Saturday, November 19, 2011

HCV News Ticker: Boehringer- BI 201335 and BI 207127 have the potential to replace Interferon in HCV Treatment

Liver Cancer & the Death of Joe Frazier

Uploaded by on Nov 13, 2011

Organ transplant provides new lease onlife
SUMMERFIELD – Every day for a year and a half, Paul Green of Summerfield, his wife Liz and their three grown children patiently waited for “the call” that would ultimately save his life.On Oct. 20, it finally came. Green, 61, now has a new liver and the hope of seeing his grandkids one day as a result of what Liz, his wife of 29 years, calls “the incredible gift” – organ donation.

Green contracted hepatitis C from tainted blood while working as an emergency room nurse in the early 1980s; several attempts were made to treat the disease, but his condition only worsened over the years. In 2010, he was diagnosed with cirrhosis and liver cancer, both common progressions of hepatitis C.
Read More Here

Can simple blood tests predict liver cancer?
Today in high-income countries such as Canada, hepatitis C virus (HCV) is most commonly spread by sharing unsterilized equipment for substance use. However, HCV (and HIV and other germs) can also be transmitted by exposure to unsterilized equipment used for tattooing or body piercing. Cases of sexually transmitted HCV have also been reported where blood-to-blood contact occurs, particularly among men who have sex with men. In previous decades HCV was also transmitted through contaminated blood or blood products such as clotting factors. Today the blood supply in high-income countries is considerably safer.
HCV infects the liver, and as the immune system fights this virus, inflammation occurs. After acute infection, HCV becomes embedded in the liver and chronic infection results. Over time, the interaction between the immune system and HCV results in ongoing inflammation, and so liver cells become less functional and die. Dead cells are replaced with scar tissue in a process known as fibrosis. Over years, as fibrosis spreads, the liver becomes increasingly dysfunctional and a range of complications occurs. If left untreated, HCV infection can lead to liver failure. The ongoing inflammation caused by chronic HCV infection can incite liver cells to develop abnormally and, in some cases, become cancers. In people co-infected with HIV and HCV, HIV infection appears to speed up the degradation of the liver caused by HCV. Co-infected people are also at risk for liver cancer. Spontaneous recovery from HCV infection is uncommon in people co-infected with HIV, as their immune systems are weakened..Read More Here

American Association for the Study of Liver Diseases Liver Meeting (AASLD 2011).

From Medscape Medical News
Two New Drugs Poised to Replace Interferon in HCV Treatment

