Thursday, February 17, 2011

News; Hepatitis C Drug TMC649128

Medivir Kicks Off Phase 1a Trial of the Hepatitis C Polymerase Inhibitor TMC649128

Wed, 16 Feb 2011 01:37:23 EST Feb 16, 2011

Medivir AB, a research-based specialty pharmaceutical company focused on infectious diseases, announced the start of a phase 1a clinical trial with TMC649128 intended for the treatment of chronic hepatitis C virus infection. The Company said TMC649128 is a nucleoside NS5B polymerase inhibitor that has already demonstrated an attractive pre-clinical profile. It is anticipated that this profile would see TMC649128 be used in combination with HCV directly acting antiviral agents, given their high genetic barrier to resistance and antiviral activity across multiple HCV genotypes. In pre-clinical studies, TMC649128 displayed in vitro activity across multiple HCV genotypes and a high genetic barrier to resistance. The phase 1a trial is a double-blind, randomized, placebo-controlled single-ascending dose trial to assess the safety, tolerability and pharmacokinetics in healthy volunteers and will be conducted in Belgium.

TMC649128 is being developed in collaboration with Tibotec Pharmaceuticals. According to a release, Medivir entered a Research and Development agreement in the field of hepatitis C virus polymerase with Ortho Biotech Products LP, an affiliate of Tibotec in May 2008. The development of TMC649128 falls under this agreement and by entering clinical development, a milestone payment of Euro 7 million has been triggered for payment to Medivir. "We are extremely excited to see TMC649128, our first HCV nucleoside inhibitor, move into clinical development", stated Bertil Samuelsson, CSO of Medivir. "The start of this phase 1a trial underlines Medivir's commitment to the development of novel and innovative hepatitis C treatments. We view nucleoside inhibitors as cornerstone components of future HCV treatment paradigms in combination with directly acting antiviral agents and a TMC649128 component could set them apart from other HCV drug classes."

The Company noted that Hepatitis C is a blood-borne infectious disease of the liver and is a cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3 percent of the world's population, are infected with hepatitis C virus (HCV). The CDC has reported that almost three million people in the United States are chronically infected with HCV. Medivir and Tibotec are also jointly developing the once daily protease inhibitor TMC435 for treatment of hepatitis C virus infections (HCV). Medivir is a research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases.
More information:

National News
at 14:55 on February 17, 2011, EST.

Harm reduction groups to intervene in court fight over safe-injection site
The Canadian Press

VANCOUVER - The operators of Vancouver's safe drug-injection site will have some allies in a Supreme Court of Canada case that will decide the future of the facility.
The high court has granted intervenor status in the case to the International Harm Reduction Association, the Canadian HIV/AIDS Legal Network and CACTUS Montreal, which will all argue in favour of facility, called Insite.
The federal government is challenging a B.C. Appeal Court ruling that found Insite is a health facility and falls under provincial jurisdiction, not federal.
The site had been operating under an exemption from federal drug laws, but the Conservative government had indicated it wanted to end that exemption and see the supervised injection site closed.
HIV/AIDS Legal Network director Richard Elliott says Insite is an international success story but the federal government is ignoring scientific evidence and the need for harm reduction policies.
Rick Lines of the Harm Reduction Association says there's extensive evidence that safe-injection sites save lives by reducing the injection behaviour that can transmit HIV and hepatitis C.
Content Provided By Canadian Press.
Lawmakers urge investigation into oversight of VA dental clinic
By Joanne Huist Smith, Staff Writer
Updated 8:45 AM Thursday, February 17, 2011 DAYTON — Three Dayton area congressmen are calling for an investigation into the lack of oversight that allowed a dentist at a Dayton VA Medical Center clinic to violate medical standards for nearly two decades, potentially exposing hundreds of veterans to blood-borne pathogens..
.From Journal of Viral Hepatitis
Optimal Combinations of Ultrasound-based and Serum Markers of Disease Severity in Patients with Chronic Hepatitis C

J. F. L. Cobbold; M. M. E. Crossey; P. Colman; R. D. Goldin; P. S. Murphy; N. Patel
Authors and Disclosures
Posted: 02/16/2011; J Viral Hepat. 2010;17(8):537-545. © 2010 Blackwell Publishing

Discussion Only/ Full Text
Enhanced Liver Fibrosis panel (ELF ), Hepatic-transit-time analysis (HTT)

Transient elastography (TE), Aspartate aminotransferase (AST) to platelet ratio index(APRI), TE, ELF and HTT. For the diagnosis of cirrhosis, ELF performed as well as TE, but better than APRI.

