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Week Ending: October 20th , 2007
Alan Franciscus
Editor-in-Chief
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This Issue:
October 15th, 2007
Hemispherx Biopharma Files New Drug Application for Ampligen as Treatment for Chronic Fatigue Syndrome
http://www.therapeuticsdaily.com
NDA of Investigational Drug Includes Four Well-Controlled Trials, More Than 1,200 Trial Subjects and 90,000 Doses
PHILADELPHIA, Oct. 11, 2007 (PRIME NEWSWIRE) -- Hemispherx Biopharma, Inc. (AMEX:HEB) announced today that it has filed a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) for its experimental therapeutic, Ampligen(r), also known as Poly I : Poly C12U, to treat Chronic Fatigue Syndrome ("CFS"). The Company is also moving forward as planned with filings in countries outside the United States.
According to data from the Centers for Disease Control ("CDC"), Chronic Fatigue Syndrome may now affect more than 1 million people in the United States alone, causing an economic impact estimated at more than $9 billion annually. The Centers for Disease Control refers to CFS as a "... disabling disease, as disabling as other severe chronic conditions like multiple sclerosis, COPD (Chronic Obstructive Pulmonary Disease) and rheumatoid arthritis" in its ongoing public awareness campaign launched in 2006. The condition may also be associated with early death due to secondary depression/suicide and cancer.
Over its developmental history, the experimental therapeutic, Ampligen(r), has received various designations, including Orphan Drug Product Designation (FDA), Emergency (compassionate) Cost Recovery Sales Authorization (FDA), and "promising" designation by the Agency on Health Research Quality (AHRQ). Four well-controlled, or pivotal, trials are now being reported in their entirety within Hemispherx Biopharma's NDA submission, which covers more than 1,200 subjects evaluated with approximately 90,000 dose administrations.
The experimental therapeutic was originally discovered and developed at The Johns Hopkins University and thereafter licensed to Hemispherx. On December 29, 2006, the FDA received the Company's pre-submission of pre-clinical information and assigned an NDA number. The Company will now move forward promptly with a series of scientific and medical peer-reviewed publications on the audited database contained within the NDA application.
William A. Carter, M.D., Chief Executive Officer and Chairman of Hemispherx, commented: "The comprehensive data package being submitted today has been possible because of the guidance, and scientific support, of the FDA, the CDC and CFS Advisory Committees to both the government and the private sector. Our profound gratitude goes out to the teams of independent clinical investigators around the country and, especially, to the individuals afflicted with CFS who supplied the courage and will to sustain the research, clinical and regulatory communities in their continuing search for better understanding and management of CFS."
The bioactivity of the experimental therapeutic, Ampligen(r), as noted in a peer-reviewed Journal of Immunology study and reported by Hemispherx on April 30, 2007, may be based on its binding to the human toll-like receptor 3 (TLR3) and activating subsequent signaling cascades. Toll-like receptors such as TLR-3 serve as "pattern recognition" receptors in the early detection of pathogens and the establishment of early defense mechanisms (innate immunity). As such, they may be critical to the first line of immunological defense against a broad range of pathogens, such as otherwise lethal viruses and various forms of cancer.
About Chronic Fatigue Syndrome
Chronic Fatigue Syndrome (CFS) has a top priority status at the Centers for Disease Control and Prevention, the governmental agency responsible for disease surveillance, as a serious and debilitating disease in the U.S. The disorder reflects a major unmet medical need. There are currently no approved therapies for CFS. The Agency for Research and Quality, a health service arm of the U.S. Department of Health and Human Services, reported that Ampligen(r), an experimental therapeutic, yielded the most promising clinical results to-date related to CFS. It should be noted that only federal regulatory agencies can determine whether any experimental therapeutic is "safe and effective" for wider distribution outside of the existing authorized clinical trials.
About Hemispherx Biopharma
Hemispherx Biopharma, Inc. is an advanced biopharmaceutical company engaged in the manufacture and clinical development of new drug entities for treatment of seriously debilitating disorders. Hemispherx's flagship products include Alferon N Injection(r) (FDA approved for a category of sexually transmitted diseases) and the experimental therapeutics Ampligen(r) and Oragens(r). Ampligen(r) and Oragens(r) represent experimental RNA nucleic acids being developed for globally important debilitating diseases and disorders of the immune system. Hemispherx's platform technology includes large and small agent components for potential treatment of various severely debilitating and life threatening diseases. Hemispherx has in excess of 100 patents comprising its core intellectual property estate and a fully commercialized product (Alferon N Injection(r)). The Company wholly owns and exclusively operates a GMP certified manufacturing facility in the United States for commercial products. For more information please visit www.hemispherx.net
Information contained in this news release other than historical information, should be considered forward-looking and is subject to various risk factors and uncertainties. For instance, the strategies and operations of Hemispherx involve risk of competition, changing market conditions, change in laws and regulations affecting these industries and numerous other factors discussed in this release and in the Company's filings with the Securities and Exchange Commission. Any specifically referenced investigational drugs and associated technologies of the Company (including Ampligen(r), Alferon LDO and Oragens) are experimental in nature and as such are not designated safe and effective by a regulatory authority for general use and are legally available only through clinical trials with the referenced disorders. The forward-looking statements represent the Company's judgment as of the date of this release. The Company disclaims, however, any intent or obligation to update these forward-looking statements. Clinical trials for other potential indications of the approved biologic Alferon N Injection(r) do not imply that the product will ever be specifically approved commercially for these other treatment indications.
CONTACT:
Hemispherx Biopharma, Inc.
Company/Investor Contact: Dianne Will 518-398-6222 ir@hemispherx.net
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October 15th, 2007
No hepatitis spread by surgeon: officials
www.cbc.ca
CBC News
Health officials in P.E.I. believe no one contracted hepatitis C from a surgeon who was discovered to have the virus earlier this year.
P.E.I.'s deputy chief health officer says more than 90 per cent of Dr. David Ashby's surgery patients from the last three years were screened for hepatitis C, said deputy chief health officer Dr. Lamont Sweet. Out of 229 people tested, two had positive results, but not for the same strain of virus Ashby has.
"What they found was that they had not come from the same source," said Sweet.
"In other words, the patients had not gotten the virus from the surgeon and the surgeon, in turn, had not gotten the same virus as the patients."
Sweet said Ashby is receiving treatment and responding well. He is not currently practising medicine.
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Quelling the spread of hepatitis in prisons
http://starbulletin.com
By Helen Altonn
haltonn@starbulletin.com
State public safety and health officials are working with community advocates to educate and support Hawaii prisoners with hepatitis B and C to prevent the disease from spreading.
The Hepatitis Support Network of Hawaii initiated the Hepatitis Prison and Outreach Ministries project, directed by Eddie Ochoa with collaborators Lusk and Dr. Kay Bauman, Public Safety Department medical director.
Lusk said she created the curriculum based on the federal correctional health care curriculum with feedback from hepatitis support volunteers, Bauman and other public safety officials.
The program will begin at Halawa Correctional Facility and eventually expand to other prisons, Lusk said. She will train some peer educators in the prisons to help with the workshops. Hepatitis is a viral liver disease, and hepatitis B can sometimes be fatal.
When she joined the Public Safety Department five years ago, Bauman said her major task was to get a hepatitis treatment program going.
"We try to treat them during their incarceration so we don't have to worry about them continuing when released."
Guidelines are updated regularly, Bauman said. "We're very careful to watch what's going on in the country and St. Francis Liver Center."
Hawaii has the highest rate of liver cancer in the nation because of high rates of hepatitis B and C, a liver disease.
Bauman works with infectious-disease specialist Alan Tice on treatments offered at all prison facilities, including the women's correctional center and mainland prisons housing Hawaii inmates.
"Our cure rate is just a little better than nationally published cure rates," she said. "It's just a challenging treatment program because patients require a lot of monitoring and support."
All inmates entering the corrections system are offered a hepatitis C test at intake, and all prisoners within the system are offered hepatitis B immunizations. (There is no vaccine for hepatitis C.)
Inmates were offered HIV/AIDS testing through the Health Department for years, but hepatitis C testing has been offered only since last January, Bauman said.
She said she is trying to get a current picture of the hepatitis infection rate among isle prisoners. Based on her testing, she believes the rate is lower than the national rate of 30 percent to 40 percent of inmates. But even if it is as low as 20 percent, it is still one out of five inmates, she pointed out.
