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New Drug Shows Promise for Curing Hepatitis C

Antiviral telaprevir works when previous treatments failed, trial results show

April 7, 2010 (HealthDay News) -- Adding the antiviral drug telaprevir to a second-round treatment for hepatitis cures about half the people who were not helped in the first round, new research shows.

"This is the first large study in patients who had not responded to standard treatment," said Dr. John G. McHutchison, associate director of the Duke Clinical Research Institute and lead author of a report in the April 8 issue of the New England Journal of Medicine.

The study is one of the last steps in a series of trials designed to get approval for the use of the drug in clinical practice. Approval of the drug will bring encouragement to people whose hepatitis C infection had not been cured by the existing treatments, McHutchison said.

"There has been no alternative for people who have been treated and have not responded," he added. "So it holds great promise for them, that potentially something will be available in the future that can cure half of them."

About 4 million Americans are infected with hepatitis C, a virus that is the leading cause of cirrhosis and liver cancer and the most common reason for liver transplantation. It is usually transmitted by infected blood, most often by using a contaminated needle.

Standard treatment for hepatitis C is a 48-week course of two drugs, peginterferon alpha and ribavirin, which cure about 40 percent to 50 percent of patients but is accompanied by side effects, such as a severe rash, that makes many discontinue the treatment. Previous studies have shown a substantial improvement in cure rates when telaprevir is added to the standard therapy.

Until now, the only recourse for those who were not helped by the first round of treatment was a second round of the same therapy. The newly reported trial, sponsored by Vertex Pharmaceuticals, the maker of telaprevir, included 453 people who had not responded to a first round of treatment. All had the most common, and most difficult to treat, form of the virus, genotype 1.

Just over half, 52 percent, of those who had telaprevir added to the two-drug regimen in the second round were virus-free after six months, compared to 14 percent of those who had a second round of the two-drug treatment.

But the therapy was not problem-free, McHutchison noted. "There were also more side effects, rashes and anemia," he said. "Also, the rate of discontinuation was higher as well."

Still, the high cure rate speaks for itself, McHutchison added. Data from the various trials probably will be submitted to the U.S. Food and Drug Administration later this year, he said.

Telaprevir is a protease inhibitor, which works by blocking reproduction of the hepatitis C virus. It is not the only protease inhibitor being tested against hepatitis C, McHutchison said. Another such drug, boceprevir, appears to be running close to telaprevir in the race for regulatory approval. It is being developed by Merck, which acquired it when it bought Schering-Plough.

If and when they are approved, both protease inhibitors probably will be used for first-line treatment of hepatitis C, McHutchison said.

A number of other protease inhibitors now are in various stages of testing, added Dr. Ira Jacobson, a professor of medicine at Weill Cornell Medical College in New York City and a member of the research team that did the telaprevir study. Jacobson has also been involved in development of boceprevir.

A new era in treatment of hepatitis C will begin when a first protease inhibitor is approved, Jacobson said. "The hope in the medical community is that the regulatory agencies will see fit to approve it for all populations," he added.

SOURCES: John G. McHutchison, M.D., associate director, Duke Clinical Research Institute, Duke University Medical Center, Durham, N.C.; Ira Jacobson, M.D., professor of medicine, Weill Cornell Medical College, New York City; April 8, 2010, New England Journal of Medicine

With newer medications expected to be approved and available for use in 2011-2012 it may seem like an easy decision to postpone treatment. Waiting for some people, however, can be dangerous – some people need to be treated now and the reality is that there are no guarantees that the new medications will work for everyone. The medications will also bring about more treatment challenges since the new HCV protease inhibitors will be combined with pegylated interferon plus ribavirin.

The group of people who are at greatest risk for severe disease progression are those with advanced fibrosis and cirrhosis. Unfortunately this is the group of people with HCV who are less likely to respond to current HCV medications. There are also concerns about treating people with severe fibrosis and cirrhosis because of a greater risk of side effects.

The results of a new study “Efficacy and Safety of Peginterferon Alfa-2a (40KD) Plus Ribavirin in Hepatitis C Patients with Advanced Fibrosis and Cirrhosis”1 conducted by Savino Bruno and colleagues is sure to help people who are debating whether or not to start treatment now or wait for the new protease inhibitors.

This study analyzed data obtained from three large international phase III studies of people who were treated with pegylated interferon alfa-2a (40KD) – Pegasys and ribavirin. The data in this retrospective analysis included:

The sustained virological response rates (SVR-6 months HCV RNA negative 24 weeks post treatment) were:

The analysis also revealed that the time it took to become HCV RNA negative was similar among the groups and it was the best predictor of achieving an SVR.