ELF performed as well as both TE and APRI for the diagnosis of moderate-to-severe fibrosis from mild disease. The diagnostic accuracy for HTT was substantially lower than that of the other markers. In addition, HTT did not contribute significantly to the marker combinations, despite a modest increase in accuracy. HTT was also the least reliable test, with an ICC of 0.8 (compared to reliability in excess of 90% for the other markers).

This study has combined markers on the basis of cost and practicality. As increasing numbers of biomarkers have been shown to predict liver disease severity, such considerations will help determine which markers enter clinical practice or are employed in clinical trials.
The use of a three-group ordinal regression analysis enabled the interactions between markers to be investigated in combinations. It should be noted that a single cheap test, the APRI score, correctly predicted fibrosis severity in 92% of those whose severity was correctly predicted by a two-test model, including either ELF or TE, and 88% of those correctly predicted by a three-test model, including both TE and ELF. Scrutiny of the multi-marker models allowed an assessment of the interplay between tests when predicting the histological stage.

When a component of the combination was significant, its removal from the model significantly altered the goodness-of-fit of that particular model and those tests were considered complementary. If there was no significant change on removal of a test, it was considered redundant. For example, both ELF and TE significantly enhanced a two-test model of fibrosis containing the APRI score, while neither ELF nor TE contributed significantly to the three-test model provided by the other two tests (Table 6).

This does not imply that either test is not a predictor of fibrosis, but that its inclusion in that model did not provide additional information to the other tests; that is, there was a degree of redundancy.

As this was a head-to-head analysis without missing data, systematic bias between tests was minimized. The tight exclusion criteria and well-matched patient groups minimized potentially confounding factors. The analysis approach enabled the contribution of each test to the accumulated combinations to be quantified.

In the context of the published literature, the diagnostic accuracy achieved for the tests using ROC curves for the diagnosis of cirrhosis from less severe fibrosis is comparable to that found by previous studies using TE and/or APRI, while the diagnostic accuracy for the separation of mild from more severe fibrosis exceeded 80% for the APRI score, ELF panel and TE, but only just exceeded 70% for HTT, which was also comparable to other studies.[23–26] Previous publications have proposed algorithms where agreement or concordance between tests of similar diagnostic accuracy lent confidence to the interpretation of a binary result and proposed avoidance of diagnostic liver biopsy.

Where results were discordant, biopsy was proposed.[23] This current study provides evidence on whether tests are complementary or redundant. This may enhance the building of optimal combinations of tests. If tests are complementary, agreement will reflect the disease state. If tests are redundant, agreement may simply reflect that the tests are measuring a similar parameter, which may or may not be closely related to the disease state or reference standard.

While this study aimed to quantify the contributions of each marker to models of disease severity, some features are qualitative. In particular, HTT may be performed at the time of abdominal ultrasound examination, which is a part of routine assessment of patients with chronic liver disease, reducing the additional costs. Examination of the dynamic enhancement of hepatic parenchyma increases the detection of hepatocellular carcinoma,[27] which is a major complication in patients with cirrhosis, but is also seen in pre-cirrhotic disease in patients with chronic hepatitis B virus infection. Such a technique may, therefore, be an appropriate addition to APRI in those without access to TE or ELF markers, and in cohorts of patients where imaging of the liver is required. However, the evidence from this study demonstrates its inferiority for the assessment of fibrosis compared to the other markers studied.

This study was limited by the use of liver biopsy with inherent sampling variability,[1,3] itself a surrogate marker of disease, as a reference standard. Sampling variability was minimized by exclusion of samples.

Biopsy criteria in many centres lead to the underrepresentation of patients with mild disease, where histology is the reference standard compared to the patient population as a whole. Moreover, a significant minority of patients with normal transaminase tests, who are less likely to undergo biopsy, are found to have a substantial degree of fibrosis.[28]

Patients with clinically overt or decompensated cirrhosis of known aetiology do not usually require biopsy for clinical purposes and hence the full spectrum of disease is unlikely to have been fully represented, leading to potential selection bias in the current study population, which may affect ROC curves and derivatives.[29] However, the ordinal regression model presented is robust to such effects, as strict cut-off values and assumptions about disease prevalence are not used.
The cohort examined in this study is large for a study examining nonserological techniques, yet small compared to a number of studies of TE and serum markers. As such, extrapolation of the results to create clinical algorithms was not considered appropriate.

