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Week Ending: February 17th , 2007
Alan Franciscus
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February 12th , 2007
Better Infection Control Programs Needed to Help Combat Hepatitis C in Egypt
http://bbsnews.net/
EGYPT: 5 million infected with Hepatitis C
BBSNews 2007-02-07 - CAIRO, (IRIN) -- At least five million people in Egypt are infected with the hepatitis C virus (HCV), a new committee formed by the country's government to tackle the disease has said. It added that action must be taken now to combat rising mortality.
US scientists, such as Dr Hong Yu of the Vaccine and Infectious Disease Organisation, are developing vaccines for hepatitis C.
For the image shown above in a larger size, see US scientists, such as Dr Hong Yu of the Vaccine and Infectious Disease Organisation, are developing vaccines for hepatitis C.
"The annual infection rate is more than 70,000 new cases, of which at least 35,000 would have chronic hepatitis C," said Dr Manal el-Sayed, Professor of Paediatrics at Cairo's Ain Shams University and member of the National Hepatitis Committee which is currently formulating an action plan to fight the disease.
Hepatitis C is a lethal virus which can cause liver cirrhosis and cancer. Egypt has one of the highest prevalence rates of the virus in the world, say specialists. An estimated 10-15 percent of the population, some 8-10 million people, are carrying hepatitis C antibodies, meaning that they either have or at one time had the virus. Five million of those are actively infected, according to government figures.
No vaccine is available for HCV although it can be treated with a combination of drugs if detected early enough.
Egypt's very high prevalence of HCV is largely the legacy of government campaigns prior to 1980 to treat rural populations for schistosomiasis (or bilharzia), a water-borne disease which at one time was endemic in Egypt. The treatment campaigns, which involved repeated injections, did not follow rigorous hygiene standards, and as such spread blood-borne HCV throughout the population.
As it may take up to 30 years for a patient to display symptoms of HCV or for the disease to become active, the full extent of the problem has only recently become known.
"The main risk factor [for HCV now], according to all the studies done in Egypt, is treatment in the past for schistosomiasis," said Dr Amr Kandeel, Director of the Communicable Disease Department at the Egyptian Ministry of Health and Population.
"At that time, the Ministry treated people in the villages without using disposable syringes," he added.
New infections
In addition to cases among the older population, new infections are still being recorded, due to poor medical practices and behavioural factors. Deaths from liver disease are, therefore, expected to increase in Egypt within the next 20 years.
"If we consider that by the year 2020 we are going to have so many patients who are having liver failure and liver cancer, treating them now is more effective than leaving them to that outcome," said el-Sayed.
Egypt's hepatitis committee is now making plans to prevent and treat hepatitis C. Treatment of HCV is usually done with a drug called Interferon. However, the most typical type of HCV in Egypt has about a 40 percent resistance to the drug. Although research is ongoing, no more effective treatment is yet available.
Nevertheless, the committee has succeeded in brokering a deal with the manufacturers of Interferon to supply the drug to Ministry of Health hospitals for one third of the usual price, and treatment under the committee's programme has begun in selected centres.
Even with the cost of Interferon reduced, the financial burden of Egypt's HCV problem is huge. The committee estimates that of the five million people actively infected with the virus, around one million currently need treatment. A year's treatment for a person with signs of liver damage from HCV costs around LE 25,000 (about US $4,500) - a sum few can afford.
In January this year, the committee began fundraising activities with the help of NGOs and international organisations including USAID, the World Health Organisation and UNICEF. The committee hopes to be able to provide free treatment to those most in need.
"We would also like to appeal to the international community to help with this campaign by whatever means possible," said el-Sayed.
Due to the cost and difficulty of treating chronic HCV patients, promoting awareness to prevent the disease, and detecting those infected before they develop liver damage are critical factors.
Screening the population
"We are going to promote screening for high-risk populations - including healthcare professionals who are at risk from needle injuries, and those who are undergoing repeated blood transfusion treatment," said el-Sayed.
The hepatitis committee has stressed the need for good infection control programmes in hospitals, and among healthcare professionals, to stem the transmission of the virus. The Egyptian Ministry of Health is co-operating through its National Infection Control Programme, which began in 2003.
Those at risk of new HCV infections in Egypt are not just those in medical contact with existing patients, however. The children and relatives of individuals affected during the schistosomiasis campaign are also a high-risk group, as widespread behavioural practices - such as the re-use of syringes, sharing of toothbrushes and even circumcision - all increase the risk of contracting blood-borne viruses such as HIV and Hepatitis C.
And although the circumcision of girls is officially banned in Egypt, the practice still continues, placing girls who are being circumcised at a very high risk of contracting HCV.
"Sometimes there is a sort of celebration for mass circumcision in certain communities. Girls are at a higher risk because it is a very bloody procedure. However, female circumcision has dramatically decreased, with more awareness and a ban by law," said el-Sayed.
As part of its Unite for Children, Unite Against Aids campaign, UNICEF Egypt has also been trying to raise awareness of the more common dangers of contracting HCV. Changing people's behaviour and attitudes toward blood safety is key, according to Wessam el-Beih, UNICEF's Unite Against Aids Egypt co-ordinator.
"Many people share razors and re-use syringes. They see no harm in just washing them and using them again. So there is a big behavioural component to the plan," she said.
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Hepatitis C Rates Soar in Sydney Addicts
http://www.theage.com.au/
Hepatitis C rates among young Sydney drug users are now among the highest in the world following the release of figures showing one in two contract the disease each year.
The city has outstripped London's alarming rates of infection, with the NSW research team warning that the "extremely high" numbers need the urgent attention of Australian policy makers.
"We obviously had an idea it was a problem but we had no idea it was going to be this high," said Professor Lisa Maher from the National Centre in HIV Epidemiology and Clinical Research.
The team studied more than 200 addicts who were either younger than 30 or who had been injecting for less than three years, in Sydney's south-west.
They found that for every 100 new users followed for a year, 46 had the infection by the end.
Rates were highest among women, under 20-year olds, people originally from South East Asia, cocaine injectors and those who had been using for less than a year.
Prof Maher said these statistics, published in the Australian and New Zealand Journal of Public Health, and unpublished figures collected from two other NSW sites, painted a grim of rates in the state.
They exceed London which recently recorded a rate of 42 per 100 new users.
"This one of the highest, if not the highest, documented rate of hep C infection in injecting-drug users in the world," Prof Maher said.
She said it shows prevention strategies implemented in the late 1980s don't appear to be working for this group.
New users appear to pick up the blood-borne disease almost immediately after they start injecting, making the window to help protect them "very, very small", she said.
"It seems you almost need to reach these people before they start injecting because otherwise they'll get the disease."
The findings also have implications for candidate vaccines currently in development.
"We'll need to be careful about who we immunise but obviously when is very important too," she said.
Hepatitis C is a slow-acting virus that causes liver inflammation and disease, as well as a range of symptoms like mood swings, itchy skin and nausea that can be managed with long-term treatment.
Prof Maher said female drug users were the most frequently infected because they were dependent on men to help them inject and were often relegated dangerous second use of the needle.
Cocaine injectors were more at risk than heroin addicts because they frequently "binged" in chaotic, risky situations where they did not have access to clean equipment.
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'One-Third' of Prisoners Have Hep C
http://www.smh.com.au/
One in three inmates of Australian prisons have hepatitis C, new statistics show.
A sample of prisoners from NSW, Queensland, Tasmania and Western Australia returned rates of 34 per cent for the blood-borne disease.
Infection numbers were almost double this among inmates who regularly injected drugs before they were incarcerated.
Previous estimates have put the prison infection rate at between 40 and 60 per cent.
The study, lead by the University of NSW Centre of Health Research in Criminal Justice, also found that one in five had hepatitis B but only one per cent were HIV positive.
Researchers tested almost 500 volunteers from a cross-section of Australia's 25,000-strong prison population.
