Research & Treatment News
March 31, 2008
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Presently, there are many clinical trials devoted to Hepatitis C. While participating in a study offers some people a chance at improved health, the decision to enroll must be carefully considered.
by Nicole Cutler, L.Ac.
A person living with Hepatitis C could have many reasons for participating in a clinical study. However, making the decision to be a subject in a trial is far from simple. Before deciding to sign up, make certain that you have all the facts. Understanding the pros and cons involved can help a person make this important decision.
What is a Clinical Trial?
A clinical trial is a research study using humans to answer specific health questions. When conducted carefully and thoroughly, clinical trials are the safest and fastest way to find effective treatments. Clinical trials for Hepatitis C could span many purposes, including:
· Finding ways to prevent the virus from proliferating
· Testing vaccines to protect someone from becoming infected
· Improving the existing treatment
· Testing a new treatment
· Investigating options for improving quality of life
Each clinical trial has its own protocol such as:
· What types of patients may enter the study
· What the schedule of tests and procedures are
· What drugs and specific dosages are administered
· The length of the study
· How the outcomes will be measured
These criteria help to reduce the amount of variation in the study without threatening the scientific integrity of the trial. Every protocol is designed to remove medical variations that might complicate analyzing the results. As a rule, each person participating in the study must agree to the rules set out by the protocol.
To see if it works as well or better, clinical trials for Hepatitis C often compare a new product or therapy to the current standard of treatment. In a blinded study, a participant is randomly assigned to one of three groups – and not informed of which group they were assigned to. In general the categories include those who:
1. Receive the product being tested
2. Receive the existing, approved therapy
3. Receive a placebo (a product such as a sugar pill that has no therapeutic action yet looks like the product being tested)
However, placebos are rarely used in Hepatitis C trials. This is because participants with serious illness are typically afforded some kind of assumed effective therapy.
Why Volunteer for a Clinical Trial?
Since clinical trials are the only way to test new ways to fight Hepatitis C, participating puts you on the cutting edge of medicine. Typically, people with Hepatitis C enroll in a study because they have already exhausted their treatment options. Either categorized as a non-responder to pegylated interferon therapy or unable to tolerate the current therapy’s side effects, clinical trials may provide additional hope.
It is important to realize that not everyone who applies for a clinical trial will be accepted. Volunteers could be excluded based on:
· the eligibility criteria
· the number of participants needed
· any number of additional complicating factors
If interested in a clinical trial, you should learn as much as possible about it. In addition to understanding what happens during the trial, the type of health care received and any costs involved, it is important to feel comfortable discussing your concerns with the facilitators of the trial.
Pro and Con Balancing
By weighing the potential benefits against the possible risks, the decision to volunteer in a study can be clarified. Benefits to being a trial participant may include:
· being actively involved in your own health care
· gaining access to potentially new research treatments
· receiving expert medical care since the investigators are likely to be Hepatitis C specialists
· helping others by contributing to medical research
It is also important to consider both the known and unknown risks. The hazards of participating in a clinical trial may include receiving ineffective treatment, suffering from serious or life-threatening side effects or even being overwhelmed by the time investment required for the study.
An additional consideration is whether or not medical care will continue after the trial’s conclusion. Some possible questions to ask include:
· If there are side effects that linger beyond the time of the trial, will the trial’s healthcare team offer you any support?
· If the treatment was beneficial, will it be continued after the trial is over?
Finding a Hepatitis C Trial
Clinical trials can be sponsored by an organization such as a pharmaceutical company, a federal agency (such as the National Institutes of Health or Veterans Administration) or an individual (such as a physician or health care provider). Determined by the sponsor, trial locations generally are at universities, medical centers, clinics, doctor’s offices, hospitals and other research sites.
You can find information about clinical trials currently being conducted by searching www.clinicaltrials.gov. This website is updated regularly and offers information on each trial’s purpose, who is eligible to participate, locations and phone numbers to call for more information. As of late March 2008, a search on this website revealed 184 interventional trials currently recruiting or about to recruit volunteers for a Hepatitis C study. Once on this site, there is an option to refine your search using various parameters, such as location of study, participant age range, conditions included and the intervention being studied. Since there is often a long list of eligibility criteria, make certain that you are a match before proceeding with an inquiry.
Participating in a clinical study is not for everyone. Taking part in an as yet, unproven therapy is frightening for some and exciting for others. However, being thorough in your evaluation of any clinical trial will help you make this potentially life-changing decision. Especially for those who feel as if they’ve run out of Hepatitis C treatment options, enrolling in a clinical trial can offer the right person another chance at returning to health.
References:
http://clinicalcenter.nih.gov, Are Clinical Studies for You?, National Institutes of Health, 2008.
www.clinicaltrials.gov, Search for Clinical Trials, US National Institutes of Health, 2008.
www.brightsurf.com, Hospitals that participate in clinical trials may provide better patient care, Journal of the American Medical Association, March 2008.
www.fda.gov, Basic Questions and Answers about Clinical Trials, US Food and Drug Administration, 2008.
Posted by Editors at 10:28 AM --- Printer-friendly version
March 28, 2008
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By interfering with RNA, drug company Santaris may have launched a new generation of drugs. Following a successful animal trial, an unusual new drug has sparked interest due to its ability to lower cholesterol and block the Hepatitis C virus.
Drug lowers cholesterol and fights hepatitis C
By Steve Connor
Thursday, 27 March 2008
www.independent.co.uk
A drug that can lower cholesterol levels and prevent the liver from being attacked by the hepatitis C virus has come a step closer following a successful trial on laboratory animals.
The drug works in an unusual way by interfering with the natural genetic mechanism in the cells of the liver that keeps cholesterol levels high and – coincidentally – allows the hepatitis virus to replicate within the organ. The study, which was carried out on African green monkeys, lowered cholesterol levels by up to 40 per cent over three months with the help of just three intra-venous injections given over five days at the start of the trial.
