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Week Ending: December 8th, 2007
Alan Franciscus
Editor-in-Chief
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This Issue:
December 2nd, 2007
Chocolate lovers feast at Hep C fundraiser
http://www.denverpost.com
By Joanne Davidson
Denver Post Society Editor
Ann Jesse started the Hep C Connection as a "patients helping patients" support network. She stepped down as executive director 10 years later but remains involved as a volunteer and adviser. Her service was recognized last year at the first Desserts & Delights.
The 2007 edition, chaired by Katie Barton and Karen Robinson Rosenthal and held at the Walnut Foundry in Denver's River North Art District, honored businessman Taylor Owen, a former president of the Hep C Connection board.
While sampling hors d'oeuvres and a lavish array of chocolate desserts, the 250-plus guests placed their silent auction bids while jazz musicians provided some lively tunes. Cynthia Hessin, an executive producer for KRMA, was mistress of ceremonies,
Among the guests: Sherry Jackson, executive director of the Colorado Democratic Party, and Adrian Miller; Jim Bernuth; Christy Calvin; Cheryl Anderson; Betsy Hoover; Jared and Sarah Hamilton; Ann McDougal; Don Rowe; Ron and Charlene Bushe; Carma Lytle; and executive director Nancy Steinfurth.
Hepatitis C is a blood-borne liver disease that affects an estimated 4 million in the United States. Symptoms include fatigue, rash and/or stomach pain, and often go unnoticed. Hep C is transmitted by IV drug use, transfusions involving tainted blood, needlestick injuries and high-risk sexual behavior. It can lead to cirrhosis, end-stage liver disease or liver cancer.
For more information, visit hepc-connection.org.
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Govt urged to provide liver transplantation centres
http://www.thenews.com.pk/
By our correspondent
Karachi
Hepatitis-B and Hepatitis-C have assumed epidemic proportions in Malir area of Karachi and the interior of Sindh due to a variety of reasons, while “faity liver disease” caused by alcohol, obesity and diabetes and Hepatitis-E among pregnant women were emerging as dangerous trends, said doctors on Sunday.
They warned against what they called the emerging liver disease of NASH (Non-Alcoholic Steato-Hepatitis) and underlined the importance of creating awareness against this “impending danger”.
Speaking at a press conference after the conclusion of three-day moot on liver diseases in the country, Prof. Wasim Jafri, President of Pakistan Society for the Study of Liver Diseases (PSSLD), said: “Nash is extremely common in people who are obese, especially females, who also suffer from diabetes, wherein extra deposition of fat inside the liver results in chronic liver disease. It may then lead to cirrhosis and may even cause the liver to decompensate”.
He said: “Our recent research showed that around 18 per cent population of Malir and 33 per cent population of Upper Sindh suffer from Hepatitis-C and the problem has been compounded because no vaccine exists against this disease. “Each third person of Jacobabad district suffers from Hepatitis-B and Hepatitis-D. It is an epidemic,” he added.
Referring to a recent research in Punjab, Dr Jafri said that seven per cent population of Hafizabad suffers from Hepatitis-C. “Faity liver disease should not be taken lightly, it has no symptoms but people with diabetes and overweight should get themselves diagnosed,” Dr Jafri suggested.
He said unsafe blood transfusion, unnecessary injections and street dentistry were playing havoc with the lives of the people. He said that owing to these factors, Hepatitis-A and Hepatitis-B have become common, which, if not treated within six months, could cause liver cancer. He said it should be a matter of utmost concern for the rulers that these diseases were increasing because of the said factors, which were quite preventable.
Dr Jafri lamented that the government hospitals did not sterilize and disinfect equipment, while the same also lacked facilities for proper diagnosis of these diseases. He said private hospitals charge around Rs 25,000-30,000 for diagnosing Hepatitis-B and Hepatitis-C, hence affordability of treatment is a big issue for majority of the people. He added that ignorance and poverty were a stumbling block in preventing the said diseases.
Dr Saeed Hamid said that Hepatitis-E was increasing among pregnant women because of contaminated water, which could prove fatal if not treated. He said it was heartening to note that a vaccine was being invented for Hepatitis-E, which would benefit pregnant women. He suggested that women should take properly boiled drinking water and eat home food in order to avoid such disease.
Dr Zaigham Abbas said that piercing of nose and ears through infected equipment also cause such diseases. The doctors urged the government to pay serious attention towards providing liver transplantation facilities in the country, saying at least the capital cities of all the provinces should have a liver transplantation programme.
Dr Jafri disclosed that they have set up a taskforce to look into the prospects in this regard.
He regretted that foreign delegates prefer to avoid attending annual international conferences in the city owing to the prevalent situation in the country.
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December 3rd, 2007
Treating patients with psychiatric disorders for hepatitis C
http://www.eurekalert.org
Sustained viral response achieved with no increased risk of side effects
People with severe mental illnesses are far more likely to be infected with Hepatitis C virus compared to the general population, however, they often do not get treatment for their liver disease because current antiviral therapies have known psychiatric side effects.
“Against this epidemiological background, the article by Schaefer and colleagues, Hepatitis C treatment in psychiatric risk patients, represents an important study in the field,” write Sanjeev Arora and Cynthia Geppert, in the December issue of Hepatology, a journal published by John Wiley & Sons on behalf of the American Association for the Study of Liver Diseases (AASLD). Their editorial is also available online at Wiley Interscience (http://www.interscience.wiley.com/journal/hepatology).
“It provides an even stronger empirical foundation for the findings of other less methodologically rigorous studies showing that patients with HCV and comorbid psychiatric and substance use disorders have comparable sustained viral responses (SVR) and rates of depression when treated with antiviral therapies,” Arora and Geppert report.
While the National Institutes of Health once advised doctors against treating HCV-infected patients who continued to use illicit drugs, drink alcohol, or who had a psychiatric history, in 2002, the agency released a statement that said “efforts should be made to increase the availability of the best current treatments” to those patients.
Research has shown this approach to be feasible and effective, and it also has important implications for public health. Still, doctors have been slow to act on the recommendation.
Arora and Geppert applaud Shaefer et. al’s work with very difficult to treat patients and point out that the key to their success was the use of a multidisciplinary team. “The patients in this study were carefully screened and monitored and received extensive education and counseling,” they point out. They also praise the work because it assessed both depressive and psychotic symptoms and demonstrates that neither diagnosis adversely affected SVR or outcome. Instead, the study adds to the growing body of evidence that shows using anti-depressant agents prior to and during HCV treatment can lessen, or even prevent, depressive reactions.
While Arora and Geppert point out that the small sample size in Schaefer et. al’s study means that the conclusion that there is no difference in SVR between controls and patients with mental health diagnosis is stronger than the data can support, they praise the forward-thinking nature of the work.
“The value of Schaefer et al.’s work is precisely in contributing to the growing body of data that challenge hepatologists and mental health professionals to develop new medications and innovative programs that can further widen the door to admit these patients to HCV treatment,” the authors conclude.
###
Article: “Widening the Door: The Evolution of Hepatitis C Treatment in Patients with Psychiatric Disorders.” Arora, Sanjeev; Geppert, Cynthia. Hepatology; December 2007; (DOI: 10.1002/hep.21891).
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Can-Fite: IND submission for Phase I Clinical Trials with its Drug for Liver Diseases CF102
http://www.therapeuticsdaily.com/
- Can-Fite develops CF102 for the treatment of liver cancer, hepatitis virus infections and other liver conditions that represent a current market of about USD 4 billion
- Can-Fite estimates that this Phase I study will be initiated in early 2008, subject to FDA approval
PETACH TIKVA, Israel--(BUSINESS WIRE)--Can-Fite BioPharma (TASE:CFBI), a biotechnology company traded on the Tel Aviv Stock Exchange, is advancing through its development pipeline and prepares for clinical trials with CF102, the second drug candidate in its product pipeline. Can-Fite announced today that it submitted an Investigational New Drug (IND) application to the US Food and Drug Administration (FDA) to initiate phase I clinical trials with CF102. Can-Fite's second pipeline drug is intended for the treatment of liver diseases including liver cancer, hepatitis virus infections and liver regeneration. The combined market potential of drugs for these conditions is estimated at about USD 4 billion. Can-Fite estimates that the first clinical trial with CF102 will be initiated in early 2008, subject to FDA approval.
