The drug, from Vertex Pharmaceuticals, is code-named VX-950. Liver specialist Henk W. Reesink, MD, of academic Medical Center in Amsterdam, Netherlands, presented the findings at Digestive Disease Week 2005, the annual meeting of several major medical specialty societies.

"This is really a breakthrough in the treatment of hepatitis C virus," Reesink tells WebMD. "This first human study was very successful. In the first two or three days of treatment there is a very rapid [1,000-fold] decline in hepatitis C virus levels. Then, over two weeks, there are further declines -- in some dosage groups, about a 25,000-fold reduction in viral levels. That has never been shown with any other drug."

Reesink warns that VX-950 is in the very earliest stage of human studies. Nobody knows if it will prove safe over time. Nobody knows whether its effects will continue long enough to cure hepatitis C virus infection.

And while the drug appears exquisitely effective against genotype 1 -- the most difficult-to-treat strain of hepatitis C virus and the one most common in the U.S. and Europe -- it's not clear whether it will work against other strains.

Despite being highly preliminary, Reesink's report excited the assembly of specialists, says Eugene R. Schiff, MD, chief of hepatology and director of the Center for Liver Diseases at the University of Miami School of Medicine.

"I was impressed, and everybody in the audience was impressed," Schiff tells WebMD. "Yes, this is preliminary, but this is an important advance. It is the most important paper presented at this meeting. They showed -- with an oral agent -- that they could drop hepatitis C viral levels, some to undetectable levels, in a relatively short period of time."

Most of the patients in the Reesink study already had failed state-of-the-art treatment for hepatitis C. That treatment is a combination of a highly active form of interferon plus an antiviral drug called ribavirin. This treatment offers long-term viral suppression -- what many experts call a cure -- in about half of patients. But this treatment takes nearly a year, and the side effects often are very difficult to endure.

VX-950: Protease Inhibitor Targets Hepatitis C Virus

VX-950 is a designer drug discovered only after huge effort. It targets a key hepatitis C protein. That protein is called protease, an enzyme the virus needs to reproduce.

It's not the first time a hepatitis C protease inhibitor has been tested in humans. Recently, an experimental hepatitis C protease inhibitor called BILN 2061 showed promising results in short-term human trials. But that drug had to be put on hold when monkey studies suggested it was toxic to the heart.

Schiff says that "seven or eight" pharmaceutical companies are nearing clinical trials of their own protease inhibitors against hepatitis C virus. He estimates that more than 20 companies are developing new "small molecule" drugs designed as oral hepatitis C treatments.

The term "protease inhibitor" may sound familiar. Drugs targeting HIV protease were a huge breakthrough for AIDS therapy. However, HIV rapidly develops resistance to these drugs. That's why AIDS drugs have to be taken in powerful combinations.

Whether hepatitis C virus will develop resistance to VX-950 or other protease inhibitors isn't known. Schiff notes that unlike HIV, the hepatitis virus doesn't hide inside cells where drugs can't reach it. So if the drug keeps viral levels low, there's a good chance the virus won't become resistant. It's even possible, Schiff says, that hepatitis C protease inhibitors will work all by themselves, without the need for combination therapy.

Shorter, Easier Hepatitis C Treatment?

In the Reesink study, the most effective dose of VX-950 was a three-times a day treatment. Four of eight patients receiving this dose for 14 days had about a 25,000-fold drop in hepatitis C virus levels. The virus became undetectable in two patients. Larger doses given twice a day didn't work as well, nor did lower doses given three times a day.

In this short study, no serious side effects seemed to happen. Possible side effects included headache, diarrhea, nausea, frequent urination, and sleepiness/drowsiness. All these side effects were mild.

It's not at all clear whether VX-950 really will work all by itself or whether it will work best in combination with other drugs. Unlike current hepatitis C treatments, it's an oral drug. That raises hopes for a much easier-to-take -- and, perhaps, shorter -- treatment regimen.

"It is difficult to say at this moment how long VX-950 treatment would take," Reesink says. "But from this first-phase trial, one can speculate -- and this is just speculation -- that the treatment duration may be substantially shorter than the current standard of therapy."

"You will see combination treatments with this drug," Schiff predicts. "But if you end up with a combination of oral agents, instead of the current medications with this big side-effect profile, that would still be much better for patients."

Message to Patients: Don't Stop or Delay Current Treatment

Reesink and Schiff both warn patients with chronic hepatitis C infection not to stop their current treatment or to delay starting current therapies. Even if everything goes perfectly -- and drug development rarely does -- it would be more than five years before VX-950 could be available to patients.

"It would be a mistake for people to stop their current treatment to wait for this stuff," Schiff says. "That would be a big mistake. What we heard today could represent a major advance in treatment. But I used to chair an FDA drug-approval committee, and I can tell you that when a new drug comes along everybody gets turned on -- and then they find side effects of something and the drug has to be withdrawn. I don't think that is going to happen here, but it's too soon to tell."

SOURCES: Digestive Disease Week 2005, Chicago, May 14-17, 2005. News release, Vertex Pharmaceuticals. Henk W. Reesink, MD, associate professor of internal medicine and hepatology, Academic Medical Center, Amsterdam, Netherlands. Eugene R. Schiff, MD, chief of the division of hepatology; director, Center for Liver Diseases, University of Miami School of Medicine.