Each injection contained a watery solution of a short, single-stranded molecule of RNA – a close relative of DNA – which found its way to the liver and bonded with a similar type of RNA which is found within the organ's cells. This prevented the natural RNA from working normally, boosting the activity of certain genes, which lowered cholesterol and blocked the hepatitis C virus.
The study, published in Nature, was carried out by the Danish drug company Santaris. Scientists believe the findings support the idea of a new generation of drugs based on the ability to interfere with the natural functions of RNA.
Human trials of the new drug are expected to begin later this year.
Posted by Editors at 10:49 AM --- Printer-friendly version
March 27, 2008
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Scripps researchers found the protein needed to assemble Hepatitis C by using technology borrowed from molecular genetics. By altering the protein NS5A, this discovery may have significant impact on the development of new therapeutic agents.
New Method Disrupts Hepatitis C Virion Production
www.sciencedaily.com
ScienceDaily (Mar. 24, 2008) — HCV is a significant human pathogen, infecting more than three percent of the world's population. The incidence of infection in the United States has been estimated to be as high as 4 million cases. In the March issue of the journal PLoS Pathogens, Timothy Tellinghuisen, an assistant professor in the Department of Infectology at Scripps Florida, and his colleagues describe how they used mutations of the viral NS5A phosphoprotein to disrupt virus particle production at an early stage of assembly. NS5A has long been proposed as a regulator of events in the HCV life cycle, but exactly how it orchestrates these events has been unclear.
"The interesting thing about this mutant is that while it triggers totally normal RNA replication, it causes severe defects in the output of infectious virus--in fact, it releases no infectious virus that we can detect," says Tellinghuisen. "And though this discovery isn't a cure for HCV, it is an important research tool that stops the assembly pathway." Total disruption of the replication process would be a cure for the disease, he adds, and that's the team's long-term goal.
HCV infection is roughly five to seven times more prevalent than HIV, underscoring the pandemic nature of HCV infection. HCV occurs when blood from an infected person enters the body of someone who is not infected. Most new HCV infections are due to illegal drug injections and sharing needles. However, those who had blood transfusions prior to blood donor screening in 1991, healthcare workers who had needle stick accidents, and hemodialysis patients are also at risk for developing HCV infection.
The virus predominantly infects the liver, and following many decades of virus reproduction serious disease such as hepatitis (liver inflammation), cirrhosis (liver scarring), and carcinoma (liver cancer) develop. Ultimately, HCV infection destroys the liver, resulting in death. Attempts at curing HCV infections with drug therapy have been only marginally successful.
Before more effective therapies can be developed, scientists need to understand, at the molecular level, the detailed mechanisms HCV uses to infect cells, replicate itself, assemble progeny virus, and exit the cell. Each of these processes could potentially be a target for a new drug to eliminate HCV infection. HCV, like all viruses, requires the normal cellular machinery for its replication and has developed strategies to utilize normal cell physiology for its own benefit (often to the detriment of the host).
The Tellinghuisen team, which includes Research Assistants Katie L. Foss and Jason Treadaway, has focused recent efforts on NS5A to understand the regulation of events used by the virus to assemble infectious copies of itself and exit the cell. NS5A is a three-domain protein, which means it is comprised of three compactly folded regions roughly 50 to 300 amino acids in length. The requirement of domains I and II for RNA replication is well documented. NS5A domain III, however, is not required for RNA replication, and the function of this region in the HCV life cycle is unknown.
Using standard molecular biology, the researchers removed from domain III of NS5A a coding sequence corresponding to roughly 15 amino acids. Then they generated a clone of the virus, transcribed the RNA from that clone, and purified the RNA. This RNA, which is directly infectious, was then transfected into a liver cell line where it produced all the HCV proteins that are encoded by that RNA genome.
"Those proteins assemble in the cell to make a structure called a replicase that then copies the viral RNA," Tellinghuisen explains. "We measured that RNA accumulation and observed no defect in RNA replication, but found, surprisingly, that no infectious viral particles were released from the cells." The team also found that no viral RNA nor nucleocapsid protein are released from cells, indicating that an early event in virus assembly had been affected.
Using genetic mapping and biochemical analyses, the authors were able to show that their deletion altered a phosphorylation signal controlling the switch from RNA replication to virus particle assembly. This signal was attributed to the activity of a cellular kinase that when inhibited by genetic or chemical means led to a reduction in infectious virus production without altering HCV RNA replication.
"These data provide the first evidence for a function of domain III of NS5A and implicate NS5A as an important regulator of the RNA replication and virion assembly of HCV," Tellinghuisen says. "The ability to uncouple virus production from RNA replication may be useful in understanding HCV assembly and may become therapeutically important."
Charles M. Rice, head of the Center for the Study of Hepatitis C at Rockefeller University, comments, "This is a spectacular advance linking a specific phosphorylation event by a cellular kinase to hepatitis C virus assembly. Remarkably, the target is a viral nonstructural protein, NS5A, and the data point to a pivotal role for this protein in regulating RNA amplification and infectious virus production. These new data make this multifunctional protein an even more attractive target for developing new anti-virals for treating hepatitis C."
This project was funded by a Career Development Award from the National Institutes of Allergy and Infectious Diseases of the National Institutes of Health, and by the State of Florida.
Adapted from materials provided by Scripps Research Institute, via EurekAlert!, a service of AAAS.
Posted by Editors at 4:21 PM --- Printer-friendly version
March 20, 2008
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Currently in clinical trials for safety, the first human has completed treatment on the therapeutic DNA vaccine known as ChronVac-C®. By utilizing an innovative electroporation-based DNA delivery system, ChronVac-C® now has concrete evidence of its safety and ability to invoke the desired immune response against Hepatitis C.
