Friday, August 31, 2012

Exeter Hospital: Turning over records to state could violate patient privacy

August 31, 2012 | By Karen Cheung-Larivee

The New Hampshire Division of Public Health Services (DPHS) ordered Exeter Hospital to release patient records as part of an ongoing investigation of the hepatitis C outbreak, thought to have originated at the community hospital, but is it legal?
Exeter Hospital said it is seeking legal guidance on whether turning over private patient information to the state violates privacy laws.
So far, 32 people, including patients and a hospital employee, have been affected by David Kwiatkowski, the traveling lab technician accused of spreading hepatitis C across the nation by diverting Fentanyl and leaving contaminated needles for other patients to use.
Although Exeter Hospital said it supports the public health department's efforts "to identify all victims of David Kwiatkowski's alleged criminal activity," the state's request for "broad access" of the hospital's medical record systems may violate federal and state laws..........

Continue Reading.....

Early treatment could clear Hepatitis C

The article "Early treatment could clear Hepatitis C" is available for viewing at Nature, although free registration is required.
 click here to begin

The full text is however available at PloS ONE

Article At Nature

Early treatment could clear Hepatitis C

Using mathematical models to understand the behavior of the deadly hepatitis C virus, Indian scientists have shown that the microbe's sensitivity towards drugs varies in various phases of the disease1. They say early treatment could actually clear the virus entirely from the system for a sustained period.

"There are multiple phases when the sensitivity of the infection to drug treatment varies. We found that early treatment of the infection is likely to result in sustained virological response," says Raghvendra Singh, an assistant professor in the Department of Chemical Engineering at the Indian Institute of Technology Kanpur....

Continue Reading At Nature After Logging In Or Registering

Full Text At PloS One

The study was published on July 24, 2012

Analysis of the Virus Dynamics Model Reveals That Early Treatment of HCV Infection May Lead to the Sustained Virological Response

Saurabh Gupta, Raghvendra Singh*
Department of Chemical Engineering, Indian Institute of Technology Kanpur, Kanpur, India

Considerable progress has been made towards understanding hepatitis C virus, its pathogenesis and the effect of the drug therapy on the viral load, yet around 50% of patients do not achieve the sustained virological response (SVR) by the standard treatment. Although several personalized factors such as patients’ age and weight may be important, by mathematical modeling we show that the time of the start of the therapy is a significant factor in determining the outcome. Toward this end, we first performed sensitivity analysis on the standard virus dynamics model. The analysis revealed four phases when the sensitivity of the infection to drug treatment differs. Further, we added a perturbation term in the model to simulate the drug treatment period and predict the outcome when the therapy is carried out during each of the four phases. The study shows that while the infection may be difficult to treat in the late phases, the therapy is likely to result in SVR if it is carried out in the first or second phase. Thus, development of newer and more sensitive screening methods is needed for the early detection of the infection. Moreover, the analysis predicts that the drug that blocks new infections is more effective than the drug that blocks the virus production.

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PodMed: Hepatitis C screening

PodMed: A Medical News Roundup from Johns Hopkins

By Rick Lange, MD, and Elizabeth Tracey
Johns Hopkins Medicine Published: August 31, 2012

Dr. Paul Sax seeks answers to three questions about the future of hepatitis C virus treatment

Paul Sax • August 25th, 2012 Categories: Infectious Diseases, Patient Care, Research
Source -

On HCV, These Questions Three

Dr. Paul Sax seeks answers to three questions about the future of hepatitis C virus treatment:
1-What does the bad news on BMS-986094 mean for other investigational HCV nucleotides?
2-When can we abandon the "alphabet soup" of terms used to describe treatment response?
3-When will new drugs become available? 
In the fastest-moving area of ID drug development, answers are eagerly sought to the following questions three:

1 - What does the bad news on BMS-986094 — formerly INX-189 — mean for other investigational HCV nucleotides?
Severe cardiotoxicity, fatal in one case, has ended the drug’s development. Importantly, nothing similar has thus far been observed with the structurally-similar IDX184, but that drug has been placed on “clinical hold” by the FDA. By contrast, the nucleotide GS-7977 is apparently different enough chemically that studies are for now continuing. One take-home message: drug development is risky business.

2 - When will the alphabet soup of terms used to describe HCV treatment response be abandoned?
HCV treatment either works, and you’re cured, or it doesn’t. But because the treatment is so cumbersome and so long, there’s a whole slew of ways to describe how things are going before you get to that point. Let’s see, there’s RVR (rapid virologic response, or no virus detected at 4 weeks); eRVR (extended rapid virologic response, or no virus detected at weeks 4 and 12 — used in this study of daclatasvir); EVR (early virologic response, which really isn’t that early, because it’s week 12, and it can be either pEVR — for “partial” — which means HCV RNA drops by more than 2 log but is still detected, or cEVR — for “complete”, which means it’s undetectable); ETR (end of treatment response, or no virus detectable at end of treatment); and of course SVR (sustained virologic response, now available in many flavors, depending on the week after stopping treatment you want to measure it — 2, 4, 8, 12, 16, 24,etc). For now, with IF/RBV +/- telaprevir/boceprevir and “response-guided” therapy still ruling the day, we’re stuck with this mish-mosh of terms, but I suspect most of this stuff will be irrelevant pretty soon, except for the bottom line — how many are cured? Doesn’t that sound better than “How many are SVR-12′d?”

3 - So when precisely will these new drugs become available?
Seems pretty obvious right now that if you’ve got HCV and can wait for better treatments, you should. Treatment became more effective with telaprevir and boceprevir, but it also got more complicated, toxic, and expensive. Things have to get better, and they will — especially with interferon-free options. Regardless, no one knows exactly when these new drugs will be available for use outside of clinical trials — 2013-2014 a broad estimate — and all kinds of things could hold up their approval (see #1 above). Plus, some patients can’t and shouldn’t wait for better options because they have advanced liver disease. Just this last week, two such individuals came in for evaluation — both with HIV, both with prior treatment failure on IF/RBV, both with Stage 3/4 fibrosis on liver biopsy. Should they wait for daclatasvir, GS-7977, TMC-435, ABT-450/r + ABT-333, etc? Probably not.

Antibody prevents hepatitis C in animal model

Antibody prevents hepatitis C in animal model

A monoclonal antibody developed by MassBiologics of the University of Massachusetts Medical School (UMMS) and tested in an animal model at the Texas Biomedical Research Institute, prevents infection by the hepatitis C virus (HCV).

Researchers found that the human monoclonal antibody targeting the virus protected chimpanzees from HCV infection in a dose-dependent manner in a study conducted at Texas Biomed's Southwest National Primate Research Center. Chimpanzees are the only species other than humans that can be infected by HCV and therefore the results from this study were critical in the development of the monoclonal antibody.

The new report by scientists from MassBiologics; Texas Biomed; the National Institutes of Health (NIH); and Merck Research Laboratories, and funded by MassBiologics and NIH, appears in the August 30th issue of PLoS Pathogens. Researchers had previously demonstrated that the monoclonal antibody, called HCV1, blocks HCV from infecting liver cells in laboratory tissue culture.

"This is an important preclinical proof-of-concept study demonstrating a high dose of neutralizing antibody can protect the liver from HCV infection using monoclonal antibodies in a study that was designed to mimic the transplantation setting," said study co-author Robert E. Lanford, Ph.D., of Texas Biomed.

"One can envision improving on these results with a cocktail of antibodies or by using this antibody with some of the newer antivirals currently in clinical trials. Infection of the new donor liver by residual virus in the patient is one of the major obstacles preventing a full recovery in these patients," Lanford added.