Results showed NSW inmates were "significantly more likely" to test positive to hepatitis C than prisoners in other states.
Most sufferers were aged over 30 and had been in prison before.
The findings, published in the Australian and New Zealand Journal of Public Health, show the need for better harm minimisation practices in prisons.
Authorities should also consider routinely including prisoners in the national surveillance of hepatitis and HIV, the study's lead researcher Tony Butler found.
"That would provide a more complete picture of blood-borne virus epidemiology in Australia," Dr Butler said in the study.
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Onyx's Liver-Cancer Drug Blew Away Trial Goals
http://www.smartmoney.com
By Will Swarts
Word that a drug trial has been halted is rarely good news, but the early end to testing of Onyx Pharmaceuticals' (ONXX) liver-cancer treatment proved a happy exception on Monday. The biotech's shares nearly doubled, closing up 97% after Nexavar proved so superior that the late-stage clinical trial was stopped so all participating patients could be switched over to the oncology drug.
An independent committee monitoring the Phase III trial of Nexavar for patients with hepatocellular carcinoma, which kills about 15,000 people in the U.S. each year and about 30,000 in Europe, found that the drug boosted survival rates without adverse side effects. Onyx, based in Emeryville, Calif., has teamed up with Bayer Pharmaceuticals (BAY) to research and market Nexavar, which was approved to treat advanced kidney cancer at the end of 2005.
"As a result of this recommendation, Bayer and Onyx will stop the trial and allow all patients enrolled in this trial access to Nexavar," the company announced Monday. There are currently no other drugs that effectively slow liver tumor growth.
"This is a really, really tough disease, and this is going to be very therapeutic for those patients," said CEO Hollings Renton. He said that while liver cancer rates are relatively low in the United States and Europe, it's the fifth most frequently occurring cancer worldwide.
Onyx and Bayer said they would pursue approval from the Food and Drug Administration and European health authorities as rapidly as possible. The two companies plan to submit the results from the trial to the American Society of Clinical Oncology at the medical association's annual meeting, which starts June 1.
"The observed superiority in overall survival for Nexavar-treated patients over patients receiving placebo demonstrates the efficacy of Nexavar in advanced primary liver cancer," said Jordi Bruix, a liver-cancer researcher in Barcelona, Spain, who was the co-principal investigator in the study.
Through Friday, shares of Onyx were down 55% for the last 52 weeks. The stock had a 30% drop between Dec. 1 and Dec. 4 after Nexavar was shown to be ineffective in treating melanoma, a form of skin cancer.
The Analysis
It doesn't get much better than this — for cancer patients, for clinicians or for investors. A drug that's already demonstrated its effectiveness in treating one form of a particularly terrible disease is shown to work on another killer illness, and is the only drug near widespread market availability that can do so.
Renton said earlier experience with Nexevar’s approval process for kidney cancer left him optimistic that it could receive fast-track approval for liver cancer treatment. The FDA, using a fast-track process, took five months to process the kidney treatment approval.
"It's possible we could get it in less time," because Nexevar has already been approved, Renton said. "And these are two tough tumors. This increases our confidence that this will become a more broadly used application."
He said Bruix will present full data when the oncology society meets.
"Today is a great day, and this is great news. Nexavar will have the opportunity all to itself for a while," says Cowen & Co. analyst Philip Nadeau. "There are other drugs in Phase III trials, but no other drug has produced proof of concept. There's no way to know what other drugs will succeed in Phase III cancer treatment, or when they would be on the market."
Nexavar already has an established market position for its existing approval in kidney cancer, where it's used as a so-called second-line drug, inhibiting the growth of detected tumors. It's approved for use in about 50 countries. Onyx reported a loss of 49 cents a share, less than the 77 cents in red ink projected by Wall Street. Analysts are looking for a fourth-quarter loss of 59 cents a share. Onyx is scheduled to release fourth-quarter and full-year results on Thursday.
Pinpointing Onyx's share of sales of Nexavar is tricky. Under the terms of its marketing agreement, as laid out in the company's 10-Q, Bayer recognizes all Nexavar revenue, which totaled $101.3 million for the first nine months of 2006. As of Sept. 30, the company had about $218 million in cash and marketable securities.
With any drug that has a relatively small patient base, costs are an issue, and smaller companies must often capitalize on the high price of marquee products. Nadeau says Nexavar costs about $3,700 a month for kidney-cancer treatment.
"This is a decent size market for a company the size of Onyx, and in fact this market is larger than renal cancer, [which has] 16,000 new cases and 12,000 deaths in the U.S. [annually]," Nadeau wrote in a Monday note.
Onyx and Bayer are also conducting mid- to late-stage trials to gauge Nexavar's effectiveness in treating lung cancer and post-surgical kidney cancer.
"This morning's results are likely to make Nexavar appear to be a broadly applicable anticancer therapy," Nadeau wrote. "Therefore investors may give it value for some of its other Phase III trials."
The Bottom Line
As most biotech investors have learned, sometimes the hard way, it's a competitive field where failure and disappointment knock down stocks as fast as the less-frequent successes send them skyward.
If you bought Onyx shares a year ago, Monday's success wouldn't have wiped out your losses. Biotech is a risky and volatile sector, and has less to do with operations than the efficacy of selected drugs as they work their way through the pipeline.
Not only do investors have little indication of how those trials turn out, they can often be blindsided by the timing of results. No one expected news on the liver-cancer trial for another 10 months, Nadeau says.
"It's tough. Not matter how much work you do, you're still going to be surprised," he says. "The timing of these events is very hard to call, and especially with small- and mid-cap biotech, the fortunes of companies are really driven by a single product, and they move on clinical data. There's a lot of volatility."
With that caveat out of the way, though, Nadeau says he's particularly optimistic about Nexavar.
He estimates that after it gets regulatory approval, the drug can be used in about 16% of the world's liver-cancer market. That translates into annual sales of about $420 million, and means that Onyx's good days on the market aren't over yet. (Nadeau didn't give a timetable for Nexavar's approval, but in a conference call Onyx officials said they hoped to have the drug on the market in 2008.)
"I actually think that even though the stock's up a lot today, there's more room for it to go," Nadeau says. "I don't think people understand how big of a game-changer this is. This is a big market where there is nothing else that works for today."
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FDA Restricts Drug Used to Treat Bronchitis after Deaths, Severe Liver Problems Reported
http://www.foxnews.com
WASHINGTON — The government on Monday restricted use of an antibiotic linked to rare reports of severe liver problems, including several deaths, saying the drug now should be used only to treat pneumonia but not less serious bacterial infections like bronchitis and sinusitis.
The Food and Drug Administration said the antibiotic, Ketek, would remain on the market but that its label will bear a new, stern warning. The agency said it and manufacturer Sanofi-Aventis SA also created a guide for patients outlining the drug's risks and its safe use.
The changes are in line with the December recommendations of a panel of FDA expert advisers that the agency modify the label of the drug, also called telithromycin. In 17-2 votes, the outside advisers said the drug's benefits don't outweigh its risks in treating bronchitis and sinusitis, which are less serious infections than pneumonia and often spontaneously resolve on their own.
"The agency has determined that the balance of benefits and risks no longer support approval of the drug for these indications," the FDA said in a statement.
The FDA announced the changes on the eve of a House subcommittee hearing on drug safety that will examine irregularities in the approval of Ketek. The FDA's handling of the antibiotic remains under investigation by the Senate as well.
A new so-called "black-box" warning on the Ketek label states the drug should not be used in patients with myasthenia gravis, a disease that causes muscle weakness, the FDA said. The label also now warns about cases of visual disturbances and loss of consciousness reported in some patients.
The label already warns of the drug's risk to the liver. An FDA review released in December cited 13 reports of liver failure in patients treated with the drug.
