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Week Ending: October 13th , 2007
Alan Franciscus
Editor-in-Chief
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This Issue:
October 8th, 2007
Data on hepatitis B virus in children discussed by researchers at Karadeniz Technical University, Department of Pediatrics
www.newsrx.com
Current study results from the report, 'Atopy in children with chronic hepatitis B virus infection,' have been published. In this recent report, researchers in Trabzon, Turkey conducted a study "To investigate whether immune responses against chronic HBV infection in children have an effect on prevalence of allergic diseases and atopy. Children with chronic HBV infection [HBV carriage (group 1) and chronic hepatitis (group 2)] were screened for allergic diseases."
"The results were compared with age-matched controls (group 3). The frequencies of doctor-diagnosed 'asthma', 'allergic rhinitis' and 'eczema' were 29.4%, 7.8% and 7.8% in group 1; 7.8%, 5.2% and 5.2% in group 2 and 12.4%, 9% and 2.8% in group 3, respectively. 'History of ever wheezing', doctor-diagnosed 'asthma' and 'eczema' were more common in group 1 than group 3 (p <0.05 for all parameters), and 'history of ever wheezing' and 'doctor-diagnosed asthma' were more common in group 1 than group 2 (p <0.05 for al parameters). Atopy was more common in group 1 (35.2%) than both groups 2 (15.7%) and 3 (18%) (p <0.05 for all parameters)," wrote M. Cakir and colleagues, Karadeniz Technical University, Department of Pediatrics.
The researchers concluded: "Vertical transmission was more common in patients with versus without atopy in HBV carrier group (33.3% vs. 9%, p<0.05). Immune responses in chronic HBV infection associated with carrier state may also lead to allergic diseases, which suggests the necessity of following these patients for the allergic diseases along with their viral reactivation.'."
Cakir and colleagues published their study in Acta Paediatrica (Atopy in children with chronic hepatitis B virus infection. Acta Paediatrica, 2007;96(9):1343-6).
For additional information, contact M. Cakir, Karadeniz Technical University, Dept. of Pediatrics, Faculty of Medicine, Trabzon, Trabzon, Turkey.
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October 9th, 2007
Study reveals sources of Hep C
http://www.ireland.com
Ciara O'Brien
Anti-D injections were the main source of hepatitis C infections among those who contracted the disease through contaminated blood, a report has found.
The National Hepatitis C Database Baseline report, published today by the Minister for Health Mary Harney, looked at people who were infected with hepatitis C through contaminated blood and blood products in Ireland.
This is the first report from the datatbase, which was set up to chart the natural history of infection among the group, and examines how various factors impact on the diseas's progression, along with the outcomes of treatment.
The report found most of those eligible for inclusion in the report were infected as a result of anti-D injections, who made up 65 per cent, followed by recipients of blood transfusions, who accounted for 24 per cent of infections.
Recipients of treatment for blood clotting disorders and those treated for renal disease made up 9 per cent and 2 per cent respectively.
The majority of participants in the report were female, and most included are now aged between 40 and 65 years.
The report found that at some time, a total of 63 per cent of participants had tested polymerase chain reaction (PCR) positive, which indicates active infection. Less than 40 per cent of PCR positive patients had received anti-viral treatment to date.
The majority of patients also suffered from other significant medical conditions, according to their charts, which were not necessarily related to hepatitis C infection. These conditions included fatigue and lethargy, depression, and arthralgia and joint pain.
Some 62 per cent of those who had a confirmed positive result remain chronically infected, while a further 13 per cent cleared the virus following treatment.
"This report and subsequent reports will provide an invaluable resource to researchers seeking to understand the nature of the hepatitis C virus and will not only facilitate research, but will also inform clinical practice and enable more effective service planning for the emerging needs of this group" said Ms Harney.
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Hepatitis C under diagnosed
http://www.nzdoctor.co.nz
Ed Gane
Hepatitis C is a blood-borne communicable disease caused by the hepatitis C virus (HCV). HCV is one of several distinct and unrelated RNA viruses, including hepatitis A, B, D, E, F and G, that cause viral hepatitis (inflammation of the liver).
WHO estimates that as many as 200 million people worldwide suffer from chronic HCV infection. Approximately 40,000 New Zealanders are estimated to carry HCV, of whom almost three quarters are yet to be diagnosed.