Hepatitis C Virus DNA Vaccine Shows Safety When Delivered by Inovio Biomedical’s Electroporation Delivery System in Phase I/II Clinical Study at Karolinska University Hospital
March 17, 2008
www.businesswire.com
SAN DIEGO--(BUSINESS WIRE)--Inovio Biomedical Corporation (AMEX:INO), a leader in enabling the development of DNA vaccines using electroporation-based DNA delivery, announced today that its partner, Tripep AB of Sweden, has reported preliminary results from the first patient to complete treatment with Tripep’s therapeutic hepatitis C virus (HCV) vaccine, ChronVac-C®, which was delivered using Inovio’s electroporation-based DNA delivery system. In this phase I/II clinical study, the treatment has so far been safe and tolerable. Samples taken before, during and after treatment showed that before vaccination the patient did not have a detectable cell-mediated immune response against HCV but such an immune response became detectable after treatment was completed. Inovio’s electroporation delivery technology is intended to enhance the potency of DNA-based immunotherapies, including DNA vaccines, against cancers and infectious diseases.
ChronVac-C® is a therapeutic DNA vaccine being given to individuals already infected with hepatitis C virus with the aim to clear the infection by boosting a cell-mediated immune response against the virus. It is known that patients who spontaneously clear their infection have also developed this type of immune response.
This clinical study is being conducted at the Infectious Disease Clinic and Center for Gastroenterology at the Karolinska University Hospital in Huddinge and Solna (Sweden), respectively. Intended enrollment is 12 patients divided into three dose groups with increasing doses of ChronVac-C®. Each patient receives four ChronVac-C® vaccinations one month apart. After the last vaccination, patients are followed for another six months. The study’s main purpose is to assess safety. It is also testing whether the treatment boosts the immune response to HCV and its effect on virus replication in the liver. If the patient is completely virus-free six months after completing treatment, he/she will be considered cured. This first reported data was from the first patient in the lowest dose group. Five patients have been treated and no unexpected side effects have been observed.
“We are pleased that this first infectious disease DNA vaccine to be delivered in humans using electroporation-based DNA delivery has provided initial evidence of being safe and inducing a cell mediated immune response against the hepatitis C virus,” stated Avtar Dhillon, MD, Inovio’s president and CEO. “We look forward to seeing additional data, particularly from the higher dose groups, relating to this potential treatment to a pervasive and difficult-to-treat disease.”
About Hepatitis C and ChronVac-C
Hepatitis is a disease characterized by inflammation of the liver. Hepatitis C virus (HCV) is spread primarily by direct contact with human blood, the major causes worldwide being the use of unscreened blood transfusions and re-use of inadequately sterilized needles and syringes. As many as 70% - 90% of newly infected patients may progress to develop chronic infection (WHO: 2002). Of those with chronic liver disease, 5% - 20% may develop cirrhosis. About 5% of infected persons may die from the consequences of long term infection (due to liver cancer or cirrhosis). Globally, an estimated 170 million people are chronically infected with HCV, representing a reservoir sufficiently large for HCV to persist, and 3 to 4 million persons are newly infected each year. In the US, while new incidences of HCV have dropped dramatically, an estimated 4.1 million Americans have been infected with HCV, of whom 3.2 million are chronically infected (Centers for Disease Control and Prevention: 2006). The total market for therapies against hepatitis C infections is estimated to be over 2 billion dollars and is expected to grow to more than 8 billion dollars by 2015.
HCV infections in the liver do not trigger an immune response very effectively. Certain antiviral therapies, while expensive, are somewhat effective in treating hepatitis C. There is no vaccine currently available to prevent hepatitis C. ChronVac-C(R) is a therapeutic DNA vaccine designed with the aim of stimulating the body's immune system. Animal experiments demonstrated that ChronVac-C vaccination activated B-cells and T-cells (the latter being regarded as the most significant to clearing the chronic infection relating to hepatitis C) that killed cells producing HCV protein. In humans, the ChronVac-C DNA plasmid is being injected into muscle tissue, where vaccinations are usually given, and taken up by muscle cells with the assistance of Inovio's electroporation-based DNA delivery system. These muscle cells are expected to produce predetermined antigens that may activate the body's immune system to attack all cells producing HCV proteins.
About Tripep AB
Tripep AB is a Swedish biotechnology research company that develops and commercializes candidate drugs based on patented and proprietary technologies. Its main focuses are research and clinical development of ChronVac-C(R), a therapeutic vaccine against hepatitis C; preclinical research focusing on the development of therapeutic and prophylactic vaccines against influenza A and HIV; and the RAS(R) technology platform. More information is at www.tripep.se. Contact Jan Nilsson, CEO, at +46 8 449 8480 or jan.nilsson@tripep.se.
About Inovio Biomedical Corporation
Inovio Biomedical (AMEX:INO) is focused on developing multiple DNA-based immunotherapies and DNA vaccines. Inovio is a leader in developing human applications of electroporation which uses brief, controlled electrical pulses to increase cellular uptake of a useful biopharmaceutical. Human data has shown that Inovio’s electroporation-based DNA delivery technology can significantly increase gene expression and immune responses from DNA vaccines. Immunotherapy partners include Merck, Wyeth, Vical, University of Southampton, Moffitt Cancer Center, the U.S. Army, National Cancer Institute, and International Aids Vaccine Initiative. Inovio’s technology is protected by an extensive patent portfolio covering in vivo electroporation. More information is available at www.inovio.com.
