Thursday, May 31, 2012

New Hampshire-Officials confirm hepatitis C outbreak at Exeter Hospital

Officials confirm hepatitis C outbreak at Exeter Hospital

Union Leader Correspondent

Dr. Jose Montero, the state's public health director, speaks at a news conference outside Exeter Hospital Thursday afternoon.(JASON SCHREIBER)

EXETER — Four patients have been diagnosed with the same strain of hepatitis C, and hundreds more will be tested as Exeter Hospital and state health officials investigate what is being called the state's first such outbreak of the disease in a medical facility.

At a news conference Thursday afternoon, several representatives from the hospital and the state's Division of Public Health confirmed that four patients were diagnosed over the past two weeks and that they share an identical strain, meaning they were infected by the same source, officials said.

Hepatitis C is a potentially fatal liver disease commonly spread through exposure to blood, said Dr. Jose Montero, the state's public health director.

A joint investigation revealed that those infected were all patients who received care in the hospital's cardiac catheterization lab and its recovery unit, which was shut down on May 25 after officials determined that the area may have been the location where the infections occurred.

Officials said they're still trying to figure out exactly how it was spread.

While rare outbreaks of hepatitis C have occurred in medical facilities in other parts of the country, Montero said this is the first incident in New Hampshire.

“Despite the low number of cases we have identified to date, we are taking this issue extremely seriously. … We are doing everything we can to quickly identify and eliminate the common source of infection. We are taking measures to identify those individuals that could possibly be affected and care for those patients and individuals that we have identified,” said Dr. Richard Hollister, chairman of the hospital's Department of Medicine.

Signs of the outbreak began May 14 when the hospital launched an investigation into three cases of hepatitis C possibly linked to the facility. A fourth case was then discovered, Hollister said, and on May 15, the hospital reported the cases to state health officials. The state began testing the patients on May 17 and later determined that the virus that infected the four patients had a “common genetic fingerprint, suggesting a common source of infection,” Hollister said.

The only common connection found between the four infected patients to date is the cardiac catheterization lab, Hollister said.

Hospital administrators voluntarily decided to suspend operations of the laboratory and its recovery unit on May 25 “out of an abundance of caution,” Hollister said.

On May 29, the hospital began testing all staff and physicians who had any possible connection to the cardiac-catheterization lab.

Some 28 staff members have been tested so far, Hollister said, and testing will continue until all staffers are cleared to return to work and resume operations.

Officials said 651 patients who were treated in the cardiac catheterization lab and its recovery unit between Aug. 1, 2011, and May 25 have been identified and are being contacted by phone and letter and urged to receive free hepatitis C testing at the hospital.

Positive test results will be reported to the patient's primary care physician and checked by the state lab to see if they share the strain found in the original four infected patients, Hollister said.

Montero said some people may not show symptoms right away and that 15 to 25 percent clear the virus without treatment. The majority of those infected develop chronic infection, which can become a lifelong illness that leads to serious liver problems, officials said.

Symptoms may include loss of appetite, abdominal pain, fatigue, nausea, and jaundice.

Patients who have been identified as possibly being exposed are being urged to call the hospital's Information and Referral center at 580-6124 to schedule a blood test. Staff will be available Monday through Friday from 7 a.m. to 7 p.m.

Press Release From Exeter Hospital In New Hampshire;

Bristol urges combo study with Gilead hepatitis drug

Thu May 31, 2012 12:14pm EDT

(Reuters) - Bristol-Myers Squibb Co renewed its call for biotechnology company Gilead Sciences Inc to test one of its hepatitis C drugs in late-stage trials alongside Bristol's own promising medicine, following stellar results from a mid-stage trial that combined the experimental products.Bristol's daclatasvir is from a new class of drugs known as NS5A inhibitors. Gilead's GS-7977 is a nucleotide polymerase inhibitor. Both are designed to block enzymes essential to replication of the hepatitis C virus.

Bristol-Myers Chief Executive Lamberto Andreotti, speaking on Thursday at the Sanford Bernstein Strategic Decisions Conference in New York, said patients and both drugmakers stand to benefit if combined Phase III trials of the two medicines are pursued.

"We have a different point of view about whether to enter Phase III (trials) with that combination," Andreotti said. "We believe for both patients and companies, it is better to move forward" in the short term.

But Andreotti said Gilead instead seemed intent on looking "in-house" -- focusing instead on combinations of its own products. Gilead officials could not immediately be reached to comment.
Andreotti said there was a "huge unmet need" for better treatments among an estimated 170 million to 180 million people worldwide believed to be infected with the virus. Transmitted by blood transfusions, sexual contact and shared drug needles, the virus invades the liver and can steadily destroy the organ over decades. It is the biggest reason for liver transplants in the United States.

Shares of Gilead jumped 11 percent on April 19 when data from a mid-stage trial were released and showed profound benefits of combining its GS-7977 -- acquired through Gilead's $11 billion purchase of Pharmasset -- with Bristol's daclatasvir.

At the time, Bristol said Gilead had balked at further collaboration on the combination under study, which began when 7977 was owned by Pharmasset.

Data from the mid-stage study combining 7977 and daclatasvir showed a 100 percent response rate in previously untreated patients with the most common form of hepatitis C.

Instead of working with Bristol-Myers, Gilead is forging ahead with a study of 7977 in combination with its own experimental NS5A inhibitor. In the meantime, Bristol-Myers is testing daclatasvir with a drug similar to 7977 that it acquired with its $2.5 billion purchase of Inhibitex, as well as with other experimental drugs in its development pipeline.

(Reporting By Ransdell Pierson; Additional reporting by Bill Berkrot; Editing by Maureen Bavdek)

BRIEF-Bristol Myers CEO says Gilead/Bristol hepatitis C drugs should be tested together

May 31 (Reuters) - Bristol-Myers Squibb Co :

* CEO says company will not "downsize" research and development, but adjust it in accordance with ongoing performance of company

* CEO says biggest mid-term company focus will be on oncology, virology, anti-coagulation

* CEO says Gilead and Bristol should combine their respective experimental medicines for hepatitis c in late-stage trials

* CEO says he suspects Gilead would prefer instead to first explore combinations of gilead's own hepatitis c medicines

* CEO says expects some form of subsequent healthcare reform even if supreme court shoots down health care law

* CEO says U.S. healthcare reform started on right foot, but then became too complicated for drugmakers and American people

* CEO says significant future company sales growth will come from Asia, not from Europe

((New York Equities Desk; tel: +1 646 223 6000))

((For more news about Bristol-Myers Squibb Co click here: ))

(C) Reuters 2012. All rights reserved. Republication or redistribution of Reuters content, including by caching, framing or similar means, is expressly prohibited without the prior written consent of Reuters.

Hepatitis C “switch” offers target for new drug research

Hepatitis C “switch” offers target for new drug research

Scientists have discovered a “switch” in the Hepatitis C virus which could be used as a target for new kinds of drug treatment.

Hepatitis C affects more than 170 million people worldwide, but current combination treatment is only effective against a limited range of this naturally highly variable virus.

However, according to new research by the University of Warwick, the newly discovered SL9266 ‘switch’ is very highly conserved and present in all Hepatitis C viruses, meaning this offers a good starting point for further research into an across-the-board treatment.

This region represents a vulnerable spot for attacking and clearing the virus from the body as it controls a critical event in the earliest stages of the virus lifecycle.

It seems the switch modulates the mutually incompatible translation and replication processes that must occur for the virus to spread inside the body.

University of Warwick scientists at the School of Life Sciences and their collaborators in the Roslin Institute at the University of Edinburgh are now working with chemists to develop custom-designed drugs that target the switch and lock it in the ‘off’ position.

By locking the virus into a translation-only phase it cannot initiate replication, a process critical for infecting other cells in the liver.

The immune response to the initially infected cell would contribute to the clearance of the virus from the body.

Despite the variability of the virus, the mechanism and function of this ‘switch’ is thought to be highly conserved, providing a means of targeting all Hepatitis C viruses.

Professor David Evans of the University of Warwick said: “Hepatitis C is a growing concern worldwide and is set to place a massive demand on the organ transplant system.
“We are already at the stage in many countries where the main need for liver transplants is due to liver damage caused by the Hepatitis C virus.

“Current medication is not effective in all cases, that’s why it’s vital that we continue to build on this early-stage research to focus drug development work on treatment which works across all Hepatitis C genotypes.”

The research, funded by the UK Medical Research Council, is published in the journal Nucleic Acids Research.

The study is entitled A twist in the tail: SHAPE mapping of long-range interactions and structural rearrangements of RNA elements involved in HCV replication.

It is co-authored by Andrew Tuplin, Madeleine Struthers and David Evans of the University of Warwick and Peter Simmonds of the Roslin Institute, University of Edinburgh.

The study is available here

New Clinical Practice Guideline Developed for Nonalcoholic Fatty Liver Disease

The American Association for the Study of Liver Diseases, in collaboration with the American College of Gastroenterology and American Gastroenterological Association, have developed new guidelines for the diagnosis and management of Nonalcoholic Fatty Liver Disease (NAFLD). The practice guideline was co-published in the June 2012 issues of the official journals of the sponsoring societies.

