Tuesday, April 19, 2011

Hepatitis C News; European Gastroenterologists Will Prescribe Telaprevir and Boceprevir to Nonresponder and Treatment-Naive Patients Following Launch

For Treatment of HCV, Surveyed European Gastroenterologists Will Prescribe Telaprevir and Boceprevir to Nonresponder and Treatment-Naive Patients Following Launch, Leading to Higher Treatment Costs Than Interviewed Payers Expect

Owing to the Increasing Use of Generics Across the EU5, Interviewed European Payers Expect Drug Makers to Implement Considerable Voluntary Price Cuts for Their Branded Ribavirin Products, According to a New Report from Decision Resources

BURLINGTON, Mass.--(BUSINESS WIRE)--Decision Resources, one of the world’s leading research and advisory firms for pharmaceutical and healthcare issues, finds that, for the treatment of hepatitis C virus (HCV), the highest percentage of surveyed gastroenterologists in the EU5 (France, Germany, Italy, Spain and the United Kingdom) indicate that they will likely use Vertex/Johnson & Johnson/Mitsubishi Tanabe’s telaprevir and Merck’s boceprevir initially after launch to a greater extent in nonresponder HCV genotype 1 patients than in treatment-naive patients. However, a significant proportion of HCV-1 treatment-naive patients will also receive these new HCV-specific antiviral agents within the first year of launch and treatment rate estimates in this subpopulation will be nearly 60 percent by 2014.

“Because the novel direct-acting antivirals have vastly improved efficacy in hard-to-treat patients over the current standard of care, surveyed clinicians expect drug-treated rates to grow as a result of an increase in the volume of patients seeking treatment”

The new European Physician & Payer Forum report entitled Hepatitis C Virus: Physician & Payer Perspective on Future Treatment and Reimbursement of Novel HCV Therapies in the European Union finds that a clash in expectations exists between surveyed gastroenterologists and interviewed payers across the EU5 as payers predict physicians will initially only use telaprevir and boceprevir in nonresponder patients, which could lead to prescribing restrictions if treatment costs become significantly higher than anticipated due to use in treatment-naive patients.

The current armamentarium for treating HCV is relatively modest and consists of pegylated interferon (peg-IFN) products—Roche’s Pegasys (peg-IFN-alpha-2a) and Merck’s PegIntron/ViraferonPeg (peg-IFN-alpha-2b)—as well as equivalent branded ribavirin products: Roche’s Copegus, Merck’s Rebetol and generic ribavirin. The current standard of care for most patients is a dual-therapy with a peg-IFN and ribavirin, which has poor cure rates in hard-to-treat patients and considerable safety and tolerability issues. As a result, significant unmet needs remain in HCV treatment.

The report also finds that surveyed European gastroenterologists expect to treat more patients when emerging HCV-specific drugs become available.

“Because the novel direct-acting antivirals have vastly improved efficacy in hard-to-treat patients over the current standard of care, surveyed clinicians expect drug-treated rates to grow as a result of an increase in the volume of patients seeking treatment,” said Decision Resources Analyst Courtney Stanton, Ph.D. “Surveyed German clinicians expect to have the greatest increase in the amount of patients they will treat once the new HCV-specific drugs are available, a maximum 77 percent increase over the amount of patients they currently treat on average each month. Increases will be much less dramatic in the other surveyed European countries, especially the United Kingdom, where clinicians only expect a maximum six percent increase over current average monthly patient numbers. The remaining countries—France, Italy and Spain—will see increases between 39 and 47 percent over current patient numbers.”

The report also finds that mounting pressure from EU5 governments for increased generic use will likely encourage uptake of generic ribavirin and trigger price-cuts from brand manufacturers. Although government regulation regarding the use of generics varies between surveyed countries, there is a shift towards increased generic use across the EU5 and interviewed payers expect drug makers to implement considerable voluntary price cuts for their branded ribavirin products in order to remain competitive.
About Decision Resources
Decision Resources is a world leader in market research publications, advisory services and consulting designed to help clients shape strategy, allocate resources and master their chosen markets. Decision Resources is a Decision Resources, Inc. company.
About Decision Resources, Inc.
Decision Resources, Inc. is a cohesive portfolio of companies that offers best-in-class, high-value information and insights on important sectors of the healthcare industry. Clients rely on this analysis and data to make informed decisions. Please visit Decision Resources, Inc. at http://cts.businesswire.com/
All company, brand, or product names contained in this document may be trademarks or registered trademarks of their respective holders.
Decision Resources, Inc.
Christopher Comfort, 781-993-2597

From HIV and Hepatitis Liz Highleyman, Editor-in-Chief and Publisher

Boosted Danoprevir Improves Response in Prior Null Responders
SUMMARY: Nearly 90% of genotype 1b prior non-responder hepatitis C patients treated with ritonavir-boosted danoprevir plus pegylated interferon/ribavirin experienced early virological response at week 12, but breakthrough reached 50% for those with genotype 1a.