CF102 was developed on the basis of Can-Fite's platform technology and tested in a series of preclinical studies over the past few months. These included Kg drug manufacturing, formulation development, drug packaging, animal toxicicology studies, blood clearance rate and metabolism. These trials have shown that the drug is safe and can be tested in human clinical studies. The drug is being developed for three leading indications in liver diseases: liver cancer, hepatitis virus infections and liver regeneration.
Liver cancer affects about 450,000 new patients each year and is highly prevalent in people with hepatitis virus infection or alcohol abuse. This type of cancer is particularly prevalent in Eastern countries due to the high rate of hepatitis virus infections. The current market size of liver cancer is estimated at about USD 0.5 billion due to lack of proper treatment.
Laboratory trials conducted by Can-Fite in collaboration with a leading laboratory at the Temple University, Philadelphia, have shown that CF102 has antiviral activity and is effective against the hepatitis virus. The number of people infected with hepatitis B and C virus worldwide is 350 million and 170 million, respectively, and rapidly increasing in the past few years. The hepatitis virus is one of the main causes of hepatitis. Market size is currently about USD 3 billion per annum due to lack of proper treatment.
Preclinical studies have also shown that CF102 is effective in liver tissue regeneration after partial hepatectomy. Partial hepatectomy is usually performed in patients with primary or metastatic liver cancer. Rapid liver regeneration is crucial in these conditions, and regeneration rates determine future liver function and chances for successful recovery. Regeneration of normal liver tissue is also needed to preserve liver function in patients with liver failure. No drugs are currently available to speed up the regeneration process; therefore, developing a drug for the treatment of patients undergoing hepatectomy or patients with liver failure is a top priority. The number of patients requiring liver regeneration is estimated at about 100 million.
Prof. Pnina Fishman, CEO of Can-Fite said today that: "we are making progress according to schedule towards the first clinical trial with CF102. We are pleased to announce that, once this trial is underway, Can-Fite will have two pipeline drugs in clinical trials for various indications, including cancer, viral infections and autoimmune inflammatory disease."
CF101, the other drug being developed by Can-Fite, is in advanced phases of clinical trials. Early this month, Can-Fite announced that CF101 may also be effective for a severe bowel condition called Crohn's disease. Can-Fite also announced that it will continue to develop CF101 for the treatment of rheumatoid arthritis. Can-Fite reported that a phase IIb trial will be initiated in early 2008 as part of the further development of CF101. Phase II clinical trials are also being conducted to test the efficacy of CF101 in the treatment of psoriasis and dry eye syndrome.
CAN-FITE BIOPHARMA LTD is a public company traded on the Tel Aviv Stock Exchange. The Company, which commenced business activity in 2000, was founded by Prof. Pnina Fishman, an investigator from Rabin Medical Center, and patent attorney Dr. Ilan Cohn, a senior associate at Reinhold Cohn Patent Attorneys. Prof. Fishman serves as the CEO of Can-Fite. The Company was founded on the basis of scientific findings made by Prof. Fishman and focuses on the development of molecule-based drugs that bind to receptors of cancerous or inflammatory cells and inhibit their development.
Can-Fite currently has two drugs in development, CF101 and CF102. The company is simultaneously conducting several clinical and preclinical trials with the two drugs for various indications. CF101 is being studied for the treatment of rheumatoid arthritis, dry eye syndrome and psoriasis. Can-Fite has also entered the development of CF102 for the treatment of liver cancer and hepatitis.
Contacts
Can-Fite BioPharma
Pnina Fishman, Ph.D., +972-3-9241114
Chief Executive Officer
Fax: +972-3-9249378
pnina@canfite.co.il
http://www.canfite.com/
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Evolution of Therapy for Chronic Hepatitis B: Progressing from the Simple to the Complex
http://www.annals.org
Jordan J. Feld, MD, and Marc G. Ghany, MD
Annals of Internal Medicine
4 December 2007 | Volume 147 Issue 11 | Pages 806-808
In the past decade, physicians treating chronic hepatitis B have gained the luxury of choice. The U.S. Food and Drug Administration has approved 6 drugs for treating chronic hepatitis B (listed in order of approval date): interferon-2b, lamivudine, adefovir, entecavir, pegylated interferon-2a, and telbivudine (1). The introduction of nucleoside and nucleotide analogues has revolutionized therapy for chronic hepatitis B. Unlike interferon, these agents are orally administered, well tolerated, safe, and very effective at suppressing hepatitis B virus (HBV) replication. They improve liver disease and reduce rates of liver transplantation and hepatocellular carcinoma (2, 3). However, because viral replication usually resumes after treatment with nucleoside and nucleotide analogues is stopped, long-term, perhaps indefinite, administration is essential (4, 5). Unfortunately, long-term treatment usually brings viral resistance to drugs and, consequently, loss of clinical response, occasional flares of hepatitis, and sometimes death (6, 7).
The wider choice of antiviral agents has raised new questions: which ones to use, how long to use them, what constitute suitable end points, and when to change therapy. The ultimate goal of therapy is to prevent the long-term complications of chronic hepatitis B: cirrhosis, decompensated liver disease, and hepatocellular carcinoma. Unfortunately, these end points are impractical for clinical trials and for measuring success in individual patients. Instead, investigators use surrogate end points. They define response by several variables: virologic (undetectable HBV DNA by a sensitive polymerase chain reaction–based assay or loss of hepatitis B e antigen [HBeAg] or hepatitis B surface antigen [HBsAg]), biochemical (normalization of serum alanine aminotransferase [ALT] levels), and histologic (2-point decrease in the histologic activity index score with no worsening of fibrosis) (8). The timing of response is also important and is described as initial, maintained (on therapy), or sustained (off therapy) (8). By using these definitions, we can compare the efficacy of the approved agents (Table).
However, these response definitions are imperfect. Achieving a response does not reliably predict long-term remission of chronic hepatitis B and therefore is not necessarily an indication to stop therapy. With few exceptions, researchers have not been able to define reliable end points of treatment. Historically, HBeAg loss was the primary therapeutic end point because patients who spontaneously cleared HBeAg (13–16) achieved long-term remission. However, regardless of treatment, only 12% to 33% of patients achieve this end point, and the response to treatment with nucleoside or nucleotide analogues is often short-lived (1). Loss of HBsAg is the most desirable end point because it correlates strongly with remission, but it occurs in only 1% to 3% of patients treated with nucleoside or nucleotide analogues (1). Histologic response is the gold-standard indicator of disease severity, but it is hard to define this measure and impractical to do repeated liver biopsies to measure response. When to test for a response is also unclear, in part because sustained response off therapy is infrequent. Most industry-sponsored trials of nucleoside and nucleotide analogues have used response at 48 or 52 weeks on treatment ("maintained" response) as the end point for defining efficacy, largely because response rates off therapy after 48 to 52 weeks of treatment are very low (4, 5).
In this issue, Chan and colleagues (17) compared the antiviral efficacy of telbivudine and adefovir dipivoxil at 24 weeks of therapy. In addition, they evaluated the strategy of switching from adefovir to telbivudine at 24 weeks. The authors randomly assigned 135 HBeAg-positive patients with elevated ALT levels to 1 of 3 treatment groups: telbivudine, 600 mg/d for 52 weeks; adefovir, 10 mg/d for 52 weeks; or adefovir, 10 mg/d for 24 weeks, followed by telbivudine, 600 mg/d for 28 weeks. To compare the 2 drugs, the authors used the reduction in HBV DNA level at 24 weeks relative to baseline DNA level as the primary end point. The secondary end point was the reduction in DNA levels at 52 weeks among the 3 groups. At 24 weeks, telbivudine achieved better viral suppression than adefovir (–6.3 log10 copies/mL vs. –4.97 log10 copies/mL [30% vs. 12% of patients with undetectable HBV DNA], respectively; P < 0.001). However, at 52 weeks, patients who received telbivudine, adefovir, or both drugs had similar viral suppression relative to baseline in the unadjusted analysis (–6.56, –5.99 and –6.44 log10 copies/mL, respectively; P = 0.28), and a similar proportion among the groups had undetectable HBV DNA (60%, 40%, and 54%, respectively; P = 0.067).