The guideline is intended for physicians and allied health professionals and provides recommendations that suggest preferred approaches to the diagnosis, therapeutic and preventive aspects of care. While obesity is a risk factor for NAFLD, there is a very high prevalence in individuals with type 2 diabetes mellitus and progression to advanced fibrosis and mortality increases in older patients. The recommendations address NAFLD in children and adults.

Download this timely and free practice guideline.

A Few Topics;
Natural History
Screening of Family Members
Non-invasive assessment of steatohepatitis and advanced fibrosis in NAFLD
Vitamin E
Ursodeoxycholic acid (UDCA), Omega-3 fatty acids, and Miscellaneous Agents
Alcohol use in patients with NAFLD and NASH
Statin use in patients with NAFLD and NASH
NAFLD in patients with other chronic liver diseases
Aspects of NAFLD Specific to Children and Adolescents
Lifestyle modification
Lifestyle intervention

People with fatty livers need to lose weight

People with fatty livers need to lose weight
By Sally Robertson
31 May 2012
Hepatology 2012; 55: 1738–1745

MedWire News: Exercising moderately for 150 to 300 minutes a week does not improve lipoprotein metabolism in obese people with nonalcoholic fatty lipid disease (NAFLD), show findings from a US study.

The marked improvement in fatty liver and lipoprotein metabolism that is associated with lifestyle intervention may be largely due to weight loss rather than increased physical activity, suggest Samuel Klein (Washington University School of Medicine, St Louis, Missouri) and colleagues.

Diet-induced weight loss and regular physical activity has previously been shown to reduce intrahepatic triglyceride (IHTG) content and improve the metabolic derangements associated with NAFLD, explain the researchers. "However, few studies have evaluated the effect of regular physical activity, independent of weight loss, on NAFLD," they say.

Current physical activity guidelines from the Department of Health and Human Services recommend that adults perform at least 150 minutes, but preferably 300 minutes, of moderate-intensity physical activity per week, note Klein et al.

The team decided to investigate the effect of following these guidelines on IHTG and very low-density lipoprotein (VLDL) kinetics in 18 obese patients with NAFLD.

The researchers randomly assigned 18 obese individuals (mean body mass index [BMI] 38.1 kg/m2) with NAFLD (IHTG content >10%) to either participate in an exercise regimen (exercise group) or to continue their current daily activities (control group) over a 16-week period. Those in the exercise group were instructed to exercise for 30-60 minutes, five times per week, at 45-55% of their peak oxygen consumption (ie, a brisk walk).

The team used magnetic resonance spectroscopy to assess IHTG content and isotopically labeled tracer techniques to examine VLDL-TG and VLDL-apolipoprotein B-100 (apoB-100) kinetics among the participants at baseline and at 16 weeks.

As reported in Hepatology, there were no differences in body weight, body fat mass, and fat-free mass values among the participants at 16 weeks, compared with baseline.
The researchers found that there was a 10.3% relative decrease in IHTG content in the exercise group, compared with the control group.

Interestingly, the exercise training did not affect plasma total TG, VLDL-TG, VLDL-apoB-100, or fasting fatty acid concentrations.

However, there was a 12.8% relative decrease in plasma alanine transaminase (ALT) concentration, compared with in the control group, and this decrease correlated directly with the change in IHTG content.

"These results demonstrate that moderate-intensity endurance exercise training alone has only modest therapeutic effects on hepatic TG and lipoprotein metabolism," say Klein et al.
The improvement in lipoprotein metabolism and steatosis observed with lifestyle intervention may be due to weight loss and not increased physical activity, they say.

"Further studies are needed to evaluate the mechanism through which moderate-intensity exercise training decreases IHTG content," concludes the team.

MedWire ( ) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2012

Free abstract

Vertex Goes From Bad Data To A Bad Promotion

Vertex Goes From Bad Data To A Bad Promotion
By Ed Silverman // May 31st, 2012
As for the letter, the FDA chastised the drugmaker for submitting a patient story that failed to match reality, at least as far as the agency is concerned. The proposed Vertex patient talk features “James M.,” a real guy who never quite says how he contracted hepatitis C, but portrays himself as an average sort who kicked around for awhile, had a good time and wound up with a diagnosis, a divorce and a four-year-old son to raise all around the same time (that’s James M. in the picture).
However, the FDA says Vertex went too far. The ad “misleadingly implies that most or all cirrhotic prior null responders (those who did not previously respond to treatment) who are infected with hepatitis C will successfully achieve Sustained Virologic Response (SVR) on Incivek combination therapy. FDA is not aware of substantial evidence or substantial clinical experience to support this implication. One patient’s treatment response does not constitute substantial evidence,” the agency writes in its May 25 letter.
Continue Reading @ Pharmalot

Read the FDA warning letter here, and the Incivek promotional story here.
Continue reading the article here. More from the Boston Business Journal

Wednesday, May 30, 2012

Study uncovers the extent of OTC acetaminophen overdose risk

New York / Heidelberg, 30 May 2012

Misuse of over-the-counter pain medication is potential health threat

11606_204x153Study uncovers the extent of OTC acetaminophen overdose risk

A significant number of adults are at risk of unintentionally overdosing on over-the-counter (OTC) pain medication, according to a new study in the US by Dr. Michael Wolf, from Northwestern University in Chicago, and his colleagues. Their work¹, looking at the prevalence and potential misuse of pain medication containing the active ingredient acetaminophen as well as the likelihood of overdosing, appears online in the Journal of General Internal Medicine², published by Springer.
Many adults in the US regularly use OTC pain medication containing the active ingredient acetaminophen, the most commonly used OTC pain medication in the US. They take it either on its own or in combination with other drugs, which may also contain acetaminophen. The ease of access to OTC drugs presents a challenge to patient safety as many individuals may lack the necessary health literacy skills to self-administer these medicines appropriately. Indeed, individuals make independent decisions that match an OTC product to a self-diagnosed symptom or condition. Worryingly, acetaminophen overdose is the leading cause of acute liver failure.
Wolf and colleagues interviewed 500 adult patients receiving care at outpatient general medicine clinics in Atlanta and Chicago between September 2009 and March 2011. Over half the patients reported some acetaminophen use and 19 percent were 'heavy users' i.e. they had taken it every day, or at least a couple of times a week, during the previous six months.
The researchers tested whether these patients understood the recommended dosage and were able to self-administer OTC acetaminophen appropriately. Firstly, could they work out the proper dosing of a single OTC medication over a 24-hour period? Secondly, what was the risk of patients 'double-dipping', or simultaneously taking two acetaminophen-containing products, and thereby exceeding the recommended dose?
To assess proper dosing, the participants were given five OTC drug bottles and, for each one, were asked to imagine that they took the first dose at time X, and wanted to take the maximum dose of this medicine in one day. They were then asked to show the researcher how many pills and at which times they would need to take them for a full 24-hour day.
To assess 'double-dipping', the patients were told to imagine they were taking a maximum dose of a primary OTC drug and asked whether it would be safe to also take a second medicine with the primary medicine - both of which contained acetaminophen.
Wolf and team found that nearly a quarter of the participants were at risk of overdosing on pain medication using a single OTC acetaminophen product, by exceeding the dose of four grams in a 24-hour period; 5 percent made serious errors by dosing out more than six grams. In addition, nearly half were at risk of overdosing by 'double-dipping' with two acetaminophen containing products.
The authors conclude: "Our findings suggest that many consumers do not recognize or differentiate the active ingredient in OTC pain medicines, nor do they necessarily closely adhere to package or label instructions. Given the prevalence of the problem, risk of significant adverse effects, and lack of a learned intermediary i.e. a physician to guide decision making and counsel consumers on proper use, we believe this to be a serious public health threat requiring urgent attention."
1. Wolf MS et al (2012). Risk of unintentional overdose with non-prescription acetaminophen products. Journal of General Internal Medicine; DOI: 10.1007/s11606-012-2096-3
2. The Journal of General Internal Medicine is the official journal of the Society of General Internal Medicine.
The full-text article is available to journalists on request.
DDW-Patients May Receive Too Much Acetaminophen in Hospital

Understanding the links between inflammation and chronic disease

Northwestern University
Understanding the links between inflammation and chronic disease Early exposure to microbes reduces inflammation related to chronic disease later

EVANSTON, Ill. --- American parents may want to think again about how much they want to protect their children from everyday germs.
A new Northwestern University study done in lowland Ecuador remarkably finds no evidence of chronic low-grade inflammation -- associated with diseases of aging like cardiovascular disease, diabetes and dementia.

In contrast, about one-third of adults in the United States have chronically elevated C-reactive protein (CRP). Acute elevations in CRP -- a protein in the blood whose levels rise as part of the inflammatory response -- are important for protecting us against infectious disease. But when CRP is chronically produced, it is associated with chronic diseases.

"In other words, CRP goes up when you need it, but it is almost undetectable when you don't, after the infection resolves," said Thomas W. McDade, professor of anthropology at Northwestern and faculty fellow at the university's Institute for Policy Research. "This is a pretty remarkable finding, and very different from prior research in the U.S., where lots of people tend to have chronically elevated CRP, probably putting them at higher risk for chronic disease."

McDade said the findings build on his previous research in the Philippines, which found that higher levels of microbial exposure in infancy were associated with lower CRP as an adult. Similar exposures during infancy in lowland Ecuador, where rates of infectious disease continue to be high, may have a lasting effect on the pattern of inflammation in adulthood.