"We think numbers are going down with a younger population," she said, explaining the hepatitis C epidemic started in the 1980s with intravenous drug use.
Hawaii's needle exchange program, one of the first in the country, "was a wise public health decision," she said. "It protects drug users from the need to share needles and get a needle-transmitted diseases. That has protected many younger patients from getting hepatitis C."
Also, the street drug of choice now is crystal methamphetamine, or "ice," which can be injected but is generally smoked, she said.
The inmate population totals about 6,000, with one-third in mainland facilities, which she visits regularly to ensure standards are met, Bauman said.
Newly released prisoners and the homeless are offered free screenings, vaccinations for hepatitis B and other services at the Prison and Outreach Ministry office in the River of Life Mission.
For more information or to volunteer to help with the project, call Ochoa, 845-9944.
Symposium on a 'Silent Epidemic'
The Hepatitis Support Network will hold a symposium on "Hepatitis in Hawaii -- unique perspectives and problem solving" from 8 a.m. to 4 p.m. Oct. 27 at the Queen's Conference Center, 510 S. Beretania St.
» The free event will address problems Hawaii medical professionals are facing with the "silent epidemics" of hepatitis B and C, the network said.
» National and Hawaii specialists will discuss epidemiology, screening, diagnosis, liver disease, therapies, research, reimbursement, vaccines and what to expect in the future.
Hawaii has the highest rate of liver cancer in the United States, and complications from end-stage liver disease are expected to increase by 60 to 200 percent in the next few years, according to the network.
» Up to 10 percent of Hawaii residents born in Asian and Pacific island countries could have chronic viral hepatitis B and not know it because most people do not feel any symptoms until it might be too late for successful treatment, the network said.
» To register for the symposium, fax your name, contact information and degree and/or title by today to 585-0206. Attendance is limited to 100 people.
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Tattoos cited in study but experts want more proof
http://starbulletin.com
Star-Bulletin staff
citydesk@starbulletin.com
Tattoos get blamed for the spread of hepatitis C in prisons, but the issue needs more study, officials say.
"Everyone wants to blame them because they use funny equipment ... guitar strings or whatever they can find," said Dr. Kay Bauman, state Public Safety Department medical director.
Heather Lusk, state Health Department coordinator for hepatitis C, said a study is needed where people are tested when they enter the prison and when they leave to see what is happening.
"Are they coming in with it because we're incarcerating drug users or because they're sharing razors or tattooing inside the prison? A lot of this unfortunately is speculation," she said, adding that the best evidence is a study reported in the Hawaii Medical Journal in November 2005.
"A Case Control Investigation of Hepatitis C Risk Factors in Hawaii" was done by a state Health Department and John A. Burns School of Medicine team including Paul Effler, state epidemiologist.
Tattoos administered by nonprofessionals were cited as a risk for hepatitis.
Because tattooing is a strong cultural tradition in Hawaii and the Pacific and the process has a ceremonial nature, they "may be more likely to be done at home by a friend," the authors said.
"Tattooing could be a risk for hepatitis C virus transmission if the tattooing instruments were used on more than one person and not sterilized between uses," they said.
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The 58th Annual Meeting of the American Association for the Study of Liver Diseases, Boston, Nov. 2-6
http://www.prnewswire.com
BOSTON, Oct. 15 /PRNewswire/ -- The Liver Meeting is the premier meeting in the science and practice of hepatology, including the latest findings on new drugs, novel treatments, and the results from pilot and multicenter studies.
Approximately 10 percent of Americans have some form of liver disease, and the diseases strike disproportionately among certain populations but mostly regardless of lifestyle choices. There are now numerous treatments for both hepatitis B and C, whereas liver cancer is one of the few cancers growing in incidence.
An AASLD President's press conference highlighting key abstracts and issues presented at the Liver Meeting is scheduled for Saturday, November 3 at 4:00 p.m.
The approximately 1500 abstracts to be presented will be available to members of the press at our Web site (http://www.aasld.org), including almost 200 abstracts that will be presented in oral sessions.
Boston, MA - November 2-6, 2007
-- Poster Presentations: November 3-6
-- Oral Presentations: November 4-6
Please contact AASLD at 703-299-9766 for information about the above presentations, or to receive any additional information about The Liver Meeting -- or visit our Web site at http://www.aasld.org.
This release was issued through The Xpress Press News Service, merging e-mail and satellite distribution technologies to reach business analysts and media outlets worldwide. For more information, visit http://www.XpressPress.com.
SOURCE American Association for the Study of Liver Diseases
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October 16th, 2007
Liver fibrosis will be treated by a potential target
http://www.eurekalert.org
The outcome of hepatitis is either self recovery or its development into liver fibrosis or, further, liver cirrhosis. Liver fibrosis is the early pathological process of cirrhosis, which is considered a reversible, wound-healing response. Since no ideal drug is available for its therapy, liver fibrosis is currently considered to be a major worldwide health problem.
Previous studies have demonstrated that activin A is involved in hepatic fibrosis formation. However, the mechanism of the fibrotic process is not well understood. Activin receptor-interacting protein 2 (ARIP2) has been recently identified as a negative regulator of activin signal pathways. The fact that ARIP2 is highly expressed in the liver suggests that ARIP2 may participate in activin-induced anti-fibrosis in the liver.
A research article published on November 7 in the World Journal of Gastroenterology addresses this question. A research team led by Dr. ZH Liu from Jilin University spent more than five years researching ARIP2. The researchers used mouse Hepal-6 cells obtained from mouse a hepatoma cell line that had functions of hepatic parenchymal cells to investigate the effects of ARIP2 anti-fibrosis on the production of collagen type IV, which is a component of the extracellular matrix (ECM) in liver fibrosis.
One conclusion reported by the investigators is that the mode of expression regulation by various activators of signaling transduction, such as PMA, foskolin and LPS, has been characterized, and its negative effect on the production of collagen type IV revealed, using Hepal-6 cells.
An additional result was that the expression level of ARIP2 mRNA in the Hapel-6 cells was elevated 12 h after treatment with activin A and endotoxin LPS. Thus, it was concluded that ARIP2 participates in the negative feedback regulation of signal transduction in the late stage by affecting the expression of ActRIIA, which further suggests that ARIP2 might be a potential target for treatment of liver fibrosis induced by activin.
Reference:
Zhang HJ, Tai GX, Zhou J, Ma D, Liu ZH. Regulation of activin receptor-interacting protein 2 expression in mouse hepatoma Hepa1-6 cells and its relationship with collagen type IV.
World J Gastroenterol 2007; 13(41): 5501-5505
http://www.wjgnet.com/1007-9327/13/5501.asp
Correspondence to: Professor Zhong-Hui Liu, Department of Immunology, School of Basic Medical Sciences, Jilin University, Changchun 130021, Jilin Province, China. zh_liu2001@yahoo.com.cn
Telephone: +86-431-85619476 Fax: +86-431-85639362
About World Journal of Gastroenterology
World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection for providing a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2003-2000 IF: 3.318, 2.532, 1.445 and 0.993. WJG is a weekly journal published by The WJG Press. The publication date is 7th, 14th, 21st, and 28th day of every month. The WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No.30424812, and was founded with a name of China National Journal of New Gastroenterology on October 1, 1995, and renamed as WJG on January 25, 1998.
About The WJG Press
The WJG Press mainly publishes World Journal of Gastroenterology.
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Cubist Pays for Option to Buy Illumigen
http://biz.yahoo.com
Cubist Pharmaceuticals Purchases Exclusive Option to Acquire Illumigen Biosciences
LEXINGTON, Mass. (AP) -- Antibiotic maker Cubist Pharmaceuticals Inc. said Tuesday it received an exclusive option to acquire Hepatitis-C drug developer Illumigen Biosciences Inc.
Cubist agreed to pay $4.7 million for the option and an additional $1 million for a study on Illumigen's Hepatitis-C drug in the late-stages of pre-clinical development and its operating costs during the option period.
If Cubist exercises the option -- which relies on success of the drug in testing -- it will pay $9 million to Illumigen shareholders and up to $75.5 million in development and regulatory costs.