MassBiologics has been pursuing the development of HCV1 as a therapy for patients with end-stage liver disease undergoing liver transplantation as a result of HCV infection. HCV1 is a monoclonal antibody that binds to the surface of the HCV virus and blocks the ability of the virus to enter liver cells.

HCV damages the liver and is the leading indication for liver transplantation, diagnosed in about half of the 6,000 patients who receive liver transplants each year in the United States. According to the US Centers for Disease Control and Prevention (CDC), 3.2 million Americans are chronically infected with HCV and approximately 10,000 die annually of the disease. Globally, as many as 170 million people are estimated to suffer from HCV infection. The CDC recently recommended that everyone born from 1945 to 1965 should be screened for HCV regardless of whether they have known risk factors.

For patients with end-stage liver disease from HCV infection, liver transplantation is the only option. While it can be a life-saving treatment, transplantation does not cure the disease. In nearly all cases, the patient's new liver is eventually infected by HCV because the virus remains in the patient's bloodstream during surgery. The course of recurrent HCV disease is accelerated after transplantation and up to 20 percent of transplant patients develop cirrhosis within five years. Unfortunately, the standard antiviral drugs currently used to treat HCV prior to the onset of end-stage liver disease are poorly tolerated after liver transplantation, leaving these patients with few options.

Source: Texas Biomedical Research Institute

TMC435 (Simeprevir)-Medivir CEO hopes hepatitis C drug candidate will multiply revenue

Medivir CEO hopes drug candidate simeprevir will multiply revenue
-- Partner Janssen will seek regulatory approval next year if trials succeed
-- Medivir plans to use simeprevir income for organic expansion, acquisitions
STOCKHOLM--Swedish biotech company Medivir AB (MVIR-B.SK) hopes soon to multiply its revenue through the planned launch of a Hepatitis C treatment, in an attempt to defy the setbacks that have recently plagued the sector.

Swedish biotech firms such as Karo Bio AB and BioInvent AB have suffered drug development failures this year, causing their shares to slump, whereas Medivir's have held up comparatively well as investors pin their hopes on the forthcoming simeprevir trial results. That said, the shares are down around 2% since the start of the year, underperforming a 6% rise in the wider Stockholm market.

"A successful launch would multiply Medivir's revenue," Chief Executive Maris Hartmanis said in a recent interview. "It would give extremely good opportunities to grow the company."

Simeprevir is undergoing late-stage clinical trials for Hepatitis C, a liver disease, with results due around the end of this year.

Medivir has outlicensed the drug to Johnson & Johnson /quotes/zigman/230812/quotes/nls/jnjJNJ+0.70%-controlled Janssen Pharmaceuticals, which aims to obtain regulatory approval in the U.S., Europe and Japan in the second quarter of next year, he added. The Swedish company aims to launch the drug itself in the Nordics and receive royalties on sales elsewhere.                           

"The [earlier] Phase II studies indicated good efficacy and there haven't been any unpleasant side effects so far," Mr. Hartmanis said.

Royalties in this type of license deals are typically around 8% to 10% of sales, Mr. Hartmanis said, but he declined to comment specifically on the deal with Janssen.

Drug companies have spent considerable efforts in recent years on developing Hepatitis C drugs that don't have side effects such as fever, anemia and hair loss, but with scant success.

Earlier this month, U.S. giant Bristol-Myers Squibb Co. /quotes/zigman/220498/quotes/nls/bmyBMY+0.65% cancelled development of a treatment candidate after tests revealed severe side effects. The U.S. Food & Drug Administration subsequently halted studies of a similar compound, developed by U.S.-based biotech firm Idenix /quotes/zigman/90571/quotes/nls/idixIDIX-1.72%.
Simeprevir will be one of the main treatment options if it reaches the market so it will become a main revenue source for Medivir, as the company looks for organic growth and complementary acquisitions within the infectious disease field, Mr. Hartmanis said, but he declined to give a specific peak sales estimate for the drug.
"One size doesn't fit all so there will be several new drugs for Hepatitis C, but simeprevir is likely to be a cornerstone in future treatment," he added.
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Achillion Pharma strikes deal to raise $41.8M as hep C results loom

Achillion Pharma strikes deal to raise $41.8M as hep C results loom

August 31, 2012 | By Ryan McBride
Fierce Biotech

Hepatitis C drug developer Achillion Pharmaceuticals ($ACHN) expects to haul in $41.8 million proceeds of a common stock sale to QVT Financial. And the funding comes ahead of some important clinical trial results from the New Haven, CT-based developer's pipeline of hep C treatments...
Achillion has several experimental oral meds in early- or mid-stage trials for hep C, a liver-damaging virus that afflicts an estimated 170 million people around the globe. The biopharma stampede is chasing all-oral regimens for the illness that can spare hep C patients from lengthy treatment on injections of interferon, which causes flu-like symptoms that make patients feel worse than the infectious disease does. And Achillion's contenders offer potential ingredients in cocktail therapies of oral meds to potentially wipe out the virus without those side effects from interferon....
Early next year Achillion is expected to report early data from an upcoming trial that tests a combo of the company's HCV NS3 protease inhibitor sovaprevir and a compound known as ACH-3102 as an interferon-free therapy for hep C, according a recent investor note from Cowen & Company...
Continue reading.......

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Achillion Pharma attracts buyout buzz as hep C rivals fall
Achillion burnishes buyout prospects, snags fast track for hep C drug
Hep C drug deal frenzy can't be slowed by growing doubts
Who's next on hep C biotech buyout hit list?
Achillion Pharma CEO talks up sale amid hep C trials


Thursday, August 30, 2012

Local and state experts say CDC's new recommendation on Hepatitis C screening makes sense

While the specific cut-off dates vary slightly by source, U.S. baby boomers were more than 75 million people born in the two decades on the heels of World War II. The CDC says members of this massive generation accounts for more than 75 percent of U.S. adults living with Hepatitis C, some of who may have contracted the virus through transfusions and other medical procedures before the widespread blood supply screening started in 1992.

"There was a time not very long ago when Hepatitis C was not a known virus ... and therefore there was no test for it," said Kevin Cranston. director of the Bureau of Infectious Disease at the Massachusetts Department of Public Health. Plus, he added, "the caution around blood exposure really became part of the American consciousness in response to HIV."

The CDC says its expanded recommendations could diagnose 800,000 more Hepatitis C cases and potentially save more than 120,000 lives.
"I think it makes a lot of sense from a population standpoint," said Dr. Paul S. Sepe, a gastroenterologist with Hawthorn Medical Associates.

Sepe said he'll still individualize his practice, likely refraining from screening absolutely every baby boomer who enters his office. But he said the new recommendations will increase his awareness and will lead him to test people more frequently.
Although some Hepatitis C cases might clear on their own, chronic disease can lead to what Sepe described as a "complicated cascade" of problems, including inflammation of the liver, followed by the gradual development of scar tissue.
Continue Reading....

Video-Dentist accused of re-using needles/syringes on patients- surrenders license

Written by Blair Shiff

Dr. Stein's former patients were tested for Hepatitis B, Hepatitis C and HIV. It is unknown at this time what the three positive cases tested positive for.

"The CDC and department confirmed it would be difficult if not impossible to conclude definitively whether the dental practice was the actual source of transmission for any of these positive test results," the CDPHE said in a release sent out in early August.

Dr. Stein is accused of re-using needles and syringes for days at a time on his patients over the course of 12 years. He had two practices - one in Denver and one in Highlands Ranch.
Continue reading..........