This press release contains certain forward-looking statements relating to our plans to develop our electroporation drug and gene delivery technology. Actual events or results may differ from our expectations as a result of a number of factors, including the uncertainties inherent in clinical trials and product development programs (including, but not limited to, the fact that clinical results referenced in this release may not be indicative of results achievable in other trials or for other indications and that results from one study may necessarily not be reflected or supported by the results of other similar studies), the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of Inovio’s technology as a delivery mechanism, the availability or potential availability of alternative therapies or treatments for the conditions targeted by Inovio or its collaborators, including alternatives that may be more efficacious or cost-effective than any therapy or treatment that Inovio and its collaborators hope to develop, evaluation of potential opportunities, issues involving patents and whether they or licenses to them will provide Inovio with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether Inovio can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of our technology by potential corporate or other partners or collaborators, capital market conditions, and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2007, and other regulatory filings from time to time. There can be no assurance that any product in our product pipeline will be successfully developed or manufactured, that final results of clinical studies will be supportive of regulatory approvals required to market licensed products, or that any of the forward-looking information provided herein will be proved accurate.
Inovio Biomedical
Bernie Hertel, 858-410-3101 (Investors)
or
Ronald Trahan Associates Inc.
Ron Trahan, 508-359-4005 ext. 108 (Media)
Posted by Editors at 9:18 AM --- Printer-friendly version
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When combined with pegylated interferon for Hepatitis C treatment, taribavirin may be a better option than ribavirin. Compared to ribavirin, preliminary results of a Phase IIb trial show that taribavirin is similar in viral load reduction yet superior with fewer incidences of treatment related anemia.
Valeant Pharmaceuticals Reports Encouraging Phase IIb Results at Treatment Week 12 for Taribavirin
March 17, 2008
www.businesswire.com
ALISO VIEJO, Calif.--(BUSINESS WIRE)--Valeant Pharmaceuticals (NYSE:VRX) today reported results at the treatment week 12 analysis point for the Phase IIb clinical trial for its antiviral compound, taribavirin, a prodrug of ribavirin in development for the treatment of chronic hepatitis C in conjunction with a pegylated interferon.
The Phase IIb trial is a U.S. multi-center, randomized, parallel, open-label study in 278 treatment-naïve, genotype 1 patients evaluating taribavirin at 20 mg/kg, 25 mg/kg, and 30 mg/kg per day in combination with pegylated interferon alfa-2b. The control group is being administered weight-based dose ribavirin (800/1000/1200/1400mg daily) and pegylated interferon alfa-2b. Overall treatment duration is 48 weeks with a post-treatment follow-up period of 24 weeks. The primary endpoints for this study are viral load reduction at treatment week 12 and anemia rates throughout the study.
The 12-week early viral response (EVR) data from the Phase IIb study showed comparable reductions in viral load for weight-based doses of taribavirin and ribavirin. The anemia rate was statistically significantly lower for patients receiving taribavirin in the 20mg/kg and 25mg/kg arms versus the ribavirin control arm.
Key Efficacy and Safety Data Table at Treatment Week 12 (ITT Population)
TBV 20 mg/kg
n = 67
TBV 25 mg/kg
n = 70
TBV 30 mg/kg
n = 68
RBV 800-1400mg
n = 70
Responders(a)
43 (64.2%) 40 (57.1%) 37 (54.4%) 36 (51.4%)
Undetectable(b)
28 (41.8%) 29 (41.4%) 17 (25.0%) 22 (31.4%)
Anemia rate(c)
6 (9.0%) 5 (7.1%) 10 (14.7%) 17 (24.3%)
(a) HCV RNA undetectable (less than 100 copies per mL) or ≥2-log decrease in viral load using the NGI SuperQuant Assay
(b) HCV RNA less than 100 copies per mL
(c) Anemia rate defined as percentage of patients with Hgb level < 10 g/dL. p=0.022 for 20mg/kg and p=0.009 for 25mg/kg
The most common adverse events were fatigue, nausea, flu-like symptoms, headache and diarrhea. The incidence rates among treatment arms were generally comparable except with respect to diarrhea, where diarrhea was approximately twice as common in taribavirin patients as ribavirin patients. However, the diarrhea was generally mild and not treatment limiting for taribavirin or ribavirin patients.
In 2006 Valeant released data from its Phase III VISER1 and VISER2 trials of taribavirin, administered in a fixed dose of 600 mg BID (approximately equivalent to 13-18 mg/kg), in which taribavirin did not meet its primary efficacy endpoint of comparable efficacy to weight-based dose ribavirin. In 2007, the company began this Phase IIb study to evaluate higher doses of taribavirin than used in the VISER trials, while also employing a weight-based dosing regimen, consistent with the dosing regimen for ribavirin.
“Ribavirin continues to be a necessary part of hepatitis C treatment, and clinicians would welcome a ribavirin prodrug with a profile of similar efficacy with decreased anemia,” stated Fred Poordad, M.D., Chief of Hepatology at the Center for Liver Disease and Transplant, Cedars-Sinai Medical Center, Los Angeles, CA. “A drug with fewer required dose reductions for anemia or a reduced need for adjunctive growth factor therapy may subsequently improve treatment adherence and overall response rate.”
“We are encouraged that these data suggest that weight-based dosing with taribavirin at higher doses may have a role in the treatment of patients infected with hepatitis C while continuing to produce lower anemia than ribavirin,” said J. Michael Pearson, Valeant’s chairman and chief executive officer. “However, we caution that these results only represent data from the first 12 weeks of a 72-week Phase II trial that was designed to identify appropriate doses for further development. We will use these data to explore the best options for taribavirin’s continued role in our portfolio, including consideration of partnering options.”
Patient Demographics
20 mg/kg
n = 67
25 mg/kg
n = 70
30 mg/kg
n = 68
Ribavirin
n = 70
Age (yrs, mean) 48.5 47.5 49.6 49.7
Gender (female) 52.2% 35.7% 36.8% 31.4%
Race (Caucasian) 74.6% 58.6% 61.8% 64.3%
Weight (>75 kg)(d)
64.2% 61.4% 63.2% 62.9%
Plasma HCV RNA ≥ 2 million copies(d)
73.1% 72.9% 72.1% 70.0%
(d) Study stratified patients by weight and viral load
In the study, the following percentages of patients completed 12 weeks of treatment in the taribavirin and ribavirin arms: 20mg/kg: 87.0%; 25mg/kg: 80.0%; 30mg/kg: 82.6%; ribavirin 74.3%. The following percentages of patients had adverse events leading to dose modification or interruption of taribavirin or ribavirin: 20mg/kg: 11.9%; 25mg/kg: 15.7%; 30mg/kg: 25.0%; ribavirin 28.6%.
