New hepatitis C drugs show encouraging results

'The revolution we've been waiting for'

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Chris Sosinski of Harrison City had been taking the new hepatitis C drug telaprevir for only two and a half weeks when a test showed the number of virus particles floating in his blood, called the viral load, had dropped from 1.4 million international units per milliliter to below 43.

That's considered technically undetectable.

Similarly, Victoria Taylor of South Park, a registered nurse at St. Clair Hospital, had been taking the same drug for only four weeks when a test showed the level of virus in her blood also was technically undetectable.

The results of the tests did not mean Mr. Sosinski, 48, a heavy equipment mechanic whose hepatitis has led to cirrhosis, and Ms. Taylor, 57, are cured of the virus -- that won't be determined until after many more weeks of treatment. But they did help to show why one local liver specialist said he thought the approval of telaprevir and a similar drug called boceprevir by the Food and Drug Administration "is the revolution we've been waiting for, for years now.

"While not perfect," added Michael Babich, program director of gastroenterology and hepatology at West Penn Allegheny Health System, "this is the first major and significant revolution in hepatitis treatment we've had in a decade."

The FDA in May approved the two drugs for treatment of a disease that affects more than 3 million Americans and which can cause cirrhosis of the liver, liver failure and liver cancer. They are both protease inhibitors, which by blocking the activity of the protease enzyme prevent reproduction of the hepatitis C virus. It's an approach similar to one used in treatment of HIV, said Kapil Chopra, director, UPMC Center for Liver Diseases, which participated in the clinical trials of the drugs.

The drugs are specifically approved to treat adults with chronic hepatitis C genotype 1, one of six genotypes. "Genotype 1 is the most difficult to treat amongst the various hepatitis C genotypes, and it is the most common," Dr. Chopra said. "Hence the new era of antiviral therapy has focused at the present time on [it]."

For the treatment, either telaprevir (tradename Incivek) or boceprevir (Victrelis) must be used in conjunction with pegylated interferon-alpha and ribavirin, the drugs that have been the standard treatment for years.

The minimum course of treatment is 24 weeks, depending on the patient's prior treatment history, status of liver damage, and viral load blood tests at four, eight and 12 weeks after onset of treatment. A 24-week course of treatment is half the time of the former regimen, one of two reasons the drugs are being hailed as a new era for hepatitis treatment.

"Over the years we have learned the concept of response-guided therapy, which essentially means the duration of your treatment should be guided by virus responsiveness to the treatment," Dr. Babich said. "So if the virus becomes undetectable sooner, you should be able to stop therapy sooner; if it took longer, you would be on treatment longer."

If successful in lowering the viral count to virtually undetectable, telaprevir or boceprevir generally is given for the first 12 weeks with the interferon and ribavirin and then interferon and ribaviron alone for another 12 to 36 weeks. With boceprevir, there is an exception: It is added after the first four weeks of interferon and ribavirin dual therapy and continued through at least week 28 in viral responders.

If Mr. Sosinski's viral load remains undetectable at eight and 12 weeks (he began treatment on Oct. 28 and was technically clear at four weeks), he would be treated with interferon and ribavirin for an additional 36 weeks, said Swaytha Ganesh, the doctor who leads his support team of nurse practitioners and specially trained nurses at UPMC. That's because of his cirrhosis and because he didn't respond to ribavirin-interferon treatment several years ago.

If Ms. Taylor's viral load remains undetectable at eight and 12 weeks, she would only have to take interferon and ribavirin for another 12 weeks, said Dr. Babich, her hepatologist. She has early-stage liver disease but no cirrhosis and responded, albeit slowly, to ribavirin-interferon treatment before.

Cure rates impressive

The second reason physicians like Drs. Babich and Chopra are so excited about the new drugs is the improvement in cure rates shown during the trials.

"For treatment-naive patients, the cure rate is 75 percent, and for treatment-experienced patients 60 percent, using a triple drug regimen," Dr. Chopra said. That compared to an interferon-ribavirin cure rate of approximately 20 to 40 percent, he said.