The study results at 24 and 52 weeks underscore something important about when to assess response to treatment: The results at 24 weeks more accurately reflect an initial treatment response. It is an interim measure of efficacy rather than a treatment end point in a disease that usually requires long-term therapy. The week-24 results clearly show that telbivudine, an l-nucleoside analogue, achieves better antiviral suppression, and they highlight one of the strengths of telbivudine: excellent potency. However, we know little about the development of viral resistance to telbivudine. In contrast, adefovir, an acyclic phosphonate nucleotide analogue, has a higher rate of primary nonresponse (defined as a failure to achieve a 1– to 2–log10 IU/mL decrease in HBV DNA level after 24 weeks) and a low rate of viral resistance. Chan and colleagues' trial illustrates the different performance characteristics of these 2 agents. Although telbivudine had advantages at week 24, the unadjusted analysis showed that by week 52, the 3 treatment groups had similar rates of HBV DNA suppression and patients who tested negative for HBV DNA. In addition, the 3 groups had similar unadjusted rates of ALT normalization and HBeAg loss or seroconversion. This pattern of results highlights the difficulty of interpreting results at 24 weeks and emphasizes the need to use long-term rates of maintained response (undetectable HBV DNA, normal ALT level, and histologic response during treatment) to evaluate efficacy. Outcomes should be measured at 48 or 52 weeks at a minimum, and 4- to 5-year data are preferable. In addition, investigators should report sustained response rates in patients who stop therapy. In this context, the purpose of testing at week 24 is not to determine efficacy but to detect treatment failure, which may be due to early development of resistance to antivirals, primary nonresponse, or poor adherence to therapy.
A second aim of Chan and colleagues' study was to evaluate the benefit of switching therapy at 24 weeks. The best way to evaluate this strategy would be to randomly assign patients with a poor initial response to therapy to switching versus continuing the assigned agent. In this trial, whether to switch therapy was randomly determined before starting any treatment, which means that patients who were responding well to adefovir may have been unnecessarily switched to telbivudine. With this caveat in mind, the authors performed a post hoc analysis, identifying a subgroup of patients with a suboptimal response to adefovir (which they defined as an HBV DNA level 3 log10 copies/mL at week 24), who may benefit from switching. This criterion is much less stringent than the usual definition of primary nonresponse (a 1– to 2–log10 IU/mL decrease from baseline at week 24). Although this post hoc, adjusted analysis seems to favor switching, it does not give us guidance about whether to switch therapy in a patient with HBV DNA level that has been persistently decreasing but is still above 3 log10 IU/mL at week 24. A predefined prospective evaluation of this strategy and longer-term outcome data are needed to answer this question.
Chan and colleagues do not tell us what happened at the end of the 52-week trial. If therapy was stopped, it is important to provide the relapse rate among the 3 groups and information on whether any withdrawal flares, hepatic decompensation, or deaths occurred. Similarly, if patients continued therapy, it would be important to know how long HBV DNA levels remained suppressed and whether efficacy eventually declined as antiviral resistance developed. In almost every trial of nucleoside and nucleotide analogues, response has eventually plateaued and then declined over time because antiviral resistance has emerged (1). Moreover, in clinical practice, the decision to change therapy depends on many factors—not just HBV DNA levels. Decision criteria should also include the potency and resistance profile of the agents selected, pretreatment HBV DNA level, history of exposure to antivirals, severity of the underlying liver disease, need for rapid viral suppression, and presence of comorbid illnesses.
A final concern about switching therapy is that sequential monotherapy (that is, switching from monotherapy with one drug to another) runs the risk for accumulating mutants that may persist and affect future response to antivirals (18). For example, resistance to entecavir, the most potent of the approved anti-HBV agents, is significantly higher in patients in whom lamivudine-resistant mutants form less than 0.1% of the viral population (19, 20). The worst-case scenario is a patient who has no treatment options left after prematurely cycling through every class of drug, ostensibly because of incomplete responses.
Although therapy has improved over the past decade and most patients with chronic hepatitis B respond to treatment, rates of sustained response and HBsAg loss remain poor. Therefore, we urgently need new drugs aimed at novel antiviral targets if we are to achieve HBsAg loss and successfully prevent and manage resistance. Until then, studies should focus on optimizing currently available drugs by finding the best regimen to treat chronic hepatitis B and the appropriate measures for changing or discontinuing therapy. Unfortunately, this study leaves us with more questions than answers.
References
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Hepatitis B vaccination not tied to MS in children
http://news.yahoo.com
NEW YORK (Reuters Health) - Vaccinating against hepatitis B virus (HBV) does not increase a child's risk of developing multiple sclerosis (MS), according to a study released Monday.
Most prior studies have not shown a link between the use of HBV vaccine and MS in children, Dr. Yann Mikaeloff, from Hopital Bicetre, Le Kremlin Bicetre, and colleagues note in the Archives of Pediatrics and Adolescent Medicine.
However, one study, which featured a slightly longer follow-up period than the others, did suggest a significant association. This led to public concerns about the safety of the HBV vaccine and a drop in vaccination rates in many countries.
Furthermore, many of the earlier studies had "methodologic" problems, the investigators say, which may have prevented them from reaching definitive conclusions.
Against this backdrop, Mikaeloff and colleagues assessed 143 children who developed MS before age 16, with a first episode of the disease occurring between 1994 and 2003. Each patient was matched to an average of eight control participants from the general French population who were the same age and sex and lived in the same location but did not have MS.
In the three years before the first episode of MS, roughly 32 percent of both the 143 children with MS and the 1,122 controls were vaccinated against hepatitis B.
Mikaeloff and colleagues report that vaccination against hepatitis B within the three-year study period was not associated with an increased rate of a first episode of MS.
"The rate was also not increased for hepatitis B vaccination within six months of the index date or at any time since birth or as a function of the number of injections or the brand of hepatitis B vaccine."
In a related editorial, Dr. Frederick P. Rivara and Dr. Dimitri A. Christakis, at the University of Washington and editors of the Archives of Pediatrics and Adolescent Medicine, write: "We have published (this study) both because of the rigor of the research and because of the need to reassure a public that is increasingly wary of vaccination."
"Going forward, we hope that the process of scientific discovery proceeds in a rigorous and thoughtful way that will increase the public's health and not harm it."
SOURCE: Archives of Pediatrics and Adolescent Medicine, December 2007.
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GSK Drug Boosts Fight against Hepatitis C, Duke Study Shows
http://www.localtechwire.com/
By Duke University News Service
Editor’s note: This article is part of WRAL Local Tech Wire’s efforts to highlight research at universities across the Carolinas and Georgia.
DURHAM – It's not a cure, but it may be some of the best news patients infected with the hepatitis C virus (HCV) have heard in a long time: A new drug, eltrombopag, appears to be effective in boosting low platelet counts, one of the major reasons why patients can't endure antiviral treatments.
Other drugs that can restore normal platelet functions are infusions or injections; eltrombopag is a pill taken just once a day.
Researchers at Duke University Medical Center and other centers world-wide studied eltrombopag (marketed by GlaxoSmithKline as Promacta in the U.S. and Revolade in Europe) in 74 patients with low platelet counts and cirrhosis of the liver due to HCV infection. They found that it boosted platelet counts in a majority of patients at each of three dosage levels, enabling most of them to continue or start conventional antiviral treatment.
The findings appear in the current issue of the New England Journal of Medicine.
"We feel this is an important development for many people infected with the hepatitis C virus world-wide," said Dr. John McHutchison, professor of medicine and associate director of the Duke Clinical Research Institute. "A significant number of patients with HCV infection will at some point develop platelet problems that will compromise their getting the best treatments we have. Anything we can do to prevent that from happening would improve their care."