As reported: 8000 former patients have been notified to get tested for HCV, HBV and HIV - Five former patients tested positive for a blood disease. Also noted in the report was the difficulty of proving if these patients contracted HCV, HBV or HIV from the dentist. This statement came next - "We want to make note who knows where they (patients) could have gotten that disease."  I was made uncomfortable by the reporters insensitive statement. Dr. Stein put 8000 people at risk, over a period of 12 years. I'm sure his former patients (victims) will also be offended.

Hepatitis C - Study Of Albinterferon Alfa-2b Every 4 Weeks for Genotype 2/3

From Journal of Viral Hepatitis

Randomized Trial of Albinterferon Alfa-2b Every 4 Weeks for Chronic Hepatitis C Virus Genotype 2/3

S. Pianko; S. Zeuzem; W.-L. Chuang; G. R. Foster; S. K. Sarin; R. Flisiak; C.-M. Lee; P. Andreone; T. Piratvisuth; S. Shah; A. Sood; J. George; M. Gould; P. Komolmit; S. Thongsawat; T. Tanwandee; J. Rasenack; Y. Li; M. Pang; Y. Yin; G. Feutren; I. M. Jacobson

While the focus of antiviral therapy for chronic HCV is projected by some to ultimately move away from IFN-based therapies, IFN-free regimens have not yet been developed beyond early trials.[21] Interferon may be required to diminish resistance to direct-acting antiviral agents, and an IFN platform with a reduced frequency of injections may be an important strategy if efficacy can be maintained with an improved AE profile. The present study demonstrates the ability to reduce the frequency of albIFN injections from q2wk to q4wk in a chronic HCV Gt 2/3 population with a small, statistically insignificant reduction in efficacy. It remains to be determined whether the combination of long-acting IFNs administered q4wk with direct-acting antiviral agents or intensification of IFN exposure in the first 4 weeks of therapy can overcome the reduction in efficacy seen in the present study

Full text available at Medscape

**Free registration required

Abstract and Introduction
  • Methods
  • Results
  • Discussion

  • Eltrombopag trial halted after thrombotic events in patients with liver disease, thrombocytopenia

    Related- Eltrombopag in Cirrhosis

    Eltrombopag trial halted after thrombotic events in patients with liver disease, thrombocytopenia

    Afdhal NH. N Engl J Med. 2012;367:716-724.

    Table 2. Adverse Events Occurring in at Least 3% of Patients in Either Study Group.

    Thrombopoietin-receptor agonist eltrombopag may have increased the risk for portal vein thrombosis among patients with chronic liver disease and thrombocytopenia, causing the early termination of an efficacy study.

    In a double blind, placebo-controlled, international trial, researchers randomly assigned 292 patients with chronic liver disease and a platelet count less than 50,000/mm3 to receive either 75 mg eltrombopag (n=145) or placebo (n=147) daily for 14 days prior to an elective, invasive procedure. Evaluated factors included platelet counts and the number of platelet transfusions performed before, during or up to 30 days after the procedure, as well as incidences of bleeding of WHO grade 2 or higher during the study.

    In the treated group, 104 participants did not require a platelet transfusion within the specified time period, compared with 28 in the placebo group (P<.001). Among those who received transfusions, the median number of transfused units was smaller in treated patients (3.0 vs. 4.0). Platelet counts were greater than 80,000/mm3 in 59% of patients after 2 weeks of treatment, compared with 5% in the placebo group. Bleeding occurred in 17% of treated patients and 23% of placebo patients, with no statistical significance for the difference.

    The study was terminated early after six treated participants experienced thrombotic events related to the portal venous system, compared with one placebo patient. Thrombotic events were significantly more common among treated patients (OR=3.04; 95% CI, 0.62-14.82), and increased risk was associated with platelet counts greater than 200,000/mm3.

    Other than the thromboses, no significant difference was observed between groups for incidence or severity of adverse events. Common events included headache, pyrexia, abdominal pain, diarrhea, nausea and hepatic encephalopathy.

    “Further exploration of eltrombopag therapy is required, including better identification of risk factors for the development of thrombosis, dose optimization and careful patient selection,” the researchers concluded. “Until such studies have been conducted, eltrombopag is not recommended as an alternative to platelet transfusion in patients with chronic liver disease and thrombocytopenia who are undergoing an elective invasive procedure.”

    Disclosure: See the study for a full list of relevant disclosures.

    Wednesday, August 29, 2012

    New 'traffic light' test could save lives with earlier diagnosis of liver disease

    A new 'traffic light' test devised by Dr Nick Sheron and colleagues at University of Southampton and Southampton General Hospital could be used in primary care to diagnose liver fibrosis and cirrhosis in high risk populations more easily than at present.

    Liver disease develops silently without symptoms, and many people have no idea they have liver failure until it is too late – one-third of people admitted to hospital with end-stage liver disease die within the first few months. A simple test available in primary care could diagnose disease much earlier, enabling those at risk to change their behaviour and save lives.

    The Southampton Traffic Light (STL) test, details of which are published in the September 2012 issue of the British Journal of General Practice (BJGP), combines several different tests and clinical markers which are given a score that indicates the patient's likelihood of developing liver fibrosis and liver cirrhosis.*

    The result comes in three colours: red means that the patient has liver scarring (fibrosis) and may even have cirrhosis, green means that there is no cirrhosis and the patient is highly unlikely to die from liver disease over the next five years. Amber means there is at least a 50:50 chance of scarring with a significant possibility of death within five years, and patients are advised to stop drinking to avoid further disease and death.

    The test was given to over 1,000 patients, and their progress was carefully followed and monitored afterwards, in some cases over several years, to assess the accuracy of the test in predicting whether they developed liver fibrosis or cirrhosis.

    The test proved to be accurate in severe liver disease, and while not a substitute for clinical judgement or other liver function tests, can provide GPs with an objective means to accurately assess the potential severity of liver fibrosis in high-risk patients – for example, heavy drinkers, those with type II diabetes, or obese people.

    Dr Nick Sheron, lead author and Head of Clinical Hepatology at the University of Southampton, and consultant hepatologist at Southampton General Hospital, said: "We are reliant on general practitioners detecting liver disease in the community so they can intervene to prevent serious liver problems developing, but so far we haven't been able to give them the tools they need to do this. We hope that this type of test for liver scarring may start to change this because the earlier we can detect liver disease, the more liver deaths we should be able to prevent."

    Study co-author and GP Dr Michael Moore said: "In primary care, minor abnormalities of existing liver tests are quite common but we struggle to know how best to investigate these further and who warrants specialist intervention. The traffic light test has the advantage of highlighting those at highest risk who should be investigated further and those in whom the risk is much lower where a watchful approach is more appropriate. This is not a universal screening test but if targeted at those in whom there is a suspicion of liver disease should result in a more rational approach to further investigation."

    Professor Sir Ian Gilmore, chair of the Alcohol Health Alliance added: "One of the challenges of liver disease, which is rising dramatically in this country, is the silent nature of the condition until it is often too late to reverse the damage. However, minor changes in standard liver blood tests are so common that it is difficult for GPs to know when to refer for specialist advice. This large study from Dr Sheron and colleagues in Southampton may prove really useful for guiding the right patients towards specialist care in a timely way."