TE and ELF were found to perform equally in this study. A larger study may have the power to detect a difference in the diagnostic performance of these tests if such a difference exists. While this study provides novel information about the relative diagnostic performance of four markers, singly and in combination in the context of cost and practicality, a larger scale cost-benefit analysis would allow further appraisal of these tests for widespread incorporation into clinical usage. Consideration should also be made of potential access to hardware, appropriately trained personnel or external laboratory services. Finally, for noninvasive techniques to replace liver biopsy, attempts to predict clinically important endpoints prospectively using marker combinations are warranted.

To conclude, this impartial head-to-head analysis of the diagnostic performance of two serum and two imaging-based markers of fibrosis shows that ELF and TE have a high diagnostic accuracy for the prediction of fibrosis and that HTT performs less well than the other tests. A combination of APRI with either ELF or TE effectively predicts fibrosis stage using a three-group model of fibrosis, but that, in combinations of three or more tests leads to redundancy of information. This study may provide a basis for future clinically based cost-benefit analyses to assess optimal combinations of markers.

Bulletin for Hep C Patients: Building on Dr. Oz's Advice
A recent, popular television show educated viewers on the importance of raising glutathione levels. Although the practical suggestions given were accurate, there is much more to know about this topic. Especially important for Hepatitis C patients, two supplements demonstrate unparalleled glutathione-boosting power. Read more.

FYI; Dr. Oz's yellow brick road: Oprah's favorite doctor promotes quackery
Aiding and abetting Oz is a rotating cast of colorful guests. For example, he gave air time to Dr. Joseph Mercola, a fan of krill oil for "support" of joint, liver and heart health. Unsurprisingly, Mercola sells the product on his Web site - where he also advanced the novel idea that cancer might be a fungus and, if so, should be responsive to baking soda. Mercola has been twice warned by the FDA about his questionable claims.


Public Release: 16-Feb-2011
Journal of Infectious Diseases

Trial suggests statin may affect markers associated with progression of HIV
A recent multicenter clinical trial of atorvastatin found that although the drug did not inhibit plasma HIV RNA levels, it did inhibit expression of cellular markers of immune activation and inflammation in patients with HIV infection. Available online, the findings are published in the Journal of Infectious Diseases.
Contact: John Heysjheys@idsociety.org703-299-0412
Infectious Diseases Society of America
Non-invasive tests can predict which HIV-positive women have increased risk of liver disease
15 February 2011
9% prevalence of hepatitis C co-infection among UK HIV patients
14 February 2011
Liver Cancer

Apricus Biosciences and FDA Initiate PrevOnco(TM) SPA Phase III Clinical Protocol Discussion
SAN DIEGO, Feb. 17, 2011 (GLOBE NEWSWIRE) --

Apricus Biosciences, Inc. ("Apricus Bio") (Nasdaq:APRI), announced today that it is currently in discussions with the U.S. Food and Drug Administration ("FDA") relating to the PrevOnco™ Special Protocol Assessment ("SPA") Phase III protocol submitted by the Company in December 2010.

In the first response received by Apricus Bio relating to this SPA, the FDA accepted some of the questions submitted by the Company and commented on the rest. The Company's Clinical Advisory Board, formed to focus on the clinical development of PrevOnco™, Apricus Bio's first oncology compound, will meet in late February to discuss the FDA response and comments, and the Company will prepare a response according to feedback from the Clinical Advisory Board. In addition, the Company may request a meeting with the FDA to accelerate the FDA's SPA Phase III protocol review process.

Dr. Bassam Damaj, President and Chief Executive Officer of Apricus Bio, noted, "We will continue to work diligently with the FDA and respond to their comments as expeditiously as possible."