This is because the vast majority of HCV-positive New Zealanders were infected many decades ago (through recreational drug use in their late teens or twenties) and have no symptoms specific for chronic hepatitis C.
Commonly, diagnosis is only made through screening of asymptomatic individuals or when symptoms develop secondary to decompensated cirrhosis or hepatocellular carcinoma.
The most common early symptoms of hepatitis C include mild fever, headache, muscle aches, fatigue, loss of appetite and anxiety or depression.
However, many people with acute and even chronic HCV infection do not experience symptoms, or, if they do, the symptoms are often mild or non-specific.
Therefore, an accurate diagnosis can only be made by screening asymptomatic individuals with previous risk factors for HCV exposure (injectable drug use or transfusion prior to 1992) or with unexplained liver dysfunction.
About 80 to 85 per cent of patients with acute HCV infection will develop the chronic form of the disease. Of these, one third will develop cirrhosis of the liver over the next 50 years, potentially leading to liver failure or liver cancer.
There are nine identified HCV genotypes. In New Zealand, type 1 makes up approximately 50 per cent of cases, with types 2 and 3 making up a further 40 to 45 per cent. Types 4–9 are much rarer and found in Egypt, South Africa, Hong Kong and Southeast Asia. Collectively, they make up approximately 5 per cent of infections in New Zealand. The HCV genotype present can impact on a patient’s responsiveness to treatment.
Genotypes 2 and 3 generally respond well to current treatment regimens when compared with genotype 1, which does not respond as well.
HCV infection is now the leading cause of referral for liver transplant and second leading cause of liver cancer in New Zealand. The easiest solution to avoid the high potential cost to the health system is for people who are at risk of having contracted the virus to get tested so they can be treated in the early stages of liver disease. Testing will also allow those with the virus to take precautions to avoid spreading the virus further.
Unlike the hepatitis B virus (HBV), there is no vaccine for HCV, although it is treatable and potentially curable using a combination of interferon and ribavirin. Recent advances in treatment mean the disease has higher cure rates than was previously achievable. Pegylated interferon is fully funded in New Zealand for the treatment of hepatitis C, delivering sustained viral response rates of 55 per cent in genotype 1 and 80 per cent in genotypes 2 and 3. Advances in the management of hepatitis C are also contributing to improved outcomes for patients, by allowing a greater number of patients to be managed and receive care.
Greater GP role in shared-care model
Unfortunately, fewer than 5 per cent of New Zealanders with chronic hepatitis C have received antiviral therapy, reflecting underdiagnosis and also real and perceived barriers to treatment. Underdiagnosis and a lack of resources mean that many patients are not being identified early enough, or are missing out on potentially life-saving treatment.
Internationally, general practice is taking a leading role in management and treatment of hepatitis C. This is helping to increase the number of patients receiving treatment as well as patient compliance with treatment regimens.
Shared-care models have been developed, and are being trialled in a number of countries, including New Zealand. While the responsibility for treatment remains with hospital-based specialists, there is an increasing trend for general practice to become more involved in overseeing and monitoring hepatitis C patients during the treatment process. This includes monitoring blood tests and helping patients manage symptoms, as well as ongoing harm reduction and nutritional advice. In some cases, primarily in the UK, hospital funded, specialist hepatitis nurses are also delivering treatment in a primary care setting.
While shared-care models offers financial savings for the treating hospital, freeing up resources allowing a greater number of patients to be seen, they also offer a more convenient and accessible service for patients, giving them a continuity of care and continuation of the relationship many patients have with their GP.
In the UK, this shared-care approach has resulted in increased attendance and compliance with treatment programmes and a greater level of patient involvement with their treatment programme. There are currently a number of shared-care pilot programmes being trialled around New Zealand, including one being run out of Auckland City Hospital.
There are also ongoing efforts, centred in Europe but gaining traction worldwide, to increase public awareness of hepatitis C.
Monday 1 October was World Hepatitis Awareness Day. Endorsed by WHO (Europe), World Hepatitis Awareness Day aims to encourage anyone who may be at risk of carrying hepatitis C to get a diagnostic blood test, whether or not they experience symptoms, so they can receive any necessary treatment before the liver is irreversibly impaired or before they unwittingly transmit the virus.