November 18, 2011 (San Francisco, California) — Two new compounds — a protease inhibitor and a polymerase inhibitor — have the potential to replace pegylated interferon in standard treatment regimens for hepatitis C virus (HCV), according to late-breaking data reported here at The Liver Meeting 2011: American Association for the Study of Liver Diseases (AASLD) 62nd Annual Meeting.
In an interim analysis of the open-label phase 2b SOUND-C2 study, investigators looked at the novel protease inhibitor BI 201335 (BI35, Boehringer Ingelheim) and the novel polymerase inhibitor BI 207127 (BI27, Boehringer Ingelheim).
The analysis involved 362 treatment-naïve patients with HCV genotype 1. In the cohort, 52% were male, 98% were white, 85% had an HCV RNA viral load of at least 800,000 IU/mL at baseline, 39% had HCV genotype 1a, 10% showed evidence of compensated cirrhosis, and 26% carried the interleukin (IL)28B polymorphism C/C genotype.
The 5 treatment groups, which all received BI35 120 mg once daily, were:
BI27 600 mg 3 times a day plus ribavirin for 16 weeks, for 28 weeks, or for 40 weeks (thrice-daily groups)
BI27 600 mg twice daily plus ribavirin for 28 weeks (twice-daily group)
BI27 600 mg 3 times daily without ribavirin for 28 weeks (no-ribavirin group).
"Having 2 investigational compounds in 1 trial is a bit unusual," noted Federico Mensa, MD, from the division of clinical research in virology at Boehringer Ingelheim Pharmaceuticals in Ridgefield, Connecticut.
"The idea is to take interferon out of the regimen equation. That treatment is associated with so many adverse events that many patients don't even want to start treatment," Dr. Mensa noted. It's thought that the combination of 2 of the so-called direct-acting antiviral agents will also prevent the emergence of resistance prior to sustained virologic response, he added.
The interim analysis was performed after all patients completed 12 weeks of treatment. Data for the 238 patients in the 16-week and 28-week thrice-daily groups were combined, since those patients received the same treatment for the first 12 weeks.
Results at week 4 show that response to antiviral treatment (HCV RNA viral load below the lower limit of quantification) ranged from 88% for the thrice-daily groups to 72% for the no-ribavirin group.
At week 12, responses ranged from 76% for the twice-daily group to 57% for the no-ribavirin group.
At weeks 4 and 8, virologic failure occurred in 3.4%, 1.3%, and 4.3% of patients in the thrice-daily, twice-daily, and no-ribavirin groups, respectively.
Virologic breakthrough at 12 weeks occurred in 13.4%, 20.5%, and 32.6% of patients in the twice-daily, thrice-daily, and no-ribavirin groups, respectively.
Patients infected with HCV genotype 1a had a lower response rate than others in the study, particularly those in the no-ribavirin group. The lowest rate of response was for IL28B non-C/C patients in the no-ribavirin group (22%); it was 100% in patients with the C/C genotype in the no-ribavirin group. Excellent response was seen in genotype 1b patients, regardless of IL28B status.
"Viral response rates at 12 weeks of up to 76% were comparable to complete early virologic responses achieved with first-generation protease inhibitors plus pegylated interferon," said Dr. Mensa.
How do low response rates observed for patients with HCV genotype 1a, IL28B non-C/C stack up? "This is an important question. Right now my understanding is that we have not seen that data published — the response rates for genotype 1a patients with the unfavorable C/C IL28b variant are not available, to my knowledge, for boceprevir or telaprivir. So it is hard to make a comparison," said Dr. Mensa.
There were some early discontinuations recorded for reasons other than virologic failure, including adverse events and patients lost to follow-up — 17% in the thrice-daily groups, 6% in the twice-daily group, and 13% in the no-ribavirin group. The most common adverse events were mild to moderate gastrointestinal or skin events.
Discussions are ongoing regarding the treatment protocol for a planned phase 3 study using these agents.
What Took So Long?
"Clearly, the protease inhibitors have shot ahead of the nonnukes [polymerase inhibitors], especially because the structural chemistry was understood earlier," said David R. Nelson, MD, associate dean for clinical research in the division of gastroenterology, hepatology, and nutrition at the University of Florida College of Medicine in Gainesville. "Protease inhibitors have also been much more potent than the typical nonnukes. There were some in development prior to protease inhibitors, but the potency of these drugs early on is what limited clinical trial results."
Dr. Nelson is the lead investigator of the ZENITH trial, in which the polymerase inhibitor VX-222 (Vertex Pharmaceuticals) is being combined with the recently approved protease inhibitor telaprevir in a population of treatment-naïve patients infected with HCV genotype 1.
The ZENITH trial is looking at the efficacy and tolerability of VX-222, telaprevir, and ribavirin with and without pegylated interferon. Response rates for the pegylated-interferon-free group will be reported at the 2012 meeting of the European Association of the Study of the Liver.
Dr. Mensa reports being an employee of Boehringer Ingelheim. Dr. Nelson reports being a consultant for Bayer HealthCare, Biolex, and Roche; and receiving grants and research support from Abbott, Anadys Pharmaceuticals, Bayer HealthCare, BMS, Gilead Sciences, Human Genome Sciences, Merck, Novartis, Roche, and Vertex Pharmaceuticals.
The Liver Meeting 2011: American Association for the Study of Liver Diseases (AASLD) 62nd Annual Meeting. Late-breaking abstract 15, presented November 7, 2011. Abstract 14, presented November 9, 2011.

Related-VIDEO-Hepatitis C : Protease Inhibitor BI 201335, Polymerase Inhibitor BI 207127 and Ribavirin
Dr. Stefan Zeuzem discusses his manuscript "Efficacy of the Protease Inhibitor BI 201335, Polymerase Inhibitor BI 207127, and Ribavirin in Patients With Chronic HCV Infection."

