February 13, 2011

HCV: Genotype & Quasispecies

Alan Franciscus Editor-in-Chief
Hepatitis C Support project
HCV Advocate

The term genotype refers to different genetic variations or strains of hepatitis C. The variance in genetic differences is approximately 1/3 between the different genotypes. There are six major groups or genotypes numbered 1 to 6 although some experts believe that there may be as many as 11. Within each genotype are further divisions called subtypes (for example 1a and 1b) and quasispecies.

HCV constantly changes and mutates as it replicates—more than 1 trillion hepatitis C virions replicate each day. During the replication process, the hepatitis C virus will make ‘bad’ copies or errors in the genetic make-up of the newly replicated viruses. The process of constant mutation helps the virus evade the body’s immune response---when the dominant quasi-species is eradicated, another quasi-species emerges. This requires the immune system to constantly identify and kill the newly emerged variants. This is one of the reasons why so many people develop chronic disease. Scientists believe there are literally millions of different HCV quasispecies in everyone infected with hepatitis C, which are unique to everyone because of the individual’s immune response to HCV and quasispecies constantly change over time. In addition, it has been suggested that quasispecies play a role in disease progression and treatment response, but this is still controversial and more studies are needed to fully appreciate the role of quasi-species.

This variability (genotype, subtypes and quasispecies) of hepatitis C has made it difficult to treat and to develop a vaccine that will protect against all HCV strains although recent advances in vaccine development have been encouraging.

Testing for Genotype, Subtype & Quasispecies

A blood test is required for the genotype test. Generally, a quasispecies test is only performed for research purposes. HCV genotype testing is only done once since the genotype does not change.

Genotype Distribution

HCV genotypes and subtypes are distributed differently in different parts of the world, and certain genotypes predominate in certain areas. Genotypes 1-3 are widely distributed throughout the world. Subtype 1a is prevalent in North and South America, Europe, and Australia. Subtype 1b is common in North America and Europe, and is also found in parts of Asia. Genotype 2 is present in most developed countries, but is less common than genotype 1. Some studies suggest that different types of HCV may be associated with different transmission routes. Subtype 3a appears to be prevalent among injection drug users and it is believed that they were introduced into North American and the United Kingdom with the widespread use of heroin in the 1960s.

Importance of Genotype Information

HCV Genotype information is important because of the role it plays in predicting HCV medical treatment response, treatment duration and the dose of ribavirin. However, it should never be used as a reason to deny treatment.

Prediction of Treatment Response

Genotype information is important because it can be used as a predictor of a positive treatment outcome or response. The sustained virological response rates for pegylated interferon plus ribavirin are much higher in genotype 2 and 3 compared with genotype 1.

Other predictors of treatment response include:

• Age of Patient – younger patients respond more favorably especially people under 30 years old.

• Sex of Patient – women are more likely to respond to therapy than men

• Histological (health of the liver) – people with minimal damage respond better to treatment

• Viral Load – the lower the viral load (less than 800,000 IU/mL) the more likely one is to respond to current medications

• Obesity or high Body Mass Index is associated with lower treatment response rates

• Steatosis or fatty liver reduces the chance of responding to treatment.

• Race—Caucasians and Asians respond better to current HCV medications.

Genotype and Treatment Response

Genotype 1 is considered the most difficult to treat with current HCV medications. However, treatment response rates with the newer forms of pegylated interferon plus ribavirin have been remarkably high--up to a 51% sustained virological response rate (SVR – undetectable viral load six months post treatment). Genotype 2 and 3 respond even better to current medications—up to 80%. There is some evidence that genotype 2 responds better to current HCV therapies than genotype 3, but this needs to be confirmed in prospective studies. The reason that a particular genotype responds to treatment differently is unknown, but it is speculated that specific genotypes of the hepatitis C virus live longer or shorter than others. For example, it has been theorized that genotype 2 and 3 of the hepatitis C virus do not live as long (viral lifecycle) as genotype 1 thus making eradication of genotype 2 and 3 easier.