If Cubist develops an Illumigen product for treating viral infections other than Hepatitis-C, it will make additional payments of up to $117 million. If Illumigen products reach sales of up to $140 million, tiered royalties will apply.
Illumigen is in late-stage trials of IB657, a lead compound that it is testing to treat Hepatitis-C virus infections. Cubist makes Cubicin, an antibiotic for treating skin and blood-stream infections.
"The unmet medical need which IB657 would address represents a substantial market opportunity," said Cubist President and Chief Executive Mike Bonney. "If we exercise our option, adding an HCV compound will be an important step as we develop a pipeline behind ... Cubicin."
Cubist shares rose 39 cents to close at $23.62.
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Peregrine Pharmaceuticals Doses First Patient in Clinical Trial of Bavituximab in HCV Patients Co-Infected With HIV
http://www.therapeuticsdaily.com
TUSTIN, Calif., Oct. 10 /PRNewswire-FirstCall/ -- Peregrine Pharmaceuticals, Inc. , a clinical stage biopharmaceutical company developing targeted therapies for the treatment of cancer and hepatitis C virus infection (HCV), today announced that the first patient has been dosed in a clinical trial designed to evaluate the safety and pharmacokinetics of bavituximab in patients co-infected with HCV and the human immunodeficiency virus (HIV). The multi-center trial is being conducted initially at Saint Michael's Medical Center in Newark, NJ under the guidance of Dr. Stephen Smith, director of the Peter Ho Memorial Clinic, the largest HIV/AIDS treatment facility in the state.
"We are delighted that patient treatment has begun in this important clinical trial that was designed to evaluate an extended bavituximab treatment schedule in an important HCV patient population," said Steven W. King, president and CEO of Peregrine. "We believe that bavituximab has the potential to act on both HCV and HIV infections, and this trial gives us our first opportunity to assess the drug's anti-viral activity in this underserved group of patients."
This open-label, dose escalation study will be conducted in approximately 24 patients chronically infected with HCV and HIV. Patient cohorts will receive ascending dose levels of bavituximab weekly for up to eight weeks. HCV and HIV viral titers and other biomarkers will be evaluated, although they are not formal study endpoints.
In the United States alone, an estimated 300,000 individuals are co-infected with HCV and HIV, representing up to 30% of all HIV-infected patients. Co-infected patients have been shown to have a lower response to current HCV treatment regimens and the adverse effects of these regimens can be especially problematic for some HIV patients.
Bavituximab is a monoclonal antibody 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, including both HCV and HIV. Bavituximab helps stimulate the body's immune defenses to destroy both the virus particles and the infected cells. Since bavituximab's PS target comes from the host and not the virus, bavituximab may be less susceptible to the development of anti-viral resistance. Peregrine has completed two bavituximab Phase l monotherapy clinical trials in patients with chronic HCV infection. In these trials, the drug appeared safe and well tolerated with encouraging signs of anti-viral activity.
About Peregrine Pharmaceuticals
Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a portfolio of innovative product candidates in clinical trials for the treatment of cancer and hepatitis C virus (HCV) infection. The company is pursuing three separate clinical programs in cancer and HCV infection in the U.S. and India with its lead product candidates bavituximab and Cotara(R). Peregrine also has in-house manufacturing capabilities through its wholly owned subsidiary Avid Bioservices, Inc. (http://www.avidbio.com/), which provides development and bio-manufacturing services for both Peregrine and outside customers. Additional information about Peregrine can be found at http://www.peregrineinc.com/.
Safe Harbor Statement: Statements in this press release which are not purely historical, including statements regarding Peregrine Pharmaceuticals' intentions, hopes, beliefs, expectations, representations, projections, plans or predictions of the future are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The forward-looking statements involve risks and uncertainties including, but not limited to, the risk that the results from the co-infected HCV/HIV clinical trial will not be consistent with the results from the Company's prior HCV clinical trials and the risk that bavituximab will not be as effective as the current standard of care for co-infected patients. It is important to note that the Company's actual results could differ materially from those in any such forward-looking statements. Factors that could cause actual results to differ materially include, but are not limited to, uncertainties associated with completing preclinical and clinical trials for our technologies; the early stage of product development; the significant costs to develop our products as all of our products are currently in development, preclinical studies or clinical trials; obtaining additional financing to support our operations and the development of our products; obtaining regulatory approval for our technologies; anticipated timing of regulatory filings and the potential success in gaining regulatory approval and complying with governmental regulations applicable to our business. Our business could be affected by a number of other factors, including the risk factors listed from time to time in the Company's SEC reports including, but not limited to, the annual report on Form 10-K for the year ended April 30, 2007 and the quarterly report on Form 10-Q for the quarter ended July 31, 2007. The Company cautions investors not to place undue reliance on the forward-looking statements contained in this press release. Peregrine Pharmaceuticals, Inc. disclaims any obligation, and does not undertake to update or revise any forward-looking statements in this press release.
CONTACT: Investors, 1-800-987-8256, info@peregrineinc.com, or Media,
Barbara Lindheim, +1-212-918-4650, both of GendeLLindheim BioCom Partners
Web site: http://www.peregrineinc.com/
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October 17th, 2007
Intrahepatic Shunt Improves Survival in Cirrhotic Patients With Ascites
www.medscape.com
NEW YORK (Reuters Health) Oct 11 - Compared to paracentesis, employment of a transjugular intrahepatic portosystemic shunt (TIPS) can improve the survival rates in certain liver cirrhosis patients who have difficult-to-treat ascites, according to pooled data from randomized trials.
"TIPS is a treatment of refractory ascites in cirrhotic patients" lead investigator Dr. Francesco Salerno told Reuters Health, "which can improve survival as well as the quality of life."
"Doctors must be careful, however, with TIPS," he added, "because it is not applicable to all patients."
Dr. Salerno of the University of Milan, Italy and colleagues conducted a meta-analysis of data from 4 recent studies in which a total of 149 patients were allocated to TIPS and the remaining 156 underwent paracentesis. The findings are reported in the September issue of Gastroenterology.
Tense ascites recurred in 42% of the TIPS patients and 89% of those given paracentesis p < 0.0001). "Sixty-five of the TIPS patients and 78 of the paracentesis patients died. However, the actuarial probability of transplant-free survival was significantly greater in the TIPS group.
The average number of hepatic encephalopathy episodes was significantly higher in the TIPS group (1.93 versus 0.63). Nevertheless, the cumulative probability of developing such an episode was similar between groups.
Subgroup analysis showed that age, serum bilirubin level, plasma sodium level, as well as treatment allocation were independently associated with transplant-free survival.
Thus, continued Dr. Salerno, "a careful selection of the patients suitable for TIPS is very important to replicate in the daily practice the results we obtained in our study."
The success of TIPS implantation," he concluded, "is related to the experience of the radiologist."
Gastroenterology 2007;133:825-834.
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Older Patients Do Well After Liver Transplantation
www.medscape.com
By Michelle Rizzo
NEW YORK (Reuters Health) Oct 09 - Results of a study suggest that patients 60 or 65 years old who undergo liver transplantation have 1-year and 5-year survival rates similar to those of younger patients. These older patients also experience fewer episodes of rejection, according to the research team.
"An increasing number of patients are undergoing liver transplantation assessment for decompensated end stage liver disease," state Dr. Michael A. Heneghan and colleagues from King's College Hospital in London. "This situation has led to a re-evaluation of selection criteria for liver transplantation, so that both survival outcomes and organ allocation are optimized."
The researchers report their experience with patients who underwent liver transplantation between 1988 and 2003. They retrospectively examined patients and graft survival among those who were older than 65 years at the time of transplantation (group 1, n = 77) and compared them with those who were between 60 and 64 years of age (group 2, n = 137), and 18 to 59 years (group 3, n = 202) at the time of transplantation.
The mean ages at the time of the procedure for groups 1, 2, and 3 were 67 years, 62 years, and 42 years, respectively. Thirty-day survival was 99% for patients in group 1, 94% for those in group 2, and 94% for those in group 3, the investigators report in the October issue of Liver Transplantation. Corresponding survival rates at 1 year were 82%, 86%, and 83%. The 5-year survival was 73%, 80%, and 78%, respectively.
There were a total of 218 episodes of ACR in the three groups, with no significant difference between groups observed.
"Older patients should not necessarily be denied liver transplantation as long as a comprehensive screen for comorbidity is undertaken as part of the transplant assessment process," Dr. Heneghan told Reuters Health.
