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Week Ending: April 21st , 2007
Alan Franciscus
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April 14th, 2007
Medical Edge: Benefits of hepatitis C drugs outweigh side effects
http://www.theeagle.com
By THE MAYO CLINIC
Associated Press
Dear Mayo Clinic: I am a 55-year-old male diagnosed with hepatitis C virus (genotype 1) in 1994. Liver biopsies in 1996 and 1999 showed mild inflammation. Now, a biopsy has shown progression to grade-2 chronic hepatitis with stage-2 fibrosis, and I am deeply concerned.
I have heard about interferon treatment with ribavirin, but am concerned about side effects. What other options may be available in the near future? Will they have fewer side effects? - Tucson, Ariz.
Answer (from gastroenterologist Michael R. Charlton at the Mayo Clinic in Minnesota): Of the six known hepatitis viruses, hepatitis B and C cause the great majority of persistent infections that result in inflammation and scarring of the liver, thereby compromising its function.
Over time, usually decades, hepatitis C virus infection can lead to cirrhosis (widespread scarring of liver tissue), liver failure or liver cancer. The virus is primarily transmitted by means of contaminated blood (transfusions or needles shared by drug users).
People with hepatitis C virus can experience fatigue, nausea, low-grade fever and persistent or recurring yellowing of the skin and eyes (jaundice). Many patients with hepatitis C virus infection, however, report few or no symptoms. This virus tends to work in silence; it can damage the liver, sometimes extensively, without symptoms.
If routine tests show only slight liver abnormalities, some doctors may decide against medical treatment at that point because the patient's long-term risk of developing a serious disease is slight.
But given the details you provide in your question, now is a good time for you to consider treatment.
Grade 2 and stage 2 respectively indicate significant, although moderate, amounts of liver-tissue inflammation and fibrosis (scar formation), both of which are measured on a scale of 0 to 4. Progression is no longer mild enough to ignore, and the benefit of treatment outweighs the risks. It could reduce or prevent any further damage.
The standard of care for hepatitis C treatment is indeed interferon combined with ribavirin (Rebetol). Interferon (brand name: Peg-Intron or Pegasys) is a protein that stimulates the immune system to attack invaders such as hepatitis C virus.
Although ribavirin doesn't appear to have antiviral properties against hepatitis C when used alone, in combination with interferon it acts to prevent the hepatitis C virus infection from returning once it has been cleared by the interferon.
Most patients have reasonably good prospects with this combination therapy, and in many cases it causes the virus to disappear altogether. Hepatitis C virus has six main "genotypes," or variants.
Among genotype 1 patients, therapy will eliminate the virus 40 percent to 50 percent of the time, and even more often - 75 percent to 80 percent - in genotype 2 or 3 patients.
But as you note, there is a price to pay.
Interferon side effects almost always include flu symptoms (which occur because the immune system has been stimulated) and may also include diarrhea, weight loss, reduced white blood cell and platelet counts, irritability, depression, insomnia, and problems with concentration and memory.
Ribavirin can cause a low red blood cell count and gout.
Both drugs can lead to skin irritation and extreme fatigue. Moreover, genotype 1 patients usually require higher drug doses and a longer course than genotype 2 and 3 patients.
Although side effects can be quite unpleasant for some, other patients hardly notice any. The good news: Medications and strategies can substantially reduce virtually all of these effects. Only about 7 percent of hepatitis C virus patients undergoing combination therapy need to stop it.
Other medications are in the pipeline.
Two classes in particular, protease inhibitors and polymerase inhibitors, show particular clinical promise. One drug in each class is in Phase III trials (with human patients) and, if successful, could be approved in about two years.
Both of these drugs, as well as others under development, will probably be used in combination with interferon, although possibly at lower doses and for shorter duration.
• To submit a question, write to medicaledge@mayo.edu or to Medical Edge from Mayo Clinic, c/o Tribune Media Services, 2225 Kenmore Ave., Suite 114, Buffalo, N.Y., 14207. For health information, visit www.mayoclinic.com.
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Isolate hepatitis sufferer, inmates say
http://www.stuff.co.nz/
By MELANIE JONES - Sunday Star Times
Prison bosses are refusing to isolate an inmate diagnosed with hepatitis B despite inmates' fears they will contract the disease.
More than 40 Paremoremo prisoners and staff had blood tests yesterday to see whether they have caught hepatitis. The results should be known later this week.
Hepatitis B is highly infectious, can lead to serious liver disease and is the leading cause of liver cancer.
The Corrections Department yesterday confirmed a Paremoremo prisoner had been diagnosed with hepatitis B and that he was still in a wing with other prisoners. The department had been in contact with the Ministry of Health and believed it was taking all the necessary steps to prevent the disease spreading.
"The risk of infection to others is believed to be low. However precautions are being taken, such as gloves being worn by staff interacting with the prisoner," said Corrections assistant general manager Bridget White.
But some inmates want the infected prisoner placed in isolation despite the assurances. "They told us it is not necessary to move him because it can only be caught if you have body fluid contact with him," a prisoner told the Sunday Star-Times.
Hepatitis B is spread mainly by the transfer of infected blood and other body fluids from one person to another. Prisoners are particularly at risk because of crowded conditions in jails and because they often share needles for drugs, tattoos and piercings.
Prisoners are not tested for hepatitis when they arrive in jail although they do have a general health check within two weeks.
White said as with all communicable diseases, Corrections was taking steps to ensure hepatitis B was not spread to other prisoners and staff. "The department has procedures in place, such as routine testing for communicable diseases to ensure that these illnesses are managed appropriately."
But Howard League for Penal Reform president Peter Williams, QC, said prison authorities needed to do more. "It's bad enough to go to prison but to come out with a disease like that is very unfair."
The spread of hepatitis in prisons had been a problem for years and Williams said he knew a couple of people who had gone into prison healthy and left diseased, "suffering for the rest of their lives".
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April 15th, 2007
Sick Canadians are dying needlessly
http://www.canada.com
RENE BRUEMMER, The Gazette
Organs from potential donors wasted. Provincial wrangling over health care preventing national transplant network, expert says
Canadians are dying needlessly while the organs from potential donors go to waste because the country lacks a national donation network, says the head of an international transplant group.