Updates @ NATAP

AASLD: ITPA Deficiency is Associated with Lower Rates of Anemia and EPO use in Patients Treated with Boceprevir (BOC) plus Peginterferon/Ribavirin (PR) - (11/20/11)

AASLD: Telaprevir at AASLD - (11/20/11)

AASLD: ITPA Deficiency is Associated with Lower Rates of Anemia and EPO use in Patients Treated with Boceprevir (BOC) plus Peginterferon/Ribavirin (PR) - (11/20/11)

Updates @ HIV and Hepatitis C

AASLD: TMC435 + Interferon/Ribavirin Raises Cure Rates for Naive and Experienced Hepatitis C Patients
Adding the HCV NS3/4A protease inhibitor TMC435 to standard pegylated interferon/ribavirin therapy led to high rates of sustained virological response for both treatment-naive hepatitis C patients and prior non-responders, according to data released last week at the American Association for the Study of Liver Diseases Liver Meeting (AASLD 2011).


Diabetic neuropathy—the agony of da feet
Posted November 14, 2011, 4:33 pm
P.J. Skerrett, Editor, Harvard Health Publications

More than half of people who live with diabetes eventually develop diabetic neuropathy, or damage to nerves. It can range from merely aggravating to disabling or even life threatening. The first nerves to be affected tend to those in the toes and feet. Diabetic neuropathy can be felt as a tingling in the toes and feet, a constant burning feeling in the feet, sharp pain that may be worse at night, or extreme sensitivity to touch. In some people, it robs the feet of their ability to sense pain. So far, there isn’t a cure for diabetic neuropathy. Controlling blood sugar is the most important step to preventing or managing it. Controlling blood pressure, not smoking, and staying active also help. People with diabetes should have a doctor examine their feet at least once a year, and should check their feet every day or so.
Read more »

MU Researchers Develop Tool that Saves Time, Eliminates Mistakes in Diabetes Care
Nov. 17, 2011
Story Contact(s):Samantha Craven,, (573) 882-9144
COLUMBIA, Mo. – In the fast-paced world of health care, doctors are often pressed for time during patient visits. Researchers at the University of Missouri developed a tool that allows doctors to view electronic information about patients’ health conditions related to diabetes on a single computer screen. A new study shows that this tool, the diabetes dashboard, saves time, improves accuracy and enhances patient care.
The diabetes dashboard provides information about patients’ vital signs, health conditions, current medications, and laboratory tests that may need to be performed. The study showed that physicians who used the dashboard were able to correctly identify data they were searching for 100 percent of the time, compared with 94 percent using traditional electronic medical records. Further, the number of mouse clicks needed to find the information was reduced from 60 to three when using the diabetes dashboard.
Richelle Koopman, associate professor of family and community medicine in the School of Medicine, says diabetes care is complex because there are so many other health conditions associated with the disease; thus coordination of treatments is required. The goal of the diabetes dashboard is to make it easier for doctors to make the right decision about treatments.
“The diabetes dashboard is so intuitive that it makes it hard for physicians not to do the right thing,” Koopman said. “Doctors can see, at a glance, everything that might affect their decision. This frees up their minds and helps them make better decisions about patients’ care.”
According to Koopman, the research has important implications for patient safety and costs. For example, the dashboard shows doctors a list of tests that are standard for diabetes patients and indicates whether patients have recently had the tests or need to have them. This eliminates the potential for physicians to order costly tests that are not necessary.
“It is difficult to quantify how much money the dashboard saves, but in terms of time and accuracy, the savings are substantial,” Koopman said. “Doctors are still going to spend 15 minutes with each patient, but instead of using a large portion of that time to search through charts for information, they can have interactive conversations with patients about lifestyle and diet changes that are important for diabetes care.”
The researchers say the dashboard was well received by doctors who tested it because it was designed by physicians familiar with their needs. The study, published in Annals of Family Medicine, was a collaboration among the MU School of Medicine, The Informatics Institute, the School of Information Science and Learning Technologies in the College of Education, the Center for Health Care Quality and the Sinclair School of Nursing.