"Since older patients have less rejection, immunologically, there may be an advantage in this cohort of patients in terms of attempting more systematic immunosuppression reduction or indeed immunosuppression withdrawal," Dr. Heneghan said. "In addition, since immunosuppression in the form of anti-rejection therapy is associated with an increased risk of malignancy, reducing anti-rejection therapy may be advantageous for this group of patients in particular."
Liver Transpl 2007;13:1382-1388.
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Discovery Of New Antiviral Mechanism In Mammals May Improve Treatment Of Hepatitis C Infections
http://www.medicalnewstoday.com
A team of researchers led by biologists at the University of California, San Diego has discovered a completely new mechanism that mammalian cells employ to fight infections of the Hepatitis C virus, which affects approximately 2.7 million Americans and 170 million people worldwide.
The achievement, detailed in a paper published in the October 18 issue of the journal Nature, could improve current antiviral regimens or result in new treatments that are more effective and possess fewer detrimental side effects for those with the Hepatitis C virus infection, which frequently leads to liver cirrhosis and/or liver cancer.
"Approximately two percent of the human population worldwide is infected with Hepatitis C virus," said Michael David, an associate professor of biological sciences at UC San Diego who headed the research team. "And about 50 to 80 percent of those people develop persistent infections and are at great risk of developing liver cancer."
The only approved therapy for Hepatitis C is alpha-interferon, a protein produced by animal cells when invaded by viruses that induces healthy cells to manufacture enzymes that counter the infection. Often alpha-interferon is used in combination with an antiviral drug called ribavirin. However, only 40 to 80 percent of patients respond to this therapy and about half of those who do respond relapse once interferon treatments are stopped. Only about 25 percent of those treated with interferon, which can also induce flu-like symptoms and kidney damage in some patients, rid themselves of the viral infections. Explaining these varying response rates is difficult, since scientists do not fully understand the mechanisms used by alpha-interferon to fight off Hepatitis C virus infection.
What David and his team discovered is that microRNAs, short strands of RNA that interfere with the expression of specific genes, may also be effective against the Hepatitis C virus, because they are used by mammalian cells to reduce the replication of the virus. Their discovery comes as a surprise because while microRNA interference has been known to occur as a defense mechanism in plants and invertebrates, many scientists doubted it was employed by mammalian cells.
David and his group began by identifying microRNAs whose expression is controlled by alpha-interferon, then used computer prediction to identify potentially affected viral RNAs. Hepatitis C virus emerged as a prime candidate and the UCSD researchers--in collaboration with Hepatitis expert Francis Chisari of The Scripps Research Institute--demonstrated that several alpha-interferon induced microRNAs are able to potently inhibit viral infection and replication.
"This is an entirely new antiviral mechanism in mammalian organisms," said David. "Use of synthetic microRNAs has become a promising strategy of antiviral treatment. However, selecting the 'right' sequence is crucial in order to avoid unwanted and potentially dangerous side effects. The microRNAs used by alpha-interferon have been selected by evolution for efficacy and safety,and might therefore provide a sound basis for the generation of new synthetic antivirals."
"Now that we have identified this new antiviral pathway or mechanism, pharmaceutical companies may be able to design a more effective therapy against the Hepatitis C virus," said Irene Pedersen, a project scientist working in David's laboratory who is the first author of the paper.
Other co-authors of the paper are Francis Chisari, Guofeng Cheng and Stefan Wieland of The Scripps Research Institute and Carlo Croce and Stefano Volinia of Ohio State University. The research was supported by grants from the National Institutes of Health.
UCSD News on the web at: http://ucsdnews.ucsd.edu
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Hepatitis C: A challenge to physicians
http://www.mailtribune.com/
By Bill Kettler
Mail Tribune
The disease is often asymptomatic, there's no vaccine and it kills 8,000 to 10,000 people a year
MEDFORD — A disease that afflicts as many as 4 million Americans is the most common cause of chronic liver disease, but it produces no symptoms in about 80 percent of its victims.
People who have liver failure associated with hepatitis C account for about half of the liver transplants performed every year in the United States, Dr. Aijaz Ahmed said during a presentation Tuesday at the Smullin Center at Rogue Valley Medical Center. The disease also kills 8,000 to 10,000 Americans annually.
The virus remains a challenge to physicians because there's no vaccine to prevent it, and it may not be diagnosed until it has caused liver damage. It progresses at different rates, and about 15 percent of people who are infected somehow manage to clear the virus from their body without treatment. The other 85 percent eventually develop chronic infection, and 20 percent of those will suffer from cirrhosis (severe scarring) of the liver.
"Some people get liver failure," Ahmed said. "Others don't."
Ahmed, an assistant professor of medicine at Stanford Medical School, spoke to a group of about 50 people who ranged in age from their 20s to their 70s, including some who have lived with the hepatitis C virus for more than half a century. He counseled people to take an active role in managing their disease to minimize stress on their weakened liver.
"Patients have to get their act together," he said. "Lose weight, no smoking and no drinking."
Ahmed came to Southern Oregon at the invitation of Dr. Martin Tice. He presented a continuing medical education program on hepatitis C as well as his public program.
Hepatitis C spreads when blood from an infected person enters the body of someone who isn't infected. Hundreds of thousands of people were infected in the 1970s and '80s before blood products were screened for the virus. It also spreads among intravenous drug users and people who engage in high-risk sexual contact.
Six types of the virus, and many subtypes, have been detected around the world. Genotypes 1, 2 and 3 are found worldwide; genotype 4 is found mostly in Africa and the Middle East; genotype 5 exists mostly in South Africa; and genotype 6 occurs mostly in Hong Kong and Vietnam.
In the United States, genotype 1 accounts for about 70 percent of all infections. Unfortunately, Ahmed said, genotype 1 is one of the more difficult types to treat. If the national infection rate (about 1 percent of the U.S. population) were extended to Southern Oregon, that would mean as many as 2,000 people in the Rogue Valley may have hepatitis C.
Ahmed said the most common symptom of infection is severe fatigue. Some people may produce dark urine, or suffer abdominal pain, loss of appetite or nausea. Very few have the jaundiced skin associated with hepatitis.
Physicians generally treat the virus with an extended multiweek course of antiviral drugs that eliminate it in some people, but not others. The medicines produce flu-like symptoms (nausea, diarrhea, aches and pains) among many patients, as well as depression or vision disorders, so the treatment is not undertaken lightly.
Many people still have little knowledge of the virus despite its prevalence. While it is spread by contact with infected blood, it's not typically spread by ordinary sexual contact or casual physical contact. In rare cases an infected mother can pass the virus to her newborn child.
Ahmed said people who are infected should never share their razor or toothbrush with anyone else.
"Every time we brush our teeth we bleed," he said. "We just don't see it."
Cuts or scrapes should be covered to prevent exposure to others, and any bloody bandages should be disposed of.
Ahmed said people with hepatitis C can be organ donors, but they can give their organs only to other people who are already infected with the virus. If the organ donor and the recipient had different types of the virus, one type usually takes over.
Reach reporter Bill Kettler at 776-4492 or e-mail bkettler@mailtribune.com.
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Initial Results of Phase II Study with HCV Protease Inhibitor Boceprevir in Treatment-Naive Hepatitis C Patients Show a High Rate of Early Virologic Response
www.schering-plough.com
Top Line Results of Phase II Study in Previous Nonresponders also Reported
KENILWORTH, N.J., Oct. 18, 2007 – Schering-Plough Corporation (NYSE: SGP) today provided an update on the clinical development program for boceprevir, its investigational oral hepatitis C protease inhibitor. Initial results from an ongoing Phase II study in treatment-naïve (previously untreated) hepatitis C patients showed boceprevir (800 mg TID) in combination with PEGINTRONTM (peginterferon alfa-2b) and REBETOL® (ribavirin, USP) achieved a high rate of early virologic response, with up to 79 percent of patients having undetectable virus (HCV-RNA) at week 12 of boceprevir treatment compared to 34 percent of patients receiving PEGINTRON and REBETOL alone.