As of late last year, doctors had prescribed the antibiotic more than 5.6 million times in the United States since it won FDA approval in 2004.
"Ketek, when used as directed in its approved indication, continues to be an important option" for fighting infections "helps to satisfy a medical need," Sanofi-Aventis said in a statement.
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Chronic Hepatitis C Tracking Urged
http://www.thetimesonline.com
BY SUSAN BROWN
sbrown@nwitimes.com
HEALTH: State officials expect virus to strike more victims
HAMMOND | The Hammond Health Department is expanding its investigation of hepatitis C cases as part of a statewide initiative into learning more about the serious liver disease, a leading factor in liver transplants.
Currently, local public health departments are mandated to follow up on only acute, not chronic, cases of the disease. Acute cases involve certain onset symptoms and laboratory criteria.
But 80 percent of acute cases will not resolve themselves in six months, according to Mike Wilkinson, a hepatitis C epidemiologist with the state health department.
Consequently, state health officials are asking, though not yet mandating, local public health departments to increase their surveillance of patients carrying the virus six months or longer.
The expansion will not only better determine the prevalence of the disease and the risk of infection but allow for the identification of new risk factors and more targeted education and prevention efforts.
Health officials expect the number of hepatitis C cases to increase given the aging of the baby boomer population, the popularity of tattoos, growing prison population and intravenous drug use, according to the state health department.
Tattoos pose a risk to those who frequent facilities lacking in sanitary practices, such as not replacing ink pots appropriately or not using sterilized needles.
In Hammond, of the 254 communicable disease cases reported in 2006, 133 involved hepatitis C. Thus far this year, of 32 reported cases, 22 involve hepatitis C.
"We are seeing more and more," Health Officer Rodrigo Panares said.
The increased follow-ups are creating an additional burden on the department, which was already in need of more nursing personnel, a social worker and clerical help, Panares said.
State officials acknowledge workloads will need to increase to follow chronic cases, but they believe enhanced reporting can lead to better control of the disease. When the program was announced in June, Indiana was one of only three states participating in the project. Officials said they hoped the state's participation would serve as an example to the rest of the country.
According to the Centers for Disease Control, an estimated 4.1 million Americans have been infected with the virus, of whom 3.2 million are chronically infected.
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Vertex Optimistic on Hepatitis C Drug
http://biotech.seekingalpha.com
Travis Johnson
There has been a bit of coverage of Vertex Pharmaceuticals (VRTX) lately, including an article at thestreet.com about the gamble the shares represent right now, and I thought I'd try to catch up a little on this high-risk, high reward company.
Vertex is a development stage biotech, famously created over a decade ago to hunt for the elusive AIDS cure (chronicled by the book The Billion Dollar Molecule by Barry Werth), and in the years since, has been subject to some serious volatility as the initial euphoria faded and clinical trials brought both the promise of success and the threat of failure.
Telaprevir: A Cure for Hepatitis C?
They've recently come to investors' attention again thanks to the extremely promising drug VX-950, now called Telaprevir, a protease inhibitor for Hepatitis C. In the year and a half or so since Vertex released its initial clinical trial results for this drug, the shares have roughly tripled, and while the company has a decent pipeline of other drugs (one for rheumatoid arthritis should go into phase III trials soon, and one for cystic fibrosis into phase II), they have also made clear that they are throwing the company's full resources behind the fast-track approval process for this potential blockbuster.
I bought shares before the first results came out for VX-950, and they were easily available for under $12... if the drug fails, which the consensus of course believes is quite unlikely, I would not be surprised if the shares fell by 60-80%. So what does "unlikely" mean?
The expectations are really remarkably high, and for good reason. For a while, at least, this was looking more like a miracle than just a plain blockbuster; initial reports and investor chatter had Telaprevir curing HCV in 12 weeks without significant side effects, whereas the existing treatment regimen with Interferon and Ribavarin generally takes at least a year, only works in about half the patients, and has sometimes debilitating side effects that cause many patients to drop treatment.
But as biotech investors have learned time and time again, potential blockbusters and miracle drugs are legion, while actual blockbusters are quite a bit more rare. What kind of confidence can we have that Telaprevir will actually make it through the approval process without significant delays, and be as popular as hoped? After all, Vertex has a bit of a lead in this space, but they're far from the only ones developing a protease inhibitor in the fight against Hepatitis C. Even if their drug does get approved on schedule, there will be competition in fairly short order.
Finding Valuable Information
Official data about the clinical trials is not released all that often, and when it is it tends to be accompanied by fairly optimistic commentary from the company, so sometimes it's valuable to look to other places for information to see if any more intelligence can be gained about the drug's prospects.
For Hepatitis C, there are a lot of sources, even for non-scientists like me. There are some blogs from the folks on the science side that cover biotech development in general, including an always interesting one called In the Pipeline that has a recent note on Vertex and the huge bet the company is placing on Telaprevir. Sources like this can give you a little bit of perspective, since they're not focused on the investment side, and in this case you can read between the lines and see the skepticism and almost feel the tension that must be running through the labs at Vertex right now.
Other science-oriented blogs and HCV-focused bloggers can also help illuminate the actual results for us non-scientific folks, including this one from November that looked in some detail at the problems with Telaprevir monotherapy that I don't think most investors were expecting.
And another interesting source that you can review for a new perspective are the legion of bulletin boards and blogs by and for Hepatitis C sufferers: HepCNet, the Hepatitis Forum at medhelp.org and the Hepatitis C Forum are a few that I've perused from time to time. At these sites you can sometimes see comments from people who are part of these clinical trials (or so they say, at least), and hear how they're tolerating the drugs (a couple of examples here and here). From these sources you can get a little color on the results - so while the official press release will explain some of the side effects, the potential (and current) patients can often be counted on to really examine those side effects.
And of course, you can see lots of comments on the other side, from people in the trial who are elated at their results (even if they don't actually know for sure whether they're getting Telaprevir or the control), or really hoping for a chance to get into a Vertex trial because of the hope this drug offers.
Along those lines, you really get a sense from these forums of the incredible frustration that those inflicted with the disease have with the existing treatments, including some terrible hard luck stories from the many people who've been forced to suspend treatment because of adverse effects or are waiting for donor livers.
These kinds of sources exist for many diseases, especially the big ones, so you might also have read, for example, the multiple sclerosis bulletin boards a couple years ago and seen that the demand was so strong for Tysabri, Elan's (ELN) new drug for MS, that patients wanted the FDA to approve it even though there was a concern that it might come at some increased risk of a rare, deadly brain disease.
And of course, you can get an idea of all the developments in treating this disease by reading the news sites that are put together by people with the strongest possible interest in seeing new treatments develop. There's a good Hepatitis C Information Center, for example, with a feed of all the HCV news you could possibly want.
That's not to say, of course, that all these sources are infallible, or that we should use them for investment decisions, any more than you should take every note you read on the Yahoo stock message boards as an actionable fact.
Estimating Value
Every drug has side effects and problems, and every disease has vocal sufferers who push for treatment at any cost. Focusing too much on those can cause you to lose sight of the important thing for biotech investors: is the disease worse than the cure, is the drug on average better or safer than existing therapies, and is there a market for it?
I continue to be an owner of Vertex shares, though I took some profits last year and have not bought any additional shares since it got out of the teens. I'm convinced enough of the promise of Telaprevir in this potentially $10 billion market that I'm willing to keep my bet on the table, but I am fully aware that, especially with the company focused primarily on this drug and already carrying a $4 billion market cap, this is far from a sure thing.
For the many people who suffer from Hepatitis C and who are not helped by the existing treatments, I certainly hope that Telaprevir is at least as successful as Wall Street is predicting. For more about my comments on the financials of the company, and my notes from when I bought and sold shares in the past, just click here http://oneguysinvestments.com/labels/VRTX.html
for a link to all of my posts on the subject.