In the Intent to Treat Analysis, the Rapid Virological Responses (RVR - virus undetectable at treatment week 4) in this study were 20mg/kg: 16.4%; 25mg/kg: 14.3%; 30mg/kg: 16.2 %; ribavirin: 11.4%.
Conference Call and Webcast Information:
Valeant will host a conference call and webcast on Thursday, March 27, 2008 at 12:00 p.m. EDT (9:00 a.m. PDT) to discuss the Company’s Strategic Plan as well as the results from this Phase IIb clinical trial. A webcast of this event will be available live over the Internet along with a slide presentation. The webcast may be accessed through the investor relations section of Valeant’s corporate Web site at www.valeant.com. The dial-in number to participate on this call is (877) 295-5743, confirmation code 39808652. International callers should dial (706) 679-0845, confirmation code 39808652. Interested parties will have access via the Internet and on the conference call to ask questions following the presentation. A replay will be available approximately two hours following the conclusion of the conference call and can be accessed by dialing (800) 642-1687, or (706) 645-9291, confirmation code 39808652.
About Taribavirin
Taribavirin is an investigational compound that has not been found by the Food and Drug Administration (FDA) or any other regulatory agency to be safe or effective in the diagnosis, mitigation, treatment or cure of any disease or illness. It may not be sold or promoted in the United States unless and until FDA has approved a New Drug Application. Similar restrictions apply in other countries.
About Valeant
Valeant Pharmaceuticals International (NYSE:VRX) is a global specialty pharmaceutical company that develops, manufactures and markets a broad range of pharmaceutical products primarily in the areas of neurology, infectious disease and dermatology. More information about Valeant can be found at www.valeant.com.
FORWARD-LOOKING STATEMENTS
This press release contains forward-looking statements, including, but not limited to, statements regarding the potential efficacy and safety of taribavirin in the treatment of hepatitis C, and the continuing role of ribavirin or taribavirin in the treatment of hepatitis C, that are based on management’s current expectations and involve risks and uncertainties, including, but not limited to, risks and uncertainties relating to the clinical development of new products, regulatory approval processes, that results from treatment week 12 in a phase IIb clinical trial are not necessarily predictive of the entire phase IIb trial or a phase III trial, and other risks detailed from time to time in the company’s SEC filings. The company cautions the reader that these factors, as well as other factors described in its SEC filings, are among the factors that could cause actual results to differ materially from the expectations described in the forward-looking statements. The company also cautions the reader that undue reliance should not be placed on any of the forward-looking statements, which speak only as of the date of this press release. The company undertakes no responsibility to update any of these forward-looking statements to reflect events or circumstances after the date of this press release or to reflect actual outcomes.
Contacts
Valeant Pharmaceuticals
Laurie W. Little, 949-461-6002
Posted by Editors at 9:04 AM --- Printer-friendly version
March 17, 2008
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People with Hepatitis C can slow the liver's cycle of inflammation by making these three healthy lifestyle changes. By eliminating certain risk factors, one can live a long life with HCV.
by Nicole Cutler, L.Ac.
The number of people affected by Hepatitis C continues to grow. Unfortunately, the medicines used to treat this virus have not yet been able to defeat it. As of 2008, the current standard of treatment for the Hepatitis C virus (HCV), pegylated interferon and ribavirin, remains effective for approximately only half of all cases. Although pegylated interferon and ribavirin can’t help millions of people get rid of this virus, Hepatitis C doesn’t have to be a death sentence. Even though those living with chronic HCV are at a high risk of developing liver cirrhosis and/or liver cancer, eliminating three vices can prevent a worsening of liver health.
Understanding Liver Inflammation
Living with chronic HCV means constantly battling liver inflammation. If this inflammation rages unabatedly, it causes liver disease to progress. The progressive cascade of Hepatitis C and liver inflammation is as follows:
· HCV results in the death of liver cells.
· The death of liver cells triggers the dispatching of inflammatory cells to the affected area. Inflammation begins the processes that lead to fibrosis, the body’s response to liver damage.
· Inflammation triggers a reaction by a group of cells in the liver called stellate cells.
· Infected and inflamed liver cells release chemical signals (called cytokines), which activate leukocytes (white blood cells) from outside the liver to travel to the affected area.
· The cytokines and leukocytes team up with Kupffer cells to signal the stellate cells to produce and lay down collagen fibers between liver cells. A fibrous protein that forms scar tissue, collagen is the body’s attempt to limit the spread of infection to other cells.
· Normally, as an infection or injury resolves, the collagen matrix enclosing the injury is dissolved and activated stellate cells die off, allowing the tissue to return to normal. In chronic HCV, this matrix of collagen grows more rapidly than it can dissolve.
· The collagen builds up scar tissue around cells causing living liver cells to lose their access to the nutrient and oxygen rich blood flow.
· The restricted access to blood causes even more quarantined liver cells to die. As such, HCV progressively scars the liver.
This vicious cycle of inflammation causing scar tissue must be stopped to prevent a person’s chronic HCV from causing more and more liver damage.
Vice Elimination
According to Norah Terrault, MD, MPH, from the University of California, San Francisco, “Hepatitis C is a major public health concern and the number of patients developing complications of chronic disease is on the rise. It is essential that we identify risk factors that can be modified to prevent and/or lessen the progression of HCV to fibrosis, cirrhosis and even liver cancer. These complications of chronic HCV infection will significantly contribute to the overall burden of liver disease in the U.S. and will continue to increase in the next decade.”