The study was sponsored by GlaxoSmithKline, which manufactures eltrombopag. McHutchison and many of the coauthors also report having received grants, consulting, advisory or speaking fees from the company.
It's estimated that 4 million people in the U.S. and 170 million worldwide carry the hepatitis C virus. The virus causes inflammation and scarring in the liver, and while it is curable in about half of those who have it, it can lead to significant liver damage, liver cancer and death in others.
HCV infection is a common cause of cirrhosis and the most common reason for a liver transplant.
Platelets are cells made in the bone marrow and are important in clot formation, and serious bleeding can occur if platelet levels fall too low. Some diseases, like HCV infection, can cripple the body's ability to manufacture platelets, but so can some medical treatments. Cancer patients, for example, can experience plummeting platelet levels when undergoing chemotherapy.
In the phase II, multi-center trial, participants were randomized to a control group or to receive 30, 50, or 75 milligrams of eltrombopag daily. The patients had platelet levels ranging from 20,000 to 70,000 (145,000 to 450,000 is normal).
A phase II trial is designed to test the safety and efficacy of a drug at different doses, and the Duke study found that eltrombopag worked in a dose-dependent manner, meaning that patients got a better response with increasing amounts of the drug. Seventy-four percent of those in the trial who took the lowest dose saw their platelet counts go up significantly, while 79 percent and 95 percent of the participants saw increases with the higher doses.
Eltrombopag does cause side effects. Some of the patients complained of headaches, dry mouth, abdominal pain and nausea.
"We are encouraged by these results and are already working on another multi-center, international, phase III trial where we hope these results will be confirmed," said McHutchison.
Colleagues who contributed to the study include Geoffrey Dusheiko, M.D., Royal Free Hospital, London; Mitchell Schiffman, M.D., Virginia Commonwealth University Medical Center; Maribel Rodriguez-Torres, M.D., Fundacion de Investigacion de Diego, San Juan; Samuel Sigal, M.D., Weill Medical College; Marc Bourliere, M.D., Hopital St. Joseph, Marseille; Thomas Berg, M.D., Charite, Berlin; Stuart Gordon, M.D., Henry Ford Hospital and Health System, Detroit; Fiona M. Campbell, B.Sc., GlaxoSmithKline, Greenford, UK; Dickens Theodore, M.D., M.P.H., GlaxoSmithKline, Research Triangle Park; Nicole Blackman, Ph.D. and Julian Jenkins, M.Sc.,GlaxoSmithKline, Philadelphia; and Nezam Afdhal, M.D., Beth Israel Deaconess Medical Center, Boston.
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MIGENIX Reports Preliminary Celgosivir Viral Kinetics Study
http://www.therapeuticsdaily.com/
VANCOUVER, and SAN DIEGO, December 03, 2007 /PRNewswire-FirstCall/ - MIGENIX Inc. , a clinical-stage developer of drugs for infectious diseases, has received preliminary four-week interim results from a Phase II viral kinetics study in hepatitis C virus ("HCV") treatment-naive patients which indicate that celgosivir (an oral alpha glucosidase I inhibitor) has no negative effects on the tolerability, pharmacokinetics and viral kinetics when combined with the standard of care drugs, pegylated interferon plus ribavirin, as compared to the standard of care drugs alone.
The interim results include 10 patients who had completed 4-weeks of treatment equally divided between: (i) pegylated interferon (alfa-2b) plus ribavirin ("PR"); and (ii) celgosivir 400mg QD plus PR ("PRC"). The results are interim as the study is designed as a 20-patient, 12-week study. The following is a summary of the preliminary interim four-week results:
- viral kinetics in both treatment groups are similar with a median reduction in HCV RNA at 4 weeks of 3.5 log(10) vs 3.8 log(10) in the PRC and PR groups, respectively. The variability of response is wide with reductions of 5.4 log(10) to 0.8 log(10) and 4.5 log(10) to 2.5 log(10) for the PRC and PR groups, respectively. Virus was undetectable in one patient who was in the PRC group (none in the PR group).
- PRC treatment was well tolerated, with both the PRC and PR groups demonstrating similar tolerability, which is consistent with observations from prior studies. Gastrointestinal tolerability of the PRC treatment was slightly better in this study compared to prior studies. No serious adverse events were reported.
Due to the small number of patients and the high response rate with standard of care alone, any conclusion about differences in efficacy between the groups is speculative at this point. The Company will be completing a thorough analysis of the data from this trial, along with data from an extension protocol with patients continuing from a previous Phase II non-responder study (see summary of the non-responder study results below), to determine the next steps in the development of celgosivir. An update will be provided as part of the Company's quarterly news release and conference call on December 13th, 2007.
About Celgosivir (MX-3253)
Celgosivir, an oral inhibitor of alpha-glucosidase I, is currently the only anti-HCV drug in clinical development that acts on host-directed glycosylation. In preclinical studies, celgosivir has shown excellent in vitro synergy with various interferons in the clinic or in development including Pegasys, PEG-Intron, Infergen, Alferon and IFN-omega (with or without ribavirin) and other drugs in development for the treatment of HCV (e.g. polymerase inhibitors) and therefore has the potential to be included as part of many combination therapeutic approaches to improve efficacy in anti-HCV therapy.
A previously completed Phase II non-responder combination study reported April 11, 2007 showed:
- a 42% Early Virologic Response(x) (EVR) with PRC compared to a 10% EVR with PR ((x) EVR = 2 log(10) or greater HCV viral load reduction at 12 weeks).
- a mean HCV viral load reduction ("VLR") of 1.63 log(10) (PRC) compared to a 0.92 log(10) reduction (PR).
- 90% viral load reduction (1 log(10)) reduction, or greater, at 12 weeks in 66% (8/12) of PRC patients, compared to only 40% (4/10) in patients in the PR treatment arm.
- EVR in 57% of null responders (4/7) in the PRC therapy arm (null responders = patients who have not achieved greater than a 0.4 log(10) viral load reduction on prior treatment with optimized PR).
Celgosivir combination therapy was well tolerated and resulted in no significant adverse events. As expected from previous experience, the most frequent side effects related to celgosivir were gastrointestinal in nature and were generally mild. Other frequently observed side effects were fatigue and flu-like symptoms - which are side effects usually associated with PR treatment.
About HCV
HCV, the most common chronic blood-borne infection in the United States, causes inflammation of the liver and may progress to more serious complications such as cirrhosis of the liver, liver cancer and death. Approximately 2.7 million people in the United States are chronically infected with HCV, and the Centers for Disease Control and Prevention (CDC) estimates that by the year 2010, the number of deaths attributed annually to HCV could surpass that due to HIV/AIDS in the US. Worldwide, the World Health Organization estimates that 170 million individuals have chronic HCV infection, with 3 to 4 million new infections each year.
Therapy for HCV currently employs a drug combination approach, which is anticipated to continue in the future. The current standard of care for treatment-naive chronic hepatitis C is pegylated interferon combined with ribavirin (PR), which fails to provide a satisfactory outcome for approximately 50% of patients infected with HCV genotype 1 (the most prevalent genotype in North America). In addition, these drugs can cause significant side effects that limit tolerance to therapy, or a frequent lack of sustained treatment response.
About MIGENIX
MIGENIX is committed to advancing therapy, improving health, and enriching life by developing and commercializing drugs primarily in the area of infectious diseases. The Company's clinical programs include drug candidates for the treatment of chronic hepatitis C infections (Phase II and preclinical), the prevention of catheter-related infections (Phase III) and the treatment of dermatological diseases (Phase II). MIGENIX is headquartered in Vancouver, British Columbia, Canada with US operations in San Diego, California. Additional information can be found at www.migenix.com.
“Jim DeMesa"
James M. DeMesa, M.D.