    Analysis of the factors motivating HCV-infected patients to accept interferon therapy

    Short Report
    Analysis of the factors motivating HCV-infected patients to accept interferon therapy

    Yumiko Nagao and Michio Sata
    BMC Research Notes 2012, 5:470 doi:10.1186/1756-0500-5-470

    Published: 29 August 2012

    Abstract (provisional)
    The aims of this study were to analyze factors motivating the acceptance of interferon (IFN) therapy and to clarify the prevalence of oral mucosal diseases in hepatitis C virus (HCV)-infected Japanese patients treated with IFN. Findings A total of 94 HCV-infected patients who were admitted to our hospital for IFN therapy were asked questions regarding their motivation to accept IFN therapy and were investigated for the presence of oral lichen planus (OLP) before and during IFN treatment. Recommendation and encouragement from other people were the most common factors motivating the acceptance of IFN therapy (49/94, 52.13%). The other motivators were independent decision (30.85%), economic reasons (5.32%), and others. According to multivariate analysis, three factors - sex (male), retreatment after previous IFN therapy, and independent decision to accept IFN therapy - were associated with patients after curative treatment of hepatocellular carcinoma (HCC). The adjusted odds ratios for these three factors were 26.06, 14.17, and 8.72, respectively. The most common oral mucosal lesions included OLP in 11 cases (11.70%). One patient with OLP had postoperative squamous cell carcinoma of the tongue. The rate of sustained virological response (SVR) was 45.45% in cases with OLP and 54.55% in cases without OLP. There were no patients who discontinued IFN therapy because of side effects such as oral mucosal diseases.

    We should give full explanation and recommend a course of treatment for a patient to accept IFN therapy. The system to support liver disease as well as oral diseases is also necessary for patient treated for IFN therapy.

    The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

    Achillion re-emerges as takeover target after recent setbacks in hepatitis C field: report

    Achillion re-emerges as takeover target after recent setbacks in hepatitis C field: report

    Last Updated:August 29, 2012 09:25

    Analysts expect renewed takeover interest in hepatitis C drug developer Achillion Pharmaceuticals after recent setbacks to experimental compounds from Bristol-Myers Squibb and Idenix Pharmaceuticals, Bloomberg reported Wednesday. JMP Securities analyst Liisa Bayko said Achillion is "well-positioned to be a candidate to be taken out, because right now, there are very few options if you want to get involved in hep C, in terms of combinations that are more advanced that are still in clinical development."

    Recently, Bristol-Myers Squibb ended development of its experimental hepatitis C drug BMS-986094, which it gained through the $2.5-billion acquisition of Inhibitex, due to safety concerns that involved heart and kidney toxicity. Meanwhile, the FDA has placed clinical holds on two of Idenix's similar drugs, IDX184 and IDX19368, due to the cardiac-related concerns with Bristol-Myers Squibb's compound.

    Bayko said that Achillion may attract interest from companies looking to gain hepatitis C drugs to use on their own or in combination with their existing therapies. Piper Jaffray analyst Ted Tenthoff suggested that Achillion could receive attention from Merck & Co., Roche and Vertex as they seek to compete against Gilead Sciences, which is seen by analysts as having the most promising oral hepatitis C drug. Gilead is scheduled to start testing two of its therapies together in a single tablet this year, with a US marketing application possibly being filed in 2014. Peter Kolchinsky of RA Capital Management added that Gilead could also look to acquire Achillion. The drugmaker "could solidify its supremacy if it had Achillion’s drugs, each best in its respective class based on what we know so far," Kolchinsky noted.

    However, Bayko said she expects a suitor to wait for data on how effective Achillion's two therapies work in combination, with good results enticing competitors to bid. Joe Truitt, Achillion’s chief commercial officer, remarked "if that combination data comes through, then we really have a commercially viable, competitive combination that will put everybody on notice," adding "we’ll make the best strategic options as they come to us." CEO Michael Kishbauch had said in November that the company was in "advanced discussions" with potential partners or acquirers.

    Tenthoff commented that although "the frenzy has been taken out of the [hepatitis C] space," Achillion will attract interest because its therapies have the potential to be the best of their type. "We expect the wave of consolidation to continue. Achillion is clearly a target," he added.

    Tuesday, August 28, 2012

    Myocardial injury common among patients with chronic HCV

    Myocardial injury common among patients with chronic HCV

    *myocardial [mi″o-kahr´de-al] -pertaining to the muscular tissue of the heart

    Maruyama S. J Hepatol. 2012;doi:10.1016/j.jhep.2012.07.045.

    August 28, 2012
    Patients with chronic HCV were prone to myocardial perfusion defects that responded to HCV treatment in a recent study.

    Researchers performed ECG, echocardiography and myocardial perfusion imagery on 217 patients with chronic HCV and without overt heart disease symptoms to detect the presence and severity of myocardial injury. Two hundred patients received treatment with interferon (IFN) for 24 or 48 weeks, and were evaluated 2 weeks before, 2 weeks after and 6 months after therapy. Sustained viral response (SVR) was defined as undetectable HCV RNA 6 months after completing treatment.

    Nine percent of patients in the cohort had abnormal ECGs, including 15 cases of sinus bradycardia and five with incomplete right bundle branch block before IFN treatment. Myocardial perfusion imaging indicated injury in 87% of patients, as represented by abnormal severity scores (SS). Histology activity index score, serum HCV RNA levels and rate of indocyanine green disappearance were independently associated with higher SS before IFN therapy via multiple linear regression (P<.0001 for all).

    Among the 200 patients who completed treatment, SVR occurred in 92 patients and 57 experienced relapse; the remaining patients were considered nonresponsive. Participants who achieved SVR indicated significant improvement to SS after treatment and follow-up (P<.01). Patients who relapsed experienced an improvement to SS during treatment as HCV RNA disappeared, but returned to baseline SS at follow-up. No significant SS change occurred among nonresponders.

    Rates of SS change from baseline were similar between patients who received 24 and 48 weeks of therapy. Differences in SS change according to response were significant for all comparisons, excluding those between patients who relapsed and those who were nonresponsive after 48 weeks of treatment (P=.2382).

    “Our study is the first to demonstrate a relationship between chronic HCV infection and myocardial perfusion defects in a large number of patients,” the researchers wrote. “Although further studies are required to evaluate the exact relationship between chronic HCV infection and myocardial injury, our study suggests that HCV infection may play an important causal role in the pathogenesis of myocardial injury.”

    Video-Law firms represent clients affected by Bristol-Myers Squibb trial

    Excerpt from Sheller, P.C. website

    Sheller, P.C. and Hilliard Munoz Gonzalez law firms are joining forces to represent clients affected by this trial, including the Texas patient who needs a heart transplant and the family of the patient who died of heart failure.

    *This video was Published on YouTube Aug 28, 2012 by

    Hepatitis C Drug Causes Death, Halts Clinical Trial

    BMS-986094-Bristol-Myers Sued Over Heart Damage In Hepatitis C Drug Trial
    Hepatitis C And Clinical Trials
    Idenix: FDA Places IDX19368 Hepatitis C Treatment on Clinical Hold
    IDX184-Idenix hepatitis C drug put on partial hold
    BMS halts the development of BMS-986094 due to patient death

    BMS-986094-Bristol-Myers Sued Over Heart Damage In Hepatitis C Drug Trial

    Janet Schaefer Vella a woman from Texas is suing Bristol-Myers and Alamo Medical Research allegedly over heart problems after taking part in the hepatitis C BMS-986094 clinical trial in early July. A week into the trial she underwent a diagnostic test which indicated possible heart problems, now Ms. Vella who is also a nurse -  needs a heart transplant, read the complete article written by John MacCormack  online here.

    An excerpt
    Janet Schaefer Vella now is in need of a heart transplant due to irreversible damage to the heart caused by BMS094,” reads the suit, which claims the drug giant rushed ahead with the clinical trials “without fully evaluating the risks and benefits of the drug.”
    The product liability suit was filed Friday in Nueces County, a day after Bristol-Myers announced it was giving up on the experimental hepatitis drug, noting that one person had died and eight more were hospitalized after participating in trials.
    In an email, Bristol-Myers declined to comment on Vella's suit, but noted that 113 people were involved in the same trials when they were halted. In an e-mail, Alamo Medical Research referred press inquiries to Bristol-Myers.

