who outlined the global HCV epidemic, barriers to treatment access, and ideas to surmount them. The session can be accessed online.
The World Health Organization (WHO) estimates that 130 million people have HCV. At least 20% of them -- or 34 million people -- will develop cirrhosis, putting them at risk for liver cancer and liver failure. Each year, more than 350,000 people die from these hepatitis C complications.
HCV can be treated -- and sometimes cured -- with six to twelve months of pegylated interferon and ribavirin. Some people are fortunate enough to live in countries where treatment is provided, but many have no access unless they can pay for it themselves. According to Viral Hepatitis: Global Policy, a recent publication from the World Hepatitis Alliance, more than 40% of people with HCV are living in countries that do not fund treatment.
Most people who have HCV cannot do anything about it, because treatment is too expensive. In Eastern Europe, where the annual per capita income is $7,382, a year of treatment costs $26,000. In Thailand, annual per capita income is less than $4,000, yet a year of HCV treatment costs $18,000. This does not include diagnostics, monitoring, other lab work, and administrative costs, which bring the total to $33,000.
Before 2000 in the global South, HIV treatment was $1,200 per person, per year. But it can come down as low as $60 to $80 ... AIDS history tells us that only when generic ARVs come on board does the price drop. We have to move down this price [for pegylated interferon] ... and we can do it.
-- Loon Gangte, President, Delhi Network of Positive People
Although branded and generic formulations of ribavirin are available, only two companies, Merck (formerly Schering-Plough) and Genentech (formerly Roche) produce pegylated interferon; this market exclusivity keeps prices high. In the United States and Western Europe, Merck's Peg-Intron is patented until 2016 and Genentech's Pegasys is patented until 2017. According to Sean Flynn, associate director of the Program on Information Justice and Intellectual Property at Washington College of Law, neither interferon itself or the pegylation process is patentable when used alone. Patents can be challenged. Governments can provide access to unaffordable drugs by issuing a compulsory license. This is a mechanism allowing countries to manufacture drugs for serious illnesses, as long as they are intended for local markets or exported to low-income countries that would otherwise lack access.
Patent protection is not the only barrier; there are regulatory and scientific issues to consider. Interferons are biologics (substances made through a biological rather than a chemical process). Both branded and generic biologic products (called biosimilars, biogenerics, or follow-on biologics) have a different regulatory pathway than drugs made through a chemical process.
Generic drugs do not need to undergo formal safety and efficacy studies; they must only demonstrate therapeutic equivalence (meaning that they contain active substances identical to those of the branded drug) and bioequivelence (meaning that absorption, distribution, metabolization, and elimination of a generic is within a similar range to that of the branded drug).
Although generic biologics do not have to go through an entire development program, they do have to demonstrate similarity in quality and in both nonclinical and clinical parameters. This means that they must be studied thoroughly in people to see if they work as well as the branded product.
Development of generic interferon is further hampered by the lack of harmonized regulatory standards, although the European Medicines Agency (EMA) and the WHO have already issued guidance. In 2006, the EMA released its Guideline on Similar Biologic Medicinal Products, and six products have already been approved through this pathway. In October of 2009, the WHO released its Guidelines on Evaluation of Similar Biotherapeutic Products. The U.S. Food and Drug Administration (FDA) is expected to release its guidance for development of biosimilars at the end of 2010. The Agency will be holding a two-day public hearing on November 2nd and November 3rd to seek input to inform the upcoming guidance.
Good manufacturing practices and adequate regulatory oversight are critical for generic biologics. Proteins such as interferon are complicated, and their structure may vary from batch to batch. Impurities from the manufacturing process -- or in the product itself -- can trigger immunogenicity, an immune response that may have an impact on safety and efficacy. Immunogenicity can cause acute or delayed hypersensitivity reactions or injection-site reactions, and it may reduce treatment efficacy.
Despite these obstacles, production of generic pegylated interferon may be underway, although it is difficult to find information about its development and regulatory status. Companies in Pakistan and Egypt are said to be producing generic pegylated interferon, and the Brazilian government is discussing production of generic pegylated interferon with partners in Cuba.
Broadening global access to HCV treatment will require the involvement of governments, the pharmaceutical industry, regulatory agencies, and civil society.