Ed Gane is associate professor in medicine at the University of Auckland School of Medicine, and hepatologist in charge of the NZ Liver Unit at AucklandCityHospital.
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October 10th, 2007
Minimal Hepatic Encephalopathy Associated With Increased Traffic Accidents
http://www.medscape.com
By Will Boggs, MD
NEW YORK (Reuters Health) Oct 02 - Patients with minimal hepatic encephalopathy (MHE) report more traffic accidents and violations than other individuals, according to a report in the September issue of the American Journal of Gastroenterology.
"I would hope for physicians who take care of patients with cirrhosis to be open about this hidden epidemic of MHE which can threaten both the patient and other drivers they interact with on the road," Dr. Jasmohan S. Bajaj from Medical College of Wisconsin, Milwaukee, told Reuters Health. "Patients with cirrhosis who are not actively drinking should always be asked about their driving history."
Dr. Bajaj and colleagues investigated the occurrence of traffic violations and motor vehicle accidents using an anonymous questionnaire survey sent to 200 cirrhotic patients with or without MHE and 100 population controls.
Significantly more cirrhotics (18%) than controls (3%) reported traffic violations within the previous year, the authors report. Among cirrhotic patients, 33% of those with MHE and 4% of those without MHE reported traffic violations or motor vehicle accidents in the prior year.
The differences were similar for the previous 5 years: 53% of cirrhotics with MHE, 23% of cirrhotics without MHE, and 7% of controls reported traffic violations or motor vehicle accidents.
Driving behavior questionnaire (DBQ) scores were significantly higher for controls (mean, 99) than for cirrhotics with MHE (90) but not for cirrhotics without MHE (100), the researchers note. In contrast, personal overall driving assessments did not differ between the groups.
"We believe that MHE patients have several areas of cognitive dysfunction that make them prone to drive poorly," Dr. Bajaj said. "Our MHE research group has just started enrollment in a trial using a non-absorbable antibiotic, rifaximin, on driving ability and quality of life in patients with MHE, which would help clarify the issue of treatment of MHE and driving problems."
"This group is to be congratulated for focusing their research on MHE, a frequent but often overlooked complication of cirrhosis," writes Dr. Santiago J. Munoz from Albert Einstein Medical Center, Philadelphia, Pennsylvania in a related editorial.
"Dietary fiber, probiotics, and even lactulose have been reported to improve MHE," Dr. Munoz points out. "Thus, the hazards of driving with MHE are in theory susceptible of effective treatment."
Am J Gastroenterol 2007;102:1903-1909,1910-1911.
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Propranolol Better First-Line Prophylaxis Than Ligation for Variceal Bleeding
www.medscape.com
NEW YORK (Reuters Health) Oct 03 - Although propranolol and ligation are both effective prophylaxis treatments for variceal bleeding in patients awaiting liver transplantation, the cost and the potentially fatal bleeding associated with ligation make propranolol the choice for first-line therapy.
Several trials have compared beta-blockers and endoscopic variceal ligation for primary prophylaxis of variceal bleeding, the authors explain, but which is the better therapy has remained unclear.
Dr. Lorenzo Norberto from University of Padova, Italy and associates compared the safety and benefits of endoscopic variceal ligation versus propranolol in the prevention of first variceal bleeding in 62 candidates for liver transplantation.
There were no significant differences in the rates of first esophageal variceal hemorrhage, overall mortality, or bleeding-related mortality between the groups, the authors report in the September issue of Liver Transplantation.
Two patients in the endoscopic variceal ligation group and 5 in the propranolol group had adverse events requiring interruption of treatment, the investigators say, but only variceal ligation was associated with fatal complications.
The study was terminated after the interim analysis, when it became clear that a much larger sample size would be required to demonstrate significant differences between the treatments.
"Both propranolol and endoscopic banding are similarly effective in reducing the incidence of variceal bleeding in cirrhotic patients with high-risk varices, candidates for liver transplantation," the researchers write, "but ligation can be complicated by severe and fatal bleeding and is significantly more expensive."
"Our results suggest that banding should not be utilized as the primary prophylaxis in candidates for liver transplantation who can be treated with beta-blockers," the authors conclude.