"Rather than having Canadians travel abroad to buy their organs in the Philippines or China, Canada needs to do a better job of harvesting and distributing the organs of the deceased in its own country," said Francis Delmonico, a professor of surgery at Harvard University.
Delmonico is medical director of The Transplantation Society, an international group of transplant surgeons that recently moved its head office to Montreal.
Provinces must put aside jurisdictional wrangling over health care and institute a national database of patients awaiting organs and potential donors, he said in an interview.
"Canada has fallen in its rates of organ donation, whereas every other country is increasing around the world."
Provinces have balked at the creation of a national network, fearing infringement on their health territory after spending decades establishing their systems.
Some sectors, like the liver and heart transplant centres, argue they already have agreements to share organs on a priority basis nationwide.
But distribution rates vary widely. According to an article in the Canadian Medical Association Journal, Ontario dialysis patients waited a median eight years for a kidney, compared with three years in Alberta.
On Jan. 1, 2006, 3,974 Canadians were awaiting an organ transplant, compared with 2,592 in 1995, the article notes. About 275 Canadians died while waiting for a transplant in 2005.
A national database doesn't have to infringe on provincial boundaries, Delmonico said. Transplant rates in the U.S. soared after new regulations compelled hospitals to bring every imminent death to the attention of local organ procurement centres. Agents assess the cases and check them against a national database of people waiting for a donation.
"In 1990, the U.S. had 4,000 donors; in 2002 we had 6,000," Delmonico said. "But in 2006, we were up to 8,000. We increased 2,000 donors in four years, whereas it took us 12 years to do it before."
Ontario, British Columbia, Manitoba and New Brunswick have instituted similar measures, requiring hospitals to report potential donors.
A heart from Newfoundland can't make it to Vancouver - it can only last four hours on ice in transit from donor to recipient - but it could go to New Brunswick, Quebec or Ontario, Delmonico said.
And a kidney, which can last a day and a half, could cross the country if needed, as opposed to going to waste because a matching recipient can't be found in its province of origin.
The lack in available organs is a worldwide phenomenon, creating "transplant tourism" where individuals from affluent nations travel to places like China to procure the kidney of death-row inmates, or buy one for $2,500 from a poor villager in Pakistan. Ethical conundrums aside, recipients are taking a major risk, Delmonico said.
The Transplant Society is in favour of incentives for donors, such as a recent British Columbia initiative that saw living donors of kidneys or livers compensated for lost income, travel and parking, up to $5,500.
In Pennsylvania, the state started a pilot project to donate $300 toward the funeral costs of a deceased donor.
But the society draws the line at selling organs for cash incentives, which has been shown in such countries as China, Iran and Pakistan to create organ "markets" with higher prices based on age, ethnicity and gender, and hefty percentages being paid to organ brokers.
Better to create a national system that would increase the availability, Delmonico said.
A national body is sensible, he said. "You know Canadians would support this.
"Organs just decay in the body if they're not donated. This just shouldn't be. We've gone long enough with this old story."
rbruemmer@thegazette.canwest.com
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Blood DNA Can Be Early Predictor of Liver Cancer
http://www.sciencedaily.com
Science Daily — Researchers at Columbia University's Mailman School of Public Health have discovered a means for early detection of liver cancer. Using DNA isolated from serum samples as a baseline biomarker, the scientists examined changes in certain tumor suppressor genes that have been associated with the development of liver carcinomas. This is the first study to prospectively examine potential biomarkers for early detection of liver cancer in high-risk populations, including those with chronic hepatitis B and C virus infections.
Since most hepatocellular or liver carcinomas (HCC) are diagnosed at an advanced and usually fatal stage, the development of screening methods for early detection is critical. HCC is one of the most common and rapidly fatal human malignancies. Worldwide, the almost 500,000 new cases and nearly equivalent number of fatalities illustrates the lack of effective therapeutic alternatives for this disease.
The Mailman School researchers and colleagues studied the blood of patients enrolled in a cancer screening program in Taiwan, who provided repeated blood samples prior to diagnosis. A total of 12,000 males and over 11,900 females recruited in 1991-2 are being followed. Screenings performed by the team of Mailman School scientists found changes associated with cancer in serum DNA, presumably released from the tumor, one to nine years before actual clinical diagnosis.
Certain clinical risk factors such as age and hepatitis B and C virus infections, are well documented risk factors for the development of HCC. According to the study findings, these factors coupled with smoking and alcohol status, and alterations found in this study in serum DNA, resulted in an overall predictive accuracy of 89% for detection of HCC.
"These are extremely encouraging findings," says Regina Santella, PhD, professor of Environmental Health Sciences at the Mailman School of Public Health, director of the Columbia's NIEHS Center for Environmental Health in Northern Manhattan, and principal investigator on the research. "Having the tools to identify hepatocellular carcinoma at earlier stages, is truly a breakthrough for addressing the challenges that result from this highly lethal form of cancer."
Dr. Santella and the team of researchers previously found that several environmental factors including aflatoxin B1, a dietary mold contaminant sometimes found in peanuts and corn; polycyclic aromatic hydrocarbons, ubiquitous environmental contaminants; and 4-aminobiphenyl, a carcinogen found in cigarette smoke, are also associated with the development of HCC. While HCC incidence is highest in East Asia and Sub-Saharan Africa, it is also increasing in the U.S primarily as a result of HCV infection.
"We are not only very excited about what this means in terms of early detection for hepatocellular cancer but optimistic about how it could also be applied to other cancers," observes Dr. Santella. The full study findings are published in the April 15, 2007 issue of Clinical Cancer Research.
Note: This story has been adapted from a news release issued by Columbia University's Mailman School of Public Health.
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April 16th, 2007
Research on B-cell lymphoma therapy described by scientists at University of Pavia, Division of Hematology
www.newsrx.com
Researchers detail in "Prevalence of HCV infection in nongastric marginal zone B-cell lymphoma of MALT," new data in B-cell lymphoma. "Hepatitis C virus (HCV) infection is frequently associated with B-cell non-Hodgkin's lymphomas. We investigated the prevalence of HCV infection in nongastric marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT) in order to define the relationship between the viral infection and the presenting features, treatment, and outcome," scientists in Italy report.