Treatment of people with cirrhosis raises concerns about safety. In this analysis, however, the treatment was tolerated similarly among the people with and without bridging fibrosis or cirrhosis. Only one patient in their database discontinued treatment due to low platelets.

It was not surprising to find that people with bridging fibrosis or cirrhosis did not respond as well as people who did not have advanced fibrosis and cirrhosis. However, if you are someone who has bridging fibrosis or cirrhosis, this might be a really good time to think seriously about treatment now – you don’t want the liver to become even more damaged. The best thing to do is to have a good hard conversation with your medical provider about whether treatment is needed now or if it is safe to wait.

March 29, 2010 - While hepatitis C incidence, or new infections, has fallen during the two decades since the HCV virus was discovered, a growing number of people who were infected many years ago are now reaching the stage where they develop advanced liver disease.

As reported in the February 2010 Gastroenterology, G.L. Davis and colleagues developed a mathematical model to project future prevalence of chronic hepatitis and its complications.

The model showed that chronic hepatitis C prevalence, or total infections, peaked at 3.6 million in 2001. Fibrosis progression was not related to age at the time of infection, so cirrhosis and its complications were most common after age 60, regardless of when infection occurred, the researchers noted.

They projected that the proportion of people with chronic hepatitis C who will develop cirrhosis will reach 25% in 2010 and 45% in 2030, though the absolute total number with cirrhosis will peak at 1 million (about 30% above the current level) in 2020. They also predicted that decompensated liver disease and liver cancer will continue to increase for about 10 more years.

But if all HCV positive people were to be treated in 2010, the risk of cirrhosis, decompensation, liver cancer, and liver-related deaths would fall by 16%, 42%, 31%, and 36%, respectively, by 2020.

"Incidence of hepatitis C cirrhosis and its complications will continue to increase through the next decade and will mostly affect those older than 60 years of age," the researchers concluded.

Source: HEPATITIS JOURNAL REVIEW: A Bi-Monthly Publication of the Hepatitis Support Project

ScienceDaily (Jan. 6, 2010) — Researchers have identified two cellular proteins that are important factors in hepatitis C virus infection, a finding that may result in the approval of new and less toxic treatments for the disease, which can lead to liver cancer and cirrhosis.

An estimated 270 to 300 million people worldwide are infected with hepatitis C and the conventional treatments -- interferon and ribavirin -- can have significant side effects. A new drug targeting cellular proteins rather than viral proteins would be a valuable addition to the treatment arsenal, said Samuel French, an assistant professor of pathology and senior author of the study.

French and his team set out to identify the cellular factors involved in hepatitis C replication and, using mass spectrometry, found that heat shock proteins (HSPs) 40 and 70 were important for viral infection. HSP 70 was previously known to be involved, but HSP 40 was linked for the first time to hepatitis C infection, French said. They further showed that the natural compound Quercetin, which inhibits the synthesis of these proteins, significantly inhibits viral infection in tissue culture.

"This is an important finding because we can block these proteins with the idea of reducing the level of the virus in people and, ideally, completely eliminate it," said French, who also is a researcher at UCLA's Jonsson Comprehensive Cancer Center.

Since Quercetin has been shown to inhibit hepatitis C infection, French said, a Phase I clinical trial will be launched at UCLA to determine if the compound is safe and effective.

Quercetin is a plant-derived bioflavonoid, and is used by some people as a nutritional supplement. Laboratory studies show it may have anti-inflammatory and antioxidant properties, and it is being investigated for a wide range of potential health benefits. Currently, there are early-stage clinical trials testing quercetin for safety and efficacy against sarcoidosis, asthma and glucose absorption in obesity and diabetes.

"Because Quercetin targets cellular proteins rather than viral proteins, there is less likelihood of developing viral resistance," French said. "Cellular proteins cannot change like viral proteins can."

Many patients in the United States have a type of hepatitis C virus that does not respond to the standard treatments. In these cases, if the virus can't be blocked, end-stage liver disease and, ultimately, death may occur. Once HSP 40 and 70 were identified, French and his team used Quercetin in an attempt to block the proteins and found that the compound "reduced infectious particle production at non-toxic concentrations," according to the study.

"Quercetin may allow for the dissection of the viral life cycle and has potential therapeutic use to reduce virus production with low associated toxicity," the study states.

The UCLA clinical trial will most likely target those with genotype 1 hepatitis C, which is the non-responsive type prevalent in this country. Only about 50 percent of those with type 1 hepatitis C respond to treatment, French said.