"In my mind the study underscores the value of an ecological approach to research on the immune system, and it may have significant implications for our understanding of the links between inflammation and chronic disease," McDade said. "This may be particularly important since nearly three-quarters of all deaths due to cardiovascular disease globally now occur in low- and middle-income nations like the Philippines and Ecuador."

The new research, which was conducted as part of the Shuar Health and Life History Project (, suggests that higher levels of exposure to infectious microbes early in life may change how we regulate inflammation as adults in ways that prevent chronic inflammation from emerging. Infectious microbes have been part of the human ecology for millennia, and it is only recently that more hygienic environments in affluent industrialized settings have substantially reduced the level and diversity of exposure.

A growing body of research has shown that higher levels of chronic inflammation are associated with diseases of aging like cardiovascular disease, diabetes and dementia. But current research is based almost exclusively on people living in affluent industrialized countries like the United States.
"We simply do not know what chronic inflammation looks like in places like the Ecuadorian Amazon and other parts of the world where infectious diseases are more common," McDade said.

As a result, McDade, director of the Lab for Human Biology Research and director of Cells to Society (C2S): The Center on Social Disparities and Health, and collaborators at the University of Oregon set out to investigate what factors in the environment and during development influence how people regulate inflammation as adults. The study was conducted in lowland Ecuador – in a group of 52 adults between the ages of 18 and 49.

Based on current clinical criteria, McDade and colleagues did not find a single case of chronic low-grade inflammation among adults living in the Ecuadorian Amazon. McDade said people in these places are still dying of diseases such as cardiovascular disease, but probably not through processes that involve inflammation.

In terms of population health, McDade said these findings suggest that the association between inflammation and cardiovascular disease frequently reported in the United States may only apply in ecological settings characterized by low levels of exposure to infectious disease.
"It builds on research on chronic inflammation and cardiovascular disease in the U.S. and other affluent, industrialized settings and suggests that patterns seen here may not apply globally," McDade said. "It also suggests that the levels of chronic inflammation we see in the U.S. are not universal, and may be a product of epidemiological transitions that have lowered our level of exposure to infectious microbes."


"Analysis of Variability of High Sensitivity C-Reactive Protein in Lowland Ecuador Reveals No Evidence of Chronic Low-Grade Inflammation" is currently available online in the Early View section of the American Journal of Human Biology ( The study's co-authors are Paula S. Tallman, Department of Anthropology, Northwestern University; and Felicia C. Madimenos, Melissa A. Liebert, Tara J. Cepon, Lawrence S. Sugiyama and J. Josh Snodgrass, all with the Department of Anthropology at the University of Oregon and its Institute of Cognitive and Decision Sciences. Sugiyama is also affiliated with the Center for Evolutionary Psychology, University of California, Santa Barbara.

GSK seeks to expand low platelet drug Promacta to hepatitis C patients

GSK seeks to expand low platelet drug Promacta to hepatitis C patients
Frank Vinluan

GSK has filed regulatory applications in Europe and the United States to add the new indication to the drug. The drug eltrombopag, which is marketed under the brand name Promacta in the United States and Revolade globally, is approved in 88 countries to treat immune thrombocytopenia, a condition in which a patient has low blood counts because the platelets are destroyed by his own immune system.
The British pharmaceutical giant, which has its U.S. headquarters in Research Triangle Park, North Carolina, is now seeking to expand approval of the drug to increase platelet counts in patients who have chronic hepatitis C virus infection. The drug would allow them to start interferon-based therapy and could also be used to optimize interferon-based therapy, according to GSK’s supplemental new drug application.

Continue Reading.....

Press release:

Regulatory Update – GSK announces submissions in the EU & US for new indications for Promacta®/Revolade®

Issued: Wednesday 30 May 2012, London UK

GlaxoSmithKline plc announced today that it has submitted regulatory applications in the European Union and United States related to eltrombopag (Promacta®/Revolade® ) and its use to increase platelet counts in patients with chronic hepatitis C virus infection and low platelets (thrombocytopenia), specifically,

*a variation to the Marketing Authorisation Application to the European Medicines Agency for Revolade (eltrombopag) as a treatment for thrombocytopenia in adult patients with chronic hepatitis C infection to enable the initiation of interferon-based therapy and during interferon based therapy.
*a supplemental New Drug Application to the US Food and Drug Administration for Promacta (eltrombopag) as a treatment for thrombocytopenia in adult patients with chronic hepatitis C infection to enable the initiation of interferon-based therapy and to optimise interferon based therapy.

About eltrombopag (Promacta®/Revolade®)
Eltrombopag, known by the brand name Promacta in the United States and Revolade in the European Union and other countries, is currently approved in 88 countries around the world as a treatment for thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenia.

Important Safety Information
Promacta may cause hepatotoxicity. Other risks for Promacta include: bone marrow reticulinformation and risk for bone marrow fibrosis, thrombotic/thromboembolic complications, hematologic malignancies, and cataracts.

About eltrombopag (Promacta®/Revolade®)
Eltrombopag, known by the brand name Promacta in the United States and Revolade in the European Union and other countries, is currently approved in 88 countries around the world as a treatment for thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenia.

Important Safety Information
Promacta may cause hepatotoxicity. Other risks for Promacta include: bone marrow reticulinformation and risk for bone marrow fibrosis, thrombotic/thromboembolic complications, hematologic malignancies, and cataracts.

For more important safety information about the currently licensed indications forPROMACTA/Revolade, please visit Revolade - Prescription medicines - Our products -GlaxoSmithKline to view the Revolade EU Patient Information Leaflet and visit Promacta - Prescription medicines - Our products - GlaxoSmithKline for full Promacta US Prescribing Information including BOXED WARNING risk for hepatotoxicity.

GlaxoSmithKline – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For further information please visit

Vertex warned over misleading hep C drug promotion

Reporter- Boston Business Journal

The U.S. Food and Drug Administration has issued a warning letter to Vertex Pharmaceuticals (Nasdaq: VRTX) saying the company published a misleading “branded story” promoting its drug for hepatitis C, Incivek. The FDA is demanding that the Cambridge, Mass.-based company, which won FDA approval for the drug in May of 2011, stop disseminating the materials in question. 
The warning letter reads in part, “The branded story is misleading because it overstates the efficacy, omits material facts and minimizes important risk information about the drug product.” 
The branded Incivek story described the experience of a patient named James, who had stage 3 cirrhosis due to hepatitis C and failed to have a response on another drug regimen. He found the drug combination including Incivek to be effective. 
The story included statements such as: 
“And six months after treatment ended, I found out I’d cleared the virus. That made me feel so good. I was so happy to know I’d be around a little longer to see my son grow up.” [page 5] 
“. . .I’m cleared, I can take my son to the batting cage. We go sailing on my boat and take nice vacations. I even retired from the railroad and started a successful cab business, which I really enjoy. I’m loving life.” [page 5] 
The FDA found that while these statements might reflect this patient’s experience, it is misleading because it implies that all such patients will successfully achieve a Sustained Virologic Response (SVR)........
Read the FDA warning letter here, and the Incivek story from the man who had stage 3 cirrhosis here.
Continue reading the article here.....
FDA Warning Letter................
Company/Individual Product/Issue Issue Date
Vertex Pharmaceuticals, Inc.
NDA 201917 Incivik (telaprevir) Film Coated Tablets 5/25/12

Clinical Implications of HCV Resistance

Continuing medical education (CME) @ CCO

In case you missed it, this month over at CCO is an interactive CME titled " Clinical Implications of HCV Resistance ."

Graham R. Foster, FRCP, PhD, provides expert opinion on how to avoid the development of HCV resistance with new direct-acting antiviral regimens through a review of 4 patient cases. 

The CME discusses appropriate stopping rules, missed doses, managing null responders and the risks and benefits of deferring current HCV therapy.

Click here to view the presentation
*Free registration required

Fake ADHD drug Adderall sold online, U.S. FDA warns

WASHINGTON | Tue May 29, 2012 6:34pm EDT

(Reuters) - Some websites are peddling fake versions of Adderall, a treatment for attention deficit hyperactivity disorder that is currently in short supply in the United States, federal regulators warned.

The U.S. Food and Drug Administration on Tuesday said it has learned of at least two cases in which people received counterfeit versions of the 30-milligram dose of the drug with the wrong active ingredients -- ones that treat acute pain, not attention problems. The fake pill is ineffective and may be harmful, the FDA said.

The popular stimulant, made by Teva Pharmaceutical Industries and others, has been in shortage since at least last year, which may make it a target for rogue websites and distributors, the FDA said.

"Consumers should be extra cautious when buying their medicines from online sources," the FDA said in a statement.

Teva informed the FDA about the counterfeit pills after learning of the problem from people who bought the drug online. The FDA said it is uncertain how many people in total may have received counterfeit medicine, or which websites were involved.

Teva, when asked for comment, said it found out about the counterfeit Adderall from a consumer who noticed misspellings on the packaging.

Adderall is made from a controlled substance, meaning it is addictive and has the potential to be abused. The Drug Enforcement Administration tightly regulates how much of the drug's active pharmaceutical ingredient can be distributed to manufacturers each year in order to prevent diversion of the drug for inappropriate uses -- such as by students who want to increase focus to improve test scores.

The DEA authorizes a certain amount of Adderall's active ingredients - mixed amphetamine salts - to be released to drugmakers each year. But companies are saying that amount may not be enough to meet soaring demand for the drug.