"The use of pharmacologic therapy for preprimary prophylaxis is clearly an area that requires further study," writes Dr. Thomas D. Boyer from University of Arizona, Tucson, in a related editorial.
"Identification of new drugs that lower portal pressure to the same or greater degree than beta-blockers with fewer side effects are being sought and if found will further improve the management of the patient with varices."
Liver Transpl 2007;13:1212-1213,1272-1278.
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Former Blood Board biochemist appears in court
http://www.belfasttelegraph.co.uk/
A former principal biochemist with the Blood Transfusion Service Board who is charged in connection with the infection of a number of women with Hepatitis C has appeared before the Circuit Criminal Court.
Cecily Cunningham, of Hollybank Road, Clontarf in Dublin, lost her High Court bid in July to stop her trial from going ahead.
Mr Justice Liam McKechnie dismissed Ms Cunningham's judicial review challenge in July and refused to halt her trial.
The charges against the biochemist relate to the infection of six women with Hepatitis C from contaminated blood products on dates in 1977, 1991 and 1992.
Today, she was listed for arraignment at the Circuit Criminal Court, but her lawyers said she was appealing the High Court decision against her to the Supreme Court.
They asked for her case to be put back pending the outcome of the appeal.
Her lawyers then predicted that the trial would last four to six months, significantly longer than the three to four-week time frame put forward by representatives for the DPP.
Judge Catherine Delahunt put the case back for mention on November 15th so a time-frame could be agreed on and a trial date set.
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Bucks County's Institute for Hepatitis and Virus Research and BioLeap Collaborate on New Discoveries
http://www.sbwire.com
Collaboration Unveils Novel Compounds for the Treatment of Hepatitis C
New Hope, PA -- (SBWIRE) -- 10/10/2007 -- Bucks County’s Institute for Hepatitis and Virus Research (IHVR) and BioLeap have entered into a collaboration to develop new therapeutic compounds for the treatment of Hepatitis C. Up to 50% of patients treated with current standard therapies do not respond adequately and often suffer serious side effects from the drugs. Thus there is a critical need for new tools to treat this disease. By combining BioLeap’s leading edge computational fragment-based design capabilities with the IHVR’s extensive experience and in-depth knowledge of viral diseases, the collaboration will result in new classes of lead drug molecules with novel modes-of-action.
Of particular interest to the IHVR is BioLeap’s proprietary technology that rapidly calculates the free energies, or affinities of interactions between small molecular fragments of potential drugs and biomolecular structures of the proteins they will target, displaying the distribution and orientation of these fragments. This information provides a unique insight into how small molecules bind into key protein binding sites that cannot be achieved from the static crystal structure alone, or from methods that can only measure the enthalpic properties of binding. In addition to lead discovery, the quantitative free-energy based analysis of protein-drug-fragment interactions adds significant value to the lead optimization process. In combination, this proprietary approach provides chemists and biologists the information they need to assemble, fragment by fragment, a completely new molecule that not only optimally binds to the targeted protein site but also has properties desirable in a drug, including solubility and bioavailability.
Commenting on the collaboration, BioLeap’s Gerry Evans, Executive Vice President of BioLeap, noted: “Dr. Tim Block and his team at the IHVR are renowned for their work in this field. We are very excited by the opportunity to focus our combined expertise on this important target.”
Dr. Tim Block, president of the IHVR, is enthusiastic about the prospects for this collaboration. “One approach in discovering new treatments is the time and labor intensive process of screening tens or hundreds of thousands of molecules from compound libraries. BioLeap’s technology provides a potential shortcut by eliminating the need to screen compound libraries, while significantly broadening the field of chemical diversity. The molecules designed by BioLeap are not limited by what is present in any compound library. This greatly increases our odds of finding a potential drug that precisely targets the hepatitis C virus and that will not easily succumb to viral resistance. Once BioLeap has identified several candidate molecules, our scientists will test their effectiveness on the hepatitis C virus. Based on these results, we will repeat this iterative process until we have found the ideal drug.”
About the Institute for Hepatitis and Virus Research:
Established as the research arm of the Hepatitis B Foundation, the mission of the Institute for Hepatitis and Virus Research is to use discovery science to find new therapies for viral hepatitis and liver cancer; to advance its research discoveries through traditional scholarship and educational opportunities; to nurture biotechnology through technology transfer and new company formation; and to promote public health outreach programs to improve the quality of life for those with viral hepatitis.