President & CEO
FORWARD-LOOKING STATEMENTS
This news release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995, and forward-looking information within the meaning of applicable securities laws in Canada, (collectively referred to as "forward-looking statements"). Statements, other than statements of historical fact, are forward-looking statements and include, without limitation, statements regarding our strategy, future operations, timing and completion of clinical trials, prospects, plans and objectives of management. The words "anticipates", "believes", "budgets", "could", "estimates", "expects", "forecasts", "intends", "may", "might", "plans", "projects", "schedule", "should", "will", "would" and similar expressions are often intended to identify forward-looking statements, which include underlying assumptions, although not all forward-looking statements contain these identifying words. By their nature, forward-looking statements involve numerous assumptions, known and unknown risks and uncertainties, both general and specific, that contribute to the possibility that the predictions, forecasts, projections and other things contemplated by the forward-looking statements will not occur.
Although our management believes that the expectations represented by such forward-looking statements are reasonable, there is significant risk that the forward-looking statements may not be achieved, and the underlying assumptions thereto will not prove to be accurate. Forward-looking statements in this news release include, but are not limited to, statements concerning our expectations for: completing a thorough analysis of the data from the celgosivir Phase II viral kinetics study, along with data from an extension protocol with patients continuing from a previous Phase II non-responder study, to determine the next steps in the development of celgosivir and providing an update as part of the Company's quarterly news release and conference call on December 13th, 2007; and celgosivir having the potential to be included as part of many combination therapeutic approaches to improve efficacy in anti-HCV therapy.
With respect to the forward-looking statements contained in this news release, we have made numerous assumptions regarding, among other things: our ability to complete the analysis of data from the celgosivir studies to provide an update on December 13, 2007; and the competitiveness of the celgosivir study results to date and future results supporting its potential in the treatment of HCV.
Actual results or events could differ materially from the plans, intentions and expectations expressed or implied in any forward-looking statements, including the underlying assumptions thereto, as a result of numerous risks, uncertainties and other factors including: potential delays; uncertainties related to early stage of technology and product development; uncertainties as to the requirement that a drug be found to be safe and effective after extensive clinical trials and the possibility that the results of such trials, if completed, will not establish the safety or efficacy of our products; and other risks and uncertainties which may not be described herein. Certain of these factors and other factors are described in detail in the Company's Annual Information Form and Annual Report on Form 20-F for and other filings with the Canadian securities regulatory authorities and the U.S. Securities & Exchange Commission.
Forward-looking statements are based on our current expectations and MIGENIX assumes no obligations to update such information to reflect later events or developments.
The Toronto Stock Exchange has not reviewed and does not accept responsibility for the adequacy or accuracy of this release.
CONTACT: Art Ayres, MIGENIX Inc., Tel: (604) 221-9666 Ext. 233,; Dian Griesel, Ph.D., Investor Relations Group, Tel:(212) 825-3210, aayres@migenix.com Theproteam@aol.com
Ticker Symbol: (Toronto:MGI.),(NASDAQ-OTCBB:MGIFF)
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December 5th, 2007
Woman joining hepatitis lawsuit becomes first to reveal her name
http://www.japantoday.com
TOKYO — A woman became the first plaintiff to reveal her name Wednesday on joining a lawsuit against the state and pharmaceutical companies, demanding they pay compensation to those who contracted hepatitis C via contaminated blood products. Tomoko Kaji, 51, a part-time teacher at a junior high school and resident of Saijo, Ehime Prefecture, is the fifth person to join the lawsuit among those on a list of 418 people who were given the blood products, whom the Health, Labor and Welfare Ministry has been criticized for ignoring, but the first to reveal her name.
Kaji told a press conference at the health ministry that she was given the hemostatic drug fibrinogen in 1991 when she was giving birth at a hospital in Saijo. She developed symptoms of acute hepatitis shortly afterward but the doctor at the hospital did not tell she had been given fibrinogen, she said. The hospital only informed her of the fact on Nov 6 this year after the health ministry was found to have failed to tell the people on the list that they had been administered the infected blood products.
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N&N consultants scoop national award
http://www.eveningnews24.co.uk
SARAH HALL
Consultants from the Norfolk and Norwich University Hospital who invented a technique to “cook cancers” have won a major national award.
Simon Wemyss-Holden, along with his colleague Dr John Cockburn, developed the Bimodal Electric Tissue Ablation (BETA) to help treat patients with cirrhosis or the fatal blood disease hepatitis C.
The innovative treatment burns away tumours on the liver to ensure cancerous cells are destroyed and minimises chances of the disease reoccurring.
The N&N consultants were regional winners in the Health Enterprise East innovation awards held in June this year and were shortlisted for the national finals held at the Wellcome Foundation in London on Monday .
And the pioneering technique saw Mr Wemyss-Holden and Dr Cockburn walk off with the spoils and the accolades at the awards ceremony held at the House of Commons.
Mr Wemyss-Holden said: “The treatment we have developed is more important than ever because of the rise in liver cancer.
“We know primary liver cancer is set to rise but no one knows how much. The BETA innovation is very important as it can lead to the development of treatments and systems that will benefit many patients in the future.
“Liver cancer really is at the top of the agenda now and we are hoping this treatment will eventually be able to help people all over the world.”
News of the consultants' success comes as the government launched a five-year strategy which predicts a cancer time bomb - and liver cancer is one of the diseases which could spiral out of control.
A government report estimates that by 2012, 299,000 cases of cancer per year will be diagnosed - up from 224,000 in 2001 - and half of all these cancers will be caused by entirely preventable causes such as smoking, overeating and drinking, and too much sunbathing.
The British Liver Trust is warning that there was a 104pc increase in cirrhosis hospital admissions in the past year, which amounts to about 65 people a day.
While a number of ablative techniques have been used for years to treat tumours on the liver BETA ensures no tissues cells are left behind so the tumour is less likely to grow back.
Potentially thousands of patients locally nationally and internationally will see the significance of the treatment, which is carried out using an intriguing development of current practice (radio frequency ablation) which keeps the tumour hydrated while it is being “cooked”.
The five-year Cancer Report Strategy was launched by Prime Minister Gordon Brown and his Health Secretary Alan Johnson which comes as ministers admitted that England has one of the worst records for cancer survival in Europe because patients are denied access to wonder drugs freely available in other countries.
Alison Rogers, chief executive of the British Liver Trust, said: “Over the past decade primary liver cancer in the UK has increased by 44pc. We would like to see the government's plan to tackle cancer include liver health as a key tool in prevention.”
Have pioneering health techniques been used to put you on the road to recovery? Call Evening News health reporter Sarah Hall on 01603 772426 or email sarah.hall2@archant.co.uk
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High Normal ALT Limit Lowered for Male Adolescents
http://www.medpagetoday.com
By John Gever, Contributing Writer, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine.
SYDNEY, Australia, Dec. 5 -- The upper limit of normal for alanine aminotransferase (ALT) in adolescent males has been too high, said researchers here. Action Points
The upper limit was calculated at 28 IU/L in 439 males 12 to 19 years old, considerably lower than standard definitions, which are in the 45 to 55 IU/L range, Jacob George, Ph.D., of the University of Sydney, and colleagues, reported in the December issue of Hepatology.
The new upper limit is the 95th percentile for ALT levels in adolescents at the lowest risk for liver disease.
The group found that 17% of those in the overall group, all juvenile offenders, had above-normal ALT.
Strong associations with elevated ALT included HCV antibody positivity, overweight and obesity, and elevated total cholesterol, they found. More than 90% of adolescents with elevated ALT levels had one or more features of the metabolic syndrome.
"There was a strong association for overweight or obesity (72% versus 25.1%; P<0.001) to predict elevated ALT," they wrote. Multivariate analysis for these factors indicated an odds ratio of 6.9 for elevated ALT with overweight or obesity (95% CI: 3.7 to 13.1, P<0.001).
"This definition will permit greater sensitivity in diagnosing early liver injury in adolescent male populations," they wrote. "By identifying those with [hepatitis B and C infection] and obesity-related liver disease, targeted interventions can and should be implemented to minimize future health-related morbidity."