In 2010, more than 18 million prescriptions were written for Adderall, up 13.4 percent from 2009, according to IMS Health. ADHD is one of the most common childhood disorders, with an average of 9 percent of children between the ages of five and 17 diagnosed with it each year, according to the Centers for Disease Control and Prevention.

The FDA said Adderall is in short supply because of problems getting active ingredients to make the drug.

Adderall is made in several doses and formulations, but it is the shorter-acting, instant release forms of the drug that are in shortest supply. These are made by Teva, as well as CorePharma LLC and Sandoz, a unit of Swiss drugmaker Novartis AG.

Normally, the drug has four active ingredients: dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate, and amphetamine sulfate. But the FDA's tests found the counterfeit versions of Adderall had only two ingredients - tramadol and acetaminophen, often used to treat pain.

The fake pills often have misspellings on the packages, and are white and unmarked. Teva's real version of the pill is orange or peach-colored, and embossed with "dp" on one side and "30" on the other. The fake Adderall also comes in foil packages, instead of the bottles that Teva uses.

(Reporting by Anna Yukhananov; Ediing by Steve Orlofsky)

Tuesday, May 29, 2012

Hepatitis C News Ticker-Preliminary Data on OCR-002 for the Treatment of Liver Cirrhosis

Body Oddities 2 By Kelsey Niziolek

Kelsey is an illustration major studying at the University of the Arts, and will receive a Bachelor of Fine Arts in May 2012. She holds a special love in her (he)art for science, health, and medical related topics, however always keeps an open mind. She is excited to learn new techniques and processes while diving into new subject areas. Aside from traditional illustration, she also enjoys printmaking methods such as screen printing and alternative non-silver processes.
See additional works by Kelsey Niziolek and visit her blog

Source: Scope

 In The News

Research-Clinical Trials

Preliminary Phase 2 Data of Ocera Therapeutics' OCR-002 for the Treatment of Liver Cirrhosis and Upper GI Bleeding Show Potent Ammonia Reduction

Data presented at the 15th International Symposium for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN)

BARCELONA, Spain and SAN DIEGO, May 29, 2012 /PRNewswire via COMTEX/ -- Hospital Universitari Vall d'Hebron Research Institute in Barcelona and Ocera Therapeutics, Inc. announced today preliminary data from an open label phase 2 study evaluating the overall effectiveness and safety of OCR-002 (ornithine phenylacetate) for the treatment of cirrhosis of the liver and upper GI bleeding. An interim analysis of the first cohort of patients demonstrated that OCR-002 is well tolerated and provided a rapid and durable ammonia reduction after 36 hours of treatment. The data were presented at the 15th International Symposium for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) in Grenaa, Denmark.

OCR-002 is a novel injectable agent that removes toxic, circulating ammonia from the blood. In patients with severe liver impairment, ammonia and other toxic substances that are normally removed by the liver accumulate in the blood and impair the function of brain cells. By removing circulating ammonia, OCR-002 may treat or prevent hepatic encephalopathy (HE), a neuropsychiatric complication of acute liver failure associated with increased levels of circulating ammonia. Signs of HE include impaired cognition, uncontrolled movements and decreased levels of consciousness leading to coma and even death.

"These early data demonstrate that OCR-002 is well tolerated, rapidly normalizes hyperammonemia and has the potential to prevent the development of hepatic encephalopathy," said Dr. Juan Cordoba of Hospital Universitari Vall d'Hebron and the lead investigator of the study. "Cirrhosis patients that present with acute upper gastrointestinal bleeding have a 30% chance of developing hepatic encephalopathy and require intensive care. A medicine that can quickly remove the toxic ammonia may help prevent or reverse this life-threatening condition, minimize the need for intensive care and shorten hospitalization."

The data presented today from the study of Upper GI bleed in patients with liver cirrhosis (n=10) shows that OCR-002 is well tolerated up to 10g/24h and provides a significant, rapid and durable ammonia reduction to normal levels after 36 hours of treatment. All patients tolerated study drug well for 5 days. There were no severe toxicities associated with the treatment and no incidence of HE, with patients doing well at the 30 day follow up. A rapid drop in ammonia from 80.01+/-13.44 uM at baseline to 41.95+/-4.99 uM was observed at 36 hours (ANOVA, p<0.05).

The Phase 2 clinical trial is ongoing and will enroll 48 patients with cirrhosis of the liver. The first part of the trial recently completed was an open-label study to confirm the safety and tolerability of OCR-002 seen in earlier clinical trials. The second phase is a double-blind, placebo-controlled study and will measure as the primary endpoint ammonia plasma concentration and improvement in HE as a secondary endpoint.

OCR-002, developed by Ocera Therapeutics, has received Orphan Drug designation in the U.S. and Europe and has fast track status in the U.S. OCR-002 is also being evaluated as a treatment of acute liver failure in the U.S. It is estimated that there are up to 1 million cirrhotic patients in the U.S., of which 150,000-200,000 patients are hospitalized due to complications of encephalopathy costing the healthcare system over $1.2 billion every year.

About OCR-002Ocera in-licensed OCR-002 (ornithine phenylacetate), an ammonia scavenger designed to rapidly lower systemic hyperammonemia and treat hepatic encephalopathy (HE) in patients with liver cirrhosis and acute liver failure from University College of London. OCR-002, through its novel mechanism of action, directly lowers circulating blood levels of ammonia by enabling alternate metabolic pathways in the muscle and kidney in patients with liver failure and is patent protected until 2031. OCR-002 is being developed as an injectable for hospitalized patients and as an oral formulation to treat HE in patients with chronic liver cirrhosis. Ocera has completed studies in healthy volunteers and cirrhotic patients and phase 2 studies are ongoing. For more information: (OCR-002)

About Hepatic Encephalopathy (HE)HE is an often reversible neuropsychiatric complication observed in patients with acute liver failure or chronic liver cirrhosis in whom the metabolic conversion of ammonia to urea in the liver fails. With severe liver impairment, toxic substances that are normally removed by the liver such as ammonia accumulate in the blood. Elevated ammonia levels can impair the function of brain cells, cause cerebral edema and may elevate intracranial pressure. Signs and symptoms of HE include impaired cognition, confusion and a decreased level of consciousness, which can progress to coma and ultimately death.

SOURCE Ocera Therapeutics, Inc.
Copyright (C) 2012 PR Newswire. All rights reserved

La Jolla Institute discovery could lead to new way to screen drugs for adverse reactions
Researchers identify mechanism key in drug allergy

SAN DIEGO – (May 29, 2012) – Adverse drug reactions are a major issue that cause harm, are costly and restrict treatment options for patients and the development of new drugs. A groundbreaking finding by researchers from the La Jolla Institute for Allergy & Immunology could lead to a new way to dramatically improve drug safety by identifying drugs at risk to cause potentially fatal genetic-linked hypersensitivity reactions before their use in man.

Hypersensitivity reactions are similar to allergic reactions, whereby the immune system responds too strongly to something foreign that is not infectious or dangerous. This response produces symptoms ranging from mild, such as rashes, to severe including anaphylactic shock, organ failure and even death.

La Jolla Institute scientist Bjoern Peters, Ph.D., led the study which illuminated, for the first time, the specific mechanism leading to HLA gene-linked hypersensitivity to the drug abacavir, a finding that will have widespread importance and applicability to the study of drug hypersensitivity in association with other drugs.

HLA is a gene that helps the immune system to identify if the body's own cells have been infected by foreign invaders such as viruses and bacteria. Individuals have many different variations of HLA. In the case of abacavir, a drug used to treat HIV, the majority of people who carry a particular HLA variant, known as HLA-B*57:01, may experience serious, and in some cases, life-threatening hypersensitivity reactions.

"Many drug hypersensitivity reactions are HLA-linked, meaning that they will occur much more often or even exclusively in individuals who have certain variants of the HLA gene," said Dr. Peters, adding that some gene variants appear to be more commonly associated with drug hypersensitivity. "The present system of clinical trials is very powerful in identifying side effects that occur in many people. However, HLA-linked hypersensitivity has been a really big problem that often doesn't surface until after the drug is approved and taken by thousands of people."

To use the example of abacavir, Dr. Peters said there is now a genetic test, which is routinely used to exclude patients carrying the HLA-B*57:01 variant from receiving abacavir and hence preventing the hypersensitivity reaction. However, during the development of abacavir thousands of patients carrying HLA-B*5701 experienced hypersensitive reactions. "We are hopeful that our enhanced mechanistic understanding of HLA-linked hypersensitivities will contribute to the identification of drugs at risk to cause these syndromes before use in man and also to the development of safer drugs," he said.

Dr. Peters and his team have established assays (tests) that can be applied to test drug compounds to determine if a specific HLA variant reaction occurs. "You wouldn't have to wait until after the drug is introduced and thousands of people are potentially affected," he said, explaining the testing could be done in human blood samples. "This type of testing could be done before human subjects are exposed to the drug, and could lead to the design of drug types that do not have this effect, or - if this is not possible - to ensure that only individuals who do not have this HLA variant are given the drug, as is now done for abacavir."

Previous scientific studies have shown a strong linkage between hypersensitivity reactions to several drugs and specific HLA variants. However, the mechanism of action leading to this hypersensitivity was not previously known and so testing for its presence was extremely difficult.