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Blood Test Index May Help Liver Patients Avoid Biopsy
http://www.healthscout.com
Robert Preidt
It's far more accurate at spotting fibrosis than current screens, researchers say
MONDAY, Feb. 12 (HealthDay News) -- A new index that involves simple blood tests might spare patients invasive biopsies used to diagnose liver fibrosis, Japanese researchers report.
Fibrosis, the formation of scar-like tissue in the liver, indicates damage that can lead to cirrhosis. In people with hepatitis C, determining the stage of liver fibrosis is important for patient prognosis and treatment, according to background information in the article.
While liver biopsy is considered the gold standard for measuring liver fibrosis, it's an invasive and expensive procedure. This study, published in the February issue of Hepatology, compared the new FibroIndex to two other indices currently in use, the Forns index and APRI (aspartate aminotransferase to platelet ration index).
The study included 402 patients with chronic hepatitis who were scheduled to undergo liver biopsy. Blood samples were collected from the patients three days before they underwent biopsy. The blood samples were then tested using FibroIndex and the two other indices.
Researchers at Tottori University found that FibroIndex was more accurate in predicting significant or severe fibrosis than either the Forns index or APRI. Based on the results provided by FibroIndex, 101 of the patients in the study could have avoided a liver biopsy, the study said.
The researchers also tested FibroIndex on 30 hepatitis C patients treated with interferon who had a second liver biopsy more than a year after treatment. The study found that changes in FibroIndex correlated with changes in the patients' fibrosis. The Forns index and APRI did not show this correlation.
More information
The American Academy of Family Physicians has more about hepatitis C.
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Virological Response Improves Quality of Life in Hep C with Fibrosis
www.gastrohep.com
A sustained virological response after peginterferon/ribavirin therapy improves quality of life in Hep C patients with fibrosis, shows the latest issue of the Journal of Hepatology.
The antiviral and histological benefits of peginterferon/ribavirin therapy are well established.
However, the effects on health-related quality of life and sexual health are less certain.
Dr Herbert Bonkovsky and colleagues from Connecticut assessed health-related quality of life, and sexual health in advanced fibrosis or cirrhosis in the HALT-C Trial.
The team reported that 1144 subjects completed Short-Form 36, and sexual health questionnaires prior to, and after 24 weeks, of peginterferon/ribavirin therapy.
The research team noted that 373 subjects were Hepatitis C virus RNA negative at week 20, and continued therapy through week 48.
Sustained virological responses patients improved in 7 domains -- Journal of Hepatology
The researchers assessed 258 patients at week 72.
The team found that 180 achieved sustained virological responses, and 78 relapsed.
At baseline, patients had poorer scores for all 8 Short-Form 36 domains compared to healthy controls.
Patients with cirrhosis had lower health-related quality of life scores than those with bridging fibrosis, as did patients with higher depression scores.
The team observed that sustained virological response patients had significant improvements in 7 domains.
In contrast, relapsers had significant worsening in 1 domain.
Sexual scores improved in sustained virological response patients and decreased in relapsers.
In multivariate analyses, improvements in health-related quality of life and sexual scores were significantly associated with sustained virological responses.
However, the team noted that these scores were less striking in patients with lower depression scores.
Dr Bonkovsky's team concludes, “Achievement of sustained virological responses after peginterferon/ribavirin therapy improves health-related quality of life, and sexual health in chronic Hepatitis C patients with advanced fibrosis or cirrhosis.”
J Hepatology 2007: 46(3): 420-31
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February 13th, 2007
Low Prothrombin Index an Indicator for Emergency Liver Transplant
www.gastrohep.com
A low prothrombin index is a reliable tool for deciding emergency transplantation, reports the most recent Journal of Hepatology.
Amanita phalloides poisoning is an uncommon cause of acute liver failure with an especially rapid course.
Dr François Durand and colleagues from France re-assessed transplantation criteria in patients with mushroom poisoning.
The investigative team studied 27 patients admitted for Amanita phalloides poisoning.
Previously reported transplantation criteria, including the recent Ganzert's criteria, were tested retrospectively.
Prothrombin index less than 10% had a 100% accuracy -- Journal of Hepatology
The investigators found that the rate of fatal intoxication was 30%.
An interval between ingestion and diarrhea less than 8 hours was a very early predictor of a fatal outcome.
Later on, non-paracetamol and paracetamol King's College criteria were superior to Clichy's and Ganzert's criteria.
The team noted that encephalopathy and renal insufficiency were not constant in the fatal intoxication group.
The investigators observed that prothrombin index below 10% 4 days or more after ingestion had a 100% accuracy for predicting a fatal outcome.
Dr Durand's team commented, “Liver transplantation should be strongly considered in patients with an interval between ingestion and diarrhea less than 8 hours.”
“Encephalopathy should not be an absolute prerequisite for deciding transplantation.”
“From day 4 after ingestion, prothrombin index lower than 10% alone is a reliable tool for deciding emergency transplantation.”
J Hepatol 2007: 46(3): 466-73
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Who Owns Your Genes?
http://www.iht.com
Michael Crichton
You, or someone you love, may die because of a gene patent that should never have been granted in the first place. Sound far-fetched? Unfortunately, it's only too real.
In the United States, gene patents are now used to halt research, prevent medical testing and keep vital information from you and your doctors. Gene patents slow the pace of medical advance on deadly diseases. And they raise costs exorbitantly: A test for breast cancer that could be done for $1,000 now costs $3,000.
Why? Because the holder of the gene patent can charge whatever he wants, and does. Couldn't somebody make a cheaper test? Sure, but the patent holder blocks any competitor's test. He owns the gene. Nobody else can test for it. In fact, you can't even donate their own breast cancer gene to another scientist without permission. The gene may exist in your body, but it's now viewed as private property.
This bizarre situation has come to pass because of a mistake by an underfinanced and understaffed government agency. The United States Patent Office misinterpreted previous Supreme Court rulings and some years ago began — to the surprise of everyone, including scientists decoding the genome — to issue patents on genes.
Humans share mostly the same genes. The same genes are found in other animals as well. Our genetic makeup represents the common heritage of all life on earth. You can't patent snow, eagles or gravity, and you shouldn't be able to patent genes, either. Yet by now one-fifth of the genes in your body are privately owned.
The results have been disastrous. Ordinarily, we imagine patents promote innovation, but that's because most patents are granted for human inventions. Genes aren't human inventions, they are features of the natural world. As a result these patents can be used to block innovation, and hurt patient care.
For example, Canavan disease is an inherited disorder that affects children starting at 3 months; they cannot crawl or walk, they suffer seizures and eventually become paralyzed and die by adolescence. Formerly there was no test to tell parents if they were at risk. Families enduring the heartbreak of caring for these children engaged a researcher to identify the gene and produce a test. Canavan families around the world donated tissue and money to help this cause.
When the gene was identified in 1993, the families got the commitment of a New York hospital to offer a free test to anyone who wanted it. But the researcher's employer, Miami Children's Hospital Research Institute, patented the gene and refused to allow any health care provider to offer the test without paying a royalty. The parents did not believe genes should be patented and so did not put their names on the patent. Consequently, they had no control over the outcome.
In addition, a gene's owner can in some instances also own the mutations of that gene, and these mutations can be markers for disease. Countries that don't have gene patents actually offer better gene testing than the United States, because when multiple labs are allowed to do testing, more mutations are discovered, leading to higher- quality tests.
Apologists for gene patents argue that the issue is a tempest in a teapot, that patent licenses are readily available at minimal cost. That's simply untrue. The owner of the genome for Hepatitis C is paid millions by researchers to study this disease. Not surprisingly, many other researchers choose to study something less expensive.
But forget the costs: Why should people or companies own a disease in the first place? They didn't invent it. Yet today, more than 20 human pathogens are privately owned, including haemophilus influenza and Hepatitis C. And we've already mentioned that tests for the BRCA genes for breast cancer cost $3,000. Oh, one more thing: If you undergo the test, the company that owns the patent on the gene can keep your tissue and do research on it without asking your permission.