The researchers also identified new upper limits of normal in male adolescents for two other liver enzymes: 32 IU/L for aspartate aminotransferase (AST), and 29 IU/L for gamma-glutamyltranspeptidase (GGT). Published values for the upper normal limits in adults range up to 42 IU/L for AST and 48 IU/L for GGT.
The 439 adolescents in the New South Wales criminal justice system agreed to participate and did not have serious mental problems or substance withdrawal or disruptive behavior when blood samples were drawn. In addition to liver enzymes, the samples were tested for blood lipids, glucose, and hepatitis B and C antibodies and viral loads.
As expected, participants with HCV infection were at significant risk for elevated ALT relative to HCV-negative participants (57.1% versus 16.3%, P<0.001). This translated into an odds ratio of 14.6 (95% CI: 3.7 to 57.6) for elevated ALT in HCV-positive participants.
When 81 of the participants gave additional blood samples one year later, about 3.7% of those who were initially HCV-negative tested positive.
"Greater education regarding blood-borne viruses, risk factors for transmission, and implementing harm minimization strategies in this population is crucial," the researchers said.
They also recommended routine hepatitis B vaccination for adolescent offenders, noting that only 30% of the participants showed immunity to HBV. Risk-taking sexual activity and drug-taking behaviors put this population at high risk for HBV infection, they said, though only 4% of participants were HBV positive.
High levels of cholesterol were also significantly associated with above-normal ALT (odds ratio: 3.6, 95% CI: 1.7 to 7.7).
The study was funded by the Australian Research Council, the University of Sydney and industry partners, and the New South Wales Department of Juvenile Justice and Justice Health.
No financial disclosures were reported.
Primary source: Hepatology
Source reference: Van der Poorten D, et al "Liver disease in adolescents: a cohort study of high-risk individuals" Hepatology 2007; 46: 1750-58.
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Thousands of Canadians may be denied access to effective new hepatitis B treatment
http://www.newswire.ca
Drug review committee recommends against full reimbursement of Baraclude(TM) (entecavir)
MONTREAL, Dec. 5 /CNW/ - Thousands of Canadians with Hepatitis B Virus (HBV) may be denied access to Baraclude(TM) (entecavir) as a result of a restrictive drug reimbursement recommendation issued by the Canadian Expert Drug Advisory Committee. If provinces follow the committee's decision, only patients with documented cirrhosis would have public access to the highly potent new treatment.
The committee's current recommendation reserves entecavir for patients who are at the highest risk of complications from chronic hepatitis infection,i.e., cirrhosis documented on radiologic or histologic grounds and a HBV DNAconcentration above 2000IU/mL.
"The committee's decision to restrict access to entecavir will result in a significant proportion of patients having to use treatment that has largely been abandoned in the USA and Europe as substandard," said Dr. Morris Sherman, Chairman of the Canadian Liver Foundation Medical Advisory Committee, Past President of the Canadian Association for the Study of the Liver and a practicing hepatologist who sees many patients with hepatitis B. "These patients will receive inadequate therapy with an unacceptably high rate of developing resistance, leading to compromise of future treatment choices."
Chronic hepatitis B is a serious disease caused by the hepatitis B virus (HBV) that attacks the liver. The virus can cause lifelong infection, cirrhosis (scarring) of the liver, liver cancer, liver failure, and death.
"All patients with hepatitis B deserve affordable access to treatments deemed appropriate by their physicians," added Dr. Sherman. "It is a shame that Canadians are being denied what in many cases might be their best chance for a positive outcome."
Entecavir was approved by Health Canada for treatment of chronic hepatitis B on June 6, 2006. It works by slowing the progression of hepatitis B by interfering with viral reproduction. It is currently the most potent inhibitor of HBV DNA replication available in Canada. Earlier this year Quebec announced that entecavir would be publicly reimbursed for treatment naive HBV patients and those who are refractory to current drugs.
"BMS is very disappointed with this decision and we intend to resubmit our data package with additional evidence as soon as possible," said Dr. Mitch Shulman, Vice-president, Medical Affairs, BMS Canada. "In all trials, entecavir has demonstrated statistically significant improvements in hepatitis B viral suppression. Furthermore, resistance to entecavir is very rare during the first three years of therapy. This stands out when it is compared to the current treatment which has been reporting resistance rates in the neighborhood of 70% after four years of therapy."
Chronic viral hepatitis continues to be a major public health and medical problem in Canada. There are an estimated 500,000 to 600,000 people in Canada infected with either the HBV or the HCV. The disease has a high mortality rate (20 per cent to 25 per cent of untreated carriers).(1)
The Canadian Expert Drug Advisory Committee is a part of the Common Drug Review process which provides funding recommendations to all publicly-funded provincial, territorial, and federal drug insurance plans (known as formularies), with the exception of Quebec.
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.
(1) Canadian Journal of Gastroenterology Vol 21 Suppl. C June 2007
For further information: Marc Osborne, Director, Public Affairs and Government Relations, Bristol-Myers Squibb Canada, (514) 333-2463, marc.osborne@bms.com ; Fiona Robinson, H&K Health, Hill & Knowlton Toronto, (416) 413-4737, fiona.robinson@hillandknowlton.ca
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December 6th, 2007
Nabi completes sale of hepatitis drug business
http://biz.yahoo.com
Nabi Biopharmaceuticals has closed on a $185 million deal to sell its only remaining drug on the market, as well as its Florida operations and headquarters, leaving Rockville its new home base.
The drug developer, which has long been based in Boca Raton, with research and development operations in Rockville, has completed the sale of its biologics business to a Biotest AG subsidiary. With that, Nabi has sold its Nabi-HB franchise for treating hepatitis B, its plasma protein production plant and nine plasma collection centers nationwide in addition to the Florida headquarters.
Nabi will hold onto the rights of Nabi-HB until Biotest wins Florida regulatory approval for the drug. The now local company will focus on its key product, a NicVax smoking cessation vaccine that recently completed its second phase of trials. Nabi has said it's searching for a larger pharmaceutical partner to help it further test and commercialize NicVax, as well as its stalled StaphVax vaccine for staph infections.
StaphVax had failed its Phase III trials in 2005, causing Nabi's shares to tank and drawing anger from shareholders who have since demanded that the company shrink its spending and refine its focus to boost shareholder value. Recent sales of Nabi's product lines and the naming of NABI interim President and CEO Leslie Hudson earlier this year were largely in response to those demands.
"The completion of this transaction marks a significant milestone in our strategic alternatives process," Hudson said Tuesday. "Nabi is now focused on building and realizing the significant value of Nabi's remaining assets."
The company has said it plans to eventually add 10 to 20 more administrative employees to its now 50-person ranks in Rockville.
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Late Settlement Little Solace: Hepatitis disaster another warning ignored
http://japantimes.co.jp
By AKEMI NAKAMURA
Staff writer
Ikuko Kuno gave birth to her first son at a maternity hospital in Ise, Mie Prefecture, in May 1988. The only thing different from when she gave birth to her daughter in 1986 was that the obstetrician gave her a blood-clotting agent to stop her hemorrhaging.
Soon after she was discharged from the hospital, she began tiring and displaying signs of jaundice. A month later, she was diagnosed with hepatitis C and immediately hospitalized.
At that time, Kuno, a dental hygienist who now lives in Chiba Prefecture, knew that contracting the virus runs the risk of developing cirrhosis and then liver cancer. What she did not know was that she was among thousands of victims of a drug-induced medical disaster that experts say could have been prevented if regulators had heeded international warnings and acted sooner.
Last year, she joined a Tokyo-based lawsuit over the infections, targeting Mitsubishi Tanabe Pharma Corp., its subsidiary, Benesis Corp., and Nihon Pharmaceutical Co. — the firms that made and sold the tainted coagulants — and the government, which approved the products from 1964 to 1976.
Now Kuno and 200 other plaintiffs — mainly women — who have filed similar suits with five district courts are waiting for the Osaka High Court to draw up a basic settlement proposal — due out Friday — in hopes it will help ease their suffering and end their legal battles.