Mitchell Kronenberg, Ph.D., La Jolla Institute president & chief scientific officer, said the finding has the potential to significantly improve the efficiency and safety of the drug development process. "Some drugs are never released because of drug hypersensitivity that turns up in clinical trials," he said. "By using this mechanism for pre-screening, drug makers could identify and work to address the problem before it is tested in human clinical trials. This could enable important therapies to move forward that might otherwise have been scrapped."

The finding is discussed in a paper entitled "Drug hypersensitivity caused by alteration of the MHC‐presented self-peptide repertoire," and was published online today in the scientific journal Proceedings of the National Academy of Sciences.

In conducting the study, Dr. Peters said they used the antiviral drug abacavir because it had previously been shown to cause hypersensitivity reactions in patients expressing the HLA molecular variant B*57:01. "In our study, we asked, 'how does that version of the HLA gene (variant B*57:01) cause those side effects?" he said.

The scientific team found a novel explanation that boils down to a case of mistaken identity. "We found that certain drugs can alter which peptides specific HLA molecules show to the immune system," said Dr. Peters. Peptides are pieces of proteins that make up the body. "Abacavir causes a self-peptide, derived from a human protein, to be shown to the immune system by the HLA variant B*57:01. This peptide would otherwise never be seen by the immune system." Having not previously recognized the peptide, Dr. Peters said the immune system mistakes it for being derived from an invader and launches an attack. This immune attack results in drug hypersensitivity.

Dr. Peters likened the occurrence to the immune system's reaction to an organ transplant. "The immune system perceives the organ as "non-self" and so rejects it. That's why you cannot transplant organs from one person into another unless the individuals have closely related HLA variants. Even then, people who receive transplanted organs have to take anti-rejection drugs, so the immune system doesn't launch an attack."

The study was done in collaboration with an international team which included clinical drug hypersensitivity experts Professors Simon Mallal and Elizabeth Phillips who discovered and championed the use of HLA-B*5701 testing to prevent abacavir hypersensitivity since 2002. They commented, " We are thrilled to see that the connection between HLA-B*5701 and abacavir hypersensitivity has provided us a roadmap for the use of personalized genetic medicine in everyday clinical practice around the world and is now also providing us a roadmap for safer drug development."

Other collaborators on the study include: David A. Ostrov (University of Florida College of Medicine), Barry J. Grant (University of Michigan), Leming Shi (NCTR, FDA), Howard M. Grey and Alessandro Sette (La Jolla Institute for Allergy and Immunology), Donald F. Hunt (University of Virginia) and Soren Buus (University of Copenhagen).

About La Jolla Institute
Founded in 1988, the La Jolla Institute for Allergy & Immunology is a biomedical research nonprofit focused on improving human health through increased understanding of the immune system. Its scientists carry out research seeking new knowledge leading to the prevention of disease through vaccines and the treatment and cure of infectious diseases, cancer, inflammatory and autoimmune diseases such as rheumatoid arthritis, type 1 (juvenile) diabetes, Crohn's disease and asthma. La Jolla Institute's research staff includes more than 150 Ph.D.s and M.D.s. To learn more about the Institute's work, visit

For Your Reading Pleasure

"HCV and the ID physician: A perfect match"

Clinical Infectious Diseases Advance Access published April 4, 2012
Barbara H. McGovern, MD
Associate Professor
Tufts University School of Medicine
Associate Editor, Viral Hepatitis
Clinical Infectious Diseases

About a decade ago, I was attending a major research meeting on liver diseases when I overheard a well-known hepatologist say, "These patients do not respond well and should not be treated"...He was referring to a research poster showing low rates of HCV viral eradication in HIV-infected patients taking standard interferon and ribavirin. His words made me flush with a combination of anger, despair, and frustration. I knew from my own clinic experience that my patients with HIV/HCV coinfection were dying of end-stage liver disease at a frightening rate [1]...Yet, the researcher was pointing out an observation that was painfully correct; HIV/HCV coinfected patients had significantly lower treatment response rates than patients with HCV alone. These discordant rates of virologic cure continued to be apparent, despite the later introduction of the pegylated interferons [2,3]. What followed was more than a decade of fractured care since few physicians felt comfortable taking care of both infections and fewer patients could successfully navigate all the barriers to HCV treatment [4].

But are the obstacles to virologic cure of HCV in the HIV-infected patient as monumental as they once were? Are HIV/HCV patients really somehow "different" in this new era of directly-acting antiviral agents (DAA)?

Although the development of effective HIV therapeutics has spanned about 25 years to date, the HCV therapeutic armamentarium is galloping at lightning speed. Greatly benefiting from the HIV experience, multiple pharmaceutical companies are now developing a stunning array of HCV drugs in the race towards the optimum therapeutic regimen. Within just a few years, it seems certain that we will be able to prescribe an all-oral HCV treatment regimen with drugs of varying classes, without any need for interferon [5]. With the advent of these antiviral agents, it seems certain that we will see comparable HCV cure rates in the HIV-infected host, as in those with HCV alone. We can base this not-so brazen prediction on the success of antiretroviral therapy (ART) for HIV, which has led to viral suppression in the vast majority of patients. Furthermore, pharmaceutical attention to issues of coformulation and once-daily dosing has facilitated excellent drug adherence to ART.

Similar principles are being applied to HCV drug development. The winners in the end will be the patients, since virologic cure is associated with regression of liver disease and a reduced risk of cirrhosis and hepatocellular carcinoma [6]. One can even imagine a bright day in the future when HCV transmission rates will dramatically decline because the human reservoir of infection no longer exists.

In light of fast paced developments in HCV therapy, ID specialists should be asking themselves one question: "Why SHOULDN'T I be treating HCV-infected patients?" As infectious disease doctors, we construct complex antiviral combinations, interpret results of drug resistance testing, devise salvage regimens, manage drug-drug interactions, and monitor patients on maintenance therapy over the course of a lifetime. Application of these same general principles would serve the HCV-infected patient well.

To start, we need to understand the similarities to HIV and where those similarities end. For example, it seems likely that combination antiviral therapy will be needed since resistance-associated variants (RAVs) emerge within days of monotherapy with certain HCV-specific agents (eg, HCV protease inhibitors, NS5A inhibitors) [8]. As seen with HIV therapeutics, some HCV agents have a high genetic barrier to resistance (eg, the nucleoside polymerase inhibitors) while others have a lower barrier (eg, the protease inhibitors) [9,10]. Knowledge of specific mutations is important since resistance to one drug (eg, telaprevir) may lead to cross-resistance to another agent within the same class (eg, boceprevir). One key difference is that while HIV is integrated into the host genome, HCV is found within the cytoplasm; thus, it is unknown if HCV-related drug resistance will be archived or if RAVs will revert to wild-type virus. Although preliminary resistance data suggest that the proportion of RAVs declines over time in the absence of drug pressure [11], the clinical implications are less clear. To date, knowledge of baseline drug resistance mutations does not appear to influence virologic outcomes; thus, baseline drug resistance testing is not recommended for HCV, as it is for HIV. Patient monitoring will be for the duration of HCV treatment, which will be as short as six months, or less, for the venerable cure.

Another major question is more historical in nature..."Why has HCV treatment traditionally been under the jurisdiction of our hepatology colleagues?"

Firstly, the need for a liver biopsy for staging of disease has been a major impediment to the ID community. The rationale for this pre-requisite was driven by the historically low treatment response rates and the substantial toxicities associated with standard interferon/ribavirin therapy. With the emergence of the pegylated interferons and high cure rates for genotype 2 and 3 infected patients, the need for a liver biopsy was questioned by many experts. Now in the era of potent directly-acting antiviral (DAA) agents, we are seeing HCV cure rates of 75 to 85 percent, even in the difficult-to-treat patient with genotype 1 infection [7]. These dramatic therapeutic advances have been coupled with the development of noninvasive fibrosis assays and novel imaging modalities (eg, elastography) [12]. Some opponents to non-invasive monitoring cite the suboptimal performance of these serum markers, as compared to liver biopsy. However, one comparative analysis demonstrated that the true accuracy of non-invasive markers will always remain underappreciated since the gold standard is flawed by its own limitations, such as sampling error [13]. In fact, non-invasive markers perform well when assessing important clinical developments, such as cirrhosis. Thus, the liver biopsy should no longer be a deterrent to greater involvement of the ID community.

The other main reason HCV has remained in the hands of our hepatology colleagues is an obvious one: patients who are not given antiviral therapy, or who fail treatment, are at risk of developing decompensated cirrhosis with its attendant complications, such as esophageal bleeding, ascites, hepatic encephalopathy and hepatocellular carcinoma. Each of these complications needs expert management by a hepatologist who has been thoroughly trained in these complex issues.

Unfortunately, the number of patients developing end-stage liver disease has climbed over the past few decades and HCV remains the leading indication for liver transplantation [14]. However, just as early initiation of HIV infection leads to better immunologic recovery compared to the treatment of late-stage AIDS, early treatment of HCV is preferred since overall efficacy rates are higher and the prevention of cirrhosis is highly desirable from the standpoint of the individual and overburdened healthcare systems worldwide. Furthermore, there are emerging data that suggest that viral eradication of HCV not only reduces liver-related mortality, but overall mortality as well [15]. These data are reminiscent of those that emerged from the HIV structured treatment interruption trials, which clearly demonstrated that the risk of mortality from common co-morbidities (eg, cardiovascular, cancer, liver, kidney) increased in HIV-infected patients who discontinued ART [16]. From a simplistic viewpoint, it appears that having a chronic infection - whether it be HIV or HCV - is unhealthy for the overall host...