The American Journal of Gastroenterology , (15 November 2011) doi:10.1038/ajg.2011.384
Risk of Hepatocellular Carcinoma in Diabetic Patients and Risk Reduction Associated With Anti-Diabetic Therapy: A Population-Based Cohort Study
Shih-Wei Lai, Pei-Chun Chen, Kuan-Fu Liao, Chih-Hsin Muo, Cheng-Chieh Lin and Fung-Chang Sung
Using population-based representative insurance claims data, the risk of developing hepatocellular carcinoma (HCC) among diabetes mellitus (DM) patients, as well as whether DM medications alter the risk of developing HCC were investigated.
From the Taiwan National Health Insurance Research Database, 19,349 newly diagnosed DM patients 20 years and older and 77,396 comparison subjects without DM were identified from claims from 2000 to 2005. The incidences of HCC at the end of 2008 and the risks associated with hepatitis B and hepatitis C were determined. Whether metformin and thiazolidinediones reduce the risk of developing HCC was also measured.
The incidence of HCC was twice higher in the DM group compared with the non-DM group (21.0 vs. 10.4 per 10,000 person-years), with an adjusted hazard ratio (HR) of 1.73 (95% confidence interval (CI)=1.47–2.03) using multivariable Cox proportional hazard regression. Male sex, cirrhosis, hepatitis B, and hepatitis C were significant independent factors that predict HCC, with HRs of 2.32, 8.65, 2.52, and 5.61, respectively. In the stratified analysis, the HR increased to 72.4 (95% CI=42.9–122) among patients with DM, cirrhosis, and hepatitis C. HCC risk reduction was greater for diabetics taking metformin than those taking thiazolidinediones (51 vs. 44% reduction).
Comorbidity with cirrhosis and/or hepatitis appears to be associated with an extremely increased risk of developing HCC among DM patients. These high-risk patients should be closely monitored for HCC. The use of metformin or thiazolidinediones may reduce the risk of developing HCC.

Big Pharma

Achillion in Talks With Potential Buyers or Partners, Chief Executive Says

By Meg Tirrell -
Nov 18, 2011 4:15 PM ET

Achillion Pharmaceuticals Inc. (ACHN), expecting clinical data on three experimental hepatitis C therapies, is in “advanced discussions” with potential partners and acquirers, Chief Executive Officer Michael Kishbauch said. The shares jumped 8.2 percent.
If the results, due about year’s end, are positive, “we become a probable ‘transactable’ company,” Kishbauch said yesterday in an interview at the Achillion’s headquarters in New Haven, Connecticut. “We’re prepared to be patient and pick the best deal.”
Licensing deals, asset sales or selling the entire company are all possibilities, Kishbauch said. Achillion doesn’t have any products on the market. The board’s preference would be for “simplicity,” he said, referring to a full sale.
“The nature of discussions suggests that’s most likely,” he said. The question is timing, as Achillion plans to have data on a combination of hepatitis C therapies by the middle of 2013. “Theoretically the value of the company is increasing” as those results approach, he said.
Achillion rose 44 cents to $5.84 at the close of trading in New York, for the biggest gain since Oct. 27. The shares have gained 41 percent this year.
The company had a market value earlier today of about $370 million, and could command double that in a sale, said Y. Katherine Xu, an analyst with William Blair & Co. in New York.
Awaiting Data
Data on the three experimental medicines would provide a “definitive point for people who want to take a look at the assets,” Xu said in a telephone interview today. Potential suitors may include GlaxoSmithKline Plc (GSK) and Novartis AG (NOVN), drugmakers that have interest in hepatitis C, with programs too early in development to be competitive, Xu said.
“They’re kind of losing the game and they have to do something,” Xu said. Achillion’s medicines “could be competitive. We just don’t know the data yet.”
“We don’t comment on rumors and speculation,” Eric Althoff, a spokesman for Basel, Switzerland-based Novartis, said by phone today. David Daley, a spokesman for Glaxo in London, couldn’t immediately be reached for comment.
To contact the reporter on this story: Meg Tirrell in New York at
To contact the editor responsible for this story: Reg Gale at