"I want the government and the companies to apologize for causing the disaster. I would not have contracted the disease if the government had taken action to stop the use of fibrinogen earlier," Kuno said.
Fibrinogen is one of the blood-clotting agents that caused the infections and was more widely used than the other two — christmassin and PPSB-Nichiyaku.
"I want (the defendants to provide) relief measures to all patients. The plaintiffs represent the tip of the iceberg. There are so many patients who cannot join the suits" because their medical records have been lost after their doctors destroyed them or retired, she said.
According to a 2002 estimate by the maker of fibrinogen, some 280,000 people were administered with the drug between 1980 and December 2001. About 10,000 of them contracted hepatitis C. There are no corresponding figures available for the other two products.
Kiyohiko Katahira, a professor of social welfare at Toyo University in Tokyo, said victims could number some 30,000 if patients who were given fibrinogen and the factor IX coagulants, including christmassin and PPSB-Nichiyaku, before 1980 are included. This would make it the largest drug-induced disaster in Japan's history.
Fibrinogen was manufactured by Green Cross Corp., now part of Mitsubishi Tanabe and Benesis, and approved by the government in 1964.
The U.S. Food and Drug Administration canceled its approval of fibrinogen in 1977 because it suspected the coagulant — made from donated blood — might have been tainted with hepatitis viruses.
Japanese authorities, however, did not take any action to halt the use of the coagulant, which was widely used to stop hemorrhaging during childbirth and surgery, until the late 1980s, when the hepatitis risk was recognized and the drugmaker began recalling the products.
Hepatitis C patients have suffered for decades.
The first adversity Kuno faced was the public misconception about the disease. When she was looking for a job in 1988, a dental clinic employee told her she could not be hired because her virus could possibly be transmitted.
She said she was shocked that someone involved in the medical profession knew so little about the virus or would use such callous words.
Hepatitis C can be transmitted via transfusion of tainted blood, use of tainted blood-clotting agents or tainted needles. The virus is not transmitted by ordinary human-to-human contact.
The medical treatment Kuno had to endure was also unpleasant. She was given interferon injections for five months in 1992 after she was diagnosed with chronic hepatitis. The treatment caused fever and hair loss, and the cost to receive interferon several times a week — several thousand yen per injection — hit her family's pocketbook.
In October, Yasuo Fukuda became the first prime minister to admit the government bears a responsibility for the mass hepatitis C infections — after four district courts in separate rulings between June 2006 and last March held the government and the three companies liable.
There is, however, no guarantee the Osaka High Court will offer a settlement plan that meets the plaintiffs' demands for an official apology, financial redress, permanent steps to help everyone infected, including those not involved in the lawsuits, proper medical treatment and an end to the social discrimination they face.
Recent media reports indicate the government wants to limit its compensation to hepatitis C patients who were infected from tainted coagulants during a set period based on a Tokyo District Court ruling last March.
The court ruled the government is liable for the infections that took place between April 1987, when an obstetrician in Misawa, Aomori Prefecture, reported to the health ministry that eight mothers given unheated fibrinogen were infected with hepatitis C, and June 1988, when the ministry finally ordered Green Cross to withdraw coagulants it had already sold — although the agent continued to be used in some cases.
The three other courts expanded the government's liability, ordering it to pay damages for infections that took place over a longer period of time.
Ryuhei Kawada, an Upper House member and hemophiliac who was infected with HIV and hepatitis C in the mid-1980s through tainted coagulants, said the health ministry has not learned anything from the HIV/AIDS fiasco of the 1990s. Here again, the U.S. had issued HIV-risk warnings about unheated blood products several years before the Japanese government and profit-hungry drug firms acted.
Kawada and other hemophiliac plaintiffs who filed lawsuits since 1989 won an out-of-court settlement with the government and drugmakers in 1996 that provided relief measures to some 2,000 hemophiliacs who contracted HIV through tainted coagulants. Green Cross was also the source of the blood-clotting agent that caused the mass HIV infections.
"The ministry has neglected the (hepatitis C) problem even though it had information" about the risk of infection, and the drugmakers have been insincere to the patients, he said.
Kawada said that although the settlement provided relief for all the HIV-infected hemophiliacs, it left unresolved key questions about how and why the mass infections occurred and to what extent the government was to blame.
Katahira of Toyo University said the collusive relationship among the government, drugmakers, academia, doctors and pharmacists has caused repeated drug-induced disasters in Japan.
"It was the government's fault that it approved fibrinogen (in 1964) and factor IX coagulants (in 1972) without sufficient examination of their safety. It was a violation of the Pharmaceutical Affairs Law," which bans manufacturing and selling contaminated drugs, said Katahira, who has studied Japan's drug-induced debacles for decades.
Katahira charges that tainted blood products were approved in the first place because of the systemic collusion, including "amakudari" (descent from heaven) — the practice in which retired bureaucrats land lucrative jobs with companies they once oversaw. In this case they went from the health ministry to drugmakers.
Bureaucrats at the ministry who authorize drugs side with the makers' safety claims when they examine the products, he says.
To prevent drug-related disasters, Katahira said it is necessary to ban amakudari and other collusion and create a system that can detect problems at an early stage and monitor how the safety of drugs is determined.
Kuno's hepatitis symptoms disappeared two years ago, but she gets a medical checkup every three months due to fear of a relapse.
"I previously felt drug-induced disasters were (someone else's) problem. After I was infected, the problem weighed heavily on me psychologically," she said. "I think health ministry bureaucrats (also) view the problem as somebody else's, and do not understand the suffering of the patients."
The virus, its symptoms, sufferers, and facts
What is hepatitis C and what are its symptoms?
Hepatitis C is a virus that weakens the liver. It was identified in 1988. It can develop into cirrhosis and liver cancer over decades if proper medical treatment is not administered.
Symptoms include fatigue, poor appetite and nausea, but they can be so mild that carriers may be unaware of their infection until they develop chronic hepatitis C or cirrhosis.
How many hepatitis C patients are there in Japan?
More than 1.5 million people are believed to have contracted the virus, according to the Health, Labor and Welfare Ministry.
How was the virus contracted?
In many cases, people undergoing treatment for unrelated ailments were infected by receiving transfusions of tainted blood or treated with contaminated blood-clotting agents such as fibrinogen, christmassin and PPSB-Nichiyaku.
Fibrinogen and christmassin were manufactured by the now-defunct Green Cross Corp., and PPSB-Nichiyaku was produced by Nihon Pharmaceutical Co. Such coagulants had been made from blood donated by thousands of people, including some infected with hepatitis C. Christmassin and PPSB-Nichiyaku output was halted by the late 1980s.
In 1992, a sophisticated examination system to screen blood for the virus was introduced in Japan, thereby reducing the infection risk from clotting agents.
How can the virus be transmitted?
The virus cannot be transmitted through ordinary social contact, including shaking hands and bathing together. Infection through sexual intercourse is rare and the risk of mother-infant transmission is low.
But public misperceptions mean hepatitis C patients still face discrimination in the workplace and at medical institutions.
Is there an effective medical treatment?
Interferon, an antibody protein that prevents the virus from increasing, can eliminate hepatitis C. The symptoms disappear in roughly 60 percent of interferon recipients.
But interferon causes serious side effects, including fever and hair loss, and costs about ¥800,000 a year. The length and frequency of the treatment varies by individual.
Beginning in 2008, the government plans to subsidize hepatitis patients who need to take interferon.
Can people be tested to determine if they are infected?
Most local governments offer free examinations at public health offices.
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Hepatitis C: Progress Toward Vaccine?
http://www.webmd.com/
By Miranda Hitti
Antibodies That Target the Hepatitis C Virus May Spur Creation of a Hepatitis C Vaccine
Scientists have discovered antibodies that target the hepatitis C virus (HCV). The findings may lead to a preventive hepatitis C vaccine.
The hepatitis C virus can cause liver damage and can be deadly.
There is no hepatitis C vaccine. That's partly because "extreme variability" in HCV makes the virus a difficult target, write Mansun Law, PhD, and colleagues.