But solutions to the overall problem are not simple, as the HCV epidemic is daunting. Worldwide, an estimated 170 million people are infected with HCV, with some endemic areas having seroprevalence rates of 20 percent [17]. There are an estimated five million HCV-infected patients in the United States alone Ð about five times the number of HIV infections nationwide [18]. With the promise of therapeutic cure for the vast majority of patients, there have been calls for increased screening efforts for this "silent killer", since the majority of individuals are unaware of their infection. The Centers for Disease Control in the United States is considering HCV screening based on birth cohort, since persons born from 1945 to 1965 have a higher prevalence of HCV infection than other age groups [19,20]. If these new guidelines are adopted, there will be a new unmet challenge of getting these patients into care. But, hepatologists are already overwhelmed by the number of HCV patients who are seeking evaluation with long waits for clinic appointments. Furthermore, the dazzling array of new drug combinations requires specialists who are at home with complicated antiviral therapies. Thus, the need for more HCV experts is great.

How can we expand the pool of HCV clinicians within the ID community to meet this enormous challenge? Several possibilities can be considered: 1) We need to have centers of excellence where infectious disease practitioners, who are already expert in treating HCV, can serve as role models for ID fellows. These young physicians should be encouraged to learn all aspects of care of the HCV infected patient as a way to improve their career opportunities. Joint fellowships, incorporating the expertise of ID and hepatology mentors, would be mutually beneficial for fellows studying infectious diseases or gastroenterology. 2) A much-needed hepatitis C task force has been created within the Infectious Diseases Society of America (IDSA); its leadership has committed a significant amount of time at the annual IDSA meetings to clinical sessions devoted to HCV evaluation and management. Needed supplements to this avenue of education are one-day conferences/workshops tailored to the need of the ID physician who will quickly understand emerging data on HCV drug resistance and viral kinetics, but will need more guidance in the management of the compensated cirrhotic. 3) Surveys of the IDSA membership should collect data on the barriers to HCV patient care so the perceived gaps can be addressed. 4) HCV treatment guidelines with real-time clinical updates will also be critical to patient care in the years to come.

Although HCV does not command the same media attention as for some emerging infectious diseases, advancing liver disease will be exacting a tremendous toll in morbidity and mortality in the decades to come if wider access to treatment is not realized in the near future. In fact, in 2007, deaths from HCV infection exceeded deaths from HIV in the United States [20]. Millions of HCV-infected patients will be depending on an expeditious response from the ID community, as we have done for many other infections in the past.

In preparation, we will need to improve our overall knowledge of the complications of liver disease and when to suspect underlying cirrhosis. We need to understand the clinical tightrope that these patients walk between compensated and decompensated disease. We must be cognizant of when we require the expert input of our hepatology colleagues who understand the pathophysiology of liver disease, better than the ID specialist can ever hope to achieve. Timely referral to our hepatology colleagues is important for overall patient safety and management. We have learned over the past decades that our HIV infected patients thrive when multi-disciplinary care is rendered. ID physicians can help hepatologists contain the floodgates of cirrhosis and hepatocellular carcinoma in the years to come by curing patients of their viral infection at earlier stages of disease. There will hopefully be a subset of fully engaged ID physicians who will take on this calling. Greater expertise in liver disease, which comes with managing many HCV-infected patients, will likely translate into better treatment outcomes, as has been noted in the past for HIV.

As part of our own contribution to this educational effort, Clinical Infectious Diseases will devote more space than ever before to the timely coverage of new developments in HCV. Within this issue, readers will see a concise synopsis of highlights from the American Association for the Study of Liver Disease (AASLD) Conference by Curtis Cooper, an ID specialist in Canada who is also expert in HCV management. We will be publishing a series of articles and supplements devoted to different aspects of HCV management by ID/HCV specialists and our esteemed hepatology colleagues. Finally, we welcome critical feedback on this HCV initiative from our community of ID specialists...with a special section on reader feedback in order to keep the conversation going. We look forward to your thoughts...

More Updates @ NATAP

What's Up, Doc? When Your Doctor Rushes Like The Road Runner
by Sarah Varney, KQED

To physician Larry Shore of My Health Medical Group in San Francisco, it's no surprise that patients give doctors low marks for time and attention.
"There's some data to suggest that the average patient gets to speak for between 12 and 15 seconds before the physician interrupts them," Shore says. "And that makes you feel like the person is not listening."
A doctor's impatience, though, is often driven more by economics than ego. Reimbursement rates for a primary care visit are notoriously low, and Shore laments the need to hustle patients in and out.
"When you have that pressure to see three, four, maybe five patients an hour, you can't wait for the exposition of the patient's story. Which is exactly what you should do. But you can't," he says.

Continue Reading.........

HCV Abstracts

Gastroenterology. 2012 May 21. [Epub ahead of print]

Factors that Predict Response of Patients with HCV Infection to Boceprevir.

Poordad F, Bronowicki JP, Gordon SC, Zeuzem S, Jacobson IM, Sulkowski MS, Poynard T, Morgan TR, Molony C, Pedicone LD, Sings HL, Burroughs MH, Sniukiene V, Boparai N, Goteti VS, Brass CA, Albrecht JK, Bacon BR; SPRINT-2 and RESPOND-2 Investigators.

Source Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Little is known about factors associated with a sustained virologic response (SVR) among patients with hepatitis C virus (HCV) infection to treatment with protease inhibitors.

Previously untreated patients (from the SPRINT-2 trial) and those that did not respond to prior therapy (from the RESPOND-2 trial) received either a combination of peginterferon and ribavirin for 48 weeks or boceprevir, peginterferon, and ribavirin (triple therapy) after 4 weeks of peginterferon and ribavirin (total treatment duration 28-48 weeks). A good response to interferon was defined as a ≥1 log(10) decrease in HCV RNA at week 4; a poor response was defined as a <1 log(10) decrease. We used multivariate regression analyses to identify baseline factors of the host (including the polymorphism IL -28B rs12979860) associated with response. The polymorphism IL -28B rs8099917 was also assessed.

In the SPRINT-2 trial, factors that predicted a SVR to triple therapy included low viral load (odds ratio [OR]=11.6), IL-28B genotype (rs 12979860 CC vs TT and CT; ORs=2.6 and 2.1), absence of cirrhosis (OR=4.3), HCV subtype 1b (OR=2.0), and non-black race (OR=2.0). In the RESPOND-2 trial, the only factor significantly associated with a SVR was previous relapse, compared with previous non-response (OR=2.6). Most patients with rs12979860 CC who received triple therapy had undetectable levels of HCV RNA by week 8 (76%-89%), and were eligible for shortened therapy. In both studies, IL-28B rs12979860 CC was more strongly associated with a good response to interferon than other baseline factors; however, a ≥1 log(10) decrease in HCV RNA at week 4 was more strongly associated with SVR than IL-28B rs12979860. Combining the rs8099917 and rs12979860 genotypes does not increase the association with SVR.

The CC polymorphism at IL-28B rs12979860 is associated with response to triple therapy and can identify candidates for shorter treatment durations. A ≥1 log(10) decrease in HCV RNA at week 4 of therapy is the strongest predictor of a SVR, regardless of polymorphisms in IL-28B.

Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.


Webinar: Health Experts Provide Update on Current Infectious Disease Threats
* Reuters is not responsible for the content in this press release.

Tue May 29, 2012 11:37am EDT
Webinar: Health Experts Provide Update on Current Infectious Disease Threats
PR Newswire May 29
An expert update and perspectives on infectious disease threats currently in the news and expected to be "hot topics" in the coming year will be presented at the 17th Richard J. Duma/National Foundation for Infectious Diseases (NFID) Annual News Conference Webinar on Infectious Diseases.
  • Updates on prevention and treatment in C. difficle infections
  • New developments in identifying hepatitis C cases
  • Updates on vaccinations for pregnant women
  • Lessons learned from the 2001 measles outbreak

This news conference webinar is sponsored by NFID, a recognized leader in US infectious disease education and awareness efforts.

Dale N. Gerding, MD, Loyola University Chicago
C. difficle Infections: Prevention and Treatment
Eliot Godofsky, MD, University Hepatitis Center

Hepatitis C
Richard Beigi, MD, MS, University of Pittsburgh, Department of Obstetrics, Gynecology and Reproductive Sciences

Vaccination for Pregnant Women
Patricia A. Stinchfield, RN, MS, CPNP, Children's Hospitals and Clinics of Minnesota
Measles 2011: Lessons Learned

Tuesday, June 5, 201211:00 am–12:15 pm Eastern Daylight Time

Online – Webinar

Sharon Cooper-Kerr
phone: 301-656-0003 x14
fax: 301-907-0878
NFID was established in 1973, as a nonprofit, tax-exempt, non-governmental organization dedicated to educating the public and healthcare professionals about the causes, treatment, and prevention of infectious diseases.