Kidney Toxicity Uncommon among People Taking Tenofovir for Hepatitis B
SUMMARY: Impaired kidney function among people with HIV, HBV, and HIV/HBV coinfection taking tenofovir mainly occurred in those with pre-existing risk factors, researchers reported at EASL 2011.

More Evidence Abacavir Does Not Raise Heart Attack Risk
SUMMARY: A large cohort study found no increased risk of myocardial infarction in people taking abacavir.

Universal Testing and Treatment Could Reduce New HIV Infections by 76%
SUMMARY: New HIV infections among gay men could decrease by 59% if all HIV positive adults now in care start antiretroviral therapy, and the number could drop further with universal annual testing, according to recently published mathematical models

Can Lowering Community Viral Load Decrease New HIV Infections?
SUMMARY: Decreased average and maximum community viral load (CVL) was associated with a decline in new HIV infections in San Francisco, and new HIV diagnoses are decreasing along with CVL in New York City, but this correlation has not yet been observed in Washington, DC, researchers reported at CROI 2011.

AHF: Gilead Must Halt FDA Approval Of Truvada As HIV Prevention After PrEP Study In Women Fails
19 April 2011
On the heels of Centers for Disease Control (CDC) announcement earlier today that an ongoing study of the use of Gilead's top selling AIDS treatment, Truvada, as a possible form of pre-exposure prophylaxis (PrEP) for HIV...

From NATAP Executive Director: Jules Levin

New Study- Boceprevir in HIV-HCV Coinfected Patients Who Have Failed to a Previous Therapy With Peg-Interferon/Ribavirin -

Pharmacokinetics, Safety and Tolerability of the HCV NS5A Inhibitor ABT-267 Following Single and Multiple Doses in Healthy Adult Volunteers

Utility of Historical Data Compared to Lead-In Response in Predicting Sustained Virologic Response in Nonresponders and Relapsers to Peginterferon/Ribavirin When Retreated With Boceprevir+Peginterferon Alfa-2b/Ribavirin

High Sustained Virologic Response Among Genotype 1 Previous Non-responders and Relapsers to Peginterferon/Ribavirin when Re-treated With Boceprevir Plus Peginterferon Alfa-2a/Ribavirin -

From GastroHep News

Revised classification system of renal dysfunction in patients with cirrhosis

May's issue of Gut reports on a working party proposal for a revised classification system of renal dysfunction in patients with cirrhosis.

News imageDr Florence Wong and colleagues from Canada proposed an improvement on the current classification of renal dysfunction in cirrhosis.
Clinicians caring for patients with cirrhosis recognize that the development of renal dysfunction is associated with significant morbidity and mortality.
While most cases of renal dysfunction in cirrhosis are functional in nature, developed as a result of changes in hemodynamics, cardiac function, and renal auto-regulation, there is an increasing number of patients with cirrhosis and structural changes in their kidney as a cause of renal dysfunction.
There is a need for a newer classification to include both functional and structural renal diseases.
Acute kidney injury is defined as a rise in serum creatinine of 26.4µmol/L in less than 48hours

A working party consisting of specialists from multiple disciplines conducted a literature search and developed summary statements, incorporating the renal dysfunction classification used in nephrology.
The research team discussed and revised these to produce this proposal.
Literature search using keywords of cirrhosis, renal dysfunction, acute kidney injury, chronic kidney injury, and hepatorenal syndrome.
Acute kidney injury will include all causes of acute deterioration of renal function as indicated by an increase in serum creatinine of more than 50% from baseline, or a rise in serum creatinine of 26.4µmol/L or more than in less than 48hours.
The team defined chronic renal disease as an estimated glomerular filtration rate of less than 60ml/min calculated using the Modification of Diet in Renal Disease 6 (MDRD6) formula, recognizing that the MDRD6 formula is not perfect for the cirrhotic patients and this may change as improved means of estimating glomerular filtration rate becomes available.
The team reported that acute on chronic kidney disease will be defined as acute kidney injury superimposed on existing chronic renal disease using the above definitions for AKI and chronic kidney injury.
Dr Wong's team concludes, "Accepting this new classification will allow studies into the epidemiology, incidence, prevalence, natural history and the development of new treatments for these subtypes of renal dysfunction in cirrhosis."