“These initial results, while preliminary, are very encouraging, and showed that boceprevir is a potent antiviral agent for hepatitis C,” said Paul Kwo, M.D., associate professor of medicine and medical director, liver transplantation, Department of Medicine, Division of Gastroenterology/Hepatology, Indiana University School of Medicine, Indianapolis, and the lead investigator of the study. “In this study, boceprevir improved viral clearance rates at week 12 in genotype 1 hepatitis C infection compared to the control group. We look forward to further results from this ongoing study.”
Boceprevir is being evaluated in combination with PEGINTRON and REBETOL for the treatment of patients chronically infected with hepatitis C virus (HCV) genotype 1 in two large Phase II clinical studies, in which more than 800 patients have received boceprevir. One study involves treatment-naïve patients and the other involves patients who were nonresponders to previous peginterferon and ribavirin combination therapy. In these boceprevir studies, the most common adverse events have been fatigue, headache, nausea and anemia. No increase in skin adverse events (rash) beyond what was seen in the PEGINTRON and REBETOL control was observed. Gastrointestinal events were the most common adverse events leading to discontinuation in the boceprevir arms.
In the treatment-naïve study, known as HCV SPRINT-1 (HCV Serine Protease Inhibitor Therapy-1), boceprevir (800 mg TID) is being evaluated in three treatment regimens: in combination with PEGINTRON (1.5 mcg/kg once weekly) and REBETOL (800-1400 mg daily) for 28 or 48 weeks; 4 weeks of PEGINTRON and REBETOL combination therapy at the doses described above followed by adding boceprevir to the combination for 24 or 44 weeks; and boceprevir in combination with PEGINTRON and low-dose REBETOL (400-1000 mg daily) for 48 weeks, compared to a control of PEGINTRON and REBETOL alone for 48 weeks (a standard of care). The primary endpoint of this study is sustained virologic response. Patients receiving these boceprevir regimens achieved a high rate of early virologic response, with 70, 79 and 54 percent of patients, respectively, having undetectable virus (HCV-RNA) at week 12 of boceprevir therapy compared to 34 percent of patients in the control arm (Roche Cobas Taqman 1.0 assay; lower limit of detection is 15 IU/mL). Treatment discontinuations due to adverse events were 12, 9, and 8 percent for patients in the boceprevir regimens, respectively, compared to 5 percent for the control arm.
A total of 595 patients have been treated in the HCV SPRINT-1 study at sites across the United States, Canada and Europe, including 491 patients treated with boceprevir. Overall, 77 percent of patients in the study were enrolled in the United States. African-Americans represent 16 percent of the patients enrolled in the study and 7 percent of patients in the study are cirrhotic.
Boceprevir in “Null” Nonresponder HCV Patients
Schering-Plough also reported top line results from a completed Phase II study evaluating boceprevir dose response and the need for ribavirin in patients chronically infected with HCV genotype 1 who were nonresponders to previous peginterferon and ribavirin combination therapy (i.e., patients who did not have undetectable HCV-RNA or who did not achieve a 2 log decline in viral load with a minimum of 12 weeks of peginterferon and ribavirin combination therapy). These “null” nonresponders to peginterferon and ribavirin combination therapy represent the most difficult-to-treat patient population. Patients who relapsed following previous HCV therapy (relapsers) were not included in this study.
This study was complex, involving seven different treatment arms. Patients were initially randomized to low doses of boceprevir (100, 200, 400 mg TID) before initiating an 800 mg TID boceprevir arm. Under the study protocol, patients received these boceprevir doses in combination with PEGINTRON (1.5 mcg/kg weekly) with or without REBETOL (800-1400 mg daily) for 24 or 48 weeks, or received PEGINTRON and REBETOL alone as a control. During the ongoing review of the study by the Data Safety Monitoring Board (DSMB), it was recommended that patients in the lower-dose boceprevir arms who demonstrated a substantial antiviral response during treatment cross over to boceprevir 800 mg TID in combination with PEGINTRON and REBETOL for an additional 24 weeks. Patients who did not demonstrate a substantial antiviral response during treatment were discontinued from the study. In addition, patients in the control arm who did not respond to PEGINTRON and REBETOL alone were allowed to cross over to boceprevir 800 mg TID in combination with PEGINTRON and REBETOL. Patients received a maximum of 24 weeks of the optimized regimen (boceprevir 800 mg TID in combination with PEGINTRON and REBETOL). In all, 357 patients were enrolled at centers in the United States and Europe, including 348 patients who received boceprevir at some point in the study.
In this study of well-documented null nonresponders, some patients achieved a sustained virologic response (SVR). Overall, 7-14 percent of patients in the boceprevir crossover arms achieved SVR compared to 2 percent in the control arm. SVR was associated with early virologic response and a longer course of therapy (more than 36 weeks). While potent antiviral activity with boceprevir was seen in the study, with viral loads in some patients decreasing below the limit of detection, viral loads for other patients decreased and then rebounded to baseline levels while on therapy and some patients relapsed following the end of treatment. Several resistant variants were observed in these patients. These HCV variants are similar to those reported after treatment with other HCV protease inhibitors and those previously observed in boceprevir in vitro studies. Whether the results of this study would have been different had all patients been started with the optimized regimen of boceprevir 800 mg TID in combination with PEGINTRON and REBETOL – and with treatment extending to 48 weeks – is not known.
“Although interferon nonresponders appear to respond to HCV protease inhibition, it seems that some significant element of interferon response is needed to achieve a sustained virologic response in the majority of these patients,” said Eugene R. Schiff, M.D., chief, division of hepatology and director, Center for Liver Disease, University of Miami Miller School of Medicine, and the lead investigator of the study.
Schering-Plough said that in patients with little to no interferon response, alternative treatment strategies are required, and the company will continue to explore regimens containing boceprevir, PEGINTRON and REBETOL in the Phase II setting, using the insights gained in this initial study.
About PEGINTRON
In the United States, PEGINTRON is indicated for use alone or with ribavirin for the treatment of chronic hepatitis C in patients with compensated liver disease who have not been previously treated with interferon alpha and who are at least 18 years of age. PEGINTRON is indicated for 48 weeks of treatment in the United States.
Important Safety Information Regarding U.S. Labeling for PEGINTRON and REBETOL
Alpha interferons, including PEGINTRON and INTRON® A, may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Patients with persistently severe or worsening signs or symptoms of these conditions should be withdrawn from therapy. In many, but not all cases, these disorders resolve after stopping PEGINTRON and/or INTRON A therapy.
Use with Ribavirin: Ribavirin may cause birth defects and/or death of the unborn child. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin causes hemolytic anemia. The anemia associated with REBETOL therapy may result in a worsening of cardiac disease. Ribavirin is genotoxic and mutagenic and should be considered a potential carcinogen
Contraindications
PEGINTRON is contraindicated in patients with hypersensitivity to PEGINTRON or any other component of the product, autoimmune hepatitis, and hepatic decompensation (Child-Pugh score greater than 6 [class B and C]) in cirrhotic CHC patients before or during treatment. INTRON A (Interferon alfa-2b, recombinant) for Injection is contraindicated in patients with hypersensitivity to INTRON A or any component of the product, autoimmune hepatitis, and decompensated liver disease. PEGINTRON or INTRON A in combination with REBETOL therapy is additionally contraindicated in patients with hypersensitivity to ribavirin or any other component of the product, women who are pregnant, men whose female partners are pregnant, patients with hemoglobinopathies (e.g., thalassemia major, sickle-cell anemia), and patients with creatinine clearance less than 50 mL/min.
Avoid Pregnancy
REBETOL therapy should not be started until a report of a negative pregnancy test has been obtained immediately prior to planned initiation of therapy. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients during therapy and 6 months post-treatment. Patients should use at least two effective forms of contraception and have monthly pregnancy tests during therapy and for 6 months after completion of therapy. A Ribavirin Pregnancy Registry has been established to monitor maternal-fetal outcomes of pregnancies in female patients and female partners of male patients exposed to ribavirin during treatment, and for 6 months following cessation of treatment. Physicians and patients are encouraged to report such cases by calling 1-800-593-2214.
Incidence of Adverse Events
There are no new adverse events specific to PEGINTRON as compared to INTRON A; however, the incidence of some (e.g., injection site reactions, fever, rigors, nausea) were higher. The most common adverse events associated with PEGINTRON were “flu-like” symptoms, occurring in approximately 50% of patients, which may decrease in severity as treatment continues. Application site disorders were common (47%), but all were mild (44%) or moderate (4%) and no patient discontinued, and included injection site inflammation and reaction (i.e., bruise, itchiness, irritation). Injection site pain was reported in 2% of patients receiving PEGINTRON. Alopecia (thinning of the hair) is also often associated with alpha interferons including PEGINTRON.