    Continue reading....

    Related -
    Hepatitis C And Clinical Trials
    Idenix: FDA Places IDX19368 Hepatitis C Treatment on Clinical Hold
    IDX184-Idenix hepatitis C drug put on partial hold
    BMS halts the development of BMS-986094 due to patient death



    FDA Issues Warning For Reumofan Plus and Reumofan Plus Premium

    A few days ago the FDA released an updated alert on Reumofan Plus and Reumofan Plus Premium. The agency warns that the dietary supplements contain undeclared active ingredients found in prescription drugs - ingredients which only should be administered under the supervision of a health care professional.

    These products are sold and promoted as natural dietary supplements for treating arthritis, muscle pain, osteoporosis, bone cancer, and other conditions.

    The first warning was issued by the FDA on June 1, 2012, since then the FDA received dozens of adverse reports which include fatalities, and stroke. The agency said other reports have included; liver injury, sudden worsening of glucose (sugar) control, severe bleeding of the gastrointestinal tract, weight gain, swelling, leg cramps, adrenal suppression and corticosteroid withdrawal syndrome.

    FDA Update 08/21/2012

    Questions and Answers: Reumofan Plus and Reumofan Plus Premium

    En EspaƱol1

    What are Reumofan Plus and Reumofan Plus Premium?

    Reumofan Plus and Reumofan Plus Premium are products marketed as natural dietary supplements that contain several potentially harmful active pharmaceutical ingredients. These products are promoted for treating arthritis, muscle pain, osteoporosis, bone cancer, and other conditions. Reumofan Plus and Reumofan Plus Premium are labeled in Spanish, but versions of these products may also exist with English labeling.

    Where are Reumofan Plus and Reumofan Plus Premium manufactured and sold?

    Reumofan Plus and Reumofan Plus Premium are manufactured in Mexico by Riger Naturals. However, these products have been sold throughout the United States in some retail outlets, at flea markets, and on various Internet sites.

    Has FDA received adverse events and/or complaints associated with Reumofan Plus and Reumofan Plus Premium?

    Yes, FDA has received dozens of additional adverse event reports, including death and stroke, associated with the use of Reumofan Plus since the agency issued its first warning2 about the product on June 1, 2012. Other reports include liver injury, severe bleeding, sudden worsening of glucose (sugar) control, weight gain, swelling, leg cramps and withdrawal syndrome, and adrenal suppression.

    What hidden ingredients were found in Reumofan Plus and Reumofan Plus Premium?

    FDA laboratory analysis revealed that Reumofan Plus contains the undeclared and potentially harmful prescription drug ingredients dexamethasone (a corticosteroid), diclofenac sodium (an anti-inflammatory drug), and methocarbamol (a muscle relaxant). Reumofan Plus Premium was found to contain diclofenac sodium and methocarbamol.

    What should consumers do if they have taken Reumofan Plus or Reumofan Plus Premium?

    Consumers taking these products are urged to immediately consult with their health care professional (e.g., doctor) to safely discontinue use of the product. The hidden drug ingredients in Reumofan Plus and Reumofan Plus Premium can lead to serious, even life-threatening, health consequences. The longer the product(s) is taken, the higher the risk of these serious health consequences.

    Reumofan Plus contains the corticosteroid, dexamethasone. Abrupt discontinuation of corticosteroids may cause serious withdrawal syndrome and life threatening adrenal suppression. These risks depend upon a number of variables that need to be assessed by a health care professional, and medical intervention may be necessary. Only licensed health care professionals can evaluate patients for the risk, or confirm the existence, of adrenal suppression.

    What are the risks associated with the undeclared ingredients discovered in Reumofan Plus?

    FDA laboratory analysis revealed that Reumofan Plus contains three prescription drug ingredients: dexamethasone, a corticosteroid; diclofenac sodium, an anti-inflammatory drug; and methocarbamol, a muscle relaxant. These ingredients are not listed on the label and could cause serious harm to consumers.

    The risks associated with these ingredients include the following:

    • Dexamethasone is a potent corticosteroid used primarily for its anti-inflammatory properties. Corticosteroids can reduce the body’s immune response to infection and have profound effects on various organ systems in the body. Dexamethasone and other corticosteroids can cause serious adverse events, including infections, increased blood glucose (sugar) levels, changes in blood pressure, damage to bones, psychiatric problems, and adrenal dysfunction.

      In addition to the adverse effects that can result from using corticosteroids, the sudden discontinuation of corticosteroids can also have health consequences. Sudden discontinuation of corticosteroids after long-term use or high doses can result in a withdrawal syndrome that includes fatigue, nausea, low blood pressure, low blood glucose levels, fever, dizziness, muscle and joint pain, and shortness of breath.

    • Diclofenac sodium is a non-steroidal anti-inflammatory (NSAID) drug that can cause increased risk of cardiovascular events, such as heart attack and stroke. Diclofenac, like other NSAID drugs, can also lead to serious gastrointestinal (GI) adverse events, including bleeding, ulceration, and fatal perforation of the stomach and intestines.

      The potential drug interactions that can occur with the hidden diclofenac sodium component of Reumofan Plus and Reumofan Plus Premium are serious. Consumers who take Reumofan Plus and/or Reumofan Plus Premium increase their risk of bleeding and the complications of bleeding. Patients already may be taking other medications/products that can cause bleeding. Taking multiple products that have a risk of bleeding significantly increases the risk and the severity of the bleeding if it does occur.

    • Methocarbomal is a muscle relaxant that can cause sedation, dizziness, and low blood pressure. Methocarbomal can also impair mental and physical abilities to perform certain tasks, such as driving a motor vehicle or operating machinery. The risk of injury or death is significantly increased when Reumofan Plus and/or Reumofan plus Premium are taken with other medications/products that can cause these impairments.
    Does FDA suspect that Reumofan Plus and Reumofan Plus Premium may contain other unlabeled ingredients?

    FDA analysis reflects only the undeclared ingredients discovered in one product from a specific lot, but ingredients may vary from product to product or from lot to lot. Products marketed as dietary supplements that are found to have hidden drug ingredients generally fail to comply with most current good manufacturing practices designed to ensure product quality and safety. Therefore, consumers should expect that the manufacturing processes for Reumofan Plus and Reumofan Plus Premium are unreliable in their ability to provide consistent amounts of active ingredients or to prevent the introduction of unknown chemicals or other impurities.

    What should health care professionals do if they suspect or confirm patients have taken Reumofan Plus or Reumofan Plus Premium?

    Health care professionals should evaluate patients who have used Reumofan Plus/Reumofan Plus Premium for drug and disease interactions involving diclofenac, methacarbamol, and corticosteroids, and treat accordingly.

    When indicated, health care professionals should evaluate adrenal function and consider whether a corticosteroid taper regimen is appropriate in patients who have used Reumofan Plus and/or Reumofan Plus Premium.

    What action is FDA taking?
    FDA has issued a public health advisory to highlight the health risks of Reumofan Plus and Reumofan Plus Premium. In addition, FDA is investigating the distribution of these products in the United States. FDA may take additional enforcement steps that may include warning letters, seizure, injunction, or criminal charges.

    How should consumers report problems to FDA?

    Consumers should report serious side effects or product quality problems with the use of these products to FDA's MedWatch Adverse Event Reporting program online, by regular mail, fax, or phone.