Genotype and Treatment Duration

Genotype is also a factor in the period of time required to treat with current HCV medications. Generally, genotype 1 is treated for 48 weeks and genotype 2 and 3 are treated for 24 weeks. However, there are studies underway to determine the most optimal treatment duration based on certain factors. For instance, some experts believe that people with genotype 1, high viral load should be treated for 72 weeks instead of 48 weeks to maximize treatment response rates. There are also studies evaluating treating people with genotype 2 for 12 weeks and genotype 3 for 48 weeks.

Genotype and HCV Medication Dosage

Genotype information is also important for establishing the appropriate dose of ribavirin. For instance, people with genotype 2 and 3 are given 800 mg a day of ribavirin (flat dose), whereas the ribavirin dose for people with genotype 1 is dosed by body weight.

Mixed Genotypes

A person can become infected with more than one genotype. Data is almost non-existent on being infected with more than one genotype, but some experts believe it may effect treatment response and HCV disease progression.

Steatosis and Genotype

Steatosis (fatty infiltrates of the liver) is a well recognized feature of hepatitis C infection. Steatosis can contribute to HCV disease progression and lower treatment response although the exact mechanism is not completely understood. People with HCV genotype 3 are more likely to develop steatosis and it is believed that HCV genotype 3 is an independent risk factor and may actually play a direct role in the development of steatosis. It has been reported that when genotype 3 individuals are successful treated that steatosis will generally improve and for some steatosis will disappear.

Genotype and HCV Disease Progression

In regards to genotype and HCV disease progression, early limited data suggested that genotype 1b was associated with a more severe disease progression than in genotype 1a or 2, but further studies have not been able to confirm this observation.

Genotype and Liver Transplantation

Genotype 1 (especially 1b) has been associated with a more rapid fibrosis progression in people who have received a liver transplant.

Source

Loving your liver: Organ crucial to good health

Published: Friday, February 11, 2011
By Dr. Allen Yudovich
Henry Ford Health System

Of all the body’s vital organs, the heart is the one that gets the most attention this month. But right underneath it is one of the hardest-working organs we have, our liver. It doesn’t carry the touch of romance the heart does, but it is crucial to our well-being.

Our livers change food into nutrients and filter out harmful substances. The vital functions it performs include:

• converting nutrients into energy, hormones and other essential chemicals;
• cleansing toxic substances (including alcohol) from the blood, then neutralizing or rerouting them for disposal;
• processing drugs;
• storing vitamins, minerals, sugars and iron;
• regulating fat and cholesterol; and
• manufacturing bile -- a fluid that helps digest food.

The liver is also generally very good at keeping itself healthy. When it stops functioning well, the term liver disease is often used. But there are actually many forms of liver disease. When symptoms appear, they may include jaundice (a yellowing of the skin or eyes), abdominal pain, lose of appetite and weight loss, dark urine and pale bowel movements. Sometimes the first indication of a problem is found in the results of liver function tests ordered by a physician.

Cirrhosis

Some forms of liver disease are more common in older adults. Cirrhosis most frequently develops after years of alcohol abuse, although moderate drinkers sometimes develop it as well. Over time, the liver becomes scarred and loses its ability to do what it was designed to. Other liver diseases, including hepatitis B, C and D, can also lead to cirrhosis.

As the disease progresses, symptoms that may develop include nausea, fatigue, itching, vomiting blood and a swollen abdomen.

When cirrhosis is caused by excessive drinking, avoiding alcohol and eating a healthy diet may be beneficial because of the liver’s ability to regenerate itself. Medication is used to treat cirrhosis caused by viral hepatitis.

Cirrhosis is also one of the risk factors for liver cancer, which most often affects people older than 40. It also affects men more frequently than women. Other risk factors include smoking, heavy drinking, hepatitis B and C and cancer in another area of the body.