By eliminating three unhealthful habits, people with HCV can single-handedly reduce the inflammation their liver must contend with. Although any toxin puts a greater strain on liver function, the following directly contribute to heightened inflammation with HCV:
1. Alcohol – There are many reasons why eliminating alcohol is imperative for living long with Hepatitis C. Researchers have demonstrated that alcohol promotes proliferation of Hepatitis C in human liver cells. Researchers at the Children’s Hospital in Philadelphia found that alcohol increases the activity of a protein called nuclear factor kappa B, which causes HCV to replicate. Aside from the cycle of inflammation that occurs with Hepatitis C, alcohol consumption on its own increases cytokine levels. Additionally, metabolized alcohol is believed to activate stellate cells directly. All of the chemical processes that occur when a person drinks alcohol exponentially worsen the damage that HCV does to the liver.
2. Marijuana – According to a study published in Clinical Gastroenterology and Hepatology, patients with HCV should not use marijuana (cannabis) daily. The researchers led by Terrault found that HCV patients who used cannabis daily were at significantly higher risk of moderate to severe liver fibrosis, or tissue scarring. Additionally, patients with moderate to heavy alcohol use combined with regular cannabis use experienced an even greater risk of liver fibrosis.
3. Fatty Food – Despite campaigns claiming that eliminating saturated fat from the diet preserves heart health, hepatologists agree that it also preserves liver health. Research from 2007 demonstrated that a high fat diet kills regulatory T cells in the liver. Less of these specialized immune cells allow a fatty liver to worsen to steatohepatitis, fatty liver with inflammation. This likely occurs because regulatory T cell death is associated with increased inflammatory cytokine production.
Although removing these three vices from one’s life may be a monumental life change for someone, it can also save their liver. The increase in inflammation that drinking alcohol, smoking marijuana and eating saturated fat can cause allows a liver with HCV to spiral into advanced liver disease. By abandoning these three unhealthful habits, the liver gets a respite from the inflammation cycle – perhaps enough for the body to break down some of the collagen matrix that contributes to the continuation of liver cell death.
References:
http://familydoctor.org, Hepatitis C, American Academy of Family Physicians, 2008.
http://pubs.niaaa.nih.gov, Alcohol and the Liver, National Institute for Alcohol Abuse and Alcoholism, 2008.
www.cdc.gov, Hepatitis C Fact Sheet, US Department of Health and Human Services, 2008.
www.hepctrust.org.uk, Liver damage and fibrosis during the chronic stage, Hepatitis C Trust, 2008.
www.medicalnewstoday.com, How Alcohol Use May Worsen Hepatitis C Infection, John Ascenzi, MediLexicon International, Ltd., 2007.
www.medicalnewstoday.com, Risk Of Hepatitis C-Related Liver Damage Increased By Regular Marijuana Use, MediLexicon International Ltd., 2008.
www.sciencedaily.com, High-fat Diet Makes Mice Susceptible To Liver Injury, ScienceDaily LLC 2008.
www.who.int, Hepatitis C, World Health Organization, 2008.
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March 13, 2008
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A national, non-profit, public charity, the Caring Ambassadors Hepatitis C Program makes it easier for people with Hepatitis C to learn about the virus, its implications and up-to-date treatments. By utilizing the internet, people can get a customized response to their specific Hepatitis C concerns.
Caring Ambassadors Hepatitis C Program Launches Internet-Based Hep C Discussion PointTM to Assist People Living with Hepatitis C
www.marketwire.com
Mar 11, 2008
VANCOUVER, WA--(Marketwire - March 11, 2008) - The Caring Ambassadors Hepatitis C Program (CAP Hepatitis C), a national nonprofit organization, announces the Internet release of its new interactive medical management tool, Hep C Discussion Point™ at www.HepCChallenge.org. Hep C Discussion Point™ takes the user through a guided series of questions about their hepatitis C experience. Custom-built software analyzes the user's responses and generates a report with information and topics specific to the user's inputs. The report is designed to be used as both a learning tool for the patient and as a guide to facilitate communication and enhance the health care partnership between people living with hepatitis C and their doctors.
Hep C Discussion Point™ was developed by CAP Hepatitis C in conjunction with leading experts in the field of hepatology to help facilitate, inform, and enhance the therapeutic decision-making process by providing discussion points on state-of-the-art hepatitis C management. Hep C Discussion Point™ is a groundbreaking effort, and is the only tool of its kind designed exclusively for hepatitis C clients and their health care providers.
According to Lorren Sandt, the Hepatitis C Program Director, many of the calls CAP Hepatitis C receives are from patients who are confused by conflicting information they read or hear about regarding hepatitis C management. "When we designed Hep C Discussion Point™, we tried to address the most common and relevant questions we receive from those living with hepatitis C."
"We are excited about the launch of Hep C Discussion Point™ and are very pleased to offer this tool to the hepatitis C community, which includes both patients and their health care providers," said Dr. Tina St. John, Executive Director and Medical Director of the Caring Ambassadors Program. "Hep C Discussion Point™ represents a new and innovative approach to CAP Hepatitis C's commitment to ensuring that all persons living with hepatitis C have accurate and adequate information by which to make decisions that match their personal medical circumstances and health care goals."
Hepatitis C is the most common chronic, blood-borne viral infection in the United States. An estimated 5 million Americans are infected with the hepatitis C virus (HCV), the most common cause of chronic liver disease and adult liver transplantation in the U.S. No vaccine is available to prevent chronic hepatitis C but medications are available to clear the hepatitis C virus from the body in up to 50% of people treated.
About Caring Ambassadors Hepatitis C Program
The Caring Ambassadors Program is a 501(c)(3) nonprofit public charity dedicated to helping people with chronic and/or life-threatening diseases through information/education, awareness, public advocacy, and support. Founded in 2001, the organization is headquartered in Vancouver, Washington, U.S.A.