    • Online3
    • Regular Mail: Use FDA postage paid form 35004 and mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787
    • Fax: 800-FDA-0178
    • Phone: 800-FDA-1088


    FDA approves Gilead's four-drug HIV treatment

    Mon Aug 27, 2012 6:27pm EDT

    (Reuters) - U.S. health regulators on Monday approved Gilead Sciences Inc's four-drug combination pill to treat HIV, the virus that causes AIDS.
    The four drugs in one pill, which was formerly called the Quad and had been considered one of Gilead's more important future growth drivers, will be sold under the brand name Stribild, the U.S. Food and Drug Administration said.

    Gilead shares were virtually unchanged from their $57.19 Nasdaq close as Wall Street has been focused on development of the experimental hepatitis C treatment that Gilead acquired with its $11 billion purchase of Pharmasset.

    "The approval was on time as expected," said RBC Capital Markets analyst Michael Yee, adding the he expects the new pill will meet or exceed current Wall Street estimates for sales of about $46 million this year and $370 million next year.

    Yee said he expects Gilead to aggressively market Stribild and deemphasize its Atripla and Complera combination therapies as Atripla contains a Bristol-Myers Squibb Co HIV drug and Complera contains a Johnson & Johnson drug.

    "The profit margins are significantly better because this drug is wholly owned by Gilead," Yee said of the quad pill.

    Stribild, a once-daily treatment, contains two previously approved HIV medicines and two new drugs. The older medicines, emtricitabine and tenofovir, are currently sold by Gilead in its combination pill Truvada, which was approved in 2004, and are also part of Gilead's Atripla three-drug combination. The newer drugs are elvitegravir and cobicistat.

    "Through continued research and drug development, treatment for those infected with HIV has evolved from multi-pill regimens to single-pill regimens," Edward Cox, director of the Office of Antimicrobial Products at the FDA's Center for Drug Evaluation and Research, said in a statement. "New combination HIV drugs like Stribild help simplify treatment regimens."

    As a condition of approval, Gilead will be required to conduct additional studies to help further characterize the drug's safety in women and children, how resistance develops to Stribild, and the possibility of interactions between Stribild and other drugs, the FDA said.

    The drug's label will also carry a boxed warning of the potential for a build up of lactic acid in the blood and severe liver problems, both of which can be fatal. The warning also states that Stribild is not approved to treat chronic hepatitis B virus infection, the FDA said.

    About 1.2 million people in the United States are infected with HIV, according to the U.S. Centers for Disease Control and Prevention.

    (Reporting by Bill Berkrot; Editing by Bernard Orr)

    Monday, August 27, 2012

    Is Interferon-Free Treatment for Hepatitis C Just a Dream?

    From Medscape Gastroenterology > Ask the Experts

    Is Interferon-Free Treatment for Hepatitis C Just a Dream?

    Posted: 08/27/2012

    William F. Balistreri, MD
    Professor of Medicine, University of Cincinnati College of Medicine; Staff Physician, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio Disclosure: William F. Balistreri, MD, has disclosed no relevant financial relationships

    What are our evidence-based treatment strategies for hepatitis C? Will we ever have an interferon-free regimen?

    The Current Standard Treatment for HCV Infection
    Combination therapy with pegylated interferon and ribavirin has long been the standard of care for patients with chronic hepatitis C (HCV) infection. Although effective in achieving high response rates, this regimen is associated with troublesome side effects.[1] Therefore, the development and approval of effective protease inhibitors, telaprevir and boceprevir, was hailed as a new era of therapy for patients with hepatitis C genotype 1 infection.[2,3]

    Interferon-Free Treatment: No Longer a Dream?
    Several studies were presented at both Digestive Disease Week (DDW) 2012 in May and at the European Association for the Study of the Liver (EASL) annual meeting in April 2012 that documented that these direct-acting antiviral agents allow more effective and shorter durations of treatment. For example, in patients infected with HCV genotype 1 for whom previous standard therapy failed to eliminate the virus, treatment with either of these protease inhibitors was shown to be significantly more effective, with sustained viral response rates 2- to 3-fold higher than with traditional therapy.

    An American Association for the Study of Liver Diseases plenary session presentation during DDW 2012 reported that when telaprevir was used in combination with pegylated interferon and ribavirin, the dose of ribavirin could be substantially reduced.[4] Reduction of the ribavirin dose to less than 600 mg/day had no substantial effect on sustained viral response (SVR) rates in patients who received telaprevir combination treatment. In another study, when boceprevir was used in combination with pegylated interferon and ribavirin, SVR was achieved in patients who had been nonresponsive to previous therapy.[5]

    Despite the optimism about the prospects for this treatment of HCV, the fact that telaprevir and boceprevir must be used in combination with pegylated interferon and ribavirin is a persisting concern. This is far from the ideal regimen. In fact, because of poor tolerability, many treatment candidates will decide not to pursue treatment or to defer treatment until a simpler regimen is available. However, other studies suggest that an interferon-free regimen (and perhaps even a ribavirin-free regimen) is no longer a dream. Various compounds encompassing several distinct drug classes are currently under development. These drugs bring us one step closer to the long sought-after ideal: the ability to remove interferon injections from treatment for HCV.

    Targeting Novel Treatment Options
    Two studies presented at the EASL annual meeting in April 2012 revealed novel treatment options for HCV genotype 1-infected patients who are unable to take interferon-based therapy. The strategy was based on a 12-week combinations of DAA (direct-acting antiviral) interferon-free therapy.

    In the first study, ABT-450, a potent inhibitor of the HCV NS3 protease, was coadministered with ritonavir (ABT-450/r), a CYP3A inhibitor, to maintain high ABT-450 exposures and support once-daily dosing.[6] ABT-072 is a non-nucleoside inhibitor of HCV NS5B polymerase. The investigators reported that 91% of treatment-naive, noncirrhotic patients infected with HCV genotype 1 (the interleukin-28B CC genotype) achieved SVR after 12 weeks, and 82% achieved SVR at 36 weeks. The combination of ABT-450/r plus ABT-072 plus ribavirin was well tolerated over the 12 weeks of treatment.

    In a companion study, ABT-450/r was coadministered with ABT-333, another non-nucleoside inhibitor of HCV NS5B polymerase.[7] The combination of ABT-450/r plus ABT-333 plus ribavirin without interferon in HCV genotype 1-infected patients was well tolerated during 12 weeks of treatment. Overall, 93%-95% of treatment-naive patients infected with HCV genotype 1 achieved SVR after 12 weeks of treatment. Therefore, ABT-450/r plus ABT-333 plus ribavirin for 12 weeks has the potential to achieve SVR in a high proportion of patients without the use of interferon. Further trials of these agents are under way.

    Predicting Response and Nonresponse
    In the interim, how can we tailor therapy and predict response rates? Investigators reported that patients infected with HCV genotypes 2 and 3 achieved SVR rates of 70%-80% in clinical trials. However, in real-life settings, lower SVR rates in the range of 55%-65% are reported. In work presented at DDW 2012, predictive factors for nonresponsive patients with genotypes 2 and 3 included daily alcohol intake greater than 40 g, HIV coinfection, low thyroid-stimulating hormone levels, the presence of cirrhosis, and the duration of infection.[8] These risk factors should be assessed and may suggest the need for an intensified treatment course.

    Further data presented at DDW 2012 documented the value of a major genetic predictive factor: a single nucleotide polymorphism in the upstream region of the interleukin-28B gene.[9] Genotype CC was the strongest factor predictive of SVR in patients with HCV genotype 1 who were treated with pegylated interferon and ribavirin. This CC genotype was also shown to be associated with a significantly higher rate of spontaneous clearance in both white and black patients with exposure to HCV. This information will be of value when counseling patients.

