By Andrew Pollack

New medicines are being developed that are expected to transform the care of patients with hepatitis C, making treatment far more effective and far less grueling.

The new drugs, which could start reaching the market as early as next year, could help subdue a virus that infects roughly four million Americans, most of them baby boomers, and 170 million people worldwide.

"I almost think this will be revolutionary, to be honest," said Dr. Fred Poordad, chief of hepatology at Cedars-Sinai Medical Center in Los Angeles. "We are chomping at the bit to try to treat as many patients as we can."

About two dozen pharmaceutical companies are now pursuing drugs for hepatitis C, which an executive at Vertex Pharmaceuticals recently called "one of the largest pharmaceutical opportunities this decade."

That is because the toll of the disease, which now kills about 12,000 Americans a year, is expected to rise in the coming decade. Although new cases have dropped sharply, hundreds of thousands of people who were infected decades ago are expected to start experiencing the effects of liver damage.

New cases of liver cancer are already rising year by year. And hepatitis C is the leading cause of liver transplants, like the one recently received by the rock musician Gregg Allman.

Hopes for new treatments were buoyed in May by the first results from a late-stage clinical trial of one of the new drugs, telaprevir from Vertex. When added to the existing treatment - a combination of alpha interferon and ribavirin - telaprevir effectively cured 75 percent of patients, compared with 44 percent of those treated with the existing drugs alone. And for many patients, the course of treatment could be halved to 24 weeks.

Dr. Poordad, who is a consultant to some of the pharmaceutical companies, said that one-fifth of his patients were being "warehoused," meaning they were forgoing treatment now to wait for the new drugs.

But even if the drugs do work, some experts and doctors warn that this virus may be particularly tough to vanquish. Three-quarters of the people who are infected do not know it because they are not tested for the virus and because the infection can be asymptomatic for years while it stealthily attacks the liver.

And because this disease is transmitted by blood, those infected largely are former or current IV-drug users - a population that characteristically has little or no health insurance - who may not be the most able to stick to a lengthy treatment regimen that can cause brutal side effects.

Pharmaceutical companies "completely ignore the real face of hepatitis C," said Dr. Diana L. Sylvestre, who runs a clinic in Oakland, Calif., that treats drug addicts and former addicts with hepatitis C. "A minority of patients who have hepatitis C will benefit from these drugs."

When she gave a recent talk at Vertex, Dr. Sylvestre's first slide showed a man in a suit, meant to be a Vertex executive, with his head in the sand.

Dr. Camilla Graham, a senior director of medical affairs at Vertex, said that addicts accounted for less than 10 percent of people with hepatitis C. While many people got infected by trying drugs in the 1960s and 1970s, they have long since kicked the habit, she said.

Hepatitis C can also be transmitted sexually, particularly when men have sex with other men. And many people got the virus from blood transfusions before 1992, when donated blood began being tested for the virus.

Nevertheless, pharmaceutical companies realize that difficulties getting patients screened and treated could limit the use of their drugs. So they are contributing to a groundswell of activism to raise awareness of what has long been known as a silent epidemic. Also contributing to the new advocacy is the highly organized HIV community, since 15 to 30 percent of those with HIV also have hepatitis C.

A report issued by the Institute of Medicine in January urged a new national strategy to improve prevention, detection and treatment of hepatitis C and hepatitis B which also causes liver disease. A hepatitis task force created by the Department of Health and Human Services is preparing an action plan by October. The House Oversight and Government Reform Committee held a hearing on hepatitis last month.

Drug makers contribute to the National Viral Hepatitis Roundtable, which helped pay for the Institute of Medicine report, and several companies have banded together into the Corporate Hepatitis Alliance to lobby for more government funding. In January, several companies started the Viral Hepatitis Action Coalition, to help finance research at the Centers for Disease Control and Prevention.

Vertex has commissioned studies projecting a rising toll from hepatitis C. One such study, done by Milliman, a health insurance consulting firm, projected that the number of people with advanced liver disease from hepatitis C would quadruple in 20 years if treatment did not improve.

Screening people for hepatitis C should become easier. In June, the Food and Drug Administration approved a rapid blood test developed by OraSure Technologies that gives an answer in 20 minutes rather than several hours needed if the sample is sent to a lab. Future versions might use a mouth swab, allowing screening to be done at churches, street fairs and other gatherings.

There is a risk that increased screening could result in treatment for people who will never need it. Only 5 to 20 percent of people with chronic infection develop cirrhosis in about 20 to 30 years, and doctors cannot predict which patients those will be.

"I think the companies have done a superb job of marketing this disease," said Dr. Ronald L. Koretz, emeritus professor of clinical medicine at the University of California, Los Angeles. Dr. Koretz said there was no good evidence that treatment made a difference since many patients cured by the drugs might never have developed serious problems anyway.

The current treatment for hepatitis C consists of weekly injections of alpha interferon - the leading brands are Roche's Pegasys and Merck's PegIntron - combined with ribavirin, a generic oral drug. It is not quite clear how these drugs work.

The regimen usually lasts either 24 or 48 weeks and costs more than $30,000. It can be rough, causing flulike symptoms, depression, anemia and other problems. And the treatment fails to cure the patient about half the time, either because it cannot clear the virus from the body or because the patient cannot tolerate the drugs.

The new drugs generally inhibit enzymes needed by the virus, a strategy that has worked well against H.I.V. The two drugs that could conceivably make it to the market by next year, Vertex's telaprevir and Merck's boceprevir, are both pills that inhibit the protease enzyme.

For a few years at least, the new drugs would have to be used along with interferon. But doctors are hopeful that starting perhaps in five years, combinations of the new pills will do away with the need for interferon.

The drugs could offer new hope to an estimated 300,000 people for whom the existing treatment has not worked. Some early data suggests that telaprevir, when combined with the existing drugs, could cure half of them.

"I was willing to try yesterday," said Kenny C. Charles, 58, of Woodbourne, N.Y., who said he got hepatitis C from blood transfusions and had undergone four unsuccessful treatment attempts with the existing drugs. Now, he said, his liver was starting to show signs of cirrhosis, or scarring.

Some people with hemophilia, who were infected more than 25 years ago by blood-clotting drugs derived from human plasma, are pressing the Food and Drug Administration to allow them to be treated with combinations of the new drugs, without interferon, even before the new drugs are approved. The F.D.A. held a public hearing on the request in April and is now formulating a policy.

Mark Antell of Rosslyn, Va., one of the organizers of the petition, said he had to stop taking interferon because of flulike symptoms, loss of hair and creaking joints. "It was as though I was aging very rapidly," he said.

Mr. Antell, 63, a retired Environmental Protection Agency employee, said hemophiliacs were typically not allowed into clinical trials to test the new drugs, so they needed another way to obtain them.

"I think there's a lot of guys in my situation, and we don't have a lot of time," he said.

Source
A Pollack. Hope Against Hepatitis C. New York Times. July 21, 2010.