Gut 2011: 60: 702-709
19 April 2011
Fatty Liver
Limiting carbs, not calories, reduces liver fat faster, UT Southwestern researchers find
DALLAS – April 19, 2011 – Curbing carbohydrates is more effective than cutting calories for individuals who want to quickly reduce the amount of fat in their liver, report UT Southwestern Medical Center researchers.

"What this study tells us is that if your doctor says that you need to reduce the amount of fat in your liver, you can do something within a month," said Dr. Jeffrey Browning, assistant professor of internal medicine at UT Southwestern and the study's lead author.

The results, available online and in an upcoming issue of the American Journal of Clinical Nutrition, could have implications for treating numerous diseases including diabetes, insulin resistance and nonalcoholic fatty liver disease, or NAFLD. The disease, characterized by high levels of triglycerides in the liver, affects as many as one-third of American adults. It can lead to liver inflammation, cirrhosis and liver cancer.
For the study, researchers assigned 18 participants with NAFLD to eat either a low-carbohydrate or a low-calorie diet for 14 days.

The participants assigned to the low-carb diet limited their carbohydrate intake to less than 20 grams a day – the equivalent of a small banana or a half-cup of egg noodles – for the first seven days. For the final seven days, they switched to frozen meals prepared by UT Southwestern's Clinical and Translational Research Center (CTRC) kitchen that matched their individual food preferences, carbohydrate intake and energy needs.

Those assigned to the low-calorie diet continued their regular diet and kept a food diary for the four days preceding the study. The CTRC kitchen then used these individual records to prepare all meals during the 14-day study. Researchers limited the total number of calories to roughly 1,200 a day for the female participants and 1,500 a day for the males.

After two weeks, researchers used advanced imaging techniques to analyze the amount of liver fat in each individual. They found that the study participants on the low-carb diet lost more liver fat.
Although the study was not designed to determine which diet was more effective for losing weight, both the low-calorie dieters and the low-carbohydrate dieters lost an average of 10 pounds.
Dr. Browning cautioned that the findings do not explain why participants on the low-carb diet saw a greater reduction in liver fat, and that they should not be extrapolated beyond the two-week period of study.
"This is not a long-term study, and I don't think that low-carb diets are fundamentally better than low-fat ones," he said. "Our approach is likely to be only of short-term benefit because at some point the benefits of weight loss alone trounce any benefits derived from manipulating dietary macronutrients such as calories and carbohydrates.

"Weight loss, regardless of the mechanism, is currently the most effective way to reduce liver fat."


Other UT Southwestern researchers involved in the study were Dr. Shawn Burgess, senior author and assistant professor of pharmacology in the Advanced Imaging Research Center (AIRC); Dr. Jonathan Baker, assistant professor of pathology; Dr. Thomas Rogers, former professor of pathology; Jeannie Davis, clinical research coordinator in the AIRC; and Dr. Santhosh Satapati, postdoctoral researcher in the AIRC.
The National Institutes of Health supported the study.

Fatty Liver Disease Can Lead to Heart Attack

Released: 4/18/2011 9:00 AM EDT
Source: Methodist Hospital, Houston

Newswise — Because of the prevalence of obesity in our country, many Americans are expected to develop a serious condition called non-alcoholic fatty liver disease (NAFLD), which can lead to cirrhosis, fibrosis, and in some cases liver failure. It is also one of the best predictors for coronary artery disease.

“Most people who have fatty liver disease are more likely to die from a heart attack than cirrhosis of the liver,” said Dr. Howard Monsour, chief of Hepatology at The Methodist Hospital in Houston. “I ask all my patients, especially those over 50, if they have had a stress test in the last year; if not then I send them to the cardiologist to get one.”

NAFLD is fat inside the liver cells. Alcohol, drugs, obesity, lipid disorders and diabetes can all be causes. However, many with this condition suffer from Metabolic Syndrome, a constellation of factors which include a large waist circumference (men greater than 40 inches, women greater than 35 inches), high blood pressure, high triglyceride levels and insulin resistance that heighten the risk of heart attack, stroke and type 2 diabetes.