PrevOnco™ is Apricus Bio's proprietary treatment for hepatocellular carcinoma (liver cancer). The Company announced in late November 2010 that it intended to file the protocol for a proposed Phase III clinical trial of PrevOnco™ with the FDA. Pursuant to the FDA's SPA program, the agency provides approval for the trial's design, clinical endpoints and statistical analysis. A company's SPA is not considered accepted until the FDA comments and agrees to all of the questions and protocol design submitted therein. Once the SPA is accepted, the PrevOnco™ Phase III study is expected to take about 12-24 months, depending on patient recruitment. If the trial shows positive results within the parameters agreed upon in the SPA, the data would then be expected to provide the basis for the filing of a New Drug Application for marketing approval of PrevOnco™ for the treatment of liver cancer in the U.S.
The FDA granted PrevOnco™ Orphan Drug status in August 2008.

The product incorporates lansoprazole, a commonly marketed anti-ulcer compound which has shown strong anti-cancer activity in mice bearing human liver tumors. Upon acceptance of the SPA, the Company expects that the Phase III study will enroll up to 218 patients who have advanced, unresectable hepatocellular carcinoma who no longer respond to Nexavar® (the currently marketed first-line anti-cancer treatment for patients with this type of liver cancer). The subjects will receive Nexavar® and doxorubicin (the widely used chemotherapy anti-cancer drug), plus either PrevOnco™ or a placebo. Nexavar® is marketed in the U.S. by Onyx Pharmaceuticals, Inc. and Bayer HealthCare Pharmaceuticals, Inc., with close to $1 billion in sales, and is approved in more than 90 countries for the treatment of patients with hepatocellular carcinoma.

For further information on Apricus Bio, visit and for information on its subsidiaries please visit or

Off The Cuff

A Summary of Social Security Disability Benefits for Viral Hepatitis
If chronic Hepatitis B or C has rendered you incapable of performing any work, Social Security disability benefits may provide a safety net. Understanding the guidelines for disability will help those truly in need to better work their way through an intensive application process.

Read more.

From Nature;
It takes two to tango: FDA ponders a new regulatory dance
February 16, 2011
Two drugs taken together can sometimes be greater than the sum of their parts. And for certain diseases, including cancer, drug combinations are essential to achieve any therapeutic benefit. But the existing regulatory framework for testing and approving new drugs focuses primarily on the effectiveness and safety of individual experimental compounds. This means that it’s been nearly impossible to conduct early clinical trials on multiple new drugs at the same time.
All that might soon change. In December, the US Food and Drug Administration (FDA) released draft guidance outlining a path toward developing combinations of unapproved drugs. “We need to enable these innovative targeted therapies in a way that isn’t possible in traditional drug development,” Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research (CDER), told Nature Medicine.

“The places we think are most likely to have interest, at least initially, are oncology and infectious diseases,” says CDER deputy director for clinical science Robert Temple. That’s because pathogens such as tuberculosis and HIV quickly develop drug resistance when only single-agent therapies are used. Similarly, tumors often harbor multiple gene mutations that allow cancer to grow and that need to be targeted simultaneously.
Combination drug development at present usually involves phase 3 trials in which fixed doses of two drugs are tested both alone and in tandem against a placebo treatment. To get to that stage, however, experimental drugs usually need to be taken through earlier-stage trials in isolation, even if they have limited utility on their own. The new proposed guidelines would allow drug makers to forego monotherapy trials and conduct combined drug studies earlier in the development process, when there are compelling reasons and preclinical data to support such a move.
Continue reading "It takes two to tango: FDA ponders a new regulatory dance" »

Is The FDA Press Office Squelching The Media?
The workings of the media may not always be clear, but one long-standing practice - especially among medical journals - is to apply an embargo on information before publication. Lately, however, this has become controversial as a growing number of journals and institutions are adding various requirements, notably barring journalists from seeking expert comment prior to the moment an embargo is lifted.....

Superbugs in the Supermarket

Check Out The Video
Canadians are becoming increasingly resistant to antibiotics. As a result, people are getting sicker and are taking longer to get well. It is now not uncommon for people to be administered antibiotics through an IV because the usual drugs in pill form can't fight off their infections.
While we've all heard that over-prescription of antibiotics to people is one cause of the resistance, what many Canadians don't know is that another major cause is because the animals we eat are also given large amounts of antibiotics. And not just when they're sick: healthy animals can be fed antibiotics every day because it makes them grow bigger, faster.
In an important story about human health, and the food we eat, Marketplace tests 100 samples of chicken bought at major supermarkets from across the country.
In Superbugs in the Supermarket, we name popular brands, and also reveal surprising information about organic poultry that claims to be raised without antibiotics.