"We retrospectively studied 172 patients with a histological diagnosis of marginal zone B-cell lymphoma of MALT, except for stomach, and with available HCV serology, among a series of 208 patients. HCV infection was documented in 60 patients (35%). Most HCV-positive patients (97%) showed a single MALT organ involvement. HCV-positive patients showed a more frequent involvement of skin (35%), salivary glands (25%), and orbit (15%). The majority of stage IV HCV-positive patients (71%) had a single MALT site with bone marrow involvement. The overall response rate was similar in HCV-positive (93%) and HCV-negative patients (87%). Overall survival (OS) and event-free survival (EFS) did not differ according to HCV infection. In multivariate analysis, advanced disease (stage III-IV) was associated with a poorer OS (p=0.0001), irrespective of HCV serostatus. This study shows that nongastric marginal zone lymphomas are characterized by a high prevalence of HCV infection. Patients with involvement of a single MALT site have the highest prevalence of HCV," wrote L. Arcaini and colleagues, University of Pavia, Division of Hematology.
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April 17th, 2007
Blood safety warnings 'ignored'
http://news.bbc.co.uk
By Susan Watts
BBC Newsnight, Science editor
Evidence UK scientists ignored warnings that could have prevented people with haemophilia being given contamined blood has been seen by the BBC.
The Newsnight programme has seen documents suggesting experts were aware of the threat at an early stage, but transfusions were not stopped.
In the 1970s and 1980s, 4,500 UK haemophilia patients were exposed to lethal viruses in blood products.
Two thousand have since died of either Hepatitis C or HIV.
Successive governments have resisted attempts to hold a full inquiry. As a result campaigners have organised a private inquiry which will hold its first hearing on Wednesday.
It is generally accepted that many people with haemophilia became infected from supplies of the clotting agent Factor 8 from abroad.
Unbeknown to them at the time, much of the plasma used to make Factor 8 came from donors like prison inmates in the US.
These prisoners were allowed to sell their blood even though there were questions over their health.
Lack of knowledge
Successive governments have said politicians, civil servants and doctors simply did not know enough about the dangers of Factor 8 concentrates to stop using them in time.
It has been difficult for those affected to challenge that, as many official documents have mysteriously disappeared.
The government claimed some were shredded, and it has refused to release others on grounds of "commercial confidentiality".
Relatives of some of those who have died have managed to get hold of some of these documents over the course of many years.
They show show many knew a lot more, much earlier than has ever been admitted.
Key letter
One of the most shocking is a letter from the head of Britain's public health surveillance centre warning the Department of Health about the risk of Aids from Factor 8 after Britain's first case in Cardiff.
It calls for all US imports to be banned.
This was May 1983, before most people with haemophilia in the UK became infected with HIV.
The letter says: "I have reviewed the literature and come to the conclusion that all blood products made from blood donated in the USA after 1978 should be withdrawn from use until the risk of Aids transmission by these products has been clarified."
Despite this warning, Factor 8 imports continued to be used.
Even when safer heat-treated versions came along, it was left to local physicians to decide whether to use them.
Many apparently chose to use up non heat-treated material first.
Secret tests
Some people with haemophilia have told us they are convinced, after studying the paperwork, that they were secretly tested, without their knowledge or consent.
And in some cases, even when those tests showed they were HIV positive, the patients themselves were not told for several years.
One of those was Robert Mackie. At the time, he had only mild haemophilia, and did not even need to be on Factor 8.
He said he would never have taken it if doctors had told him about the risks.
"They are saying they didn't know about the Aids virus.
"I'm sorry. By June 1983 when the European Commissioners put out a warning that all haemophiliacs in Europe, including the UK were to be informed of the risk of Aids. Why weren't we warned of the risks?"
Not told
Mr Mackie discovered by accident that his doctor, Professor Christopher Ludlam of the Edinburgh Royal Infirmary, was doing a lot more than looking after patients.
In a medical newsletter in 1990, Professor Ludlam described a unique group of patients in Scotland that had formed the basis of several years of important research he had published on Aids.
When Mr Mackie saw this, he examined his records.
He has discovered that although he was infected in 1984, he was not told until 1987.
And strangely, the words "Aids study" were clearly written in his medical notes before he was infected.
Mr Mackie is convinced he was part of scientific attempts to understand the virus behind Aids, but he was not told.
Patient group
He has discovered that in April 1983 - before he was infected - Aids specialists at one of the US's top medical institutions wrote in the Lancet about how valuable it would be to locate a group of haemophilia patients in a country not yet affected by Aids.
That was the position that the UK was in at the time, and Professor Ludlam offered up his patients in response.
We approached Professor Ludlam him but he said he had a duty of confidentiality to individual patients - even though Mr Mackie himself wants answers.
He declined to speak because of a potential investigation by the General Medical Council.
There is intense pressure now on the privately-funded inquiry that starts tomorrow, and it has got heavyweight backing.
It is being chaired by the former solicitor general Lord Archer of Sandwell.
Several former health ministers have already said they will appear, and haemophilia patients hope it may convince the government to release any documents it is still sitting on.
Government response
The Department of Health said in a statement it had been open and transparent on the issue in the past.
It said it was reviewing all documents on hepatitis C from 1970-1985, including some which had previously been considered missing from a firm of private solicitors.
"Reference to HIV is made in some of the documents, and we plan to release as many of these documents as possible."
A full report will be broadcast on Newsnight on BBC 2 at 2230 BST on 17 April.
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Contaminated blood inquiry begins
http://news.bbc.co.uk
An independent public inquiry into the supply of contaminated NHS blood to haemophilia patients is set to hear evidence from those affected.
During the 1970s and early 1980s, nearly 5,000 people were exposed to hepatitis C and of these more than 1,200 were also infected with HIV.
More than 1,700 patients have since died, and many more are terminally ill.
The inquiry is being funded privately, and not by the government who said treatments were given in "good faith".
Labour peer Lord Archer of Sandwell, a former solicitor general, is leading the inquiry which is due to report in late summer.
In his opening statement, Lord Archer said the inquiry would investigate the circumstances surrounding the supply of contaminated NHS blood and blood products and make recommendations to assess the needs of patients and bereaved families.