    The Bottom Line
    The bottom line is that the intense interest in developing and validating new strategies for the treatment of chronic HCV promises to eliminate the need for interferon and perhaps even ribavirin.

    Hepatitis C genotype affected predictive value of virologic response for SVR

    HCV genotype affected predictive value of virologic response for SVR

    Marcellin P. Hepatology. 2012;doi:10.1002/hep.25892.

    August 27, 2012

    The predictive value of viral response during HCV treatment to achieve sustained virologic response after therapy varied according to genotype in a recent prospective study.

    Researchers evaluated 7,163 patients with chronic HCV who received treatment with pegylated interferon (PEG-IFN) and ribavirin. All participants had an HCV RNA level of 50 IU/mL or more at baseline. Viral response (VR) at 2, 4 and 12 weeks of treatment was assessed as a potential predictor of sustained virologic response (SVR) after 24 weeks of follow-up without treatment, based upon HCV genotype.

    Across the entire cohort, SVR was achieved by 49.4% of patients (95% CI, 48.3%-50.6%). SVR according to VR and genotype occurred at 2, 4 and 12 weeks, respectively, at the following rates (all 95% CI):
    • Genotype 1: 66.2%, 68.4% and 60.3%
    • Genotype 2: 82.0%, 76.3% and 74.2%
    • Genotype 3: 67.3%, 67.3% and 63.8%
    • Genotype 4: 59.4%, 63.3% and 54.3%
    The overall SVR rate among evaluable participants after 24 weeks of untreated follow-up (SVR24) was 55.2%, and 45.9% for genotype 1 (n=4,119 patients), 80.2% for genotype 2 (n=913), 71.8% for genotype 3 (n=1,063) and 46.1% for genotype 4 (n=282).

    Patients who achieved VR at weeks 2, 4 or 12 had consistently high SVR24 rates. A VR by week 4 had the highest positive predictive value (PPV) among patients with HCV genotypes 1 (68.4%) and 4 (63.3%), while VR at week 2 had the highest PPV for genotype 2 (82.0%) and weeks 2 and 4 had the highest for genotype 3 (67.3%). The highest negative predictive value was lack of VR at week 12 for all genotypes.

    “The results of this large multinational trial demonstrate that, in the ‘real-world’ setting, high SVR24 rates can be achieved with [PEG-IFN] plus ribavirin in patients with HCV genotypes 1-4 who achieve early virologic response,” the researchers concluded. “However, the data also indicate that there is no universal prediction rule for SVR24 that applies to all patients and that the best PPV for SVR24 differs by genotype.”

    Disclosure: See the study for a full list of relevant disclosures.

    How Common is Portal Hypertension in Patients With NAFLD?

    How Common is Portal Hypertension in Patients With NAFLD?

    Patients with nonalcoholic fatty liver disease (NAFLD) are at risk for portal hypertension and esophageal varices, according to the September issue of Clinical Gastroenterology and Hepatology.

    The study also shows that factors such as advanced liver disease, type 2 diabetes, and obesity can be used to identify patients most likely to have portal hypertension, who should be examined by endoscopy for esophageal varices.

    With the increasing prevalence of obesity, NAFLD has become a common liver disease. NAFLD is characterized by a range of liver disorders, ranging from simple steatosis to features of cellular injury including necrosis and inflammation, with or without fibrosis.

    In some patients, NAFLD progresses to advanced fibrosis and cirrhosis, and even to end-stage liver disease and portal hypertension. In fact, portal hypertension might develop even before cirrhosis in patients with NAFLD. The most feared complication of portal hypertension is bleeding from esophageal varices, which can be fatal.

    It is not clear whether patients with NAFLD should undergo endoscopy examinations for esophageal varices before they develop cirrhosis. And little is known about how to identify patients with NAFLD who are most likely to develop esophageal varices or other signs of portal hypertension.

    Flavia Mendes et al. investigated the prevalence of portal hypertension and esophageal varices in a large series of patients with well-characterized and liver biopsy-confirmed NAFLD. They also looked at markers that could be used to identify patients most at risk for portal hypertension and esophageal varices.

    They found that portal hypertension and esophageal varices were not uncommon among patients with NAFLD. Among the 354 patients with NAFLD, 100 had portal hypertension at the time they were diagnosed with NAFLD (28.2%). Of these, 88 also had septal fibrosis or cirrhosis—the remaining 12 patients had either no fibrosis (stage 0) or mild fibrosis (stages 1–2), based on biopsy analysis (see figure).

    Correlation between portal hypertension and fibrosis, of various stages, among patients with NAFLD.

    In fact, among 204 patients with no or mild fibrosis (stages 0–2), 12 had portal hypertension (6%). However, these patients had a significantly higher grade of steatosis, based on biopsy analysis, compared with the 192 patients without portal hypertension.

    Splenomegaly was the most common sign of portal hypertension in patients with NAFLD; it was found in 25%, with ascites and portosystemic encephalopathy present in 12% and 7%, respectively. Splenomegaly might therefore be an early indicator of presence or risk of portal hypertension—spleen size should be measured routinely during abdominal imaging studies during diagnostic evaluation of patients with suspected NAFLD.

    The patients that developed portal hypertension were also likely to have thrombocytopenia, hyperbilirubinemia, cirrhosis, and obesity. Esophageal varices were associated with thrombocytopenia, type 2 diabetes, and splenomegaly.

    Mendes et al. conclude that portal hypertension and esophageal varices are common among patients with NAFLD. Signs of portal hypertension correlated with more advanced fibrosis, but also occurred in patients without fibrosis or with mild fibrosis.

    Features of advanced liver disease and insulin resistance can be used to identify patients with NAFLD who are likely to have or to develop portal hypertension—these patients should undergo endoscopy to identify esophageal varices.

    More Information on NAFLD:
    Read the article online.
    Mendes FV, Suzuki A, Sanderson SO, et al. Prevalence and indicators of portal hypertension in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2012;1028-1033.e2.

    Idenix: FDA Places IDX19368 Hepatitis C Treatment on Clinical Hold

    August 27, 2012

    Today Idenix placed a clinical hold on IDX19368, a nucleotide polymerase inhibitor - (no patients have been exposed to IDX19368). The FDA verbally informed Idenix of concerns related to serious heart issues seen in Bristol-Myers nucleotide polymerase inhibitor BMS-986094. On August 23 Bristol-Myers discontinued the phase II trial after one patient died, also nine patients were hospitalized and two remained hospitalized. As of yet, Bristol-Myers has not established a definitive relation between BMS-986094 and heart and kidney toxicity.

    Recently IDX184 which is another experimental nucleotide polymerase inhibitor from Idenix Pharmaceuticals, was put on partial hold because of the potential for heart damage. In today's press release (see below) the company stated under the request of the FDA patients who took part in the IDX184 trial are undergoing cardiac testing. 
    As part of the partial clinical hold placed on IDX184, the FDA has requested additional cardiac testing of patients in the ongoing phase IIb clinical trial of IDX184. More than 50 patients have been scheduled for echocardiograms, and the Company is on track to submit these data to the FDA in the coming weeks. To date, echocardiograms have been performed on a small number of these patients, and the results are normal.

    FDA places clinical hold on Idenix Pharmaceuticals’ hepatitis C drug IDX19368
    Last Updated:August 27, 2012 12:25

    Idenix Pharmaceuticals' shares fell as much as 12 percent on Monday on news that the FDA placed a clinical hold on its hepatitis C compound IDX19368 due to cardiac-related concerns about Bristol-Myers Squibb's BMS-986094, which belongs to the same nucleotide polymerase inhibitor drug class. The company also said the FDA had requested additional cardiac testing of patients in an ongoing Phase IIb trial of its other hepatitis C treatment, IDX184, as part of a recent partial clinical hold on the compound stemming from the BMS-986094 concerns, and that it expects to submit the data in the coming weeks.