The Caring Ambassadors Hepatitis C Program (CAP Hepatitis C) is devoted exclusively to meeting the needs of the hepatitis C community. The CAP Hepatitis C mission is to improve the lives of people living with hepatitis C through information and awareness.
For additional information about the Caring Ambassadors Hepatitis C Program and Hep C Discussion Point™, contact Lorren Sandt at 360.816.4186 or Lorren@HepCChallenge.org.
Posted by Editors at 3:44 PM --- Printer-friendly version
March 7, 2008
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According to new research from Sweden, grabbing a quick burger and fries is just as harmful to the liver as drinking alcohol. Since liver damage carries a graver risk to those living with Hepatitis C, eating low-fat meals is more important to this population than ever.
by Nicole Cutler, L.Ac.
New research from Sweden confirms that eating fast food can cause substantial liver damage. Luckily, the liver is one of our few organs capable of regenerating new, healthy cells. Thus, the injury inflicted from occasionally ordering dinner from a drive-through window can be reversed with a focused effort. Unfortunately, those battling Hepatitis C have a diminished ability to regenerate new liver cells and therefore have a harder time reversing liver damage. This means that the liver cell death incurred from eating the high-fat meals typical of fast food restaurants may be more detrimental to those already living with a chronic liver disease such as Hepatitis C.
The Hepatitis C virus (HCV) is one of the most common causes of chronic liver disease in the United States. Accounting for about 15 percent of acute viral hepatitis, 60 to 70 percent of chronic hepatitis and up to 50 percent of cirrhosis, end-stage liver disease and liver cancer, experts estimate that 4.1 million Americans are currently infected with HCV. While many more people live with HCV than die from it, the distinguishing factor between the two is learning how to prevent incurring further liver damage.
The HCV Disadvantage
The progression of liver disease is marked by a greater proportion of liver cell death than the creation of new, healthy liver cells. Due to a buildup of localized scar tissue, the following cascade of events demonstrates why those with HCV are prone to a worsening of their condition:
1. The Hepatitis C virus infects and kills liver cells.
2. In response to liver cell death, the body initiates an immune response, which causes inflammation.
3. In an attempt to limit the spread of infection, the immune system lays down collagen fibers between liver cells. These fibers are the building blocks of scar tissue.
4. Normally, as an infection or injury resolves, the collagen matrix enclosing the injury is dissolved and allows the tissue to return to normal. However, this web of collagen in people with chronic HCV grows more rapidly than it can dissolve.
5. As more collagen accumulates, the resulting scar tissue restricts living liver cells from access to nutrients and oxygen-rich blood.
6. The restricted access to blood causes even more quarantined liver cells to die. As such, HCV progressively scars the liver.
Since people living with HCV have this consistent battle being waged in their liver, they are more vulnerable to toxins that could damage this organ.
The Danger of Fast Food
Many things we breathe, ingest, swallow or otherwise absorb into our bodies pose a threat to the liver. A universally acknowledged cause of chronic liver disease, drinking alcohol is one of the most obvious ways to poison a liver. While most people might not categorize their lunch as toxic, millions of Americans are damaging their liver by eating fast food. A small Swedish study published in the February 2008 edition of the journal Gut found that even a brief fast-food binge combined with too little exercise can induce liver damage.
In this study, 18 slim, healthy participants stuck to a fast food diet, mostly consuming of hamburger meals from popular chains twice a day for four weeks while refraining from exercise. At the end of the experiment, participants not only gained an average of 16 pounds, but blood tests also showed evidence that those eating fast food incurred liver damage.
In the Swedish study, those gorging on fast food meals showed a dramatic increase in alanine aminotransferases (ALT) levels over a very short period of time. An enzyme produced in liver cells, ALT leaks into the bloodstream as liver cells are damaged. A result of liver cell damage, ALT elevations can be caused by any liver disease, hepatic inflammation or toxin.
Previous research has shown that a diet high in fat and calories, the hallmark of greasy, fast food, puts people at greater risk for obesity and type 2 diabetes, cardiovascular disease and heart failure. However, this Swedish study shows that doubling caloric intake without adding exercise also puts hepatic health in jeopardy. When excessive calories and fat overloads the liver’s ability to filter the blood, fat builds up in the liver cells and leads to liver damage. Considering that a majority of the study participants developed pathological ALT levels within just one week after eating fast food, this negative impact can occur relatively quickly.
Most people with HCV are aware that drinking alcohol causes liver cell death and can accelerate the severity of their liver disease. However, now their physicians must relay that alcohol is not the only thing they must navigate away from. Since eating a large quantity of high-fat foods (even for a short time period) while refraining from physical activity can damage the liver, people with HCV must avoid this combination. Since harboring the Hepatitis C virus makes recovery from liver damage a great challenge, hepatologists across the globe will be putting greater emphasis on sticking to a healthy, low-fat diet and adhering to an active lifestyle.
References:
http://abcnews.go.com, Fast Food: The Fast Track to Organ Damage, Radha Chitale, ABC News Internet Ventures, February 2008.
http://digestive.niddk.nih.gov, Chronic Hepatitis C: Chronic Disease Management, National Digestive Clearinghouse, 2008.
Diseases International http://en.wikipedia.org, Super Size Me, Wikimedia Foundatin Inc., 2008.
Kechagias, S, et al., Fast food based hyper-alimentation can induce rapid and profound elevation of serum alanine aminotransferase in healthy subjects, Gut, February 2008.
www.medpagetoday.com, Fast-Food Bender Can Convert to Liver Damage Swiftly, MedPage Today LLC, 2008.
Posted by Editors at 4:54 PM --- Printer-friendly version
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Michigan researchers have found that a new combination of markers may best predict the progression of cirrhosis for people with chronic Hepatitis C. Although requiring additional study for confirmation, these three serum fibrosis markers demonstrated a higher level of accuracy than other non-invasive tests.