Hopefully, we may discover something that will help for the future and we can learn some lessons – Lord Archer
BBC's Newsnight programme has reported seeing documents suggesting experts were aware of the threat at an early stage, but transfusions were not stopped.
Lord Archer said the first purpose of the inquiry was to find out why and how this contamination occurred to help those affected come to terms with what had happened.
He added: "Hopefully, we may discover something that will help for the future and we can learn some lessons."
Lord Archer said the Department of Health had told him it would help as far as it could and he promised to ask officials for documents that could be relevant.
Any evidence "of anything which is blameworthy" would be investigated, he added.
If we had gone in for self-sufficiency, I am pretty confident we would have had a substantial reduction in contaminated blood supplies – Lord Owen
Asked about the Newsnight allegations, Lord Archer said: "I cannot comment on what evidence we are going to have, because we have not heard any evidence."
He said if allegations were made against particular doctors or consultants they would be asked to the inquiry.
Former health ministers had also offered to help the inquiry, Lord Archer added.
Meanwhile former health minister Lord Owen said he had secured extra money in 1975 to help avoid using blood donations from abroad, but had later found out it had not been spent.
Lord Owen said: "If we had gone in for self-sufficiency, I am pretty confident we would have had a substantial reduction in contaminated blood supplies.
"It would not have completely ruled it out, but I think much fewer people would have got Hepatitis C and fewer people would have got Aids."
Bleeding disorder
Haemophilia is a rare inherited bleeding disorder in which blood does not clot normally.
There's a huge number of questions that need to be answered – Roddy Morrison, Haemophilia Society
The main problem is internal bleeding into joints, muscles and soft tissues.
Currently, the condition can only be treated by injections of the clotting chemical, known as factor VIII.
In the early 1970s, patients were treated with blood proteins that came in dry powder form and could then be reconstituted with water - plasma from 10,000 donors went into the product.
The treatment, which often came from patients in the United States who were paid for giving blood, exposed 4,670 patients to hepatitis C infection.
In 1981 it was also found that some plasma products were infected with HIV.
After the mid-1980s the plasma products were treated with heat to kill viruses.
Successive governments have refused to admit any fault but payments of varying amounts have been made to people who caught HIV.
In 2004, the Skipton Fund was set up for those infected with hepatitis C virus but no payments were made to those who died before 2003.
Campaign
Roddy Morrison, chairman of the Haemophilia Society said he was absolutely delighted the inquiry was going ahead.
"It's taken 19 years of campaigning.
"There's never been a chance for people to tell their stories and to know that people with the right skills will be able to look at this and establish what happened and could things have been done to prevent this.
"There's a huge number of questions that need to be answered."
A spokesperson for the Department of Health said they had been open and transparent about the issue.
"We have great sympathy for those who were infected with Hepatitis C and HIV and understand why they want to know how it happened and why it could not have been prevented.
"However, the government of the day acted in good faith, relying on the information available at the time."
Professor Christine Lee, emeritus professor of haemophilia in the University of London agreed there was a lot of misunderstanding about what was known at the time.
"The hepatitis C virus wasn't isolated until 1989 and there wasn't a blood test until 1991.
"Also there was no alternative and the life expectancy of someone with haemophilia was 20 years," she said.
But she added that the inquiry may give patients the chance to vent their feelings and get some closure.
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IMO seeks Hep C re-testing increase
http://www.irishmedicalnews.ie
The IMO says it has written to the IBTS seeking an increase in fees payable to GPs in respect of their participation in the Hepatitis C re-testing scheme. An increase in the fee payable from E31.22 at present to E75.00 has been sought.
Responding to the IMO’s request, consultant haematologist with the IBTS, Dr Emer Lawlor, said she had forwarded details of the IMO’s claim to Mr Andy Kelly, Chief Executive of the IBTS, and that she will respond further once the issue was discussed with him.
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New drugs in the works in battle vs. hepatitis C
http://www.nj.com/
BY GEORGE E. JORDAN
Star-Ledger Staff
Tests on humans spark hope as firms pledge cooperation
Hepatitis C, the leading reason for liver transplants, incubates in the body for 20 years or more before causing irreparable damage.
Treatment options are limited: Fewer than half of hepatitis C patients respond to standard drug therapy, and those who do too often are sickened by the medicine or develop drug resistance. The virus infects 4 million people in the United States, 170 million worldwide.
That helps explain the optimism at a liver disease conference in Europe last week after data was presented from early human testing of five experimental drugs. It also helps explain the unusual degree of cooperation among the drugmakers developing the compounds, including Schering-Plough, Hoffman-LaRoche, Vertex Pharmaceuticals and partnerships of Wyeth-ViroPharma and Novartis-Idenix Pharmaceuticals.
Researchers are sharing information with the hope of creating potent combination medicines, like the drug "cocktails" that transformed HIV/AIDS treatment.
"We're very interested in collaborating with other companies to advance the science," Robert Consalvo, a spokesman for Schering-Plough, said from the European Association for the Study of the Liver conference in Barcelona.
"Down the road, especially with nonresponders, maybe you need a quad-combination pill. Maybe that would be the best way to treat this disease."
As many as 28 new hepatitis C therapies are under development as companies in the United States, Europe and Japan chase a share of the $4 billion global hepatitis C market. Wall Street analysts predict a breakthrough drug could double the size of the market in five years to $8 billion.
"It's a big deal, and we feel that it is good news for patients with hepatitis C," Paul Pockros, head of gastroenterology at Scripps Clinic in La Jolla, Calif., and a leading liver disease expert, said of the latest trial results. "The likelihood of at least one of those drugs making it is good."
Hepatitis C, an inflammation of the liver, is the leading cause of cirrhosis and liver cancer and the No. 1 reason for liver transplants in the United States. Infection typically happens during sex, childbirth or the sharing of hypodermic needles by intravenous drug users. As a result, it also infects about two of every five HIV sufferers in the United States, mainly because both viruses are transmitted by contact with blood.
The existing optimal therapy -- a synthetic version of pegylated interferon, a protein that bolsters the immune system, and ribavirin, which slows viral replication -- has severe side effects, including flu-like symptoms, depression, fatigue and rashes. In most cases, it must be administered several times a day.