Psychiatric adverse events, which include insomnia, were common (57%) with PEGINTRON but similar to INTRON A (58%). Depression was most common at 29%. Suicidal behavior including ideation, suicidal attempts, and completed suicides occurred in 1% of patients during or shortly after completing treatment with PEGINTRON.
The following serious or clinically significant adverse events have been reported at a frequency less than 1% with PEGINTRON or interferon alpha: Severe decreases in neutrophil or platelet counts, hypothyroidism, hyperglycemia, hypotension, arrhythmia, ulcerative and hemorrhagic colitis, development or exacerbation of autoimmune disorders including thyroiditis, RA, systemic lupus erythematosus, psoriasis, pulmonary disorders (dyspnea, pulmonary infiltrates, pneumonitis and pneumonia, some resulting in patient deaths), urticaria, angioedema, bronchoconstriction, anaphylaxis, retinal hemorrhages, and cotton wool spots.
In the PEGINTRON/REBETOL combination trial, the incidence of serious adverse events was 17% in the PEGINTRON/REBETOL groups compared to 14% in the INTRON A/ REBETOL group. The incidence of severe adverse events in the PEGINTRON/REBETOL combination therapy trial was 23% in the INTRON A/REBETOL group and 31-34% in the PEGINTRON/REBETOL groups. Dose reductions due to adverse reactions occurred in 42% of patients receiving PEGINTRON (1.5 mcg/kg)/REBETOL and in 34% of those receiving INTRON A/REBETOL.
Additional Safety Information
Relapse of drug addiction/overdose has occurred in patients on PEGINTRON therapy. Aggressive behavior sometimes directed towards others has occurred in patients with and without a previous psychiatric disorder during PEGINTRON and/or INTRON A treatment and follow-up. If patients develop psychiatric problems, including clinical depression, it is recommended that patients be carefully monitored during treatment and in the 6-month follow-up period. If psychiatric symptoms persist or worsen, or suicidal ideation or aggressive behavior towards others is identified, it is recommended that treatment with PEGINTRON and/or INTRON A be discontinued, and the patient be carefully followed with psychiatric intervention, as appropriate. Cases of encephalopathy have been observed in some patients, usually elderly, treated with higher doses of PEGINTRON and/or INTRON A. Ischemic and hemorrhagic cerebrovascular events have been observed in patients treated with interferon alpha therapies, including PEGINTRON and INTRON A. Dental and periodontal disorders have been reported in patients receiving PEGINTRON or INTRON A in combination with REBETOL therapy.
About Schering-Plough
Schering-Plough is a global science-based health care company with leading prescription, consumer and animal health products. Through internal research and collaborations with partners, Schering-Plough discovers, develops, manufactures and markets advanced drug therapies to meet important medical needs. Schering-Plough’s vision is to earn the trust of the physicians, patients and customers served by its approximately 33,500 people around the world. The company is based in Kenilworth, N.J., and its Web site is www.schering-plough.com.
SCHERING-PLOUGH DISCLOSURE NOTICE: The information in this press release includes certain “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to the company’s clinical development plans and the potential for boceprevir. Forward-looking statements relate to expectations or forecasts of future events. Schering-Plough does not assume the obligation to update any forward-looking statement. Many factors could cause actual results to differ materially from Schering-Plough’s forward-looking statements, including market forces, economic factors, product availability, patent and other intellectual property protection, current and future branded, generic or over-the-counter competition, the regulatory process, and any developments following regulatory approval, among other uncertainties. For further details and a discussion of risks and uncertainties that may impact forward-looking statements, see Schering-Plough’s Securities and Exchange Commission filings, including Part II, Item 1A, “Risk Factors” in the company’s second quarter 2007 10-Q.
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October 18th, 2007
Over 2 decades experiences shows that ultrasound-guided liver biopsy is the procedure of choice
http://www.news-medical.net/
Liver biopsy is a widely used tool in the investigation of liver diseases. It is invasive and has a mortality risk ranging between 0.01% and 0.17%. A liver biopsy should therefore only be performed in patients who would potentially benefit from it.
Over the last two decades, we have seen a staggering increase in patients with type 2 diabetes mellitus and obesity. These are likely to reflect changes in our socio-economic status and life-styles. Non-alcoholic steatohepatitis, the liver manifestation of the metabolic syndrome, is now one of the leading causes of chronic liver diseases and an indication for liver transplantation.
A review was therefore undertaken in a typical district general hospital in the UK, looking at the indications, findings and complications of liver biopsies. The changes in liver biopsy practice and the utility of a liver biopsy were explored. All liver biopsies between 1986 and 2006 were analysed. Clinical data was available for 88 patients who underwent 95 liver biopsies.
Between 1986 and 1996, 95% of all biopsies were performed “blind” (USS-guided in 5%). 33% of biopsies were performed for patients with primary biliary cirrhosis. Between 1996 and 2006, 18% of all biopsies were performed “blind” (USS-guided in 78%; other routes in 4%). The majority of liver biopsies (>40%) were performed in patients with raised liver tests and hepatitis C infection. The reduced number of liver biopsies for primary biliary cirrhosis is the result of the development of reliable marker for confirming diagnosis and predicting outcome. Investigators also noted an increasing number of patients diagnosed with non-alcoholic fatty liver disease (17% vs. 26%).
In the analyses, investigators found that a liver biopsy was useful in confirming diagnoses in over 90% of patients with abnormal liver function tests but non-specific liver screening investigations. It was also found to be helpful in staging diseases, allowing clinicians to detect the development of cirrhosis (scarring) and to place patients on appropriate treatment or surveillance protocols.
Pain was the most common complication after a liver biopsy (5.2% of biopsies). There was no biopsy-related mortality, but there was a trend towards greater technical failures and complications with the “blind” liver biopsy technique. These complications included pneumothorax and bleeding around the liver capsule.
This study confirms the safety and utility of the liver biopsy, even in small district hospitals; ultrasound-guided liver biopsy is the procedure of choice.
http://www.wjgnet.com/
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Westbrook warm to needle exchange
http://pressherald.mainetoday.com
By ANN S. KIM Staff Writer
A program based in Portland wants to expand to Westbrook, where many of its clients live.
Operators of a needle-exchange program in Portland are looking to open a satellite operation in Westbrook.
While the program for injection drug users is operated by Portland's Public Health Division, it is a regional resource funded by state money and foundation grants. A survey of clients revealed that many live in Westbrook, though the exact number was not available on Tuesday.
"Our overall goal is to make sterile equipment available to folks who wouldn't otherwise have access to it," said Martin Sabol, the manager of Portland's infectious-disease program. "We go where the people are."
The specifics of a Westbrook program have not been worked out. Portland public health officials made their initial presentation to the Westbrook City Council's public safety committee on Monday.
The idea was well received by the committee, according to Councilor Michael Foley, who is chairman of the panel.
"The general consensus was, 'Yup, we'll work with you to get it done,'" he said. "They just wanted our blessing."
Because injection drug use comes with a high risk of contracting human immunodeficiency virus and hepatitis B and C, sterile syringes are an important tool in fighting transmission, according to supporters. But the practice of exchanging dirty needles for clean ones has drawn criticism from those who believe it condones drug use and can contribute to its spread.
The state passed a law allowing needle-exchange programs 10 years ago. Portland's is the only one in southern Maine.
Other programs are based in Augusta, Bangor and Ellsworth. The Frannie Peabody Center is awaiting review for licensure by the state and plans to offer needle exchange at its office in York and at the Sanford Unitarian Universalist Church, according to Jacob Roberson, the center's development director.
The Westbrook satellite program would be Portland's first outside the city.
The program's main site, on India Street, and a satellite program at the Preble Street Resource Center in the Bayside neighborhood have fixed walk-in hours.
Staff members also meet clients within Portland as part of their outreach activities.
The needle exchanges are part of Portland's larger prevention efforts against HIV and sexually transmitted diseases.
Needle exchange clients also have access to screening for HIV and hepatitis C, immunization for hepatitis A and B, and referrals to drug treatment services.