Liver cancer

Liver cancer can be either primary (meaning it started in the liver) or secondary (beginning elsewhere in the body and spreading to the liver). Secondary liver cancer is far more common than primary, because blood that may carry cancer cells is filtered through the liver.

Symptoms include abdominal pain or swelling, jaundice and weight loss, but these rarely appear in the early stages of the disease. Various tests are used to confirm a cancer diagnosis. These may include a biopsy, CT scan, an MRI, ultrasound and blood tests.

Treatment options include surgery, chemotherapy and radiation, along with newer treatments such as radiofrequency ablation, which uses heat to destroy tumors, and cryosurgery, which uses cold to do the same thing. A liver transplant could also be necessary.

Treatment is most successful when the cancer is diagnosed in an earlier stage and when the patient does not also have cirrhosis.

Hepatitis

All forms of hepatitis are inflammations of the liver. The symptoms are similar to other forms of liver disease, but are often mild. A blood test is needed to confirm a hepatitis diagnosis. Treatment ranges from bed rest and avoiding alcohol to medication, depending on the form of hepatitis someone has.

Primary biliary cirrhosis

This is a chronic inflammation of the liver’s bile ducts that affects women more than men. Those who contract it are usually between 40 and 60 years old. It can lead to cirrhosis and eventually destroy the bile ducts. A healthy diet and medication can alleviate the symptoms, which include itching, fatigue and jaundice. A liver transplant may eventually be recommended.

Alcoholic liver disease

As its name implies, this disease is tied to alcohol abuse, although not all heavy drinkers develop it. Alcoholic liver disease generally develops over a period of years and leads to cirrhosis. Symptoms often don’t appear in the early stages of the disease. When they are present they may include abdominal pain, jaundice, fever, excessive thirst and a loss of appetite. They may also worsen after heavy drinking.

All of the above symptoms could also be indicators of a different illness. Anyone who experiences these symptoms should discuss them with their physician.

Allen Yudovich, M.D., is a gastroenterologist at the Henry Ford Medical Center - Fairlane in Dearborn. For an appointment call (800) HENRYFORD.

Source
Antiviral Res. 2011 Feb 1. [Epub ahead of print]

Rai R, Deval J.

Alios BioPharma, South San Francisco, USA.

Abstract

Current therapy for chronic hepatitis C virus (HCV) infection constitutes a combination of pegylated interferon alfa-2a or alpha-2b and ribavirin. Although successful for many patient populations, this regimen has numerous limitations, including non-response, relapse, poor tolerability and long duration of treatment. To address these shortcomings, new small molecule agents are advancing in clinical development. Most of the current clinical candidates act by directly inhibiting key enzymes in the viral life-cycle: the NS5B polymerase, or the NS3/4A protease. Less well-studied, the non-structural 4B (NS4B) protein has recently emerged as an alternative target for Direct-acting Antiviral Agents (DAAs). NS4B is a 27-kDa membrane protein that is primarily involved in the formation of membrane vesicles-also named membranous web-used as scaffold for the assembly of the HCV replication complex. In addition, NS4B contains NTPase and RNA binding activities, as well as anti-apoptotic properties. This review summarizes the current understanding of the structure and functions of NS4B, an essential component of the replication machinery of HCV. In this literature and patent review, we report the recent developments in anti-NS4B drug discovery. These advances open the possibility for future combination therapies with other DAAs.

Copyright © 2011. Published by Elsevier B.V.

PMID: 21295075 [PubMed - as supplied by publisher]

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Cirrhosis Patients at Increased Risk of Extrahepatic Cancer

Last Updated: February 07, 2011

Patients with liver cirrhosis have more than double the risk of developing extrahepatic cancer than the general population, and they also have a significantly increased risk of hepatocellular carcinoma, according to a study published in the February issue of Clinical Gastroenterology and Hepatology.

MONDAY, Feb. 7 (HealthDay News) -- Patients with liver cirrhosis have more than double the risk of developing extrahepatic cancer than the general population, and they also have a significantly increased risk of hepatocellular carcinoma (HCC), according to a study published in the February issue of Clinical Gastroenterology and Hepatology.