For reasons unknown to science, African-Americans have a lower response rate to interferon-based drugs, if those drugs work at all.
The drugs under study by Schering-Plough, Vertex and Hoffman-LaRoche -- once- or twice-a-day tablets -- are being watched closely because they are specifically designed for "nonresponders."
Schering-Plough's drug, known as boceprevir, is at the midway point of Phase II clinical trials. The results, which include drug-resistant and other difficult-to-treat patients, are scheduled for release in November.
Both Schering-Plough's drug and Vertex's compound, code named VX 950, are known as protease inhibitors. The other drugs in the pipeline are antivirals called polymerase inhibitors. All are designed to disrupt the reproductive cycle of hepatitis C virus.
The compound being developed by the Novartis-Idenix partnership, called valopicitabine, is the furthest along in clinical trials.
Researchers in Spain heard 13 papers at last week's conference about valopicitabine, all Phase IIb studies exploring the once-a-day treatment in combination with existing therapies and various investigational drugs.
In a 2005 study, the drug reduced hepatitis C virus levels by more than 90 percent after only two weeks of therapy.
The next step for the stable of hepatitis drug candidates is late-stage clinical trials involving as many as 10,000 people. The wide-scale trials will answer an important question: Do the investigational drugs work well with HIV/AIDS medications, known as highly active antiretroviral therapy, or HAART?
"You will need to test whether the new drugs interact with HAART therapy, because that would inhibit what therapy the patient is on," said Pockros, the California liver specialist. "Secondly, we will need to find out if HAART blocks the hepatitis C therapies."
George E. Jordan may be reached at gjordan@starledger.com or (973) 392-1801.
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Bristol-Myers Squibb's Baraclude to Dominate the Hepatitis B Virus Market through 2015
http://biz.yahoo.com/
Baraclude Outperforms Current Therapies in Efficacy and Safety, According to a New Report from Decision Resources
WALTHAM, Mass., April 17 /PRNewswire-FirstCall/ -- Decision Resources, Inc., one of the world's leading research and advisory firms focusing on pharmaceutical and healthcare issues, finds that Bristol-Myers Squibb's Baraclude will dominate the hepatitis B virus market through 2015. According to the new report entitled Coping with the Rise in Drug Resistance: A Hepatitis B Virus Study, Baraclude outperforms current therapies in efficacy and safety.
"In clinical trials, Baraclude has proved to be more efficacious in reducing viral load, which is the key end point influencing physicians' prescribing decisions," said Kaitlyn Sullivan, associate analyst at Decision Resources. "Also, Baraclude also more effectively reduces liver fibrosis and inflammation than the other therapies currently on the market, and the agent is less prone to viral resistance than GlaxoSmithKline's Epivir."
Most therapies in the pipeline for the treatment of hepatitis B virus do not have clinical profiles that can compete with Baraclude's efficacy and safety profiles.
About Coping with the Rise in Drug Resistance: A Hepatitis B Virus Study
Coping with the Rise in Drug Resistance: A Hepatitis B Virus Study covers the current and future state of the hepatitis B virus market. The report includes the following:
- More than 3,000 physician responses that define drug attributes that drive prescription now and in the future.
- Clinical end point tradeoffs that are most influential to physicians.
- Areas of unmet need with highest potential.
- Benchmark trial results for specific drug opportunities.
- Patient share potential for emerging therapies and target product profiles.
- Decision Resources proprietary analysis of commercial factors that accelerate or constrain a drug's market potential.
- Promotion: DTC spend, detailing intensity.
- Reimbursement: formulary tier, prior approval restriction, quantity limits.
- Labeling: black box warnings, approved patient segments, contraindications.
- Competition: order of entry, pricing, generic entry, pipeline sales forecast.
- Medical practice: decision trees, treating physician type, line of therapy.
- Comparisons of the key clinical attributes of current and emerging therapies in the areas of efficacy, safety, and delivery.
- Analysis and supporting data that identifies the clinical "Gold Standard" now and over the next ten years.
- Key insights as to which clinical end points have the greatest influence on physician decision-making.
The report can be purchased by contacting Decision Resources. Members of the media may request an interview with an analyst.
About Decision Resources
Decision Resources, Inc., (http://www.decisionresources.com) is a world leader in market research publications, advisory services, and consulting designed to help clients shape strategy, allocate resources, and master their chosen markets.
All company, brand, or product names contained in this document may be trademarks or registered trademarks of their respective holders.
For more information, contact:
Elizabeth Marshall
Decision Resources, Inc.
781-296-2563
emarshall@dresources.com
Source: Decision Resources, Inc.
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April 18th, 2007
Researchers find hepatitis A and hepatitis C attack same protein to block immune defenses
http://www.spiritindia.com
Hepatitis A and hepatitis C, two otherwise unrelated liver viruses have one important thing in common: a trick for avoiding destruction by the immune system. Both dodge immune attacks by attacking the same protein -- an essential link in a chain of molecular signals that triggers antiviral responses.
Despite the fact that they both infect the liver, the hepatitis A and hepatitis C viruses actually have very little in common. The two are far apart genetically, are transmitted differently, and produce very different diseases.
Hepatitis A spreads through the consumption of fecal particles from an infected person (in pollution-contaminated food or water, for example), but hepatitis C is generally transmitted only by direct contact with infected blood. Hepatitis A produces fever, nausea and abdominal pain that can last for weeks, but rarely lead to de ath; hepatitis C, by contrast, often spends decades quietly damaging the liver, until a victim’s only hope for survival is an organ transplant.
According to researchers at the University of Texas Medical Branch at Galveston (UTMB), though, these two otherwise unrelated liver viruses have one important thing in common: a trick for avoiding destruction by the immune system. Both dodge immune attacks by attacking the same protein — an essential link in a chain of molecular signals that triggers antiviral responses.
"With 30,000-plus proteins in the cell, it’s really remarkable that these two very different viruses have chosen to strike at the same one," said Dr. Stanley Lemon, director of UTMB’s Institute for Human Infections and Immunity and National Institutes of Health-funded Hepatitis C Research Center. Lemon is senior author of a paper on the research appearing online this week in the Proceedings of the National Academy of Sciences. "This identifies the protein — called MAVS, for mitochondrial antiviral signaling protein — as extremely important for the survival of any virus in the liver."