Don't like it? Too bad.
The plain truth is that gene patents aren't benign and never will be. When SARS was spreading across the globe, medical researchers hesitated to study it — because of patent concerns. There is no clearer indication that gene patents block innovation, inhibit research and put us all at risk.
Even your doctor can't get relevant information. An asthma medication only works in certain patients. Yet its manufacturer has squelched efforts by others to develop genetic tests that would determine on whom it will and will not work.
Such commercial considerations interfere with a great dream. For years we've been promised the coming era of personalized medicine — medicine suited to our particular body makeup. Gene patents destroy that dream.
Fortunately, two U.S. congressmen want to make the full benefit of the decoded genome available to all Americans. Last Friday, Xavier Becerra, a Democrat of California, and Dave Weldon, a Republican of Florida, sponsored the Genomic Research and Accessibility Act, to ban the practice of patenting genes found in nature. Becerra has been careful to say the bill does not hamper invention, but rather promotes it. He's right. This bill will fuel innovation, and return our common genetic heritage to us. It deserves our support.
Michael Crichton is the author, most recently, of the novel Next.
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Transgene Initiates A Phase I Trial of its Therapeutic Vaccine Candidate TG4040 for Patients Chronically Infected With the Hepatitis C Virus
http://www.therapeuticsdaily.com
PR Newswire Europe
STRASBOURG, France, February 13 /PRNewswire-FirstCall/ -- Transgene S.A. (Eurolist Paris: FR0005175080) announces today that the first patients have been enrolled in a Phase I trial of its therapeutic vaccine candidate TG4040 (MVA-HCV) for patients chronically infected with the Hepatitis C Virus (HCV). The trial is part of a development programme supported by Lyonbiopole, one of France's six world-class competitiveness clusters.
The trial, conducted in France, will enroll 15 chronically infected patients who have never received any therapy for their condition. The patients will receive one subcutaneous injection of TG4040 per week over a 3-week period. Dosing will be escalated from 106 pfu (3 patients), 107 pfu (3 patients), to 108 pfu (9 patients). The patients treated with the highest dose will receive a boost injection of TG4040 at Month 6. The trial's primary endpoint is safety and secondary endpoints are immunological response to the vaccination and effect on viral load.
Availability of safety data is planned by year end 2007 and virological and immunological response parameters by the third quarter of 2008.
TG4040, which expresses non structural proteins of the hepatitis C virus, aims at inducing a strong and broad immune response against the infected cells. TG4040 shares the same MVA-vector technology as Transgene's other infectious-disease therapeutic vaccine TG4001 which has been shown to be effective in a Phase II trial for the treatment of patients with high-grade cervical intraepithelial neoplasia (CIN2/3) caused by Human Papilloma Virus infection.
"We are very pleased to have our new vaccine candidate TG4040 entering clinical development", said Philippe Archinard, Chief Executive Officer of Transgene. "We believe that TG4040 is a promising candidate to address the largely unmet medical need of treating chronic hepatitis C infection. This trial initiation shows our further commitment to apply therapeutic vaccination in the field of infectious diseases following our recent positive results with TG4001 in cervical precancerous lesions caused by Human Papilloma Virus."
About chronic hepatitis C:
Hepatitis C currently represents a major public health concern. The number of persons chronically infected with HCV in the world is estimated at 170 million to 200 million and hepatitis-C-related deaths at approximately 470 000 annually. Peak of incidence is expected to occur in 2025-2030 in developed countries. HCV infection leads to liver diseases such as fibrosis, cirrhosis and liver carcinoma which are the prime reason for liver transplants. The current standard of care for patients infected with the HCV genotype 1 (a combination of pegylated interferon alpha and ribavirin), effective in 50% of patients completing therapy, is lengthy and often poorly tolerated. In addition, a substantial number of patients never receive therapy. Therefore, there is a strong need for new alternative approaches, including combination therapies.
About TG4040:
Transgene's TG4040 product candidate is based on the MVA virus carrying and expressing non-structural proteins (NS3, NS4 and NS5B) of the hepatitis C virus. The MVA vector is a highly attenuated strain of vaccinia virus that combines an extensive history of safety with the ability to stimulate a strong immune response to antigens.
In January 2006, Transgene was awarded a EUR1.3 million grant by the Lyonbiopole Competitiveness Cluster for the development of its therapeutic vaccine TG4040 against hepatitis C chronic infection. The funding, which originates from the French Ministry of Industry, is expected to cover approximately 30% of the research and development costs for this programme.
About Transgene:
Transgene is a France-based biopharmaceutical company dedicated to the development of therapeutic vaccines and immunotherapeutic products in oncology and infectious diseases. The company has three compounds in Phase II trials and one compound in Phase I studies. Transgene has bio-manufacturing production capacities for viral-based vectors and technologies available for out-licensing. For further information about Transgene, please visit http://www.transgene.fr/.
Cautionary note regarding forward-looking statements
This press release contains forward-looking statements referring to the planned clinical testing and development of one of Transgene's therapeutic vaccine candidates. However, clinical testing and successful product development depend on a variety of factors, including the timing and success of future patient enrolment and the risk of unanticipated adverse patient reactions. Results from future studies with more data may show less favorable outcomes than prior studies, and there is no certainty that product candidates will ever demonstrate adequate therapeutic efficacy or achieve regulatory approval or commercial use. For further information on the risks and uncertainties involved in the testing and development of Transgene's product candidates, see Trangene's Document de reference on file with the French Autorite des marches financiers on its website at http://www.amf-france.org/ and Transgene's website at http://www.transgene.fr/.
Transgene S.A.
CONTACT:
Press Contacts: Transgene, Philippe Poncet, +33-3-88-27-91-21.
Capital MS&L, Mary Clark, Halina Kukula, +44-(0)20-7307-5330.
Estelle Guillot-Tantay, Tiphaine Hecketsweiler, +33-1-53-70-74-93
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Among Chinese, Fear and Prejudice about Hepatitis B
http://www.washingtonpost.com/
By Maureen Fan
Washington Post Foreign Service
Tuesday, February 13, 2007; Page A15
Job Discrimination Is Widespread In Land With 120 Million Carriers
WUJIANG, China -- Liao, a 28-year-old engineer, worked at a large electronics company in this coastal province town, two hours west of Shanghai. He helped decide where to place large production machines on the factory floor, and how many workers were needed on which assembly lines. Last year, he won an award for good performance.
But it wasn't enough to save his job. In December, after a compulsory company physical revealed he was a carrier of the hepatitis B virus, Liao was told he was unfit for the job. He said a human resources manager told him: "You're a hepatitis B carrier. You're not fit for collective life, for working in a factory with colleagues."
Liao, who declined to give his full name for fear of being rejected by other potential employers, was astonished. "I thought it was impossible. . . . I didn't think I would lose my job," he said.
In China, however, discrimination against people who carry the hepatitis B virus is not only possible but widespread. Even though at least 10 percent of the Chinese population carries the virus, which can attack the liver and cause lifelong infection, cirrhosis or liver cancer, there is a failure among many to understand that it cannot spread through casual contact.
Experts say the barriers faced by people with the virus fit into a larger context of job discrimination in China, where labor laws are not enforced or are contradictory. Institutions such as universities and the Foreign Ministry are said to discriminate against applicants based on height -- they prefer taller candidates -- while private employers routinely push middle-age women to retire early in favor of younger, cheaper employees, for example.
A 13-year-old labor law prohibits discrimination on the basis of ethnicity, race, sex or religious beliefs, but the regulation is too vague to be of use, experts say. In a survey of more than 3,000 people in 10 cities, results of which were published last month by the Beijing Morning Post, 85 percent of respondents said they believed there was discrimination in the workplace.