It is too soon to say whether those numbers will stand up under everyday clinical use. "The shortest course of therapy with the new drugs would be 24 weeks of treatment, and a cure rate would be defined by blood tests six months out from cessation of treatment ... and the drugs have just been out on the market since May," Dr. Babich said.

But, because of the early-treatment blood tests on his patients, he is optimistic.

"The majority of our patients have achieved blood-testing negativity quite early in their course," he added.

Asked if there were any shining examples of what the drugs can do for some hepatitis C patients, he answered, "The shining example is the proportion of patients who achieve virus negativity on blood tests within the first one and two months of treatment, considering these are all genotype 1 patients." Historically, the rate of genotype 1 patients testing negative to the virus after one month of treatment with interferon and ribavirin is 10 percent. "We are seeing early viral response rates in the range of 75 percent."

Side effects

There are side effects involved with taking the new drugs, many of them the same side effects that came with the interferon-ribavirin regimen.

Ms. Taylor, who isn't sure if she got hepatitis C from a blood transfusion 20-some years ago or when she was stuck by a dirty needle as an operating room nurse for a liver transplant at a different hospital 18 years ago, had nausea, tiredness, brain fatigue, headaches, insomnia, mood swings and decreased appetite from the drugs during the 38 weeks she "lasted" on interferon and ribavirin about a year ago. Her red and white blood-cell counts dropped; she lost 35 to 40 pounds and she was very dehydrated.

With the addition of telaprevir, "it's the same side effects but they're occurring much quicker. In the middle of the sixth week, they're as bad as three months into previous treatment."

Mr. Sosinski, who got hepatitis about 35 years ago from a blood transfusion during surgery, had far fewer side effects than Ms. Taylor when he took interferon and ribavirin for about three months some four years ago: He was very achy, nauseated, irritable and had a persistent cough and the drugs had no effect on his hepatitis C.

But telaprevir hasn't caused him any additional problems -- in fact it's been the reverse.

"The achiness is not as severe; basically the flu-like symptoms aren't as bad as they were the last time," he said. "I do have the cough." He's less irritable.

He also feels better overall. "Compared to the last time, I'm not feeling as lazy. I still have energy to do things, where last time I had no desire to do anything. Before it just wiped me out."

Other potential side effects "unique to the new antiviral agents are skin rashes, anemia and altered taste," Dr. Chopra said,

The drug regimen itself is very difficult.

"Both drugs require relatively complicated algorithms. Both require taking a few extra pills; require strict adherence to a rigorous dosing regimen and require careful review of the patient's history for possible side effects and possible drug interactions," Dr. Babich said.

"The side effect profiles are slightly different, but in my experience to date, they have really been the key deciding factor for patients in choosing one drug over another."

Mr. Sosinski takes two telaprevir pills three times a day -- at 6 a.m., 2 p.m. and 10 p.m. -- with a food containing fats, like peanuts or peanut butter, He also takes three ribavirin by mouth twice a day and an interferon injection once a week.

Ms. Taylor eats a food with fat content 30 minutes before she takes her two telaprevir every eight hours, one ribavirin twice a day and one interferon injection a week.

But despite the side effects and the rigid dosing schedule, she is determined to stay the course.

"If it's only six months [of treatment], that's a piece of cake when you've been thinking a year," she said. "... If I'm undetectable at weeks eight and 12, it not only cuts the treatment time in half, it'll increase the cure rate."

Curing his hepatitis C will at least delay the need for Mr. Sosinski to have his cirrhotic liver transplanted.

"He may not need a transplant for a long time," Dr. Ganesh said, noting his cirrhosis was in early stages when he started treatment.

"I was told four years ago that within five to seven years I'd need a transplant," Mr. Sosinski said. "Now with [the new] drug, it could prolong for another five years before I need the transplant. The hepatitis will go away and not be damaging the liver any longer."

Pohla Smith: or 412-263-1228. First Published January 9, 2012 5:00 AM


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