Hall Of Shame

Conn. doctor gets 5 years in insider trading case
LARRY NEUMEISTER , Associated Press

NEW YORK (AP) — A Harvard-trained physician was sentenced Friday to five years in prison for evading $30 million in investment losses by obtaining inside information from a fellow doctor.
Joseph "Chip" Skowron III apologized to his wife and friends in a packed Manhattan courtroom before U.S. District Judge Denise Cote announced the sentence.
Turning around to look at his wife in the first row of spectators, Skowron said she was the most harmed by his insider trading venture, which helped him avoid millions of dollars in losses.
"I am not what she expected when she married a young doctor 15 years ago," he said.
The 42-year-old Greenwich, Conn., resident pleaded guilty in August to conspiring to commit securities fraud and obstructing justice.
He called the last year "devastating" and "incredible" with glimpses of the best parts of humanity emerging from the most unexpected of circumstances.
"I was not aware of the changes that were happening in me that blurred the line between right and wrong," he said. "I allowed myself to slip into the world of relativism where the ends justified the means."
Skowron admitted gaining an advantage in his work as a hedge fund analyst in 2007 and 2008 by using tips gained through meetings and conversations with a French doctor who knew inside information about clinical drug trials.
Skowron was charged after the French doctor, Yves Benhamou, pleaded guilty to conspiracy to commit securities fraud and other charges in a cooperation deal with prosecutors. Benhamou was widely known in Europe and the United States as an expert in the treatment of hepatitis C.
"Chip Skowron's medical training and expertise, along with his knowledge of the health care industry, undoubtedly gave him a legitimate trading edge," U.S. Attorney Preet Bharara said. "But that wasn't enough. He still took a corrupt path to protect his hedge fund and himself from sustaining a multimillion-dollar loss, and then corruptly tried to obstruct the government's investigation."
As part of his plea deal, Skowron has agreed to forfeit $5 million to the United States. The judge also ordered him to pay restitution of $5.96 million.
The probe began after the Securities and Exchange Commission spotted trading irregularities in the stock of a liver disease drugmaker.
It then learned of the relationship between Skowron and Benhamou, who worked as a consultant to Human Genome Science Inc., a biopharmaceutical company, on clinical drug trials evaluating the safety of the drug Albuferon for the treatment of chronic hepatitis C. Albuferon is the commercial name for a drug the company developed and planned to market with Novartis AG, a Switzerland-based pharmaceutical company.
After meeting in April 2006 at a Vienna conference staged by the European Association for the Study of the Liver, the pair met face-to-face again in Boston, Barcelona, Manhattan and Milan.
Authorities said Skowron in 2006 and 2007 gave Benhamou an envelope with 5,000 Euros in his Barcelona hotel suite, paid the $4,600 hotel bill when Benhamou and his wife visited Manhattan, offered Benhamou future employment with a biotechnology hedge fund he planned to start and gave Benhamou free investment advice.
In December 2007, Benhamou began tipping Skowron about serious adverse effects that occurred with two patients involved in the Albuferon clinical trial, authorities said. One of the patients later died.
The FBI has said Skowron was tipped again a month later that part of the clinical trial was going to be discontinued. According to court papers, Skowron was able to sell all his hedge fund's shares before the stock of Human Genome Science dropped 44 percent following the public announcement.
The FBI also said Skowron gave Benhamou $10,000 in cash in April 2008 in a hotel bar in Milan, Italy, and told him to continue to tell securities regulators who were investigating suspicious trades that the two had only discussed publicly available information.
Benhamou, who pleaded guilty in April, is scheduled to be sentenced Dec. 8.
Skowron studied at Vanderbilt University before he obtained his medical degree in 1998 from Yale University. He also earned a doctorate in cell biology from Yale before beginning his residency at Harvard University.
He was on the board of directors of the disaster relief agency AmeriCares Foundation, where his volunteer work took him to Kosovo, Cuba, India and Baton Rouge, La., after Hurricane Katrina.

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