Biomarker Panel May Improve Disease Staging in Chronic HCV
By Michael Smith, North American Correspondent, MedPage Today
Published: March 05, 2008
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco
www.medpagetoday.com
ANN ARBOR, Mich., March 5 -- A panel of three biomarkers may be useful in identifying patients with chronic hepatitis C who have progressed to cirrhosis, researchers here found.
The three-marker panel was highly correlated to Ishak score in a prospective sub-study of the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial, according to Robert Fontana, M.D., of the University of Michigan, and colleagues.
The biomarkers were also more accurate than other non-invasive tests that have been proposed, the researchers reported in the March issue of Hepatology.
The three markers evaluated by the researchers were serum tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), hyaluronic acid (HA), and platelet count.
All were significantly associated with cirrhosis in a univariate analysis (as were several other markers) but in multivariate analysis, the three biomarkers had an area under the receiver operating curve of 0.81.
(A receiver operating curve measures the trade-off between sensitivity and specificity for a given test; if the area under the curve were 1.0, the test would correctly identify both positives and negatives.)
By comparison, Dr. Fontana and colleagues said, three other published models -- the Lok model, the AST-to-platelet ratio index, and the cirrhosis discriminant score -- had lower areas under the curve of 0.79. 0.73, and 0.70 respectively.
For this study, the researchers compared the model's predictions with the biopsy results of 513 patients with chronic hepatitis C and Ishak scores of between two and six. Those with Ishak scores of five and six (38%) were considered to have cirrhosis, while the remaining 62% had fibrosis.
Among those patients, the researchers found, the model would have correctly categorized 153 patients as having a low likelihood of cirrhosis with 86% accuracy.
An additional 146 subjects would have been categorized as having a high likelihood of cirrhosis with 73% accuracy.
The study was limited by the nature of the HALT-C patient population, the researchers said, which meant that there was no independent cohort of patients who also had stored serum available for testing for comparison.
Also, they noted, the model was not tested in an external validation cohort.
Nevertheless, the model "distinguished patients with non-cirrhotic (chronic hepatitis C) from those with cirrhosis" and "performed significantly better than other models based on routine laboratory tests," the researchers concluded.
The implication is that serum fibrosis markers "provide useful, incremental information in estimating disease stage" in chronic hepatitis C that can be obtained without biopsy, they said.
The study was supported by the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, the National Center for Minority Health and Health Disparities, the National Center for Research Resources of the NIH, and Hoffmann-La Roche Inc.
Dr. Fontana reported being on the speakers bureau for Hoffmann-La Roche.
Posted by Editors at 2:52 PM --- Printer-friendly version
March 3, 2008
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People treated at a Nevada Health Center may have been infected with Hepatitis C from an unsafe medical procedure. Thousands of people are being notified that they may have been exposed to this and other blood-borne viruses from the re-use of contaminated anesthesia equipment.
Nevada Hepatitis C Outbreak Tied to Las Vegas Clinic. Thousands Now At Risk for Hepatitis, HIV
Date Published: Thursday, February 28th, 2008
www.newsinferno.com
Hepatitis C and other blood borne diseases now threaten thousands of people in Nevada, thanks to the unsafe way anesthesia was administered at the Endoscopy Center of Southern Nevada in Las Vegas. At least six people who received treatment at the Endoscopy Center of Southern Nevada have already tested positive for Hepatitis C, but health officials in the state have urged another 40,000 to be tested for the virus, as well as HIV.
Hepatitis C is a blood disorder that is transmitted through blood-to-blood contact. Hepatitis C for the most part is asymptomatic and often leads to chronic, and long-term infection resulting in approximately 70% of those infected developing liver disease. Hepatitis C is a risk factor for liver cancer and can lead to the need for a liver transplant. HIV is the virus that causes AIDS, and is transmitted through the exchange of bodily fluids, including blood-to-blood contact.
The Endoscopy Center of Southern Nevada Health has been under investigation since early January, after health officials learned of three people who had been diagnosed with Hepatitis C. According to the Southern Nevada Health District, a total of six people contracted Hepatitis C after being treated at the Endoscopy Center of Southern Nevada. Five of them were treated the same day in late September; the sixth is believed to have been infected in July, the district said. The Southern Nevada Health District investigation revealed that “unsafe injection practices related to the administration of anesthesia medication might have exposed patients to the blood of other patients,” the statement said.
The Hepatitis C virus may have been spread when clinic staff reused syringes and used a single dose of anesthesia medication on multiple patients, the district said. A syringe would become contaminated by the backflow of blood when patients with a blood-borne disease were injected with medication, health officials said. That syringe, in turn, would be reused to withdraw medication from a different vial. That vial could become contaminated and result in infection.
The Southern Nevada Health District said that the unsafe practices had been in place for several years at the Endoscopy Center of Southern Nevada, and may have put others at risk. About 40,000 patients who received injections of anesthesia at the clinic will be told of the potential exposure in letters arriving next week. Anyone who received anesthesia at the clinic from March 2004 to Jan. 11 should be tested for the virus, along with Hepatitis B and HIV. The Southern Nevada Health Districts patient notification will be the largest of its kind in the country.
This is not the first time an outbreak of Hepatitis was blamed on medical practitioners who reused syringes or reused multidose vials of anesthesia on more than one patient. Late last year, the New York State Department of Health warned thousands of people treated by Long Island anesthesiologist Harvey Finkelstein that they were at risk for Hepatitis C, B and HIV. Finkelstein also was known to reuse syringes. At least one person is known to have contracted Hepatitis C as a result of Finkelstein’s unsanitary practices, and another six patients tested positive for the disease, although it is not absolutely certain that the virus was the result of Finkelstein’s treatment. Another six tested positive for Hepatitis B.
Posted by Editors at 9:22 AM --- Printer-friendly version
