Gary Davis, is the Director of the Division of Hepatology, at Baylor University Medical Center in Dallas and Chair of AASLD’s special interest group on hepatitis C.
I thought that Professor Davis could be in the right position to summarize how the hepatitis C landscape is changed and fast moving. I met him last November, during The Liver Meeting in San Francisco.
In 1991, we were using only one drug, interferon, in fighting against hepatitis C, and it seems we were entering in the future. Now, after twenty years, we have a lot of choices, most of them shortly available. Can you summarize the story of the therapeutics in hepatitis C?
In 1991, we were using standard interferon, which was three times a week. The chance of eradicating the virus was, in retrospect, about 6%. We didn’t know that when we did those studies, we had only ALT levels to go by. We later added pegylated interferon and ribavirin, which improved these responses significantly and then, this last year, we have had the introduction of direct-acting antiviral agents, specifically protease inhibitors, which have allowed us to increase the responses to therapy significantly to the point where we have about 70% of patients who are able to eradicate the infection, that’s cured of the infection.
The landscape of hepatitis C is going to change: how is easy to use these drugs?
Every time we add a drug, we add side effects, we add cost, so it increases the complexity of managing your patients. The payback, of course, of that is that you have greater chance of getting a treatment response and curing your patient, preventing them from getting progressive liver disease.
This Conference is hosting many studies related to costs. How is relevant this kind of issue in the management of hepatitis C?
Cost is very relevant. It’s relevant to the individual patient, it’s probably even more relevant to society. There are abstracts at this meeting talking about ways to better screen for patients, 75% of the patients with hepatitis C don’t know they have it. If we screen better and identify those patients, we bring, in this country, the US, more than a million new patients into physicians’ offices to treat. The cost of doing that, both in personnel, as well as the cost of buying drugs, is phenomenal and we have no way of knowing how we are going to pay for that. So, cost is a real societal issue and access to care is a societal issue and these are becoming as big a challenge as is developing new therapies now.
We know the efficacy of the new drugs that are now approved. What about their safety profile and side effects?
The two protease inhibitors that have just come out in the market, the major side effects are anemia and rash, with one of the drugs, these are problems to manage.
Probably, the most bothersome thing that we have to deal with is drug-drug interactions.
As the infectious disease physicians have been dealing with for years in HIV therapy, these specific antiviral agents go through a complex drug metabolism and they can interfere with the metabolism of other drugs, so that makes management of them very difficult.
In comparison with the HIV field we have a more complex situation, considering that we have to deal with a lot of virus genotypes and with different answers from the virus and the host, regarding these new drugs.
Fortunately, with genotypes 2 and 3, which are the other common genotypes of this infection, we are able to have pretty good responses with interferon and ribavirin themselves. A lot of the new agents are more pan-genotypic, meaning they don’t just work in genotype 1 but they can work in other viral genotypes as well and we expect, as this field develops, that we’ll have more agents that work across genotypes and will improve the responses in all genotypes of hepatitis C.
The patient schedule is going to become more complex: we have to add new pills to the combination interferon plus ribavirin. In this Conference, there are some studies related to the adherence. Many of them are studies related to adherence regarding interferon or standard therapy. We know that interferon produces mood disturbances, depression and other kinds of problems: how is relevant adherence considering the new drugs?
The currently available proteases have to be given every eight hours, that’s difficult for the best patient to be compliant with or adherent with and the new drugs that are in development may not offer a big efficacy advantage, they may not increase the number of patients who clear the virus, but the advantage is they can be taken once a day or twice a day, which is much easier to be adherent to. Hopefully, as we get away from interferon-based therapy, we’ll have less side effects, better tolerated therapies, perhaps taken all by mouth and that should improve adherence as well.
There were presented some studies related to a possible future therapy without interferon…
We hope so. We are not there yet but it’s very encouraging, some of the early results shown at this meeting and the last European study at the Liver Disease meeting were very encouraging that we are going to be able to achieve this. We know we can achieve it in a proportion now with these therapies that are in trial, we need to achieve it in a 100%.
There are many new drugs that are coming, can you list the most hopefully drugs that are arriving?
There are two protease inhibitors that are in Phase III trial in the United States and they should, if all goes well, possibly be approved by the FDA in 2014. There are some drugs right behind that, there is a replicase complex inhibitor, cyclophilin inhibitor, so 2014 and after we’ll see another wave of new agents start to come out, there are many right on the heels of that, so, a lot of drugs coming in the next few years.
It’s interesting that here, in San Francisco, we see downtown, on the buses and trains panel “a new hope, a new era of hepatitis”: when a disease arrives on such display on buses and trains, it means that the story is changing?
Oh, yes, the story is changing a lot. For somebody who has been working in the field for thirty-five years or so, this is very exciting to see the discovery of a virus and within your own career see the potential to eradicate the infection.
Articolo presente in – HAART and correlated pathologies n. 13 –
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