About BioLeap:
Bioleap is a leader in computational fragment-based drug design. The company’s proprietary design technology and process successfully addresses one of the biggest problems in preclinical drug discovery: limited chemical diversity of compound libraries. Development collaborations span a broad spectrum of target proteins including: kinases, nuclear hormone receptors, metalloenzymes, and metalloproteases.
Contact
Michael S. Campbell, Ph.D.
Coordinator
Hepatitis B Foundation
215-589-6329
http://www.hepb.org
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October 11th, 2007
Singer Faithfull has hepatitis C
http://news.bbc.co.uk
Faithfull became a household name in the 1960s
Singer Marianne Faithfull has revealed she was diagnosed with the hepatitis C virus in the 1990s.
Faithfull, 60, let slip that she had the virus while discussing her recent treatment for breast cancer on ITV1's This Morning programme.
"I found out about 12 years ago," she told host Phillip Schofield, adding she had received treatment at the time.
Hepatitis C is a virus carried in the blood that, if left untreated, can cause fatal liver problems.
There is currently no vaccine for the virus, which is has sometimes been called the silent epidemic.
'Incredibly lucky'
Faithfull, a former heroin addict, made no link between her reckless youth and her having the virus.
However, she admitted she had taken "a lot of risks". "I was incredibly lucky," she said. "I shouldn't be alive, I know that."
"Life has become much more precious to me and my health has become much more precious to me."
Hepatitis C is usually transmitted through blood-to-blood contact and can lay dormant for years.
In an interview given two months before her death, Body Shop founder Dame Anita Roddick revealed she had been infected from a blood transfusion in 1971.
The gravelly-voiced Faithfull first found fame in the 1960s as the muse of Rolling Stones lead singer Mick Jagger.
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Researching Cure For Liver Cirrhosis
http://www.medicalnewstoday.com
The diffusion of hepatitis C virus infection worldwide is astonishing. Liver cirrhosis is present in at least 10-20% of these infected patients, with highly increasing health care and emotional costs. In patients with compensated (early stage) hepatitis C virus-related cirrhosis, antiviral combined therapy offers an interesting rate of response, ending in viral clearance. Unfortunately post-therapy data on different aspects of the illness, such as the residual liver function, measured as Total Overnight Salivary Caffeine Assessment (TOSCA, a liver test of microsomal function), and hepatic hemodynamics to indirectly evaluate the portal hypertension, measured as the Resistive Index of Splenic Artery (SARI) at Ultra Sound Doppler are still lacking, because to date only the survival rate and hepato-carcinoma appearance have been studied in depth.
Thirty five cirrhotic patients (24 grade A5 and 11 grade A6 of the Child-Pugh classification system, used to assess illness severity), with active virus replication and treated for a mean period of three years with moderate doses of Interferon-alpha and Ribavirin were compared to a cohort of 36 patients with similar characteristics and without antiviral treatment. TOSCA was determined at the starting point and three times throughout the course of therapy after a mean period of one year. Meanwhile, the SARI was only measured at the beginning and end of the study.
The more notable findings are as follows. Thirteen treated patients showed a significant TOSCA improvement. A reduction greater than 20% on the Resistive Index of Splenic Artery was obtained in eight of the patients with improved liver function. This previously abnormal Doppler parameter showed a clear total decreasing tendency at the end of therapy. Hepatitis C virus clearance was achieved in four patients at a median period of eight months of combined therapy. In the cohort of non-treated cirrhotic patients, not only the considered parameters remained unchanged, but three patients ended with a worse Child-Pugh score.
Dr. Tarantino and his team from the Federico II University Medical School believes that moderate-dosed, prolonged antiviral therapy can make stable or ameliorate residual liver function, the entity of portal hypertension and the compensation status, all at acceptable costs. In this way, more severe liver cirrhosis complications, such as variceal hemorrhage, the appearance of refractory ascites and advanced encephalopathy, are can be delayed, thereby prolonging the survival period of many patients. His team, however, still emphasises the need to evaluate individuals affected by liver cirrhosis using alternative, non-invasive, and easily repeatable parameters of outcome to better understand the progression of this illness.