The program now has 435 clients enrolled. So far this year, the program has had 495 exchanges, up from 376 last year, and disposed of 4,752 syringes, Sabol said. Until recently, clients were limited to exchanging 10 needles at a time; a state law lifting the cap took effect last month.
Clients receive identification cards but remain anonymous.
Between 70 percent and 80 percent of patients treated for opiate addiction at Mercy Hospital's Recovery Center in Westbrook test positive for hepatitis C, said Dr. Mark Publicker, the center's medical director.
The disease is the most common blood-borne infection in the United States and the leading reason for liver transplants. There is no vaccine.
One clear trend is the movement from prescription drug abuse to intravenous heroin use -- a cheaper, more powerful method that is also efficient at transmitting hepatitis C, Publicker said.
"You may be dealing with an 18- or 19-year-old woman who may not be particularly sophisticated, who may be introduced to intravenous drug use by peers and may not know how to obtain clean needles, how to dispose of them, or the dangers involved in their use," he said. "As a consequence, transmission rates are pretty high."
City Councilor John O'Hara Jr., vice chairman of the Westbrook council's public safety committee, said the program may generate some controversy but noted that the community has already accepted a methadone clinic within its boundaries.
He expects the needle exchange program to reduce disease transmission and help protect citizens and public works employees from being stuck by improperly disposed syringes.
"If we can eliminate it to a certain point, it's beneficial for all," he said.
Mayor Bruce Chuluda said he supports the idea so far and does not expect it to increase drug use in the city.
"I don't think we're going to be getting people into the city of Westbrook that aren't already using," he said.
It appears that a satellite program would not need official approval from the City Council, according to City Administrator Jerre Bryant.
Portland is not seeking funding from Westbrook because the program is funded by state and foundation money, and the program would not fall into categories that require licenses from the city, he said.
"I think the question is a moot point. If the Westbrook City Council didn't want it, they wouldn't do it," Bryant said.
Staff Writer Ann S. Kim can be contacted at 791-6383 or at: akim@pressherald.com
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OctoPlus says hepatitis C phase IIa study complete
http://www.pharmabiz.com/
Leiden, Netherlands
OctoPlus N.V, the drug delivery and development company, has announced the successful completion of the phase IIa clinical study with its lead product Locteron, a controlled release interferon alfa product for the treatment of chronic hepatitis C (HCV).
Results from this study confirm Locteron's potential to substantially improve patient care in HCV. Safety data from the study show a substantially improved tolerability profile for Locteron compared to other interferon products on the market or in development. Efficacy data from the study indicate Locteron's strong antiviral effect, with 100 per cent of the patients achieving early virologic response in the two highest dose groups. In addition, Locteron is a more convenient therapy than existing treatments due to its controlled-release profile, allowing for once every two weeks drug administration versus the current once a week regimen. OctoPlus is co-developing Locteron with its partner Biolex Therapeutics.
"We are excited that the results of this study demonstrate Locteron's potential for a convenient, safe and efficacious hepatitis C therapy with less side effects than its competing products. In addition, we believe that the emergence of new oral antiviral products, which are associated with additional side effects, will further add to the opportunity for Locteron to be the interferon of choice for future combination therapy as a result of its potential for improved tolerability. We are on schedule to proceed with the development plan for Locteron and are preparing to commence a phase IIb clinical study in the first half of 2008," said, Joost Holthuis, CEO, OctoPlus
The dose response in antiviral effect that was observed in the first three dose cohorts continued in the final cohort: average viral reduction after 12 weeks of treatment was greater than 4 logs for the 320 microgram (ug), 480 ug and 640 ug dose cohorts, and 1.8 logs for the 160 ug dose.
The early virologic response (EVR, defined as at least a two-log reduction in hepatitis C virus after 12 weeks of treatment) that was observed in the first three dose cohorts, also continued in the final cohort: the percentage of patients who achieved this was 38% for the 160 ug dose, 88 per cent for the 320 ug dose, and 100 per cent for both the 480 and 640 ug doses. These results compare favorably with results for the currently marketed pegylated interferon alfa products and for Albuferon for which EVR rates ranging from approximately 74 per cent to 90 per cent in clinical trials have been reported.
Complete and final results of the study, including viral kinetics and pharmacokinetic results, will be presented at the Annual meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston, USA, on November 6.
Locteron is designed to be a best-in-class therapeutic for patients with chronic hepatitis C, with the potential to induce less side effects, improve patient compliance and provide a more convenient once every two week dosing schedule compared with current therapies.
OctoPlus N.V. is a product-oriented biopharmaceutical company committed to the creation of improved pharmaceutical products that are based on OctoPlus' proprietary drug delivery technologies and have fewer side effects, improved patient convenience and a better efficacy/safety balance than existing therapies.
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Schering's Hepatitis C Data Dull Vertex's Shine
http://www.thestreet.com/
By Adam Feuerstein
Senior Writer
Schering-Plough's (SGP - Cramer's Take - Stockpickr - Rating) experimental hepatitis C drug, once thought to be in trouble, has roared back to life, and now appears to be formidable competition to a similar drug from Vertex Pharmaceuticals (VRTX - Cramer's Take - Stockpickr - Rating).
Preliminary, but positive, efficacy and safety data from a phase II study of Schering-Plough's hepatitis C drug boceprevir were released Thursday morning. The announcement sent shares of Vertex down $5.25, or 14.6%, to $30.62, as Schering-Plough shares were up 53 cents, or 1.6%, to $32.78.
Boceprevir is a pill designed to attack hepatitis C by inhibiting the protease enzyme, one of the key enzymes the virus uses to copy itself. This "direct antiviral" approach differs from current hepatitis C drugs, which boost the immune system's ability to tamp down and eliminate the virus.
Vertex's hepatitis C drug telaprevir works via the same mechanism of action.
Vertex has pushed telaprevir's clinical development with alacrity, but Schering-Plough has moved at a slower pace. Also, some of the earlier clinical data on boceprevir was lackluster, leading many of the Wall Street investors following the race to develop new hepatitis C drugs to believe boceprevir's future was in doubt.
Today's new clinical data, however, suggest that boceprevir is alive and kicking.
In a phase II study of newly diagnosed hepatitis C patients, a three-drug combination of boceprevir, pegylated interferon and ribavirin achieved a rate of early virologic response in 70% of patients, which means these patients had undetectable levels of the hepatitis C virus in their systems at 12 weeks.
By comparison, 34% of patients receiving peglyated interferon and ribavirin alone (the current standard treatment) reached an undetectable viral level.
Vertex shares were weak Thursday morning because this boceprevir data stands up well to telaprevir.
In an ongoing phase II study, the three-drug combination of telaprevir, pegylated interferon and ribavirin achieved a rate of early virologic response in 70% of patients when measured at 12 weeks.
On the safety and tolerability side of the ledger, Schering-Plough says there were no increased reports of skin-related toxicities, including rash, among boceprevir patients. This is potentially important because rash -- sometime severe -- has been reported by patients given Vertex's telaprevir.
Now, a word of caution: Comparing two drugs across separate studies, especially when the design of the studies is different, is fraught with problems. Boceprevir and telaprevir have never been tested directly against each other in a clinical trial.
But with that cautionary statement made, boceprevir does appear to be an active hepatitis C drug, which is more than many gave it credit for before Thursday morning. At this point, all we have on boceprevir is a press release from Schering-Plough, so the clinical data will get a lot of scrutiny when it is presented at a medical meeting.
Vertex is still ahead in the race to be the first new approved hepatitis C drug. It plans to push telaprevir into phase III studies by the end of 2007 or early in 2008. Schering-Plough hasn't announced phase III plans yet, but those trials are likely to be well behind Vertex's timetable.
Some are calling for Vertex to be bought on today's weakness. Summerstreet Partners, an independent healthcare research firm, is telling clients today that the selloff in Vertex shares is unjustified because of telaprevir's big lead in development. The firm says Schering-Plough is 18 months to two years behind. Moreover, Vertex will be presenting new telaprevir data at next month's big liver disease meeting being held in Boston.
But for others, the new boceprevir data changes the hepatitis C landscape. It's good news for hepatitis C patients, potentially not so good for Vertex.