In the case of hepatitis B, experts say, discrimination is on the increase, partly because the dangers of the virus have been exaggerated by medical testing companies touting services and advertisers pushing fake cures. Such ploys gain attention in China, where 120 million carry the hepatitis B virus.
The virus is transmitted in body fluids, primarily blood and semen, but occasionally saliva as well. About 90 percent of people infected at birth, and about 10 percent infected later, become carriers, able to infect others for years. Many Chinese were infected by needles that were reused during mass vaccination programs for tuberculosis, tetanus and encephalitis from the 1970s to the 1990s.
Although many carriers have no symptoms, at least one-quarter will ultimately suffer some complication from the infection.
"It's not a lack of knowledge; it's knowing the wrong things," Lu Jun, the moderator of an online forum for the rights of hepatitis B carriers, said of common misunderstandings related the virus. "Advertisers want people to know the wrong things about the disease, so they can drum up more business."
Discrimination also extends to academia. University students who carry the virus often say they are forced to live in segregated dormitories. Last fall, 19 new students who were carriers were expelled by state-run schools in Urumqi, the capital of western Xinjiang province. Several sued the city, which then banned the student-led group that publicized the case.
In 2005, China lifted a ban that prohibited hepatitis B carriers from becoming civil servants, but the government still bars them from the food industry and is considering barring them from working in beauty parlors, public bathrooms and hotels, experts said.
"If the government turns these people down, the public will turn against them, too. Since the law already discriminates, nobody will violate the law to hire these people," Lu said.
In Wujiang, Lu said, 22 employees were fired from companies or divisions under Cal-Comp Electronics, which is based in Thailand and which produces products for Hewlett-Packard, among other companies.
After Liao was given the bad news by his supervisor, he said he immediately went to a hospital for a second round of tests. A doctor confirmed that Liao was a carrier but told him that his liver and DNA were both normal and that his condition ought not to affect his job.
"He said the biggest difference between carriers and the sick is whether your liver is normal, and since mine is normal it will not affect my work," Liao said. "He advised me to be tested every three to six months and told me not to share a toothbrush or a razor with others."
He added, "I thought if I show this to the company, they will not ask me to leave."
He brought the results to the human resources manager, and she passed them to the company doctor. Later, the doctor told Liao, "Personally, I don't think this will affect your job, but I'm not the one who makes the decision."
The day after that conversation, Liao said, an e-mail from the doctors, copied to the head of human resources, said the company would rely on the result of its own blood test, which Liao has never seen. He was offered $996 -- three months' salary -- and asked to fill out a form that said he was "unfit for the position."
The company denies it has discriminated against Liao or any of the other employees who contend they were fired, insisting they left voluntarily or were given an option to rest at home for three months and return after they recovered.
In people acutely infected with hepatitis B, the virus is usually cleared in that amount of time. However, among those who become chronic carriers, no amount of recuperation will rid them of the virus.
"China's law says that laborers have equal rights of jobs, and our company has already fully considered the equal opportunities of employees. We didn't discriminate against them," said Wu Qunsheng, vice manager of the company.
"We need to take into consideration the health of the 6,000 employees in the company, and we already offered well-meaning suggestions to them. We ask them to go rest at home, and if they recover, they can come back," Wu said. "Our explanation at that time was that among our 6,000 employees, some are infectious, so they need to rest at home, and we can keep their positions for them. But some were not willing to take our suggestion -- it was their idea to leave."
Wu said they found 1,268 employees who had not yet received the hepatitis B antibody, and immediately asked the local epidemic prevention clinic to vaccinate them.
Asked how the dismissed employees could be expected to return to work, Wu said, "As long as they can prove that they are not infectious." Asked how a rest period would be helpful if carriers cannot "recover" in three months, Wu replied, "At that time, we didn't consider everything in details."
The Beijing office of HP said in a statement: "HP has been made aware of these allegations against one of our suppliers and is in the process of finding out more information."
A supervisor in charge of quality control at Cal-Comp said she was also dismissed because she carries the hepatitis B virus.
"I asked several times, 'Are you firing me because I'm a carrier?' " said the employee, Li, who spoke on condition that her full name not be used. "The human resources manager didn't admit it directly. First she said, 'I don't think you are suitable for collective life.' I did have a dorm room there, but at most stayed there once a week. The main reason is because of eating together -- there's a public cafeteria, they share the dishes. It's enough to worry the company."
Li said she was offered more money than her colleague Liao because she threatened to take the story to the news media. She received $2,308, which she said was for salary and medical compensation, but what she really wants is her job back.
Forced to leave the company in January, Li now makes $128 a month selling clothes, half of what she used to earn. "The company is not giving us an equal opportunity. They are treating my colleagues and us hepatitis B carriers differently, and that's illegal and unfair," she said. "They are depriving me of an opportunity to develop my skills and to work."
Researcher Li Jie in Wujiang and staff writer David Brown in Washington contributed to this report
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February 14th, 2007
Body Shop's Roddick has Hepatitis C
www.cnn.com
LONDON, England (Reuters) -- The Body Shop founder Anita Roddick is suffering from liver damage after contracting the Hepatitis C virus more than 35 years ago, she said on her Web site on Wednesday.
Roddick, 64, one of Britain's best known businesswomen, developed the potentially deadly disease from infected blood given to her during the birth of her youngest daughter, Sam, in 1971.
"I have Hepatitis C -- it's a bit of a bummer but you groan and move on," she said. "I had no idea that I had this virus. I was having routine blood tests when it showed up."
Roddick, who agreed to sell her stake in the beauty retailer to France's L'Oreal last year, said she faces an increased risk of liver cancer.
"I do have cirrhosis. I could still have a good few years -- even decades -- of life left but it's hard to say," her statement said. "Having Hep C means that I live with a sharp sense of my own mortality."
Hepatitis C is a virus that attacks the liver and can be carried in the blood for decades. It can cause liver failure or cancer.
There are an estimated 200 million people worldwide infected with the disease, according to the British charity, The Hepatitis C Trust.
There is no vaccine but drug treatments can help between 50 percent and 80 percent of sufferers, the Trust said.
Roddick has become a patron of the Hepatitis C Trust.
"I want to blow the whistle on the fact that Hep C must be taken seriously as a public health challenge and must get the attention and resources that it needs," she said.
Roddick founded The Body Shop in Brighton in 1976, selling toiletries made from natural ingredients, preferably sourced from the developing world.
It grew into an empire of more than 2,000 stores, selling everything from seaweed moisturizer to ylang ylang massage oil.
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Quebec is the First Province in Canada to Reimburse New Drug Developed to Treat Chronic Hepatitis B
http://www.therapeuticsdaily.com
MONTREAL, Feb. 8 /CNW Telbec/ - Bristol-Myers Squibb Canada announced today that Baraclude(TM), a drug administered orally to treat chronic hepatitis B virus infection, will be reimbursed by the Régime général d'assurance médicaments du Québec to naive patients and those who are refractory to current drugs.
Quebec is consequently the first province in Canada to enter Baraclude on its list to treat adults suffering from chronic hepatitis B virus infection, with evidence of active viral replication and either evidence of persistent elevations in serum levels of aminotransferases (ALT or AST) or histologically active disease.
"We're delighted with the Conseil du médicament's decision to make Baraclude available on the list of refundable drugs under Quebec's public plan. We're convinced that patients battling with hepatitis B will enthusiastically welcome the availability of a more effective alternative than the present treatment for chronic hepatitis B virus infection," stated Jean-Paul Bédard, Vice-President, Corporate Affairs.