Article adapted by Medical News Today from original press release.
Reference:
Tarantino G, Gentile A, Capone D, Basile V, Tarantino M, Di Minno MND, Cuocolo A, Conca P. Does protracted antiviral therapy impact on HCV-related liver cirrhosis progression" World J Gastroenterol 2007; 13(36): 4903-4908
Correspondence to:
Giovanni Tarantino, MD, Department of Clinical and Expermtal Medicine, Federico ¢ò University Medical School of Naples,Via S. Pansini, 5, Naples 80131, Italy.
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Gilead Submits Marketing Applications in the United States and European Union for Viread(R) (Tenofovir Disoproxil Fumarate) for the Treatment of Chronic Hepatitis B
http://biz.yahoo.com
FOSTER CITY, Calif.--(BUSINESS WIRE)--Gilead Sciences, Inc. (Nasdaq: GILD - News) today announced that it has submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) and a Type II variation to the European Medicines Agency (EMEA) for marketing approval of Viread® (tenofovir disoproxil fumarate) for the treatment of chronic hepatitis B in adults. Viread is already approved in the United States and European Union for the treatment of HIV as part of combination antiretroviral therapy.
"New treatments are critically important in the fight against chronic hepatitis B, a potentially life-threatening infection that impacts millions of people worldwide," said Eugene Schiff, MD, Chief of the Division of Hepatology and Director of the Center for Liver Diseases at the University of Miami School of Medicine. "We've made great progress in our ability to diagnose and treat the disease, but a significant unmet medical need remains and ongoing efforts in research and development are essential."
The submissions contain data from two Phase III pivotal clinical trials, Studies 102 and 103, in patients chronically infected with the hepatitis B virus (HBV). These studies evaluate the efficacy, safety and tolerability of Viread compared to Gilead's Hepsera® (adefovir dipivoxil). Gilead announced the primary results from Study 102 and 103 on June 6 and June 25, 2007, respectively. Detailed data from both studies will be described in late-breaker presentations at the annual meeting of the American Association for the Study of Liver Diseases (The Liver Meeting 2007) in Boston, Massachusetts, November 2-6.
"The active ingredient in Viread -- tenofovir disoproxil fumarate -- is the most widely prescribed molecule for the treatment of HIV in the United States," said Franck Rousseau, MD, Vice President, Clinical Research, Gilead Sciences. "With positive data from two pivotal studies now available, we look forward to extending the use of this important therapy to patients with chronic hepatitis B."
Chronic hepatitis B affects more than 400 million people worldwide. The complications of chronic hepatitis B, which include liver cancer and cirrhosis, kill up to 1.2 million people each year, making it one of the world's top 10 causes of death. In the United States, an estimated 1.3 million people are currently living with chronic hepatitis B, of whom more than half are Asian American. In the European region, one million people are estimated to become infected with HBV each year and approximately 90,000 go on to develop chronic hepatitis B.
While there is no cure for the disease, anti-HBV medications can have beneficial effects on chronic hepatitis B throughout the course of infection, potentially preventing fatal liver damage and liver cancer. In many cases, this requires prolonged treatment over the course of many months or years.
About Viread (tenofovir disoproxil fumarate) for HIV
In the United States, Viread is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination with other antiretrovirals. Viread is not approved for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy of Viread have not been established in patients coinfected with HBV and HIV. Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued Viread. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are co-infected with HIV and HBV and discontinue Viread. If appropriate, initiation of anti-hepatitis B treatment may be warranted.
It is important for patients to be aware that anti-HIV medicines including Viread do not cure HIV infection or AIDS, and do not reduce the risk of transmitting HIV to others.
Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported in association with the use of Viread. It is recommended that creatinine clearance be calculated in all patients prior to initiating therapy with Viread and as clinically appropriate during therapy. Routine monitoring of calculated creatinine clearance and serum phosphorous should be performed in patients at risk for renal impairment. Dosing interval adjustment and close monitoring of renal function are recommended in all patients with creatinine clearance less than 50mL/min. Viread should be avoided with concurrent or recent use of a nephrotoxic agent.