/PRNewswire-USNewswire -- May 29, 2012/
SOURCE National Foundation for Infectious Diseases


"The Weekly Report" segment on Hepatitis C 

Published on May 29, 2012 by

Filmed and edited at the City of Kansas City, Mo., Health Department and City Communications Office for the 5/25/12 episode of "The Weekly Report" on City Cable Ch. 2. Speaker is Lisa Mertz, Senior Disease Investigator (incorrectely identified as Lia Mertz in the video). Emcee is Jeff Hershberger. Photogs are Bill Snook and Jeff Hershberger.

Hepatitis B

ACRG and BGI report findings from genomics research on recurrent hepatitis B virus integration


Posted On: May 29, 2012 - 5:00pm

May 29, 2012, Shenzhen, China – The Asian Cancer Research Group (ACRG)—an independent, not-for-profit company established by Eli Lilly and Company, Merck (known as MSD outside the United States and Canada) and Pfizer Inc.—in collaboration with BGI—the world's largest genomics organization—today announced the publication of results from a whole genome-wide study of recurrent hepatitis B virus (HBV) integration in hepatocellular carcinoma (HCC) in Nature Genetics. Results from this first-of-its-kind study provide important insights that may be used to improve diagnosis and treatment of HCC, the most common form of liver cancer worldwide.

"This study provided new insight into mechanisms of HBV integration, which promote liver cancer and affect clinical outcomes," said Dr. Ken Sung, lead author of the publication, National University of Singapore (NUS) and Honorary Associate Professor of Hong Kong University (HKU). "We expect further investigation may lead to improved diagnosis and treatment of HCC."

HBV integration is thought to be one of the major causes of HCC and research has shown that the DNA of HBV could integrate into a host genome in such a manner as to induce chromosomal instability (a defining characteristic of most human cancers) or alter expression and function of endogenous genes. Previous studies of HBV integration into the HCC genome have been limited by technological hurdles and relatively small sample sizes.

In this study, ACRG, BGI and other collaborators carried out whole-genome sequencing in a large sample cohort of Chinese patients with HCC to characterize genome integration patterns and determine the prevalence of integrated HBV. Through the sequencing and analysis, researchers found that HBV integration was a common event in liver tumors and was observed more frequently in tumors (86.4 percent) than in adjacent normal liver tissues (30.7 percent). In addition to the previously reported TERT and MLL4 genes, researchers discovered three novel genes (CCNE1, SENP5 and ROCK1) associated with recurrent HBV integrations, each of which are known to play an important role in cancer development and progression.

"This study is of great interest to the scientific community, which is working toward better understanding HBV integration in HCC," said Hancheng Zheng, Primary Investigator of this project at BGI. "Based on these results, we can better explore the detailed molecular mechanism and clinical impact of HBV integration, promoting the discovery and development of future liver cancer treatments."

Researchers also observed that the number of HBV integration events (recurrences) is positively associated with the tumor size, serum HBsAg and α-fetoprotein level. Patients with no or low numbers (n<3) of detected HBV integrations in their tumor survived longer than those with a high number of HBV integrations (n>3), suggesting that HBV integration events are a negative prognostic indicator in HCC patients.

"A deep understanding of the recurring HBV insertions in HCC will help the research community identify novel molecular targets in liver cancer, for which effective treatments are still limited," said John Luk, Honorary Professor of HKU, Adjunct Professor of NUS and IMCB, Head of Oncology, Roche Shanghai.

The researchers indicated that HBV integrations have some characteristics that may help the virus to control specific genes in the host tumor. They found HBV integration sites are typically found close to or inside of the targeted genes, which may be a mechanism for HBV to control the expression of some oncogenes or tumor suppressor genes. More than 40 percent of the integrations were observed to break the HBV genome at position 1,800 and integrate into the human genome. This may be due to the fact that the HBV enhancer and the HBV ORF replication sites are found at this locus. Moreover, they observed that HBV integrations correlated with increased DNA copy number around HBV integration breakpoints, which provides evidence that HBV integration initializes the chromosomal instability of the HCC genome.

"Molecular characterization of these tumors in a relatively large patient population ultimately provides the basis for more targeted and effective medicines, and will lead to improved outcomes for liver cancer patients," said Christoph Reinhard, Ph.D., Director of the Board of ACRG, and Senior Director, Oncology Translational Science, Eli Lilly and Company. "The ACRG was established to fuel research directed towards improving our understanding of cancers affecting Asian populations. This study underscores that in a short period of time, by working together, we are able to generate important evidence that can be further investigated in the fight against liver cancer."
Source: BGI Shenzhen


First Human Clinical Study of HIV Vaccine Vacc-C5 Approved to Begin

Animal Studies Indicate Vacc-C5 Generates Immune Responses to HIV, Similar to Those in HIV Patients who Naturally Suppress the Virus
-- 05/29/12 -- Bionor Pharma ASA (OSLO: BIONOR)

News Summary

  • Open, clinical study, dose escalating, phase I/II, with Bionor Pharma's second therapeutic HIV vaccine to begin at Oslo University Hospital.

  • Researchers hope Vacc-C5 will prevent hyperactivation of immune system that leads to AIDS, and possibly thereby make patients able to control HIV replication without the need for medication.

  • The study will investigate whether humans develop antibodies to HIV as a result of vaccination with Vacc-C5, and if these antibodies have same properties as antibodies found in "long term non progressors," in other words patients who live with HIV but are able to naturally suppress the virus.
Bionor Pharma ASA (OSLO: BIONOR) announced today that the first study of Bionor Pharma's Vacc-C5 is now approved to begin at Oslo University Hospital. Vacc-C5 is a therapeutic HIV vaccine developed to slow down or stop induction of immune hyperactivation, a feature that drives the production of HIV and is damaging the immune system, leading to AIDS. Vacc-C5 also may have the potential to be a preventive vaccine, alone or in combination with Vacc-4x.

The phase I/II study will use Vacc-C5 at three different dose levels, in order to evaluate safety and provide a determination for the optimal dose of the vaccine, when given intradermally (in the skin) or intramuscularly.

"The pre-clinical studies of Vacc-C5 in rabbits, and sheep, as well as data confirming an association between high antibody levels and slow progression of HIV in humans have generated considerable interest," said Dag Kvale, MD, PhD, Principal Investigator at Oslo University Hospital. "We look forward to see how people living with HIV respond when on Vacc-C5."

The study seeks to recruit 36 patients who have been infected with HIV for at least one year. Study participants must have been stable on antiretroviral therapy (ART, traditional HIV medicine) for at least six months with a viral load of less than 50 copies per milliliter. The primary endpoint of the trial is to evaluate safety of the vaccine at three different dose levels. Secondary endpoints include measuring specific antibody and T-cell responses to Vacc-C5 and to evaluate T-cell activation markers. Vacc-C5 will be given in combination with two different adjuvants, (that enhance the immune response), either GM-CSF (Granulocyte Macrophage Colony Stimulating Factor) or Alhydrogel (an aluminum-based treatment).

How Vacc-C5 is considered to Work, in Comparison to Vacc-4x
Vacc-C5 generates antibodies based on modified, manufactured (synthetic) peptides from the C5 region (of gp 120) at the HIV-virus surface. Data suggest that anti-C5 antibodies may play a crucial role for Natural Viral Suppressors, a group of people who are able to control the HIV infection without the need of HIV medication.

Bionor Pharma has filed a patent application covering Vacc-C5.

The further strategy is to use Vacc-C5 in combination with Vacc-4x since Vacc-4x already has via T-cell (killer cell) responses shown to lower the viral load set point (stabilized virus level) by statistically significant levels compared to placebo.

"Where Vacc-4x appears to kill virus-producing cells, Vacc-C5 has the potential to reduce the damaging immune activation," said Birger Sørensen, EVP Head of Vaccines. "Looking ahead, we're very excited to study the two vaccines in combination, pending that safety and dosing are confirmed in this trial."

Bionor plans on studying the two treatments Vacc-4x and Vacc-C5 in combination.

Objectives and indications
Vacc-C5 has potential both as part of a preventive vaccine, and as a therapy, by preventing or reversing immune collapse in chronically infected patients.

Researchers believe the antibodies induced by Vacc-C5 can be beneficial at all stages of HIV infection by slowing down or halting the disease progression, and by significantly reducing the production of virus.

Theoretically, Vacc-C5 could be used at any point in patient treatment, forming a part (together with Vacc-4x) of both therapeutic and preventive therapy:

1. Treatment of existing patients at risk of immune collapse

  • Newly infected patients
  • Patients developing treatment-resistant HIV strains
  • Patients intolerant of existing therapies

2. As a preventative vaccine for high risk populations

Early Research Provides Clue to New Strategy for HIV ManagementBionor Pharma started its research on Vacc-C5 by testing blood samples from HIV-infected patients. These demonstrated significant antibody reactivity to Vacc-C5 in blood from Natural Viral Suppressors.

The study was performed in collaboration with Professor Robert Redfield at the University of Maryland, Baltimore, USA, using ELISA tests on blood samples from a total of 57 HIV-infected patients, of which 43 were HIV natural viral suppressors with very low viral load. Reactivity to Vacc-C5 was significantly greater in these patients compared to patients with medium/high viral load. The study showed statistically significant difference in reactivity towards Vacc-C5 between the two groups (p=0,018).

This study confirms that antigens identified previously by the Company are directly associated with the antibodies of Natural Viral Suppressors. The immunogenicity of Vacc-C5 has recently also been confirmed in animal studies.

These studies received partial funding from the Research Council of Norway.