Law works in the immunology department at the Scripps Research Institute in La Jolla, Calif.
Law's team found antibodies that neutralize various forms of the hepatitis C virus. They tested those antibodies against the HCV virus in mice.
The researchers injected the antibodies into some mice. For comparison, other mice didn't get the antibodies.
After that, all of the mice were exposed to HCV. Six days later, the HCV virus was gone from the mice that had received the antibodies -- but the hepatitis C virus lingered in the other mice.
The antibodies' effects against HCV faded with time, and high doses of the antibodies were needed to curb HCV.
More work is needed, but the results are "favorable" for the prospects of developing a hepatitis C vaccine, write Law and colleagues.
Their findings appear in today's advance online edition of Nature Medicine.
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L.I. Hepatitis Scare Affects More Than 1,200
http://wcbstv.com
Jennifer McLogan
Doctor Said To Reuse Syringes On Patients; 12 More Test Positive
MELVILLE, N.Y. (CBS) ― The number of people infected with hepatitis from dirty syringes used by a Long Island doctor is growing and thousands more could be at risk, CBS 2 has learned.
A hearing was held in Farmingdale on Thursday where angry patients demanded answers from the state health department about the frightening practices of Dr. Harvey Finklestein, who is accused of reusing syringes multiple times on patients.
Kerrilyn Wilson, one of Finklestein's patients, recently received the dreaded letter sent out that she must be tested for hepatitis B and C, as well as HIV. She said she's been a nervous wreck ever since.
"I am, that is why I am going to wait until after the holidays," she said.
But while Wilson speaks positively of her experiences with the now notorious Finklestein, whose Plainview clinic remains open for business, former patient Brian Matarrese is outraged.
"I was tested and told to come back in six months. I am angry, why should this guy be practicing? He should be punished," Matarrese said.
Why Finklestein has yet to be punished is one of the major questions being asked at the hearing chaired by the head of the Senate's Health Committee.
"How did the public health system not function here? Why did it take so long to get notice to other patients of this doctor?" asked state Sen. Kemp Hannon (R-Garden City).
It took three years, in fact, to notify hundreds of patients that Finkelstein had been reusing syringes in multi-dose vials. Raymond Bookstaver is sure his the hepatitis C he's been diagnosed with stemmed from Finkelstein's improper practices.
So far, 1,200 patients have been notified by the state, and of the 119 tested in the past few weeks, six tested positive for hepatitis B while six other tested positive for hepatitis C. None had HIV.
Meanwhile, the new state Health Commissioner Richard Daines was put on the hot seat at the hearing, but he insisted all that could be done has been done.
"He shouldn't have been doing it, we put a stop to it, and we've notified all people put at risk as near as we can tell," he said.
But patient Michael Gruber did not hear the answers he was listening for. "It's unconscionable that it takes three years for the information to come out. But that's not why I'm here, I want my files and I want to know," he said.
As patients continue to stream into Nassau clinics to be tested for the possibly fatal blood-borne infections, lawmakers are asking the case against Finkelstein be reopened, and are demanding immediate changes in notification policies.
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2 men file first lawsuit over hepatitis from fibrinogen adhesive
http://www.japantoday.com
TOKYO — Two men who launched a lawsuit in late November against the state and pharmaceutical companies over the contraction of hepatitis C represent the first plaintiffs seeking compensation for contracting the disease from the use of a fibrinogen-based adhesive agent, the plaintiffs' lawyer said Friday.
Other plaintiffs are expected to come forward given the high number of people estimated to have contracted the disease in the same way.
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UC Davis Pushes Limits of Infectious Disease Research with New Waters Mass Spectrometry Laboratory
http://money.cnn.com
SYNAPT HDMS enables advanced molecular characterization with analysis of dynamic biological structures
DAVIS, Calif., Dec. 6 /PRNewswire-FirstCall/ -- University of California, Davis, and the Waters Corporation today dedicated the new Waters Corporation Facility for Advanced and Integrated Mass Spectrometry within Dr. Julie Leary's laboratory for mass spectrometry (MS). Prof. Leary, together with collaborators at UC Davis, UC Berkeley and Stanford University, is currently using this laboratory to study eukaryotic translation, the process by which messenger RNA is translated into proteins within the human 40S ribosome, to better understand how infectious diseases like hepatitis C and polio virus are transferred to humans.
The centerpiece of the new laboratory is the Waters(R) Synapt(TM) High Definition MS(TM) (HDMS(TM)) System, the world's only MS system to integrate high performance ion mobility separation within a high resolution mass spectrometer to enable characterization of samples based on size, shape and charge, as well as mass.
"A key to our current research is to understand the shape of large, complex proteins as they come in contact with each other and with messenger RNA," said Julie Leary, Ph.D., Professor of Molecular Biology and Chemistry University of California, Davis. "Are these proteins folded or are they elongated? What is the topography of the complex? For example, our lab is also using the Synapt to measure the eukaryotic initiation factor, an intact 13 protein complex from human tumor cells which we use to study protein translation. We are investigating how the individual protein subunits conform as they come off the intact complex. Biological molecules are dynamic and ever changing, presenting scientists with a challenge when we try to fully characterize or describe them. We hope that by tackling the issue of molecular shape during eukaryotic translation, we can better understand the process and in turn persuade others to develop effective treatment options."
"Waters is dedicated to expanding the capabilities and use of mass spectrometry to support research of molecular structures and functions," said Mark Groudas, Vice President, Americas Field Operations, for the Waters Division, who represented Waters at the laboratory dedication ceremony hosted by University of California, Davis. "We believe that SYNAPT HDMS will attract more biologists and biochemists to use mass spectrometry for their analysis. We are very excited to work with Dr. Leary as she advances our collective understanding of the infectious diseases translation process research."
The Waters Corporation Facility for Advanced and Integrated Mass Spectrometry at UC Davis has been completely equipped with a Waters SYNAPT HDMS and LCT Premier(TM) XE electrospray time-of flight mass spectrometer.
Waters SYNAPT HDMS
Designed for leading researchers working at the boundaries of conventional mass spectrometry capabilities who need to further characterize and define their samples, Waters SYNAPT HDMS system offers unique, enabling functionality. Using Waters patented TriWave technology, the SYNAPT HDMS system combines high-efficiency, ion mobility based, measurements and separations with high-performance quadrupole, time-of-flight mass spectrometry. The SYNAPT HDMS system enables researchers to analyze samples that are differentiated by size, shape and charge, as well as mass, to deliver increased specificity and sample definition beyond that achievable by conventional mass spectrometers.
About University of California, Davis
The University of California, Davis, makes a difference in the lives of people every day. Fueled by learning and energized by discovery, the UC Davis tradition of engagement with the local community, the nation and the world guides all that it does. The university's commitment to providing a rigorous, attentive and research-enriched education creates a supportive learning environment for both students and faculty. UC Davis is a pioneer in interdisciplinary problem-solving, and its four colleges, five professional schools, more than 100 academic majors and 86 graduate programs provide a comprehensive learning environment for students, faculty and researchers.
About Waters Corporation
Waters Corporation creates business advantage for laboratory- dependent organizations by delivering practical and sustainable innovation to enable significant advancements in such areas as healthcare delivery, environmental management, food safety, and water quality worldwide.
Pioneering a connected portfolio of separations science, laboratory information management, mass spectrometry and thermal analysis, Waters technology breakthroughs and laboratory solutions provide an enduring platform for customer success.
With revenue of $1.28 billion in 2006 and 4,700 employees, Waters is driving scientific discovery and operational excellence for customers worldwide.
Waters, Synapt, Synapt HDMS, HDMS, High Definition MS, High Definition Mass Spectrometry, LCT Premier EX are trademarks of Waters Corporation.
Media Contacts:
Brian J. Murphy
Waters Corporation
Public Relations Manager
508-482-2614
Brian_J_Murphy@waters.com
Bethany Daniels
UC Davis, College of Biological Sciences
Marketing Officer
530-752-5824
bfdaniels@ucdavis.edu
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