Hepatitis C, a bloodborne liver disease, primarily acquired via unscreened blood products or blood transfusions, IV drug use, or inadequate sterilization of medical equipment in the healthcare setting, can potentially result in a condition known as cirrhosis or scarring of the liver and lead to liver cancer.
Hepatitis C represents the most common chronic viral infection in the US, ranging in severity from a mild illness lasting a few weeks to a serious, lifelong ailment. It is estimated that 130–150 million people globally have chronic hepatitis C infection, with about 3.5-4 million in the US alone, and nearly 350,000 to 500,000 people globally die each year from hepatitis C-related liver diseases.
With an estimated 4 million people in the US with chronic hepatitis C, the disease is now the nation’s leading cause of liver cancer and liver transplantation, and is more common than HIV/AIDS as a cause of death. While research is progressing, there is currently no available vaccine for hepatitis C.
On May 4, at the 45th annual Digestive Disease Week (DDW) meeting in Chicago, Dr. David Bernstein, chief of the division of hepatology at North Shore University Hospital, presented research involving a novel drug regimen for chronic hepatitis C. The study involved more than 400 subjects with a subgroup of the disease, known as genotype 1A, who did not have cirrhosis.
The study was published May 4 in the online edition of the New England Journal of Medicine (NEJM).
In the study, subjects were given the experimental medications ABT-450/Ombitasvir and Dasabuvir with and without the antiviral drug ribavirin for 12 weeks. At the conclusion of the study period, investigators reported that the experimental drugs cured 97 percent of the subjects.
“The majority of patients with hepatitis C in the United States are genotype 1A,” said Dr. Bernstein. “Historically, this has been one of the most difficult patient population’s to treat and cure.”
“This is an exciting advance in the treatment of chronic hepatitis C,” added Bernstein.
With the advent of a new and powerful group of oral drugs called directly acting antiviral agents (DAAs) evaluated in this study, patients now have the opportunity for a high cure rate for a disease that used to involve lengthy treatments with injectable drugs with potentially serious side effects.
Pegylated interferon (peg-IFN) and ribavirin (RBV), combination antiviral therapy, had been the standard treatment for hepatitis C prior to arrival of DAAs with FDA approval in December, 2013. This combination, involving up to 48 weeks of therapy, is effective against all the genotypes of hepatitis viruses (pan-genotypic). Unfortunately, interferon is poorly tolerated in some patients and not widely available globally to help all patients. As a result, the majority of patients will not complete their treatment.
As a class, the DAAs are much safer, more effective and better tolerated than currently available options. Oral directly acting antiviral agents (DAAs) have significantly changed hepatitis C management by greatly decreasing requirements for monitoring and evaluation, while drastically improving cure rates.
“You have to take a step back and look at all of these steps as positive,” explained Bernstein, describing the multiple new drug regimens (DAAs) being evaluated for hepatitis C. “There are going to be multiple types of regimens with various combinations for hepatitis C treatment,” according to Bernstein.
“This trial examined the efficacy of these new drugs on their own merit–not comparing these drugs to sofosbuvir (Sovaldi),” explained Bernstein. “These are three new DAAs with or without ribavirin for the treatment of patients who are non-cirrhotic genotype 1A.”
“What you are getting is a 12-week response rate in the ribavirin group of 97% and in the non-ribavirin group, 90 %. “It a high number and it’s very impressive”.
The current standard of care is interferon, ribavirin and now sofosbuvir which leads to about a 90% cure rate, explained Bernstein.
“What is unique about this study is that genotype 1A non-cirrhotics are the most common group seen in the US–and this is a large study that looked specifically at this population.” emphasized Bernstein. “This is an exciting time– and this is a very important regimen, I believe.”
The key is that while the response rate to the medication regimen in this study is phenomenal, less than 1 percent of patients treated experienced an adverse event. “Thats quite important”, Bernstein emphasized.
As the new regimen in this study has not yet been approved, the cost of this regimen is an unknown, according to Bernstein. But he ultimately believes that the high cost of the DAA class is ultimately related to the great amount of research and development involved in producing the drug.
In relation to the hefty price tag of this drug, Bernstein believes that as a society we have to look at cost vs value. In the US, he believes that we are more focused on cost. That said, he firmly believes that this drug represents more of a value proposition because it leads to a cure in such a high percentage of patients.
“We in this country look at cost, because it costs a lot,” explained Bernstein. “But you are curing 97% percent of patients in 12 weeks–so, what is the value of that?”
The tremendous cost ($84,000 per course) of sofosbuvir (Sovaldi), while being equally efficacious to the response rates observed in the current study, has rattled many insurers, patient advocacy groups, as well as medicaid programs who believe that the cost of the drug could bankrupt the system. With the potential to significantly inflate the cost of treating hepatitis C, some believe that this may ultimately leave patients with a greater share of the cost of the expensive treatment. Some advocates believe that Gilead has taken corporate greed to a new level when they announced the price for the 12 week regimen.
Bernstein commented that the tremendous cost is obviously a concern because “it is all up-front” over a 12 week period, as opposed to an alternative scenario where such therapy might be spread out over a longer period (3 years) with a similar cost. In other words, if such a regimen required a longer time period for treatment, the outcry, Bernstein believes, might not be as forceful.
Bernstein does not in any way defend the cost of these drugs. He does, however, attempt to emphasize the intrinsic value of the 3 month therapy regimen.
“You will prevent the development of cirrhosis, you will prevent the need for liver transplantation, you will prevent the development of liver cancer– and there is a value to that long term. We have never been in this situation before–to cure hepatitis C–we are so successful that we are now concerned about it,”
According to Bernstein,we are now in a position to actually reduce the need for liver transplantation, as well as improve all-cause mortality since we can rid the patient of a virus which will slow disease progression as well as progression to liver cancer.
“The medical side has really progressed, but we have to figure out a way to pay for it,” said Bernstein. “Competition will likely bring prices down, but by what degree it’s not clear.”
Based on studies thus far, Bernstein said that 12 weeks of therapy produced the highest cure rates. Whether reducing the duration of therapy to 8 or 10 weeks would be as efficacious is unclear. However, it may effect a cost savings, Bernstein commented, if cure rates could approach results achieved at 12 weeks.