The U.S. package insert advises that co-administration of Viread and didanosine should be undertaken with caution. Patients should be monitored closely for didanosine-associated adverse events and didanosine should be discontinued if these occur. Patients on atazanavir and lopinavir/ritonavir plus Viread should be monitored for Viread-associated adverse events and Viread should be discontinued if these occur. When co-administered with Viread, it is recommended that atazanavir be given with ritonavir 100 mg. Atazanavir without ritonavir should not be co-administered with Viread.
Decreases in bone mineral density (BMD) at the lumbar spine and hip have been seen with the use of Viread. The effect on long-term bone health and future fracture risk is unknown. Cases of osteomalacia (associated with proximal renal tubulopathy) have been reported in association with the use of Viread.
Changes in body fat have been observed in patients taking anti-HIV medicines. The mechanism and long-term health effect of these changes are unknown. Immune Reconstitution Syndrome has been reported in patients treated with combination therapy, including Viread.
The most common adverse events among patients receiving Viread with other antiretroviral agents in a pivotal clinical study (Study 903) were mild to moderate gastrointestinal events and dizziness. Moderate to severe adverse events occurring in more than 5 percent of patients receiving Viread included rash (rash, pruritis, maculopapular rash, urticaria, vesiculobullous rash and pustular rash), headache, pain, diarrhea, depression, back pain, fever, nausea, abdominal pain, asthenia (weakness) and anxiety. In another pivotal study (Study 907), less than 1 percent of patients discontinued participation because of gastrointestinal events.
For full prescribing information outside of the United States, physicians should consult their local product labeling.
The parent compound of Viread was discovered through a collaborative research effort between Dr. Antonin Holy, Institute for Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic (IOCB) in Prague and Dr. Erik DeClercq, Rega Institute for Medical Research, Katholic University in Leuven, Belgium.
About Hepsera (adefovir dipivoxil)
Hepsera, a nucleotide analogue, works by inhibiting HBV DNA polymerase, an enzyme involved in the replication of the virus in the body.
In the United States, Hepsera is indicated for the treatment of chronic hepatitis B in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.
The U.S. package insert advises that the adverse reactions considered at least possibly related to treatment reported in 3 percent or greater of patients in the first 48 weeks in Hepsera pivotal clinical studies were asthenia, headache, abdominal pain, nausea, flatulence, diarrhea and dyspepsia. With extended treatment, mild to moderate increases in serum creatinine were observed uncommonly in patients with chronic hepatitis B and compensated liver disease treated with Hepsera for a median of 49 weeks up to a maximum of 240 weeks. Changes in serum creatinine were observed very commonly in patients pre- and post-transplantation with lamivudine-resistant liver disease and multiple risk factors for changes in renal function who were treated with Hepsera for up to 129 weeks, with a median time on treatment of 19 and 56 weeks, respectively. Clinical and laboratory evidence of exacerbations of hepatitis have occurred after discontinuation of treatment with antiviral therapies for hepatitis B, including Hepsera. Special warnings and precautions for use are included in the U.S. package insert regarding monitoring of renal function, post-treatment exacerbations of hepatitis, and the occurrence of lactic acidosis and severe hepatomegaly with steatosis. For physicians in the United States, dosing instructions for patients with underlying renal impairment and for patients co-infected with HIV are also provided in the U.S. package insert, which is available for download online at www.hepsera.com.
For full prescribing information outside of the United States, physicians should consult their local product labeling.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Australia.
Forward-Looking Statement
This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, that are subject to risks, uncertainties and other factors, including risks related to Gilead's ability to successfully commercialize Viread for chronic hepatitis B. For example, the FDA and EMEA may not approve Viread for the treatment of chronic hepatitis B, and marketing approval, if granted, may have significant limitations on its use and physicians may not see advantages of Viread over other treatment options and may therefore be reluctant to prescribe Viread for chronic hepatitis B. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead's Annual Report on Form 10-K for the year ended December 31, 2006 and its Quarterly Report on Form 10-Q for the first and second quarters of 2007, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.
U.S. full prescribing information for Viread is available at www.Viread.com
U.S. full prescribing information for Hepsera is available at www.Hepsera.com
Viread and Hepsera are registered trademarks of Gilead Sciences, Inc.
For more information on Gilead, please call the Gilead Public Affairs Department at 1-800-GILEAD-5 (1-800-445-3235) or visit www.gilead.com.