MAVS proteins project from tiny structures called mitochondria, which are found in large numbers in each liver cell. When specialized receptor molecules detect viruses in the cell, they dock with the MAVS proteins, thereby triggering a sequence of signals ending with the production of interferon beta— a potent inhibitor of virus replication. Recent research has shown that hepatitis C generates a protein called NS3/4A that chops up MAVS, interfering with immune signaling and possibly providing the cover the virus needs to survive so long in the liver. Now, Lemon and his group have demonstrated that hepatitis A does the same thing with a different protein, known as 3ABC.
"Hepatitis A never manages to establish a long-term infection like hepatitis C even though it also destroys MAVS," Lemon said. "This suggests that the degradation of this cell protein is not the main reason that hepatitis C becomes persistent. These results thus provide a new perspective on the chronicity of hepatitis C, which is a highly relevant virus clinically."
Hepatitis C has received far more research attention than hepatitis A in recent years, according to Lemon, largely because of hepatitis C’s chronic nature and the lack of a vaccine against it. But while better sanitation has driven a decline in hepatitis A cases in the United States, Lemon said, "It’s a significant risk for many people traveling overseas, because they fail to receive the vaccine." Hepatitis A has also been the cause of large food-borne outbreaks in the U.S. in recent years, including one in Pennsylvania that caused three de aths in otherwise healthy adults.
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Low-cost, free hepatitis testing to be offered in May
http://the.honoluluadvertiser.com
Advertiser Staff
With Asian Americans and Pacific Islanders having the highest prevalence of hepatitis B in the nation, the Hepatitis Support Network of Hawai'i is urging residents to take advantage of free or low-cost hepatitis B or C testing during May, the National Hepatitis Awareness Month.
Testing will be done with the assistance of Dr. Alan D. Tice's team, located at 550 S. Beretania St., Room 400.
Dr. Tice's testing times will be each Monday during May from 10 a.m. to 2 p.m. Appointments can be made outside of these times by calling 221-6204.
The network suggests if you've had a blood transfusion in the U.S. before 1992, snorted drugs or shared needles even once you should be tested for hepatitis B.
More information can be found by calling the Hepatitis Support Network of Hawai'i at 373-3488.
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Hepatitis C is treatable virus
http://therecordherald.com
By Nancy Mace The Record Herald
Dr. Fawaz Hakki is shown with his staffers Jody Fleagle, left, a licensed practical nurse, and Nicole Tacelosky, a medical assistant.
WAYNESBORO - A local physician wants to increase awareness about hepatitis C, a chronic but curable illness celebrities Pamela Anderson and Naomi Judd have struggled with.
Dr. Fawaz Hakki is trying to get the word out about the risk factors for the virus that attacks the liver, an organ as vital as the heart.
“It's the only virus in the body we can cure or eradicate with a combination therapy,” noted Hakki of Potomac Gastroenterology in Waynesboro Hospital.
Who's at risk?
Those at risk for hepatitis C include people who received blood transfusions before 1992 and blood products before 1987.
Of the more than four million people in the United States who have hepatitis C, 30 percent will develop chronic liver disease with complications - liver failure, cirrhosis or liver cancer.
“The good news is it can be detected early with a simple blood test,” Hakki said.
Hakki and his staffers, Jody Fleagle, a licensed practical nurse, and Nicole Tacelosky, a medical assistant, began treating patients with the illness two months ago. The treatment also is available at Chambersburg Gastroenterology Associates.
Patients receive an injection of interferon once a week and take ribavirin pills daily.
The treatment takes six months to a year and patients are monitored closely, according to Hakki.
How it's spread
In the United States, hepatitis C is the most common infection that is carried in the blood.
Anyone can get the disease, but about 1 in 10 people don't know they have it.
“Hepatitis C was not identified prior to 1992. Hepatitis that was not caused by hepatitis A or hepatitis B was referred to as non-A or non-B,” Hakki noted.
Having more than 15 sexual partners without using protection also puts someone at risk for hepatitis C, he said.
Sharing needles, even once, as well as snorting drugs due to blood on a shared straw or bill, are other risky behaviors.
“You can get hepatitis C when you get a tattoo - even if they use a sterilized needle, because sometimes they don't change the ink,” he said.
Along with tattoos, body piercings also are a way to contract the disease.
There are some simple steps to help other people from getting hepatitis C.
“Even though the risk through sexual transmission is low, use protection. That extra precaution is not going to hurt,” he said.
Hakki also advises against sharing toothbrushes, nail clippers, razors or other personal care items.
No symptoms
The majority of people are symptom free during the early stages of hepatitis C, he noted, but the most chronic symptom is fatigue.
Other complaints include aches and pains, stomach problems, blood sugar problems, moodiness and problems sleeping.
The sooner someone finds out they have hepatitis C the better - treatment can slow down or stop the liver damage.
“One of the strongest indications for liver transplantation in the United States is for people with chronic hepatitis C,” according to Hakki.
People being treated for hepatitis C are encouraged to make healthy lifestyle changes - avoid alcohol and drugs, exercise and pay attention to how they feel.
“We're very excited - hopefully we're providing a service to the community,” Hakki said.
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April 19th, 2007
Hepatitis doctor given jail term
http://news.bbc.co.uk
Daniel Mutunda had claimed to be medically fit
A doctor who put thousands of patients at risk by working at hospitals across the UK while suffering from hepatitis B has been jailed for 18 months.
Emergency doctor Daniel Mutunda, 43, of Barking, east London, asked a friend to provide a blood sample for him after a routine test showed he had the virus.
He was jailed at Hull Crown Court on Thursday after earlier admitting falsely claiming to be medically fit.
Judge Simon Jack said the damage done by Mutunda was "incalculable".
'Huge worry'
Mutunda, of Ventner Gardens, had worked in accident and emergency departments in Barnsley, Exeter, Hull, York, Preston and numerous hospitals in London.