Evangelos Kalaitzakis, M.D., of the University of Gothenburg in Sweden, and colleagues investigated the incidence of malignant neoplasms in patients diagnosed with cirrhosis between 1994 and 2005. Of the 1,019 patients, 68 percent were men, 48 percent had alcoholic liver disease (ALD), 10 percent had hepatitis C virus (HCV), and 12 percent had both ALD and HCV.

The researchers found that, compared to the general population, patients with cirrhosis were at increased risk of HCC (26-fold); cholangiocarcinoma (13-fold); colorectal cancer (four-fold); and cancers of the esophagus (eight-fold), pancreas (five-fold), and lung (five-fold). HCC occurred more frequently among patients with HCV than other diseases, and the risk of HCC among patients with HCV was similar whether they had ALD or not. Patients with non-ALD cirrhosis were at increased risk for cholangiocarcinoma; whereas, the risk for extrahepatic cancers increased mainly among patients with ALD and cirrhosis.

"This study confirms the association of liver cirrhosis with HCC and further indicates that non-HCC malignant neoplasms may be more common in patients with cirrhosis compared with the general population," the authors write.

Abstract
Full Text (subscription or payment may be required)

Source
Norra MacReady

February 7, 2011 — Even with conscientious care and state-of-the-art medication, HIV-infected men are at risk for hepatitis C virus (HCV) seroconversion and should have access to ongoing HCV surveillance, the authors of a new study say. Their findings were published online January 31 and appear in the February print issue of Clinical Infectious Diseases.

HCV has become "a leading cause of non-AIDS related morbidity and mortality for HIV-infected persons in the highly active antiretroviral therapy (HAART) era," lead author Lynn E. Taylor, MD, from Brown University, Providence, Rhode Island, and coauthors write. They estimate that up to 30% of HIV-infected people in the United States are coinfected with HCV.

At this time, the US Public Health Service recommends testing for HCV when a patient is initially diagnosed with HIV infection, but not thereafter. However, reports are now surfacing of acute HCV outbreaks in Europe, Australia, New York, and California among HIV-infected men who have sex with other HIV-infected men and engage in potentially traumatic practices such as unprotected anal sex, use of sex toys, multiple partners, and manual insertion, which may involve some exchange of blood. Because HCV treatment is most effective during the acute stages of infection, "it is vital to diagnose incident HCV infection in HIV-infected persons," the authors say.

For a better idea of the risk for acute HCV infection among HIV-infected men, the researchers studied behavioral and demographic factors associated with HCV antibody seroconversion in men participating in the AIDS Clinical Trial Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) study. The ACTG was established in 1987 by the US Department of Health and Human Services, the National Institute of Allergy and Infectious Diseases, and the National Institutes of Health Division of AIDS, and is the largest HIV clinical trials organization in the world. ALLRT is a randomized cohort study of the long-term immunologic, virologic, pharmacologic, and clinical outcomes associated with the use of HAART by HIV-1-seropositive patients. It was started by ACTG in 2000.

Starting in 2002, patients participating in ALLRT have been tested for HCV on entry, with follow-up testing every 96 weeks beginning in 2006. Seventeen other ACTG-funded trials also test patients for HCV on entry and at various follow-up intervals, between 1996 and 2002. The authors determined the incidence of HCV infection from 1996 to 2008 among men participating in these studies. Of those 2848 patients, 2629 had at least 1 HCV antibody test result, with 264 (10%) of those individuals testing positive at baseline. Of the remaining 2365 patients, 1830 had at least 1 subsequent HCV antibody test and were included in this analysis. Their mean age at the time of the initial negative HCV antibody result was 42 years; other demographic information is shown in the table. The mean interval for HCV testing was 2.8 years for HCV seroconverters and 2.6 years for nonseroconverters.