    CEO Ron Renaud stated that "based on our discussions with the FDA, we understand the clinical hold [on IDX19368] is a precautionary decision." Idenix confirmed that no patients were exposed to IDX19368 thus far. Last week, Bristol-Myers Squibb reported that it would halt development of its therapy after one patient died and eight others were hospitalised in clinical trials.

    Renaud explained that while "both IDX184 and IDX19368 fall into the same broader class of NS5B inhibitors, and share the same active metabolite as BMS-986094,…there are many attributes of our compounds, particularly the prodrug approach, that we believe favourably differentiate the toxicity profiles" from BMS-986094. He added that Bristol-Myers Squibb "agreed to share relevant information on BMS-986094 with us and hope this helps us to resolve this issue quickly."

    Commenting on the news, Brean Murray Carret & Co. analyst Brian Skorney remarked, "I don’t think it takes both Idenix drugs off the table, but it does slow them down."

    Idenix Drops After FDA Places Hold on Hepatitis C Drug - (Bloomberg)
    Idenix Provides Update on IDX19368 Development Program - (GlobeNewswire)
    Idenix: FDA Places Hepatitis C Treatment on Clinical Hold - (Morningstar)
    Idenix Hep C Fortunes Fade Fast - (TheStreet)

    Press Release - Idenix Provides Update on IDX19368 Development Program

    IDX19368, for Which Idenix Has Submitted an IND Application, Has Been Placed on Clinical Hold by FDA

    CAMBRIDGE, Mass., Aug. 27, 2012 (GLOBE NEWSWIRE) -- Idenix Pharmaceuticals, Inc. (Nasdaq:IDIX), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today announced that the Company received verbal notice from the U.S. Food and Drug Administration (FDA) that a clinical hold has been placed on IDX19368, the Company's next-generation nucleotide polymerase inhibitor under development for the treatment of hepatitis C virus (HCV) infection. This news follows an announcement that Idenix made on August 16, 2012 related to a partial clinical hold placed on IDX184, the Company's lead nucleotide polymerase inhibitor also under development for the treatment of HCV.

    The FDA verbally informed Idenix that it placed IDX19368 on clinical hold due to concerns related to the serious cardiac-related adverse events reported for HCV patients treated with BMS-986094, a nucleotide polymerase inhibitor previously under development by Bristol-Myers Squibb Company. To date, no patients have been exposed to IDX19368.

    "Based on our discussions with the FDA, we understand the clinical hold is a precautionary decision made by the FDA in light of the adverse events seen with BMS-986094," said Ron Renaud, President and CEO. "Both IDX184 and IDX19368 fall into the same broader class of NS5B inhibitors, and share the same active metabolite as BMS-986094. However, there are many attributes of our compounds, particularly the prodrug approach, that we believe favorably differentiate the toxicity profiles from that of BMS-986094. We recently learned that Bristol-Myers Squibb has agreed to share relevant information on BMS-986094 with us and hope this helps us to resolve this issue quickly."

    As part of the partial clinical hold placed on IDX184, the FDA has requested additional cardiac testing of patients in the ongoing phase IIb clinical trial of IDX184. More than 50 patients have been scheduled for echocardiograms, and the Company is on track to submit these data to the FDA in the coming weeks. To date, echocardiograms have been performed on a small number of these patients, and the results are normal. Idenix's primary concern is patient safety and it will work diligently to expedite this review process and continue its discussions with the FDA with the goal of further advancing its drug candidates, IDX184 and IDX19368, in clinical development.

    ABOUT IDX19368
    IDX19368 is an unpartnered liver-targeted nucleotide prodrug of 2'-methyl guanosine and was selected from a prodrug series of approximately 350 compounds. It has shown high triphosphate levels in vivo, with a low potential for drug-drug interactions.

    In the third quarter of 2012, Idenix submitted an investigational new drug (IND) application for IDX19368 with plans to initiate clinical trials in the third quarter of 2012. However, these clinical trials will not commence until the FDA removes the clinical hold.

    ABOUT IDX184
    IDX184 is an unpartnered, novel, liver-targeted nucleotide prodrug of 2'-methyl guanosine, which includes Idenix's proprietary liver-targeting technology. This technology enables the delivery of nucleoside monophosphate to the liver, leading to the formation of high levels of nucleoside triphosphate, potentially maximizing drug efficacy and limiting systemic side effects with low, once-daily dosing.

    In July 2012, an independent data safety monitoring board reviewed the safety data for this study and confirmed that the side effect profile of IDX184 combined with PegIFN/RBV is consistent with that of PegIFN/RBV alone.

    The FDA placed IDX184 on partial clinical hold as reported on August 16, 2012. In previous clinical trials as well as the ongoing phase IIb clinical trial of IDX184 in combination with pegylated interferon and ribavirin (PegIFN/RBV), there has been no evidence to date of cardiotoxicity in patients dosed with IDX184 with PegIFN/RBV beyond that seen with PegIFN/RBV alone. There are currently no patients receiving IDX184 worldwide.

    Idenix Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts, is a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases. Idenix's current focus is on the treatment of patients with hepatitis C infection. For further information about Idenix, please refer to

    This press release contains "forward-looking statements" for purposes of the safe harbor provisions of The Private Securities Litigation Reform Act of 1995, including but not limited to the statements regarding the Company's development of drug candidates and its future business performance. For this purpose, any statements contained herein that are not statements of historical fact may be deemed forward-looking statements. Without limiting the foregoing, the words "expect," "plans," "anticipates," "intends," "will," and similar expressions are also intended to identify forward-looking statements, as are expressed or implied statements with respect to the Company's potential pipeline candidates, including any expressed or implied statements regarding the Company's ability to continue clinical development of IDX184 and IDX19368, the efficacy and safety of IDX184 and IDX19368; the likelihood and success of any future clinical trial involving IDX184 and IDX19368 and the successful development of these compounds. Actual results may differ materially from those indicated by such forward-looking statements as a result of risks and uncertainties, including but not limited to the following: there can be no guarantees that the Company will advance any clinical product candidate or other component of its potential pipeline to the clinic, to the regulatory process or to commercialization; management's expectations could be affected by unexpected regulatory actions or delays; uncertainties relating to, or unsuccessful results of, clinical trials, including additional data relating to the ongoing clinical trials evaluating its product candidates and clinical trials of compounds under development by other companies; changes in the Company's business plan or objectives; competition in general; and the Company's ability to obtain, maintain and enforce patent and other intellectual property protection for its product candidates and its discoveries. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. These and other risks which may impact management's expectations are described in greater detail under the heading "Risk Factors" in the Company's annual report on Form 10-K for the year ended December 31, 2011 and the quarterly report on Form 10-Q for the quarter ended June 30, 2012, each as filed with the Securities and Exchange Commission (SEC) and in any subsequent periodic or current report that the Company files with the SEC.

    All forward-looking statements reflect the Company's estimates only as of the date of this release (unless another date is indicated) and should not be relied upon as reflecting the Company's views, expectations or beliefs at any date subsequent to the date of this release. While Idenix may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so, even if the Company's estimates change.
    CONTACT: Idenix Pharmaceuticals Contacts:
             Kelly Barry (617) 995-9033 (media)
             Daniella Beckman (617) 224-4471 (investors)
    Source: Idenix Pharmaceuticals

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