About Bristol-Myers Squibb Canada
Bristol-Myers Squibb Canada is an indirect wholly-owned subsidiary of Bristol-Myers Squibb Company, a global pharmaceutical and related health care products company whose mission is to extend and enhance human life. Bristol-Myers Squibb Company of Canada is a leading provider of medicines to fight cancer, cardiovascular and metabolic disorders, infectious diseases (including HIV/AIDS), nervous system diseases and serious mental illness. Bristol-Myers Squibb Company is listed on the New York Stock Exchange under the BMY symbol (NYSE:BMY). Bristol-Myers Squibb Canada's operations are headquartered in Montréal, Québec.
Marc Osborne, Director, Public Relations, Bristol-Myers Squibb Canada, (514) 333-2463, marc.osborne@bms.com
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Blood Tests Perform Similarly at Staging Liver Fibrosis in HCV
www.gastrohep.com
Researchers report in the latest Journal of Hepatology that various blood tests have a similar performance in staging or diagnosing significant fibrosis.
Dr Philippe Halfon and colleagues from France evaluated the test performance profile of blood tests of liver fibrosis.
The research team assessed 356 patients with chronic Hepatitis C in 2 centers.
Metavir staging of liver specimens was conducted by 2 independent pathologists.
The team evaluated the Fibrotest, aspartate aminotransferase to platelet ratio index, FibroMeter, and Hepascore.
Metavir stage 1 was identified in 55% of patients -- Journal of Hepatology
The team found metavir stage 0 in 4%, stage 1 in 55%, stage 2 in 26%, stage 3 in 11%, and stage 4 in 4% of patients.
The researchers observed that the area under the receiving-operating-characteristic were not significantly different.
The test performance profile relies on the paired comparison of blood-test misclassification based on liver specimen.
The research team observed no center effect.
Dr Halfon's team concludes, “In those populations, the 4 blood tests had a similar performance for significant fibrosis in stage 2.”
“The tests lay in the lower range of published results, which is attributable to a low stage 2 prevalence, and for stage 3 and 4.”
“However, the FibroMeter and Fibrotest had performance profiles significantly different as a function of fibrosis stages or diagnostic target.”
“This has to be considered during the interpretation process.”
“Moreover, the performance should be reported with different diagnostic targets.”
J Hepatol 2007: 46(3): 395-402
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Peregrine Pharmaceuticals Reports Positive Phase Ib Results for Its Targeted Immunotherapy Bavituximab in Chronic Hepatitis C Infection
http://biz.yahoo.com
- Appeared Generally Safe and Well Tolerated at All Doses Tested -
- Showed Signs of Dose Dependent Biologic Effects with 83% of Patients at the 3mg/kg Dose Showing Signs of Antiviral Activity -
- Positive Phase l Results Set the Stage for New Bavituximab HCV Therapy Trials Slated To Begin Later This Year -
TUSTIN, Calif., Feb. 14 /PRNewswire-FirstCall/ -- Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM - News), a biopharmaceutical company developing targeted therapeutics for the treatment of cancer and hepatitis C virus (HCV) infection, today reported preliminary top-line results from a Phase lb study of its targeted immunotherapy bavituximab in patients with chronic HCV infection. The repeat dose, multi-center open label study was designed to assess the safety, distribution and pharmacokinetic properties of four ascending dose levels of bavituximab administered as twice-weekly monotherapy in HCV patients. The results indicate that Peregrine's novel immunotherapeutic drug was generally safe and well tolerated, with no dose limiting toxicities or serious adverse events reported. The preliminary results also indicate that bavituximab showed positive signs of dose dependent anti-viral activity.
Eliot W. Godofsky M.D., a principal investigator of the Phase Ib study and director of the University Hepatitis Center in Sarasota, Florida, noted these findings set the stage for testing bavituximab in combination with other antiviral therapies: "As a targeted immunotherapy, bavituximab represents an entirely new approach to treating chronic HCV infection. Current HCV immunotherapies, such as interferon, act by stimulating a general hyper-immune response, which can cause significant side effects in many patients. In contrast, bavituximab has the potential to specifically target HCV infected cells for destruction by the immune system. The key findings of this repeat dose trial confirm our findings from the Phase 1a study showing that bavituximab is generally safe and well tolerated in HCV patients, with good signs of anti-viral activity. Based on these positive results, we are looking forward to working with Peregrine to proceed to trials that will further assess bavituximab's potential for the treatment of chronic HCV infection."
In contrast to antiviral therapies, which attack hepatitis C viral particles, bavituximab primarily works by homing in on a specific molecular target that is expressed only on certain stressed cells, including both HCV viral particles and patient cells infected with HCV. These infected patient cells produce new viral particles that can cause the disease to reoccur. Bavituximab flags these infected cells for destruction by the immune system, enabling a highly targeted immune response. When used in combination with antiviral drugs that lower virus levels, bavituximab may have the potential to help permanently eradicate the HCV infection by eliminating the infected cells that fuel disease resurgence.
The Phase lb study results indicate that 83% of patients at the 3 milligram per kilogram (mg/kg) dose level showed at least a 75% (0.6 log) reduction or better in HCV RNA levels, with an average of an 84% (0.8 log) reduction for the entire cohort. In this cohort, 50% of the patients showed signs of greater antiviral activity, with an average HCV RNA load reduction of 1 log. Patients showing signs of antiviral activity typically achieved peak viral load reduction three to seven days after the initial dose. The signs of antiviral activity in this repeat dose study compare favorably with results previously reported for bavituximab administered as a single dose infusion, with a higher percentage of patients in the current study showing signs of antiviral activity with a similar safety profile. Based on these positive data, Peregrine plans to advance bavituximab into new HCV trials, including combination therapy and additional dosing studies shortly.
"These results are particularly significant since they represent an important milestone in Peregrine's efforts to develop targeted immunotherapeutics, which are already transforming therapy for diseases such as cancer, for life threatening viral infections including HCV," said Steven W. King, president and CEO of Peregrine. "We believe that our targeted immunotherapy agent bavituximab has the potential to change the way HCV infections are treated, and we are delighted with the promising safety results and positive signs of antiviral activity observed in this repeat dose study. These results and the pharmacokinetic data also generated by the study should be of great value as we finalize patient dosing schedules for our next series of HCV clinical trials."
Mr. King added, "There are currently many new approaches in development to treat chronic HCV infection that are aimed at directly inhibiting production of the virus. All of these agents are being tested in combination with various forms of interferon, which act by causing a general stimulation of the immune system, resulting in toxic effects for many patients. To achieve sustained antiviral responses with a regimen that is both effective and safe, we need new immunotherapy agents that can work with antiviral drugs to reduce or eliminate the need for these non-specific immunotherapies. We believe bavituximab could be just this sort of agent, targeting the immune system to act precisely where it is needed, with the promise of reducing or eliminating the need for general immune stimulators with their high potential for adverse effects."
In the Phase lb study, 24 patients were enrolled in four cohorts, with each cohort receiving four doses of bavituximab over a 10-day period. Patients received bavituximab at escalating dose levels of 0.3, 1, 3, or 6 mg/kg of body weight, and were followed for 12 weeks. All patients in the study suffered from chronic HCV infection based on their medical history and the presence of detectable serum HCV RNA. More than half of the study cohort had genotype 1 HCV. This study included treatment naive patients as well as partial responders and those who had either failed to respond to, or relapsed after, standard-of-care HCV treatment.
"Combination regimens are a mainstay of hepatitis C treatments, and as a clinician treating patients with chronic HCV infection, I am acutely aware of the need for new agents that could minimize the toxicities we currently see with the interferon-based component of these regimens," said Dr. Eric J. Lawitz, a principal investigator of the Phase lb study and director of Alamo Medical Research. "Bavituximab has a novel targeted immunomodulatory mechanism that we hope will be complementary to emerging new antiviral therapies for HCV infection. During this first multi-dose trial, we found bavituximab was well tolerated, and we look forward to additional trials that will help us understand the role that bavituximab may play in the HCV treatment paradigms now in development."