Table

Characteristic   Percentage

Race
 * White 57%
 * Black 22%
 * Hispanic 18%
 * Asian/Pacific Islander 2%
 * Native American 1%

College-educated 70%

Using HAART 94%

Current or prior injection drug use at study entry 6%

HCV seroconversion occurred in 36 of the men studied (2%), for an overall incidence of .51 cases per 100 person-years. Twenty-five percent of the seroconverters reported a history of injection drug use compared with 5% of patients who remained seronegative (P < .001). However, the authors write, "compared with men with initial HCV antibody positivity, seroconverters were more likely to be white and less likely to be black and were more likely to have never injected drugs and to have attended college."

Patients who seroconverted also were more likely to have an HIV RNA level greater than 400 copies/mL compared with those who did not seroconvert. There is an association between less adherence to the HAART regimen and participation in risky sexual practices, and both of these may have figured in the higher seroconversion rate among patients with a higher viral load, the authors suggest. People in the acute stages of HCV infection are also less tolerant of HAART, which may have contributed to their poor compliance.

There were several study limitations. Only half of the participants underwent follow-up HCV testing at intervals shorter than 3 years, so the authors could not determine exactly when seroconversion occurred in these patients, making it impossible to report incidence trends over time. In addition, 23% of the participants did not undergo any follow-up HCV screening, which raises the possibility of selection bias. However, there was no difference in baseline data between those patients and the patients who did have follow-up testing, so "it is likely that the HCV seroconversions represent the true incidence among HIV-infected patients in care," the authors write.

These findings suggest that HIV-infected patients should undergo regular screening for HCV, the researchers conclude. Early detection "may permit more successful treatment and provide opportunity for intervention to mitigate disease spread among drug-using or sexual partners and education to limit liver damage."

This study was supported in part by the AIDS Clinical Trials Group funded by the National Institute of Allergy and Infectious Diseases; National Institute on Drug Abuse; Lifespan/Tufts/Brown Center for AIDS Research; Center for Drug Abuse and AIDS Research; and the National Institutes of Health. The Miriam Hospital is one of the Clinical 340 Research Sites under Harvard/Partners Clinical Trials Unit. Study authors report various financial relationships with Roche, Vertex, Genentech, BMS, Merck, SciClone, GlaxoSmithKline, Three Rivers, Johnson & Johnson, Regulus, and Tibotec.

Clin Infect Dis. Published online January 31, 2011.

Source
Posted February 8, 2011

Stramer S. N Engl J Med. 2011;364:236-247.

A triplex nucleic acid assay detected potentially infectious hepatitis B virus, hepatitis C virus and HIV after analyzing the serologic, biochemical and molecular features of 3.7 million blood donations, according to study findings.

All blood donations in the US have been screened for hepatitis B surface antigen, but the researchers said a small proportion of donors with antibodies against hepatitis B core antigen in the absence of hepatitis B surface antigen have circulating hepatitis B virus (HBV) DNA and may have a risk of infectivity. Additionally, blood collected during the early window period of HBV infection is highly infectious, but the risk decreases as hepatitis B develops.

In 2008, 2,137,275 donors made a total of 3,694,858 donations. Using the Ultrio assay (Gen-Probe), researchers discovered 26 confirmed infections (nine HBV, 15 hepatitis C virus [HCV] and two HIV), giving the assay a positive predictive value of 35%.

The nine patients with HBV had seronegative HBV DNA-positive samples, and all but one was detected on mini-pool nucleic acid testing. Researchers had expected to find no more than four seronegative HBV DNA-positive samples.

Six infected donors had been vaccinated for HBV. Researchers said routine screening for hepatitis B surface antigen or antibodies against hepatitis B core antigen would not have uncovered those infections.

They said the infections were of “inconsequential clinical significance, but their potential for transmission remains unresolved.”

“Our findings show the efficacy of the HBV vaccine for the prevention of clinical disease but not infection, and the cost of interdicting donations that contain HBV DNA from seronegative donors is high in the face of unknown benefit,” they wrote.

