Combining an experimental drug from Bristol-Myers Squibb (BMS) with a new Gilead drug yields best-ever cure rates for a wider range of people with the hepatitis C virus, according to a study published in the January 16 issue of the New England Journal of Medicine.
Hepatitis C is an infectious blood-borne virus that attacks the liver. When left untreated, the virus can lead to cirrhosis, liver failure, and death.
In the U.S., 3.2 million are infected, many of whom are still undiagnosed. Each year in the U.S., the virus causes 15,000 deaths. Since 2007, deaths from hepatitis C have exceeded those from HIV.
Hepatitis C is classified into several major strains also called "genotypes." Type 1 is most common in the U.S. Type 2 and Type 3 are found worldwide.
The new study examined an experimental BMS drug called daclatasvir plus a newly FDA-approved Gilead drug called sofosbuvir (Sovaldi).
These two drugs were studied with and without a third drug called ribavirin. The duration of the study was 24 weeks.
The term "cure rate" is a non-scientific phrase to describe what doctors call sustained virologic response (SVR). SVR is when the virus level stays below the current limit of detection for a given length of time after stopping treatment. The longer, the better. For this study, SVR at 12 weeks post-treatment was used as a benchmark.
- For treatment-naïve and treatment-experienced people with Type 1, the SVR was the highest yet to be published in a medical journal—98%
- For treatment-naïve people with Type 2, the SVR was 92%
- For treatment-naïve people with Type 3, the SVR was 89%
For people with Type 3, the daclatasvir / sofosbuvir combination represents a substantial improvement over older drug combinations for this genotype. A previous study of sofosbuvir / ribavirin taken for 12 weeks produced a SVR of 56%. A combination of interferon / ribavirin taken for 24 weeks yielded a SVR of 63%.
Both interferon and ribavirin are problematic drugs. Interferon causes flu-like symptoms and often severe, intolerable depression.
Ribavirin has two major drawbacks. About 10 percent of people who take ribavirin experience cardiac or pulmonary issues related to anemia.
Another problem with ribavirin is that it's teratogenic. This means the drug could potentially harm unborn children. Men are not supposed to take ribavirin if their female partners are pregnant.
Female partners of men (taking ribavirin) must agree to use contraceptives. Ribavirin can cause birth defects and fetal death. For this reason, the drug should never be used by pregnant women.
What's promising about the new BMS-sponsored study is that the problematic drug ribavirin is replaced with daclatasvir.
"In our study, response rates were similar among patients treated with ribavirin and those treated without it," wrote the authors of the current BMS study. "Ribavirin-sparing regimens are therefore desirable and warrant further investigation."
The authors concluded that the once-daily daclatasvir / sofosbuvir combination was associated with high rates of SVR among patients with hepatitis C virus genotypes 1, 2, or 3, including people who did not respond to previous treatment.
The most common side effects of the daclatasvir / sofosbuvir combination were fatigue, headache, and nausea.
Gilead is very close to marketing its own replacement for ribavirin, a new drug called ledipasvir. The company has combined ledipasvir and sofosbuvir into a single pill. It plans to submit a New Drug Application to the FDA for the sofosbuvir / ledipasvir pill in the first quarter of 2014.
"Our priority is to advance Gilead’s fixed dose combination of sofosbuvir and ledipasvir for genotype 1 hepatitis C patients," according to an email statement from Gilead.