“Data has shown that nearly 30 million Americans have NAFLD. Many times it is missed until the person’s liver enzyme levels are high,” said Dr. Kathleen Wyne, director of clinical research for the Diabetes Research Center at The Methodist Hospital Research Institute (TMHRI). “Much like type 2 diabetes, it can be cured with diet and exercise.”

“Vigorous exercise, such as weight lifting, swimming, running or aerobics, between 75 and 150 minutes a week with a heart rate of 120 or above will help you tackle this problem,” Monsour said. “If you lose 12 percent of your current weight, no matter how much you weigh, you can also eliminate fat from your liver.”

Between five and 20 percent of people with fatty liver will develop serious liver disease. Developing cirrhosis, fibrosis or liver cancer depends on whether the person has inflammation in the liver caused by the fat resulting in an inflammatory response called steatohepatitis. This often, but not always, causes liver enzyme elevation on routine blood tests.

“The key is to catch it early. If we do, we can help the patient avoid cirrhosis, fibrosis and type 2 diabetes,” Monsour said. “Letting it go without evaluation can lead to liver disease, liver cancer, stroke, heart disease and a very difficult life.”


Cancer Patient invented low radio frequency machine to fight liver cancer

With boost from Southwest Florida, possible cancer treatment advances

Researchers have tried John Kanzius’ cancer treatment on rabbits with liver cancer, and the cancerous cells were killed.
More importantly, the rabbits experienced no side effects, and healthy tissue was left unharmed.
They tested animals with pancreatic cancer, introducing antibodies into the body through microscopic gold nanoparticles. Those antibodies attach to cancer cells and enter inside the diseased cells, after which the gold nanoparticles are heated up using radio frequency waves to kill the bad cells.
Now researchers are looking toward the next phase in a treatment they believe holds potential for fighting some cancers.
“I’ve been blown away,” said Dr. Steven Curley, a professor of surgical oncology at M.D. Anderson Cancer Research Center in Houston. “We really haven’t found any side effects with this treatment.”
..continue reading

Study shows how inflammation can lead to cancer
A new study shows how inflammation can help cause cancer. Chronic inflammation due to infection or to conditions such as chronic inflammatory bowel disease is associated with up to 25 percent of all cancers.

This study by researchers at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) found that inflammation stimulates a rise in levels of a molecule called microRNA-155 (miR-155).

This, in turn, causes a drop in levels of proteins involved in DNA repair, resulting in a higher rate of spontaneous gene mutations, which can lead to cancer.

“Our study shows that miR-155 is upregulated by inflammatory stimuli and that overexpression of miR-155 increases the spontaneous mutation rate, which can contribute to tumorigenesis,” says first author and post-doctoral researcher Dr. Esmerina Tili. “People have suspected for some time that inflammation plays an important role in cancer, and our study presents a molecular mechanism that explains how it happens.”

“Our findings also suggest that drugs designed to reduce miR-155 levels might improve the treatment of inflammation-related cancers,” Tili says.

The findings were published recently in the Proceedings of the National Academy of Sciences.

MicroRNAs form a large family of non-coding genes involved in many important cell processes. They carry out this function by suppressing the amount of particular proteins in cells, with each type of microRNA often affecting many different proteins.

MiR-155 is known to influence blood-cell maturation, immune responses and autoimmune disorders, and high levels of this molecule have been directly linked to the development of leukemias, and breast, lung and gastric cancers.

For this study, Tili and her colleagues examined the effects of inflammation-promoting substances such as tumor necrosis factor or lipopolysaccharide (found in the outer walls of bacteria) on miR-155 expression and on the frequency of spontaneous mutations in several breast-cancer cell lines.

When the researchers exposed breast-cancer cells to the two inflammatory factors the levels of miR-155 rose abnormally high, and the mutation rate increased two- to three-fold. To understand why, the investigators focused on the WEE1 gene, which stops the process of cell division to allow damaged DNA to be repaired.

The investigators learned that miR-155 also targets WEE1 and showed that high levels of miR-155 lead to low levels of WEE1. They reasoned that low levels of WEE1 allowed cell division to continue even when DNA damage is present, leading to a growing number of mutations.

“It is believed that cancer is caused by an accumulation of mutations in cells of the body,” says principal investigator Dr. Carlo M. Croce, professor and chair of molecular virology, immunology and medical genetics, and director of the Human Cancer Genetics program the OSUCCC – James. “Our study suggests that miR-155, which is associated with inflammation, increases the mutation rate and might be a key player in inflammation-induced cancers generally. This could make it an important therapeutic target.”