The court heard that about 60,000 patients had to be screened for hepatitis B as a result of his actions, though none was believed to have been infected.
“He betrayed a position of trust in a public office . . . he's let his family down, the church, the public” – Det Sgt Dave Wescott
Sentencing him on Thursday, Judge Jack described Mutunda as "something of an enigma".
He said: "You put patients at risk.
"If you had made a mistake and failed to use gloves or something of that sort a patient could have been infected.
"When the true position came to light and the investigation took place there must have been a huge amount of worry for anybody who became aware that they had been treated by you.
"The damage that has been done is incalculable."
Sentence 'lenient'
When a routine blood screening showed Congo-born Mutunda had the life-threatening virus, he asked a friend to provide a blood sample for him and continued working.
He was suspended in 2004 after an investigation by the General Medical Council (GMC), but continued to work, securing employment through an agency.
Mr Jack said due to the fact Mutunda continued to practice despite being suspended, his only option was to impose a prison sentence.
Speaking after the sentencing, Det Sgt Dave Wescott of Humberside Police described the sentencing as "lenient".
He said he did not believe Mutunda was "the only one" and said the case exposed "a lot of flaws in the system and a lot of inconsistencies with the way locums are appointed".
"I would be surprised if there weren't other people doing the same thing", he said.
"He betrayed a position of trust in a public office. He's let his family down, the church, the public more than anything."
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April 20th, 2007
"Decoding" Hepatitis
http://news.ert.gr
By Tina Valaoura
The Cologne University Genetics Institute has made a significant step towards decoding hepatitis C and liver cancer. According to an article in Deutsche Welle website, laboratory tests carried out by a group of scientists headed by Greek geneticist, Manolis Pasparakis have indicated how certain viruses damage liver cells.
A three- year research indicates that a particular protein, named Nemo plays an important role in the generation of hepatitis C and liver cancer.
The scientific group believes that this discovery will lead to the production of medicine to cure hepatitis and liver cancer, even speaking of a most optimistic view that is the prevention of these diseases as in most cases hepatitis C-inflamation of the liver- develops into cancer if it is not effectively cured.
Asia and Africa have the largest percentage of hepatitis victims, which in the majority of cases develops into liver cancer, due to inefficient medical treatment and hygiene which favor the spread of hepatitis.
Till present, however, scientists did not know how a virus affected a healthy cell. Pasparakis group recent discovery about Nemo protein is that it regulates an important channel, named NF Kappa B which determines liver cell reactions. If the liver cell fails to activate NF Kappa B channel it becomes vulnerable to virus attacks and may be damaged. Pasparakis said by achieving to block Nemo protein we noted a parallel block NF Kappa B channel. In response to what this achievement meant for future treatment, medicine and prevention of the disease he said since we found that a virus can block NF Kappa B channel this means that we have found how a viruses affects cells to develop into cancer.
Sources: ΑNA-ΜNA
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Peregrine Pharmaceuticals Highlights Significant Advances in the Company's Clinical and Preclinical Cancer Programs Presented This Week at the AACR Annual Meeting
http://www.redorbit.com/
TUSTIN, Calif., April 20 /PRNewswire-FirstCall/ -- Peregrine Pharmaceuticals, Inc. , a clinical stage biopharmaceutical company developing targeted monoclonal antibodies for the treatment of cancer and hepatitis C virus infection, today reported that data from multiple studies presented at the recent Centennial Annual Meeting of the American Association for Cancer Research (AACR) reinforced the versatility and broad anti-cancer potential of bavituximab, its clinical stage targeted anti- phospholipid (PS) monoclonal antibody; provided important new preclinical data confirming the potential anti-tumor efficacy of the company's selective VEGF inhibitors; provided validating data for its immunocytokine fusion proteins developed using the company's proprietary Vascular Targeting Agent (VTA) technology; and highlighted the clinical potential of Peregrine's earlier stage VTA and Vasopermeation Enhancement Agent (VEA) cancer platforms.
"We are extremely pleased with the quality, breadth and diversity of the studies we were selected to present at this historic Centennial AACR Annual Meeting," said Steven W. King, president and CEO of Peregrine. "We believe these studies are a testament to the scientific, medical and commercial potential of our core technology platforms. In particular, multiple studies presented data that support the broad anti-cancer utility of our anti-phospholipid platform, including our lead product candidate bavituximab, in a variety of applications and indications. Research confirming the versatility of our anti-PS antibodies in different anti-cancer combinations is especially encouraging. In addition, we also presented data that supports advancement of potentially important anti-cancer development programs based on our selective anti-VEGF, VTA and VEA technologies. These positive developments in our clinical and preclinical programs reinforce our belief that the future for Peregrine has never been brighter, and we look forward to progressing these programs both on our own and with partners and collaborators going forward."
Highlights of seven of Peregrine's AACR presentations this week follow. Peregrine's Selective Anti-VEGF Antibody Program
Drugs blocking vascular endothelial growth factor (VEGF) are proving very successful as anti-cancer agents, and for the first time researchers presented animal data on Peregrine's anti-VEGF antibodies that selectively block binding to the second of the two VEGF receptors. Current anti-VEGF drugs such as Avastin(R) block binding to both receptors, yet in preclinical studies comparing Peregrine's selective anti-VEGF antibody to Avastin, the selective antibodies compared favorably on all efficacy parameters assessed, inhibiting tumor growth by 90% in preclinical cancer models. Antibodies with greater selectivity may have advantages in clinical use since they have the potential to only inhibit angiogenesis while not impairing other functions of VEGF. Additional data that was presented showing the efficacy of Peregrine's fully human selective anti-VEGF antibody (R3) is expected to help facilitate the progress of this program towards clinical trials.