Louisiana Attorney General Sues Glaxo Over Avandia
Yet another state attorney general has filed a lawsuit charging GlaxoSmithKline with fraudulently marketing its controversial Avandia diabetes pill. This time, Louisiana Attorney General Buddy Caldwell has gone to court; a few months earlier, his counterpart in Utah did the same (back story). At issue is the allegation that the drugmaker knowingly marketed a pill that caused harm to citizens, leading a state Medicaid program to dramatically overpay.

FDA urged to ban cola caramel coloring
by Food Safety News Rn T.Com
Washington, D.C.-based Center for Science in the Public Interest filed a petition Wednesday asking that the U.S. Food and Drug Administration ban two types of carcinogenic chemicals often labeled as "caramel coloring," most often on products like Coca-Cola, Pepsi and other dark-colored colas.According to CSPI, the artificial brown coloring is made by reacting sugars with ammonia and sulfites under high pressure and temperatures and those reactions "result in the formation of 2-methylimidazole and 4 methylimidazole, which in government-conducted studies caused lung, liver, or thyroid cancer or leukemia in laboratory mice or rats."CSPI referred to a National Institutes of Health National Toxicology Program study that found "clear evidence" that both 2-MI and 4 MI are animal carcinogens.
Click here to read the story
Read more: - FDA urged to ban cola caramel coloring
Voluntary Nationwide Recall of Jantoven® Warfarin Sodium Tablets, USP, 3mg, Due to Mislabeled Bottles
By Upsher-Smith LaboratoriesFeb 17, 2011 - 8:51:06 AM - MAPLE GROVE, Minn., -- Upsher-Smith Laboratories, Inc., of Maple Grove, Minnesota is voluntarily recalling one lot (lot #284081) of Jantoven® Warfarin Sodium, USP, 3mg Tablets, an anticoagulant with an expiration date of September 2012, NDC # 0832-1214-00. The company is initiating the recall as a precautionary measure after a single bottle labeled as Jantoven® Warfarin Sodium, USP, 3mg Tablets was found to contain tablets at a higher, 10mg strength before it was dispensed. To date, the company has identified no additional mislabeled bottles.

At Upsher-Smith, patient safety is of foremost concern.

The primary risk of substituting 10mg warfarin for 3mg warfarin is overdosing more than 3 times the labeled amount which leads to excessive anticoagulation that could be expected to result in life-threatening hemorrhage in patients.Consistent, continuous dosing of warfarin is necessary for optimal care for many ill patients. For this reason, patients' doses must be adjusted by regular measurements of the degree of anticoagulation to assure warfarin use is safe and effective. Either abrupt interruption of this medication, or administration of an inappropriately high dose, could present a serious health risk. Patients should check with their health care provider regarding the appropriateness of their current therapy prior to making any change.

The two Jantoven tablets can be readily identified by color: the 3mg tablet is tan and the 10mg tablet is white. In addition, the 3mg tablet is imprinted with the letters WRF, a line, and the number 3 below the line. The reverse side of the 3mg tablet carries the number 832. The 10mg tablet is imprinted with the letters WRF, a line, and the number 10 below the line. The reverse side of the 10mg tablet carries the number 832.Upsher-Smith Laboratories is working cooperatively with the U.S. Food and Drug Administration to implement a nationwide recall as quickly and efficiently as possible.The product lot was distributed to wholesalers, retail chains and independent pharmacies throughout the United States.

The company is notifying its pharmacy customers and wholesalers, and arranging for the return of all recalled product. The product was packaged at the Upsher-Smith plant in Plymouth, Minnesota.Consumers and pharmacists can call the Upsher-Smith medical information line at 1-888-650-3789 for more information and to access product details, Monday-Friday between 8:00 a.m. and 5:00 p.m. (CST).Any adverse reactions may be reported to the FDA's MedWatch Adverse Event Reporting program either online, by regular mail or by fax.Online: Use postage-paid, pre addressed Form FDA 3500 available at: .
Mail to address on the pre-addressed form. Fax: 1-800-FDA-0178

About Upsher-SmithUpsher-Smith Laboratories, Inc., founded in 1919, is a privately held pharmaceutical company that develops, manufactures and markets prescription and over-the-counter products. Upsher-Smith's product portfolio focuses in the areas of women's health, dermatology, cardiology, and CNS diseases. Upsher-Smith is headquartered in Maple Grove, Minn. For more information, visit
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