Funding from the National Cancer Institute supported this research.

Croce is also the John W. Wolfe Chair in Human Cancer Genetics.

Other researchers involved in this study were Jean-Jacques Michaille, Dorothee Wernicke, Hansjuerg Alder, Stefan Costinean and Stefano Volinia of The Ohio State University.

The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (http://cancer.osu.edu) is one of only 40 Comprehensive Cancer Centers in the United States designated by the National Cancer Institute. Ranked by U.S. News & World Report among the top cancer hospitals in the nation, The James is the 205-bed adult patient-care component of the cancer program at The Ohio State University. The OSUCCC-James is one of only seven programs in the country funded by the NCI to conduct both Phase I and Phase II clinical trials.

From Medgaget
Delcath Receives Notice of European Regulatory Approval for Hepatic CHEMOSAT(TM)
The technology involves placing an extracorporeal filter that can clean blood of chemotherapeutic agents that leave the liver. The system allows for greater dosages of chemo to reach the target while preserving the rest of the body from serious side effects.

Chemosaturation system used in the treatment of patients with metastatic melanoma in the liver through the percutaneous intra-arterial administration of melphalan hydrochloride

1. Isolation

The Delcath Isolation-Aspiration catheter is inserted through the femoral vein and guided into the inferior vena cava and positioned so that when the balloons on the catheter are inflated they isolate the normal hepatic outflow of blood from the patient’s general circulatory system.

2. Saturation

The chemotherapeutic agent is delivered directly to the liver by a specialized chemo delivery catheter placed in the hepatic artery. In this procedure the chemotherapeutic agent is administered at dose levels several times higher than the currently approved limit of traditional systemic chemotherapy delivered via a standard IV infusion.

3. Filtration

The chemo saturated blood is filtered by an extracorporeal filtration circuit that uses a proprietary plasma cleansing technology to reduce toxic levels of the drug before returning it to the patient.

Delcath Receives Notice of European Regulatory Approval for Hepatic CHEMOSAT(TM) Delivery System
NEW YORK, April 13, 2011 /PRNewswire via COMTEX/ --

Delcath Systems, Inc. (NASDAQ: DCTH) today announced that the Company has been notified of CE Mark approval for its proprietary Hepatic CHEMOSAT(TM) Delivery System. The product has been approved with an indication for the percutaneous intra-arterial administration of a chemotherapeutic agent (melphalan hydrochloride) to the liver.

CE Marking confirms that a medical device complies with the Essential Requirements of the Medical Device Directive, and that the device has been subjected to conformity assessment procedures. Receipt of the CE Mark allows Delcath to market and sell the product in countries in the European Economic Area.

"Receipt of our CE Mark represents the first regulatory approval for this product, and marks the beginning of the Company's transition into a fully commercial enterprise," said Eamonn P. Hobbs, CEO & President of Delcath Systems. "With its rising liver cancer rates, Europe represents a large opportunity for this product. We believe the Hepatic CHEMOSAT Delivery System may ultimately fulfill an annual unmet clinical need for as many as 100,000 liver cancer patients in this region. With the CE Mark in hand, we will now begin to build inventory and establish the commercialization infrastructure in Europe, including assembling a direct sales organization to cover countries in Northern Europe and establishing a network of third party distributors in Southern Europe. We will also begin establishing and training initial sites in select European countries as Centers of Clinical Excellence for the chemosaturation procedure."

About Delcath Systems

Delcath Systems, Inc. is a specialty pharmaceutical and medical device company focused on oncology. Delcath's proprietary system for chemosaturation is designed to administer high dose chemotherapy and other therapeutic agents to diseased organs or regions of the body, while controlling the systemic exposure of those agents. The Company's initial focus is on the treatment of primary and metastatic liver cancers. In 2010, Delcathconcluded a Phase III metastatic melanoma study, and the Company recentlycompleted a multi-arm Phase II trial to treat other liver cancers. The Company has not yet received FDA approval for commercial sale of its system. For more information, please visit the Company's website at http://www.delcath.com/.

America’s Most Popular Drugs

In the entire listing of the 25 most popular drugs, which I’ve included below, there are only three branded medicines: Lipitor, Plavix, the blood-thinner made by Sanofi-Aventis and Bristol-Myers Squibb that clocks in at number 23 and Singulair, the asthma and allergy pill from Merck, which ranks number 25. (Click here for The Best-Selling Drugs In America.)... Continue reading.......

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