Broad Applicability and Versatility of Bavituximab, Peregrine's Targeted Anti-PS Antibody
Researchers affiliated with Peregrine presented a number of preclinical studies demonstrating the versatility and broad anti-cancer utility of bavituximab in major cancer models. They also reported data validating bavituximab's unique mechanism of action and supporting potential new applications of Peregrine's anti-PS technology platform. These included:
* Data supporting the potential use of bavituximab to enhance immune responses to existing tumors and as a potential enhancement to cancer vaccines. In a challenging model of aggressive brain cancer, 57% of animals immunized with a bavituximab equivalent and irradiated, inactivated tumor cells achieved long-term survival compared to 0% in untreated animals and only 16% survival in animals receiving inactive tumor cells with an antibody that does not block PS. To achieve this survival result, the vaccine-like bavituximab regimen is estimated to have enabled these animals to destroy 99.99% or more of the huge tumor cell challenge they were given. These impressive results provide important confirmation of the ability of bavituximab's anti-PS mechanism to reverse the immune system inhibition caused by cancer and offer another potential application for bavituximab and Peregrine's other anti-PS antibodies. * Data demonstrating the potent anti-cancer efficacy of bavituximab in combination with chemotherapy. A bavituximab equivalent in combination with the common cancer chemotherapy docetaxel reduced the growth of both hormone-dependent and hormone-independent prostate cancer by up to 94%. Bavituximab is currently being assessed in a Phase lb cancer clinical trial that includes patients receiving docetaxel. Prostate cancer is one of the most common cancers affecting men and is a leading cause of cancer deaths. * Data supporting use of anti-PS antibodies as the targeting agent for immunocytokine fusion proteins based on Peregrine's VTA platform. Their ability to target phospholipids primarily expressed on the surface of tumor blood vessels enables bavituximab-like antibodies to also serve as targeting agents for Peregrine's Vascular Targeting Agent (VTA) technology platform. Studies presented at AACR assessed the anti-cancer properties of VTA-based immunocytokine fusion proteins. These are combinations of vascular targeting agents such as bavituximab and immune system-stimulating cytokines such as interferon and interleukin-2. Peregrine's immunocytokine fusion proteins showed robust anti-tumor efficacy in animal models of melanoma and B-cell lymphoma, without the signs of toxicity that have limited the wide use of cytokines as anti-cancer agents. In particular, the 85% reduction in tumor growth observed in the B-cell lymphoma model serves as an important validation of Peregrine's VTA immunocytokine approach, and hematological cancers such as lymphoma also represent potential new cancer indications for the company.
Data on Peregrine's VTA coaguligand and VEA anti-cancer development programs.
Researchers working with Peregrine presented data on progress in the company's VTA coaguligand development program, its VEA program and its initiatives to develop second-generation anti-PS monoclonal antibodies.
* Peregrine's VTA coaguligands program has developed fusion proteins that combine a vascular targeting antibody with modified tissue factor, a protein that can induce blocking and destruction of targeted blood vessels. Since Peregrine's VTAs specifically target tumor blood vessels, the fusion proteins are intended to affect only the established blood vessels that are essential for the survival and growth of tumors. Researchers reported on their progress in successfully developing and testing a series of VTA coaguligands that currently are in further testing in animal cancer models. * Peregrine researchers gave an oral presentation on novel methods the company is employing in its drug discovery efforts for its VEA program. VEAs are a new class of therapeutics comprised of tumor-specific antibodies fused to vasoactive compounds such as interleukin-2. They are designed to increase the uptake of cancer therapeutics at the tumor site, thereby increasing anti-tumor efficacy without having to increase the dose and risk greater toxicity. The novel R&D methods described by Peregrine scientists enabled the company to identify potential VEA clinical candidates for further evaluation in animal cancer models. * Peregrine researchers also reported on their successful efforts to develop second-generation fully humanized anti-PS antibodies for possible use in a variety of Peregrine development programs. Data assessing the fully human version of the antibody indicated that it was equivalent to the current chimeric version. Fully humanized antibodies may have advantages in some applications and also provide Peregrine with greater flexibility in designing and differentiating new drug candidates. About Peregrine Pharmaceuticals
Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a portfolio of innovative product candidates in clinical trials for the treatment of cancer and hepatitis C virus (HCV) infection. The company is pursuing three separate clinical programs for HCV infection and a range of solid cancers in the U.S. and India with its lead product candidates bavituximab and Cotara(R). Peregrine also has in-house manufacturing capabilities through its wholly owned subsidiary Avid Bioservices, Inc. (http://www.avidbio.com/ ), which provides development and bio-manufacturing services for both Peregrine and outside customers. Additional information about Peregrine can be found at http://www.peregrineinc.com/ .
Safe Harbor Statement: Statements in this press release which are not purely historical, including statements regarding Peregrine Pharmaceuticals' intentions, hopes, beliefs, expectations, representations, projections, plans or predictions of the future are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The forward-looking statements involve risks and uncertainties including, but not limited to, the risk that efficacy results in the various preclinical animal models noted above will not correlate to the related efficacy studies in human clinical trials, the risk that future studies may not support the initiation of human clinical trials, and the uncertainty as to whether the Company will be able to obtain regulatory approval for any of its current product candidates. It is important to note that the Company's actual results could differ materially from those in any such forward-looking statements. Factors that could cause actual results to differ materially include, but are not limited to, uncertainties associated with completing preclinical and clinical trials for our technologies; the early stage of product development; the significant costs to develop our products as all of our products are currently in development, preclinical studies or clinical trials; obtaining additional financing to support our operations and the development of our products; obtaining regulatory approval for our technologies; anticipated timing of regulatory filings and the potential success in gaining regulatory approval and complying with governmental regulations applicable to our business. Our business could be affected by a number of other factors, including the risk factors listed from time to time in the Company's SEC reports including, but not limited to, the annual report on Form 10-K for the year ended April 30, 2006 and the quarterly report on Form 10-Q for the quarter ended January 31, 2007. The Company cautions investors not to place undue reliance on the forward-looking statements contained in this press release. Peregrine Pharmaceuticals, Inc. disclaims any obligation, and does not undertake to update or revise any forward-looking statements in this press release.
Contacts: GendeLLindheim BioCom Partners Investors Media info@peregrineinc.com Barbara Lindheim (800) 987-8256 (212) 918-4650
Peregrine Pharmaceuticals, Inc.
CONTACT: Investors, +1-800-987-8256, info@peregrineinc.com , or Media,Barbara Lindheim, +1-212-918-4650, both of GendeLLindheim BioCom Partners, forPeregrine Pharmaceuticals, Inc.
Web site: http://www.peregrineinc.com/
Source: PRNewswire-FirstCall
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