About Bionor Pharma ASA
Bionor Pharma is a leading vaccine company, listed at Oslo Stock Exchange. The Company's investments in developing therapeutic vaccines exceed US$70 million. Bionor's vaccines are based on the proprietary technology platform developed following more than two decades of research on peptides. The vaccines are designed to safely activate each person's immune system to combat viral diseases.

HIV/AIDSGlobal leader in developing HIV vaccine:
The Company's lead investigational product, the therapeutic HIV vaccine Vacc-4x, has in a completed phase IIb multinational (USA, Germany, UK, Spain and Italy), placebo controlled, double-blind study, shown a statistically significant reduction in viral load.

Step towards long lasting HIV viral control with Vacc-4x:
Conventional HIV medication (antiretroviral therapy, ART) is not a cure, but blocks virus production only while patients take this medication. ART must therefore be a lifelong treatment. In contrast, Bionor Pharma's therapeutic vaccine aims to induce long lasting virus control by training immune cells to seek out and kill virus-producing cells. The observed 64% CTL induced reduction (reduction by killer cells) in viral load set point in patients who received Vacc-4x compared to placebo in the phase IIb study therefore represents a step towards long-lasting viral control. Because most patients who are given ART are known to stop taking it for various reasons (high costs, limited access, development of resistance, and serious adverse events), Bionor believes Vacc-4x could be a vital treatment option that can stabilize patients if they stop taking ART. HIV vaccine inducing antibodies: Bionor`s second therapeutic HIV vaccine, Vacc-C5 is developed to induce antibodies to HIV that can reduce viral production (lowering the set point) and the harmful hyperactivation of the immune system that leads to AIDS. Subsequent to the Vacc-C5 phase I/II trial, Bionor intends to combine Vacc-4x with Vacc-C5, which could form the basis for both a therapeutic and a preventative vaccine.

Global HIV challenge:
According to the UN organization UNAIDS, 34 million people were living with HIV in 2010. Approximately three million new people are infected annually. Only one out of six HIV-infected patients currently has access to ART treatment. According to recent CDC studies, less than 25 percent of people prescribed conventional HIV medicine stay on the treatment.

Pharmaceutical sales to treat HIV are US$ 10.6 billion (NOK 63 billion) annually, and treatment cost per patient is approx. US$ 15,000 (NOK 90,000) per year.

Pathways to market for Bionor Pharma's HIV vaccines

Bionor researchers will investigate various independent pathways to market for the HIV vaccine candidates Vacc-4x and Vacc-C5, through further clinical studies starting this year:

1. Vacc-4x revaccination in patients who participated in the phase IIb study, with the aim of reducing viral load even further by killing of virus producing cells.

2. Vacc-4x combined with Revlimid® (lenalidomide), in patients with a weakened immune system which does not recover despite being seemingly well controlled on ART.

3. Vacc-C5 clinical trial phase I/II, to document whether Vacc-C5 increases HIV antibodies in humans. The company aims to subsequently study Vacc-C5 in combination with Vacc-4x, a treatment that potentially can eradicate and prevent HIV and thereby revolutionize HIV treatment.

Nasal administration of Vacc-4x:
A placebo controlled study with Vacc-4x at Oslo University Hospital demonstrated safety and successful immunization in treated patients by nasally delivered vaccine. This option may offer easier treatment access for HIV patients globally. Further analyses are ongoing, and will be published at a later stage.

The Company's innovative technology platform is also well suited to develop vaccines for other viral diseases, such as Influenza, HCV (Hepatitis C), HPV (Human Papilloma Virus) and CMV (Cytomegalovirus).

Vacc-Flu (Universal Influenza vaccine) and Vacc-HCV (Hepatitis C vaccine) are in preclinical phase of development.

More information about Bionor Pharma, its research and products, is available at

This information is subject of the disclosure requirements acc. to §5-12 vphl
(Norwegian Securities Trading Act). Vacc-C5 and Vacc-4x are investigational treatments that have not been approved for marketing by any regulatory authority.

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Bionor Pharma ASA, Oslo: +47 23 01 09 60
Bionor Pharma laboratories: +47 35 90 85 00
Steen Krøyer
Birger Sørensen
EVP, Head of Vaccines
Vidar Wendel-Hansen

USA Contact:
David Sheon
202 422-6999
Email Contact

May 29, 2012
Study updates risks of HRT in postmenopausal women
Last Updated:May 29, 2012

Study findings published in the Annals of Internal Medicine suggest that while oestrogen-only and oestrogen-plus-progestin formulations of hormone replacement therapy (HRT) reduce the risk of fractures in postmenopausal women, both increase the odds for stroke and other conditions. In addition, findings suggest oestrogen-plus-progestin therapy raises the risk of breast cancer and probable dementia, while oestrogen alone reduces the risk of breast cancer.

The findings come from an update of available evidence compiled for the US Preventive Services Task Force, which the group will use to revise existing HRT guidelines. Heidi Nelson, who led the work, noted that the researchers "looked at all the published studies on hormone therapy for the prevention of chronic disease," including nine trials, with the majority of data coming from the Women's Health Initiative (WHI) study. She noted that in the latest analysis, which included around 11 years of follow-up to the WHI study, some protective effects found in earlier research now appear weaker, while some risks look even stronger.

The new results confirmed that both oestrogen alone and combination therapy reduce the risk of fractures, as previously shown, but both types of HRT increase the risk of stroke, thromboembolic events, gallbladder disease and urinary incontinence. Further, while oestrogen alone seems to reduce the risk of breast cancer, Nelson noted that for every 10 000 women, eight more cases of breast cancer per year are expected in those on combination therapy. Women who smoke, used oral contraceptives, or took HRT to control menopausal symptoms experienced higher risk of developing the disease.

Previous HRT data also indicated that those who took combination therapy had a significant increased risk for heart disease, although the new data suggest the association is weaker. Furthermore, oestrogen-progestin combination was also thought to protect against colon cancer, according to earlier findings, but Nelson said this link also now looks weaker.

The Preventive Services Task Force said its decision to recommend against HRT for the prevention of chronic diseases was based on "at least fair" evidence that the harm outweighed the benefits, or that its use was ineffective. According to Nelson, the differences in risks and benefits between oestrogen-only HRT and combination treatment are probably explained more by the risk profiles of the women who take each therapy rather than whether progestin is included in the regimen or not. She added that although it may not be advisable to take HRT to prevent chronic conditions, the best strategy remains to take the therapy, if needed for symptoms, at the lowest dose for the shortest time possible.

Initial results of the WHI study released in 2002 linked oestrogen-plus-progestin HRT to higher rates of invasive breast cancer, while two years later concerns were also raised about oestrogen-only therapy, prompting the Preventive Services Task Force to recommend against both types of treatment for the prevention of chronic disease.

Menopausal Hormone Therapy for the Primary Prevention of Chronic Conditions: A Systematic Review to Update the U.S. Preventive Services Task Force Recommendations
- (Annals of Internal Medicine)

Great Benefit to Simply Eating More Fruits and Vegetables and Reducing Inactivity

Source- Insider Medicine

From Chicago -Simple lifestyle changes can greatly improve healthy behaviour, according to a report published in the Archives of Internal Medicine. Researchers randomized over 200 adults with unhealthy habits to either increase fruits and vegetables and physical activity, decrease fat and inactive leisure, decrease fat and increase physical activity or increase fruits and vegetables and decreases inactive leisure. They found that all participants improved their fruit and vegetable consumption and activity levels and successfully maintained these improvements through the course of the study

Off The Cuff

Princess Royal opens Scottish Centre for Regenerative Medicine

A £54m cutting-edge stem cell research centre in Edinburgh has been officially opened by the Princess Royal.

The Royal opened the Scottish Centre for Regenerative Medicine as well as the £24m bio-incubator facility, Nine, in the Edinburgh BioQuarter.

Research into conditions such as multiple sclerosis and heart and liver disease will benefit from the new facilities in Little France.

The Princess Royal unveiled plaques at the centres.

Scottish Centre for Regenerative MedicineEdinburgh University's Scottish Centre for Regenerative Medicine is the first large-scale, purpose-built facility of its kind and provides accommodation for up to 250 stem cell scientists.
The Scottish Centre for Regenerative Medicine is at Little France in Edinburgh

The centre, funded by Edinburgh University, Scottish Enterprise, the Medical Research Council (MRC) and the British Heart Foundation through its Mending Broken Hearts Appeal, is being opened by the Princess Royal in her role as Chancellor of Edinburgh University.

It includes the most up-to-date facilities in the UK, which meet the highest guidelines, to manufacture stem cell lines that could be used for patient therapies.

Nine, which has been jointly funded by Scottish Enterprise and the UK government's department for business, innovation and skills, has 85,000 sq ft of laboratory and office space for both established biotechnology companies and start-up ventures.

The Edinburgh BioQuarter is in the city's Little France area and includes the Royal Infirmary of Edinburgh and Edinburgh University's Queen's Medical Research Institute and Chancellor's Building.

Professor Charles French-Constant, Scottish Centre for Regenerative Medicine's director, said: "Recent research into stem cells has heralded the beginning of a revolution in modern medicine.

"The Scottish Centre for Regenerative Medicine's great strength lies in bringing world-class clinicians and scientists to work together, encouraging the translation of laboratory discoveries into treatments for patients.

"The research will help in finding treatments for devastating conditions, for which there are currently no cures."