A drug that targets hepatitis C in an entirely new way was highly effective at suppressing the virus in chimpanzees and kept working for several weeks after the treatment stopped, U.S. researchers said on Thursday.
The hope is that the drug -- made by Danish company Santaris Pharma AS under the experimental name SPC3649 -- could replace more toxic drugs as part of a cocktail to fight hepatitis C, said Robert Lanford of the Southwest Foundation for Biomedical Research in San Antonio, Texas.
As the study unfolded, just how well the drug worked became amazing to us, Lanford said in a telephone interview.
Lanford, who has no financial ties to Santaris, regularly tests new hepatitis C compounds in chimpanzees, which are the only animals besides humans that are susceptible to the virus.
Hepatitis is blood-borne and damages the liver, causing chronic liver problems, liver cancer, cirrhosis and death.
It is the leading cause of liver disease worldwide, affecting an estimated 3.2 million people in the United States alone and 170 million worldwide.
Typical treatment involves 48 weeks of interferon plus the antiviral drug ribavirin. The combination works in only about half of all patients, and some develop such taxing side effects that they have to stop.
Lanford said most current drugs and newer experimental compounds being tested in clinical trials take direct aim at the virus. But often the virus will mutate and develop resistance. This can happen in a matter of days. The drug knocks down the virus and it comes right back, Lanford said.
The Santaris drug tries a new approach, Lanford's team reported in the journal Science. Rather than targeting the virus, we are going to take something away from the virus that it needs, he said.
The drug targets a tiny stretch of genetic material called a microRNA, which works by directing the activity of genes.
In hepatitis C, the virus uses microRNA 122, active in liver cells, to replicate. The Santaris drug is designed to block this process.
Two chimpanzees given a higher dose of the drug had a 350 percent drop in levels of the virus in their blood and liver.
That is a very good knock down of the virus. There are other drugs that can do that, but ... we did this for 12 weeks and there was no sign of resistance, he said.
This molecule is so stable that even after we stopped delivering it, it continued to knock down the virus.
In chimps, it showed no toxic side effects. Lanford said the findings were so strong that the company has begun human clinical trials.
The drug also cut total cholesterol levels by 45 percent, but as it is delivered intravenously, it is unlikely to replace cholesterol-fighting pills known as statins.
For patients with hepatitis C, Lanford said the drug could become part of a cocktail that, when combined with newer agents now in clinical trials, may allow patients to avoid having to take interferon, a chief reason many people fail treatment.
Lanford said the study also suggests that Santaris' new method of making genetic-based therapies shows promise.
Several drug companies have already signed partnership deals with the private company, including Enzon Pharmaceuticals, GlaxoSmithKline, Wyeth Pharmaceuticals, part of Pfizer Inc, and Shire plc.