Mr. King concluded, "We are encouraged that in these initial studies, bavituximab's targeted mechanism shows signs of fewer side effects than is typical of conventional immunotherapy with interferon, while as monotherapy-- as expected--it is comparable to existing immunotherapies as measured by viral load reductions. We believe that these positive findings from our Phase lb study confirm that bavituximab may have the potential to meet the pressing need for safe and effective immunotherapy agents for patients with chronic HCV, and we also believe it may have the potential to help eradicate chronic HCV in patients when used in combination with antiviral drugs. We look forward to assessing these parameters in combination therapy HCV trials in the near future."
Planning for dose optimization and combination therapy HCV studies is nearly complete and several new bavituximab HCV studies are expected to begin shortly.
About Bavituximab
Bavituximab is the first investigational agent in a new class of anti- phosphotidylserine (PS) immunotherapeutics that targets and binds to cellular components that are normally not present on the outside of cells, but which become exposed on certain virally infected cells and on the surface of enveloped viruses. Bavituximab helps stimulate the body's immune defenses to destroy both the virus particles and the infected cells. Bavituximab has completed two Phase l trials for the treatment of chronic hepatitis C infection, and results from the Phase la study were presented at the American Association for the Study of Liver Disease annual meeting in late 2006. Similar to the proposed anti-viral mechanism, anti-phospholipid immunotherapeutic agents also bind to phospholipids exposed on tumor blood vessels in all solid cancers tested to date, and they have shown promise in a number of preclinical cancer models. Bavituximab is currently in two Phase l clinical trials for the treatment of advanced refractory solid cancers.
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 HCV infection. The company is pursuing five separate clinical trials in cancer and HCV infection in the U.S. and India with its lead product candidates bavituximab and Cotara®. Peregrine also has in- house manufacturing capabilities through its wholly owned subsidiary Avid Bioservices, Inc. (www.avidbio.com), which provides development and bio- manufacturing services for both Peregrine and outside customers. Additional information about Peregrine can be found at www.peregrineinc.com.
SafeHarbor Statement:
Statements in this press release which are not purely historical, including statements regarding Peregrine Pharmaceutical's 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 bavituximab's safety profile in a combination therapy trial will not be at the same safety level as was found in the phase 1b trial, the risk that the results of future trials will not correlate to the results from the phase 1b trial, and the uncertainties as to whether bavituximab will reduce or eliminate the need for general immune stimulators or eradicate chronic HCV when used in combination with antiviral drugs. 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 all 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 October 31, 2006. 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
info@peregrineinc.com
(800) 987-8256
Media
Barbara Lindheim
(212) 918-4650
Source: Peregrine Pharmaceuticals
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February 15th, 2007
Transgene Starts Enrollment in Hepatitis Trial
http://www.pharmaceutical-business-review.com
By Victoria Harrison
Transgene has said that the first patients have been enrolled in a phase I trial of its therapeutic vaccine candidate for patients chronically infected with the hepatitis C virus.
The trial will enroll 15 chronically infected patients who have never received any therapy for their condition. The trial's primary endpoint is safety and secondary endpoints are immunological response to the vaccination and effect on viral load.
AdvertisementAvailability of safety data is planned by year end 2007 and virological and immunological response parameters by the third quarter of 2008.
TG4040, which expresses non structural proteins of the hepatitis C virus, aims at inducing a strong and broad immune response against the infected cells.
TG4040 shares the same MVA-vector technology as Transgene's other infectious-disease therapeutic vaccine TG4001 which has been shown to be effective in a phase II trial for the treatment of patients with high-grade cervical intraepithelial neoplasia caused by human papilloma virus infection.
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February 16th, 2007
Hepatitis C Cases in Macedonia on Rise
http://www.makfax.com
Macedonia's reported cases of hepatitis C are on the rise, as eight new cases have been reported last month.
The hepatitis C is a serious blood-borne disease and the incidence rose sharply, said the Association for Fight against Blood-Transmitted Diseases HEPTA at today's presentation of the grant comprising hepatitis C detection tests.
Reported cases of hepatitis C had risen from 92 in 2005 to 114 in 2006.
According to general estimates, the Association says the number of hepatitis C cases ranges from 25.000 to 30.000, as number of people who contracted the disease in the past now are discovering they have the virus.
"The state must find a way to help the people infected with hepatitis C virus," Rozalinda Isijanovska, HEPTA president, told the press conference.
She stressed that there was an apparent lack of therapy and medical treatment for people who have been diagnosed with hepatitis C.
"According to unofficial information, the Health Insurance Fund provides therapy to 10 persons infected with this virus on early basis," Isijanovska said, adding that there is a lack of communication between HEPTA and the Health Insurance Fund. The Fund does not provide any information as to the funds set apart for treatment of hepatitis C.
Hepatitis C is a blood-borne, infectious, viral disease of the liver caused by hepatotropic virus called hepatitis C. It is spread by blood-to-blood contact. The infection can cause liver inflammation and permanent impairment of the liver, accompanied by other health disorders.
Roughly 180 million people across the world have been infected with hepatitis C virus. It is largely deemed as the disease of the 21st century, as the number is expected to triple and claim more lives than AIDS.
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McGuinty Government Invests in Nursing Support Program for Hepatitis C Patients
http://www.newswire.ca
$2.3-Million Investment Will Help 1,500 Patients A Year Complete Their Treatment
TORONTO, Feb. 16 /CNW/ - The McGuinty government is helping people with hepatitis C get the nursing care and support they need to complete their treatment regimen and lead healthier and more active lives, Health and Long-Term Care Minister George Smitherman announced today.
"People with hepatitis C often find it difficult to stick to their treatments because of the side effects they suffer," said Smitherman. "We want to provide patients with the nursing care and support they need to complete their treatment program and improve their chances of beating this disease."
The government is providing $2.3-million to hire up to 20 nurses who will provide support to approximately 1,500 patients a year in Ontario and ensure they follow their hepatitis C treatment plans. The funding includes salaries, administrative costs, ongoing program evaluation and nurse training. Nurses will help manage patients' treatment - individualized services could include helping patients monitor their side effects and better cope with them through counselling. The nurse will consult with the treating physician who may decide to change the course of treatment depending on the type and severity of the side effects.
Treatment for hepatitis C lasts between 24 weeks and 48 weeks through a combination drug therapy of interferon and ribavirin. This treatment causes many side effects including severe depression, fatigue, mood swings and anemia. These side effects cause many patients to discontinue their treatment, potentially worsening their condition.
A provincial advisory committee will identify where nurses will be located based on hepatitis C statistics on rates of infection and identify local agencies that can best support additional care needs of people undergoing treatment for hepatitis C.
Studies have shown that up to 90 per cent of patients are able to complete their treatment with nursing support - compared to only 30 per cent who do so with no support. Successfully completed treatment can cure up to 60 per cent of patients with hepatitis C.
Hepatitis C is an infection of the liver caused by the hepatitis C virus (HCV). The disease is spread through contact with the blood of an infected person. While some people with HCV may show no symptoms, others develop jaundice. Chronic hepatitis can lead to cirrhosis (scarring of the liver) which occurs in about 20 per cent of patients. In severe cases, this can lead to liver cancer or death.
An estimated 110,000 people in Ontario have hepatitis C and of those, 35,000 don't know they have the virus. Hepatitis C is a silent and potentially fatal disease that can show no signs or symptoms for years.
In 2006 the Ministry of Health and Long-Term Care launched a province-wide public awareness campaign encouraging individuals at risk to talk to their doctors and get tested for hepatitis C.
Today's initiative is part of the McGuinty government's plan for innovation in public health care, building a system that delivers on three priorities - keeping Ontarians healthy, reducing wait times and providing better access to doctors and nurses.
For further information: Media Contacts: David Spencer, Minister's
Office, (416) 327-4320; A.G. Klei, Ministry of Health and Long-Term Care,
(416) 314-6197; Members of the general public: 1-866-532-3161
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