Without question, the recent approvals of telaprevir (Vertex) and boceprevir (Merck) for the treatment of hepatitis C infection marks the beginning of a new time for hepatitis C. This advance is genuinely significant, and after all the me-too drugs and incremental gains we’ve all grown used to reading about, it’s exciting to see two medications that are making a real difference for a large portion of the 170 million people worldwide infected with the virus. The drugs are protease inhibitors; they work by blocking the enzyme that enables the virus to survive in a host.
And yet, much more remains. Here’s a look at what is still needed in the realm of hepatitis C care:
First, HCV comes in a variety of genotypes. The nucleotide sequence in one strain of hepatitis C varies up to 35% from another strain. Genotypes 1 and 4 have been the most difficult to treat, until the advent of the new drugs, which work excellently for patients with genotype 1. Genotypes 2 and 3 have traditionally responded well to the previous standard drugs (pegylated interferon plus ribavirin), with 80–90% of patients having the virus cleared from their body. The problem is that peg-IFN and ribavirin cause harsh side effects, and a lot of patients aren’t eligible because of pre-existing conditions, including, sometimes, depression. So there is a need for additional drugs that work in the other genotypes. Plus, even among genotype-1 patients, the new combination does not clear the virus in everyone.
Second-generation protease inhibitors are already in development and will likely be available in the next five years or so. These compounds will probably be less genotype-specific. Location could be a problem here. Genotype-1 is in North America, Europe and Asia. Genotypes 4 and 5 are prevalent in Africa, genotype 6 in Hong Kong, Macau and Vietnam, genotype 7 in Thailand, genotype 8 in Vietnam, and genotypes 10 and 11 in Indonesia. Will drug developers be willing to create new protease inhibitors for HCV patients in Vietnam and Indonesia? A non-specific inhibitor would do the trick, but whether the drugs will reach these patients of course remains to be seen.
There’s also the question of why not all genotype-1 patients respond to telaprevir and boceprevir (either of which is given in combination with peg-IFN and ribavirin). There are several possible explanations, according Ralf Bartenschlager, of Heidelberg University, and Charlie Rice, of Rockefeller University, both of whom were integral in the basic science that led to the new drugs. Interactions between these and other drugs might interfere with their potency. Patients not sticking with their treatment is another component. Some patients might metabolize the drugs too quickly, clearing them from their system before they have a chance to work their magic. And there might be variants of HCV that are already resistant to the new drugs. The virus can also become resistant during the course of treatment.
And HCV is, of course, a virus, capable of mutating any time. There could be hundreds of more genotypes in five years. It might be impossible to create a protease inhibitor that is nonspecific enough to work in everyone without losing the drug’s power.
Which leaves the looming issue of a vaccine. Hepatitis B has one; why not hepatitis C? The variety of genotypes is one reason. That many varieties makes vaccination just as hard as creating a universal protease inhibitor. Developing a vaccine might not be possible until scientists come to thoroughly understand the origins of hepatitis C – where it came from, how it got into people, and how it made its way around the world. There’s an amazing tale to be told about that, but because no one wants to ruin a good story, I’ll save it for another time.
All of this focus on medications leads naturally to the question of prevention. Dirty needles are the primary route by which HCV is spread. (The virus is also spread through sex, but less easily, and through maternal transmission to the fetus.) So what’s going to be done about that? Helping people get off addictive injection drugs and to not start in the first place. Needle and syringe exchange programs. Increased access to treatment for chronic opiate addiction. There are few if any profits to be made in preventing dirty needle drug use, but when it comes to reducing the worldwide incidence of hepatitis C virus (3% of the world is infected), it’s really the only definite approach. And! It’s not genotype-specific.