Sofosbuvir, a new drug, is offering impressive cure rates for Hepatitis C patients with two subtypes of the disease – genotypes 2 and 3, according to researchers led by Weill Cornell Medical College.
Approximately 1 in every 4 hepatitis C patients in the USA has one of these two subtypes.
Sofosbuvir, which is much safer than Interferon, offered more effective treatment for the majority of patients involved in a Phase 3 clinical trial. The participants had no other treatment options, the scientists reported in NEJM (New England Journal of Medicine).
Interferon can have serious side effects, including loss of vision, sepsis, heart failure, and leucopenia (a decrease of white blood cells).
The following response rates were reported after three months therapy with sofosbuvir combined with ribavirin:
- 93% among those with genotype 2
- 61% among participants with genotype 3
Several drugs being tested for hepatitis C were published in the online edition of NEJM (April 23, 2013 edition). This issue of the journal coincides with the International Liver Congress 2013 in Amsterdam, the Netherlands.
Study leader, Dr. Ira Jacobson, chief of the Division of Gastroenterology and Hepatology and Vincent Astor Distinguished Professor of Medicine at Weill Cornell Medical College, said:
“The new sofosbuvir therapy offers a much-needed alternative to standard therapy with interferon, which can cause significant side effects for hepatitis C patients.
“We have dreamed for years of being able to eliminate interferon from our hepatitis C regimens and this study is one of several that are finally bringing us very close to realizing that goal.”
The POSITRON trial included 207 participants. The patients either had not responded to interferon, were unwilling to use it, or unable to tolerate it, in spite of there being no other treatment options available.
Dr. Jacobson said “This new treatment represents a paradigm shift in the way that hepatitis C is going to be treated. We are achieving the same or higher cure rates in many patients with sofosbuvir, compared to interferon, and we are doing it in half the time with a drug that has a remarkable safety profile.”
The authors estimate that up to 50% of hepatitis C patients are either unable to use interferon or refuse to use it. They see Sofosbuvir as an extremely promising treatment for these patients. They believe that potent antiviral drug combos will eventually replace interferon use for the majority of patients with hepatitis C.
Sofosbuvir interferes with the hepatitis C virus’ ability to replicate. It also makes it more difficult for drug resistance to occur. Sofosbuvir has yet to be approved by the Food and Drug Administration (FDA). The four clinical trials, the results of which were published in NEJM, were used to support the regulatory filing of the medication by Gilead Sciences Inc., the makers of sofosbuvir.
Globally, about 170 million people are infected with hepatitis C; the disease kills 350,000 people annually. According to US statistics, approximately 4 million Americans are infected with hepatitis C. Often patients have no symptoms, so the majority of hepatitis C infected people don’t know they are infected.
Hepatitis C, if left untreated, can progress to cirrhosis, liver cancer and liver failure.
The hepatitis C virus spreads by contact with infected blood, such as injection drug use, sexual contact or through blood transfusions.
Of the 7 major genotypes of hepatitis C, 1, 2 and 3 are the most common. In the USA, genotype 1 is the most common, while the most prevalent in Europe are genotypes 2 and 3. In the Indian subcontinent genotype 3 is the most common.
75% (207) of all the patients in the POSITRON trial were randomly selected to receive a sofosbuvir and ribavirin combo, while the rest (71) were given a placebo treatment. All of the participants either had not responded to interferon or refused to use it. Dr. Jacobson said “This mirrors what happens frequently in the clinic. Between 15 and 30 percent of patients with hepatitis C genotype 2 or 3 infections do not have a response to interferon therapy and do not have alternate treatment options.”
Participants were enrolled at sixty-three sites in New Zealand, Canada, Australia and the USA.
The study should that the response rates were:
- 78% among the sofosbuvir plus ribavirin patients
– 93% among those with genotype 2
– 61% among the genotype 3 patients
– 81% among patients without cirrhosis
– 61% among those with cirrhosis - 0% among the placebo patients
This trial was led by Dr. David R. Nelson from the University of Florida at Gainesville. The results were incorporated into this NEJM manuscript publication. The trial tested the sofosbuvir plus ribavirin combo in hepatitis C patients with genotypes 2 or 3 who had not responded to interferon treatment.
Patients were tested at 12 and 16 weeks of therapy. The findings showed that the longer people were on the sofosbuvir combo, the higher their cure rate was, regardless of genotype. However, the difference seen in genotype 3 was “highly significant”.
- For those with hepatitis C genotype 2, there was a response rate of 86% at 12 weeks and 94% at 16 weeks.
- For genotype 3 patients, there was a response rate of 30% at 12 weeks and 62% at 16 weeks
Dr. Jacobson said:
“Given the absence to date of alternative therapies for patients with genotype 2 or 3 who have failed interferon therapy or for whom it is not an option, treatment with the new sofosbuvir regimen offers a vast improvement. But the optimal duration of treatment for genotype 3 patients, in order to maximize their chance of cure, remains undefined. It could be longer than 16 weeks.”
Further studies will decide what the optimum treatment duration for those with genotype 3 should be. Additional studies will also determine whether different sofosbuvir combos might shorten treatment times.
Written by Christian Nordqvist