Volunteers with genotype 1 hepatitis C who opt not to undergo conventional therapies would be recruited for the study. In other studies in other diseases, Quercetin has resulted in no significant side effects, French said.

"A non-toxic treatment for chronic hepatitis C would be great because our current therapies have significant side effects and only a certain percentage of the patient population responds," French said.

The three-year study was funded by the National Institutes of Health, the Cure Digestive Diseases Research Center and the Stein Oppenheimer Endowment Award.

MIAMI (Ivanhoe Newswire) – March 24, 2010 - Fifteen-thousand men and 6,000 women will be told they have liver cancer this year. For patients whose cancer hasn't spread, a liver transplant offers the option of a cure … but the surgery comes with a risk of rejection and a lifetime of medications. One new procedure offers hope of a cure without a transplant.

The Gomez's have had 47 years of marriage to make memories -- some sweet, and some they want to forget.

Maria was diagnosed with liver cancer three years ago, major surgery her only option.

Last year, the cancer came back. Maria chose to delay a liver transplant with a new treatment called IRE, or irreversible electroporation. Guided by CT scans, interventional radiologists used thin needles to insert probes around Maria's tumor.

"Once we have identified the appropriate placement of the probes, we then connect them to a generator, and it kills the tumors by using very high-voltage electricity," Govindarajan Narayanan, M.D., chief of Vascular Interventional Radiology at the University of Miami in Miami, Fla., told Ivanhoe.

The 45-second electrical pulses create multiple holes in the membrane of the cancer cells, destroying the tumor.

"Almost like a neutron bomb, where you kill everything inside but the structure remains," Dr. Narayanan explained.

The body naturally removes the cell structure that's left behind. Unlike traditional ablation, the approach allows radiologists to reach tumors close to blood vessels and leaves no scar tissue behind. No large incisions are required.

"When the healing process takes place, it almost looks like the tumor was not there," Dr. Narayanan said.

Patients are sent home the next day. Forty-eight hours after her procedure, Maria is back soaking in the memories.

Dr. Narayanan says ideal candidates for IRE have liver tumors smaller than 5 centimeters, or they aren't eligible for a transplant. Patients with tumors on multiple organs or who have a pacemaker aren't candidates for the procedure. Doctors plan to use the treatment for cancers of the lung and kidneys and have successfully performed it on the first case of pancreatic cancer.

FOR MORE INFORMATION, PLEASE CONTACT:
Lisa Worley - Media Relations
University of Miami Miller School of Medicine
(305) 243-5184

February 26, 2010 – Self-professed drug addict and surgical tech, Kristen Diane Parker was sentenced to 30 years in jail for stealing the liquid painkiller Fentanyl from syringes laid out in operating rooms for surgical patients,

According to a recent Denver Post article, this surgical tech stole the painkillers from Rose Medical Center and Audubon Ambulatory Surgery Center in Colorado Springs and replaced the painkiller with water or saline solution so that other medical staff were not aware. However, many of the patients for whom the drugs were intended said they suffered pain upon waking from surgery. In what U.S. District Court Judge Robert Blackburn called "incomprehensible and unconscionable" actions, Parker, age 27, infected at least 18 patients with hepatitis C when the dirty syringes were used to inject them with the water or saline that Parker had used to replace the painkiller.

Rose Medical Center sent out 4,700 letters to patients who were at risk and are still taking steps to make sure nyone impacted is properly treated.

Parker, worked at Rose Medical's operating rooms from October 2008 to April 2009 when she was fired for testing positive for narcotics. In the meantime, Rose has updated its drug security procedures according to a statement.

March 29, 2010 - One of the challenges facing Specifically Targeted Antiviral Therapies for hepatitis C, or STAT-C, is that the virus can develop mutations that confer drug resistance, especially when single agents are used alone.

In the February 2010 Journal of Antimicrobial Chemotherapy, T.L. Kieffer from Vertex (developer of telaprevir) and coauthors presented an overview of viral resistance to these new types of drugs.

"Because of the remarkable sequence variation in HCV (resulting from the high viral replication rate and intrinsically error-prone nature of HCV polymerase), variants with reduced susceptibility to STAT-Cs can occur naturally before treatment, usually at low levels, and can be selected in patients not responding to potent STAT-C treatment," they wrote. The review described how resistance can develop and provided an overview of specific mutations that confer varying degrees of resistance.

Most studies to date have combined single directly targeted agents with pegylated interferon and ribavirin, but trials of all-oral regimens of drugs that target different steps of the HCV lifecycle are currently underway

Source: HEPATITIS JOURNAL REVIEW: A Bi-Monthly Publication of the Hepatitis Support Project