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ACG: Gene Expression Predicts Sustained Response in Chronic Hepatitis C
http://www.medpagetoday.com
By Charles Bankhead, Staff Writer, MedPage Today
Reviewed by Robert Jasmer, MD;
Associate Clinical Professor of Medicine,
University of California, San Francisco
PHILADELPHIA, Oct. 18 -- A panel of gene expression biomarkers can identify patients with chronic hepatitis C genotype 1 who are likely to achieve sustained virologic response to interferon-based therapy, results of a study reported here suggest.
Within seven days after the start of treatment, the gene expression panel had a sensitivity of 100% and a specificity of 92% for sustained virologic response, Zobair Younossi, M.D., of Inova Fairfax Hospital in Falls Church, Va., told attendees at the American College of Gastroenterology.
The biomarkers predicted response independent of conventional prognostic factors such as obesity and ethnicity, he added.
An estimated 75% to 80% of patients infected with HCV in the United States are genotype 1, which tends to confer the greatest resistance to treatment. Conventional clinical, demographic, and environmental prognostic factors have fairly limited utility for early identification of patients who will respond to treatment.
Dr. Younossi and colleagues performed mRNA profiling using six housekeeping genes and 317 mRNA transcripts from 160 genes. They performed logistic regression analysis to identify genes associated with response to therapy. They also evaluated patterns of gene expression in patients before and during treatment.
The researchers then developed predictive models that they applied to 44 patients chronically infected with HCV genotype 1. The study group comprised 19 treatment-naive patients and 25 who had not responded to prior therapy. Gene expression patterns were evaluated in each patient at baseline and then at days one, seven, 28, and 56.
Dr. Younossi reported data from analyses of gene expression models for predicting sustained virologic response before treatment, 24 hours after initiation of treatment, and seven days after starting treatment. Treatment consisted of pegylated interferon-alfa plus ribavirin.
In the treatment-naive cohort, a two-gene panel consisting of EP300 and SOC56 had a sensitivity of 86% and a specificity of 91% for predicting response before treatment.
During the first 24 hours after initiation of treatment, the combination of IL1B and ADAM9 yielded a sensitivity of 86% and a specificity of 91% for sustained virologic response.
At seven days a model focusing on changes in expression of PRKRIR yielded a sensitivity of 100% and a specificity of 75%.
Dr. Younossi said pretreatment gene expression in the treatment-experienced patients included upregulation of IFR-2 a negative regulator of interferon signaling. After initiation of therapy, changes in activity were observed in a variety of signaling cascades involved in apoptosis, proliferation, and lymphocyte metabolism.
IRF-2 provided the best pretreatment prognostic accuracy for the treatment-experienced patients. The model had a sensitivity of 62.5% and a specificity of 87.5%.
At 24 hours after the start of treatment, a model derived from expression patterns of two genes-IFIT2 and JAK1-resulted in a sensitivity of 100% and a specificity of 75%.
At seven days, a six-gene panel had a sensitivity of 100% and a specificity of 92.3% for predicting sustained virologic response.
Although the results are promising, Dr. Younossi said the prognostic strategy requires validation in additional studies involving more patients.
Action Points
- Explain to interested patients that genetic testing might help identify patients with the most common type of hepatitis C infection who are likely to respond to treatment.
- Note that the findings were reported at a medical conference and should be considered preliminary until they have appeared in a peer-reviewed journal.
Dr. Younossi disclosed no conflicts. The study was supported by Celera Diagnostics in Alameda, Calif., and several of the investigators are Celera employees.
Primary source:
American College of Gastroenterology
Source reference:
Yousonni Z et al. "Gene expression biomarkers can predict sustained virologic response early after initiation of pegylated interferon alfa and ribavirin in patients with genotype 1 chronic hepatitis C." American College of Gastroenterology Annual Meeting and Postgraduate Course. Oct. 12-17, 2007. Philadelphia. Abstract 29
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October 19th, 2007
Hepatitis C Testing Recommended for Anyone with a Tattoo
http://biz.yahoo.com
ARLINGTON, Va., Oct. 19 /PRNewswire/ -- The connection between tattoos and hepatitis C virus (HCV) has long been suspected but never completely substantiated. Tattoos and the connection to the disease were clouded by a perceived propensity to other risk factors, such as injection drug use. "Other studies did not exclude patients with other risk factors for hepatitis C," explains principal investigator Dr. Edmund Bini, "which made it difficult to assess the association between HCV and tattoos. The strength of that association surprised us."
Researchers in New York studied 3871 people, approximately half of whom were control subjects. Patients with HCV were more likely to have had one or more tattoos, and this remained so even after adjusting for age, sex and race/ethnicity.
Patients with tattoos but also with traditional risk factors for HCV -- injection drug use and drug transfusion prior to 1992 -- were excluded from the final analysis of the data of the remaining 1887 patients with tattoos and no other risk factors for HCV, patients with HCV were approximately three times more likely to have had tattoos. This connection was significant even after, once again, adjusting for age, sex, and race/ethnicity.
The researchers concluded that all patients with tattoos should be tested for HCV. "It helps to be able to identify patients early who are eligible for treatment," said Dr. Bini. This information will be further refined when they complete analysis of assessing the risk of having multiple tattoos, as well as whether the patient received the tattoo in the US or abroad.
Abstract title: Strong association between tattoos and hepatitis C virus infection: A multicenter study of 3,871 patients
AASLD is the leading medical organization for advancing the science and practice of hepatology. Founded by physicians in 1950, AASLD's vision is to prevent and cure liver diseases. This year's Liver Meeting, held in Boston, Massachusetts November 2-6, will bring together almost 5,000 researchers from 55 countries.
A pressroom will be available from November 3 at the annual meeting. Abstract and press release copies, or to arrange for pre-conference research interviews, contact Gregory Bologna, 703-299-9766. To pre-register, call Ann Tracy, 703-299-9766.
Press releases and abstracts available online at www.aasld.org.
This release was issued through The Xpress Press News Service, merging e- mail and satellite distribution technologies to reach business analysts and media outlets worldwide. For more information, visit http://www.XpressPress.com
Source: American Association for the Study of Liver Diseases
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Blood drive scheduled in honor of firefighter
http://news.enquirer.com
Cindy Schroeder
cschroeder@nky.com
Crescent Springs-Villa Hills Fire & EMS is sponsoring a blood drive Nov. 13 for a longtime firefighter/EMT who's in the hospital battling complications from hepatitis C.
Jim Ramler, who was inspired to go into fire service after losing his mother in the deadly Beverly Hills Supper Club fire, has received between 16 and 20 units of blood and platelets in recent weeks, friends and family members say.
Now Hoxworth Blood Center needs to replenish its supplies.
"There's no telling how much more (Ramler) will need," said Patty Grimes, a member of Crescent Springs-Villa Hills Fire & EMS who helped organize the blood drive. "We want to replace what he's used."
Anyone is encouraged to donate blood or platelets no matter what their blood type, Grimes said.
Jeff Wendt, chief of the fire department, said Ramler is "still going to need plenty of blood and platelets."
The blood drive isn't the only way the community has helped. Ramler's fellow firefighters have donated money to his family to help cover his medical expenses. Some in the department also are organizing meals to take to Ramler's wife, Linda, who's a member of the life squad and the ladies auxiliary, Grimes said.
Also, Ramler's sister, Shirley Welch, has been staying with her brother's family this week, and she hopes to give blood before returning to Los Gatos, Calif.
Ramler, 50, is described by friends and family as a fun-loving but dedicated person who has been battling various health issues for some time. The 25-year firefighter/EMT is also part of a first aid response team for General Electric, and before his illness he was active in the Villa Hills Civic Club.
"The doctor said (Jim) probably had the virus a good 15-20 years," Linda Ramler said in an e-mail Wednesday. "... At this point, it's hard to determine where he got the virus. We are just going forward and working on getting rid of it."
Earlier this week, Ramler "had not been responsive" to treatment, his wife said, but he's since shown signs of improvement.
"He slowly started coming out of it (on Tuesday) and did say a few words," his wife said. "I was feeding him some ice chips, and he asked Nick, our son, what I was feeding him. It was a pretty comical moment, one we won't forget."
Linda Ramler says she can't say enough for the support her family's received since her husband's latest hospitalization.
"The fire department and the Villa Hills community are great," she said Wednesday. "We have made some wonderful friends at the fire house and throughout the city."
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