Contact:
Gilead Sciences, Inc.
Susan Hubbard, 650-522-5715 (Investors)
Cara Miller, 650-522-1616 (Media)
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October 12th, 2007
OctoPlus announces positive Phase IIa efficacy and tolerability results for Locteron in hepatitis C
http://biz.yahoo.com
LEIDEN, NETHERLANDS--(MARKET WIRE)--Oct 12, 2007 -- OctoPlus N.V. (Euronext: OCTO), the drug delivery and development company, announces today the successful completion of the Phase IIa clinical study with its lead product Locteron(TM), 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% 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.
Joost Holthuis, CEO of OctoPlus, says: "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."
Top-line results from the complete study confirm Locteron's strong antiviral effect:
- 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% for the 320 ug dose, and 100% 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(TM) for which EVR rates ranging from approximately 74% to 90% in clinical trials have been reported.
Top-line results from the complete study confirm substantial tolerability improvement:
- Locteron was well tolerated at all doses
- Approximately 90% of adverse events that were experienced were rated as mild
- There were no serious adverse events in the 160 ug, 320 ug, and 480 ug dose cohorts
- There was one serious adverse event in the 640 ug cohort. This was a case of inflammation of the ear, which completely resolved.
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.
About Locteron
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.
Locteron combines OctoPlus' proprietary PolyActive(TM) drug delivery technology with BLX-883, a recombinant interferon alfa produced by OctoPlus' co-development partner Biolex Therapeutics in its patented LEX System(SM). Locteron is produced in OctoPlus' cGMP manufacturing facilities in Leiden, the Netherlands.
About hepatitis C
More than three million people in the United States, and more than 180 million people worldwide, are currently infected with hepatitis C. The standard treatment for patients with chronic hepatitis C is pegylated interferon alfa administered in combination with the antiviral drug ribavirin. The currently available pegylated interferon alfa products require administration once per week for up to 48 weeks and are associated with substantial side effects, particularly during the period following each administration. Independent market research predicts that modified interferons will continue to be a key component of combination therapy for hepatitis C patients and is expected to be complementary with new agents under development. These sources estimate that total interferon sales for the treatment of hepatitis C will exceed $5 billion by 2014.
About OctoPlus
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. Rather than seeking to discover novel drug candidates through early stage research activities, OctoPlus focuses on the development of long-acting, controlled release versions of known protein therapeutics, other drugs, and vaccines.
Our pipeline consists of 5 products in preclinical and clinical development. Our lead product is Locteron, a sustained-release formulation of interferon alfa for the treatment of chronic hepatitis C, which we are co-developing with Biolex Therapeutics. Locteron has completed Phase IIa clinical development. Furthermore, our pipeline comprises a product candidate for the treatment of chronic middle ear infection, which is in Phase II development, a pre-clinical GLP-1 product candidate for the treatment of diabetes and two preclinical-stage single-shot vaccines.
In addition, OctoPlus is a leading provider of advanced drug formulation and clinical scale manufacturing services to the pharmaceutical and biotechnology industries, with a focus on difficult to formulate active pharmaceutical ingredients in injectable formulations. The earnings and expertise that we derive from rendering formulation and manufacturing services help to support our own drug development programs.
OctoPlus is listed on Euronext Amsterdam under the symbol OCTO. For more information about OctoPlus, please visit our website www.octoplus.nl .
This document may contain certain forward-looking statements relating to the business, financial performance and results of OctoPlus N.V. and the industry in which it operates. These statements are based on OctoPlus N.V.'s current plans, estimates and projections, as well as its expectations of external conditions and events. In particular the words "expect", "anticipate", "predict", "estimate", "project", "plan", "may", "should", "would", "will", "intend", "believe" and similar expressions are intended to identify forward-looking statements. We caution investors that a number of important factors, and the inherent risks and uncertainties that such statements involve, could cause actual results or outcomes to differ materially from those expressed in any forward-looking statements. In the event of any inconsistency between an English version and a Dutch version of this document, the English version will prevail over the Dutch version.
Press release in PDF: http://hugin.info/137076/R/1159488/224672.pdf
Contact:
For further information, please contact:
Rianne Roukema
Corporate Communications:
+31 (71) 524 1071
Source: OctoPlus
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