[A friend just sent me this rather discouraging news article from yesterday, on Telaprevir. I think it's still up in the air whether the PIs will be approved, because of this issue with it.
Vertex's Experimental Telaprevir Resisted by Some Strains of Hepatitis C
By Rob Waters - May 05, 2010
Vertex Pharmaceuticals Inc.’s experimental hepatitis C treatment knocks out so much of the rapidly mutating virus it lets drug-resistant strains grow instead, requiring multidrug cocktails to defeat it, a study said.
In patients infected by a common strain of the hepatitis C virus, as many as 20 percent of viral particles became resistant to Vertex’s telaprevir within two days of taking it, according to researchers at Los Alamos National Laboratory in New Mexico. They used patient data from clinical trials of the drug to create a mathematical model based on the number of virus mutations found during treatment.
Doctors and drugmakers are searching for new hepatitis C treatments because the standard two-drug therapy works in only half of patients and causes side effects that are hard for many to tolerate. The study published today suggests those current medicines still will be needed given the degree of resistance to telaprevir.
“That’s the most rapid drug resistance for any agent that’s ever been observed,” said Alan Perelson, a Los Alamos scientist and the senior author of the study published today in the journal Science Translational Medicine.
About 170 million people, 3 percent of the world population, are infected with hepatitis C, according to the World Health Organization. The liver disease, spread by contact with infected blood, develops slowly, scarring livers over years or decades and may lead to liver cancer and require a transplant.
Many people don’t know they’re infected and aren’t getting treatment. Among those who are, most take a two-drug combination of the generic antiviral pill ribavirin and alpha interferon, sold under the brand name Pegasys by Swiss drugmaker Roche Holding AG and as Pegintron by Whitehouse Station, New Jersey- based Merck & Co.
The two drugs fortify the immune system, helping it clear the virus from the patient’s blood, and generate about $2 billion a year in sales. They also can cause protracted flu-like symptoms and trigger anemia.
Telaprevir, from Cambridge, Massachusetts-based Vertex and its partner, Johnson & Johnson of New Brunswick, New Jersey, is racing against another experimental drug, boceprevir from Merck, to become the first new hepatitis C treatment approved in a decade. Both are so-called protease inhibitors, similar to drugs used against the AIDS virus HIV, that block an enzyme that viruses use to copy themselves.
1 Trillion Particles
Hepatitis C copies itself so quickly that the typical patient makes about 1 trillion viral particles a day, Perelson said. With each new copy, there’s a chance of a genetic mutation and some of these mutations make the virus resistant to drugs.
“You’re making so much virus that it is literally a certainty” that every letter of genetic code will be changed at least once in the course of a day, Perelson said.
When patients take telaprevir, it kills off the normal, unmutated viral particles. The few mutants that are resistant grow in number and become increasingly hard to kill, Perelson said in a telephone interview.
The findings are consistent with what Vertex has learned from its clinical trials, said Robert Kauffman, the company’s chief medical officer.
“For all direct-acting antivirals against hepatitis C, resistance is likely to develop fairly quickly,” Kauffman said in a telephone interview yesterday. “The solution to that problem is a cocktail.”
Vertex fell 92 cents, or 2.4 percent, to $37.55 at 4 p.m. in Nasdaq Stock Market composite trading. The shares have fallen 12.4 percent this year.
For now, any drug combination, or cocktail, will need to include interferon and ribavirin and the side effects they cause, Perelson said. If the Vertex or Merck drugs are approved next year and become part of a patient’s cocktail, as company executives predict, it may reduce treatment time to six months from a year.
Treatment that avoids the current regimen may still be some years away, Kauffman said. Vertex this month began a trial of telaprevir with an experimental drug called VX-222, a different type of antiviral, to see if the two drugs can defeat the virus.
To contact the reporter on this story: Rob Waters in San Francisco at ***@****.