Source
Posted on: Fri, 11 Feb 2011 07:00:01 EST

ATLANTA, Feb 11, 2011 (BUSINESS WIRE) --

Inhibitex, Inc. (Nasdaq: INHX
PowerRating) today reported that the U.S. Food and Drug Administration ("FDA") has designated the investigation of INX-08189 ("INX-189"), a potent guanosine nucleotide polymerase inhibitor for the treatment of chronic hepatitis C viral infection, as a Fast Track development program. Under the FDA Modernization Act of 1997, Fast Track programs are designed to facilitate the development and expedite the review of new drugs that are intended to treat serious or life threatening conditions and that demonstrate the potential to address unmet medical needs. The characteristics of INX-189 that contributed to it being granted Fast Track status include a high genetic barrier to resistance, its pan-genotypic activity, and once-daily oral dosing.

"The FDA's fast track designation for INX-189 is reflective of its unique features and the need for novel antiviral drugs that demonstrate the potential to provide better clinical outcomes and improved tolerability for the millions of individuals suffering from chronic hepatitis C infection," commented Dr. Joseph Patti, Inhibitex's Chief Scientific Officer and Senior Vice President of Research and Development.

The Company reported interim data from the first two cohorts of its ongoing Phase 1b clinical trial of INX-189 on January 9, 2011 and anticipates completing this trial by the end of the first quarter of 2011.

About HCV and INX-189

Hepatitis C is a disease of the liver caused by HCV. It is estimated that over 4 million Americans and 170 million individuals worldwide are infected with HCV, the majority of which represent chronic infections that can cause liver disease, cirrhosis and cancer. Chronic hepatitis C is the leading cause of liver transplants in the United States.

Inhibitex is developing a series of proprietary nucleotide inhibitors that target the RNA-dependent RNA polymerase (NS5b) of HCV. INX-189 is a protide of a 2'-C-methylguanosine analogue. The Company believes that preclinical and clinical studies of INX-189 completed to-date support its potential as a potent, once-daily, low dose oral therapy amenable to combination with other antivirals for the treatment of patients with all known genotypes of HCV.

About Inhibitex

Inhibitex, Inc. is a biopharmaceutical company focused on developing products to prevent and treat serious infectious diseases. In addition to INX-189, the Company's clinical stage antiviral pipeline includes FV-100, a bicyclic nucleoside inhibitor in Phase II development for the prevention and reduction of shingles-associated pain. The Company also has additional HCV nucleotide polymerase inhibitors in various stages of preclinical development and has licensed the use of its proprietary MSCRAMM(R) protein platform to Pfizer for the development of active staphylococcal vaccines. For additional information about the Company, please visit www.inhibitex.com.

Safe Harbor Statement

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties. All statements, other than historical facts included in this press release, including statements regarding the Company's belief that the results of preclinical and clinical studies of INX-189 to-date support its potential as a highly potent, once-daily, oral therapy amenable to combination with other anti-virals for the treatment of patients with all known genotypes of HCV, are forward looking statements. These intentions, expectations, or results may not be achieved in the future and various important factors could cause actual results or events to differ materially from the forward-looking statements that the Company makes, including the risk that; the results of ongoing or future preclinical or clinical studies of INX-189 alone or in combination with other anti-viral compounds not supporting its further development for lack of safety, tolerability, anti-viral activity, or any other reason; either the Company, the FDA, a data safety monitoring board or an investigational review board suspending or terminating the clinical development of INX-189 at any time for lack of safety, tolerability, anti-viral activity, or any other reason; obtaining, maintaining and protecting the intellectual property incorporated into and supporting the commercial viability of the Company's product candidates; and other cautionary statements contained elsewhere herein and in its Annual Report on Form 10-K for the year ended December 31, 2009, as filed with the Securities and Exchange Commission, or SEC, on March 26, 2010, and its Quarterly Report on Form 10-Q for the quarter ended September 30, 2010, as filed with the SEC on November 15, 2010. Given these uncertainties, you should not place undue reliance on these forward-looking statements, which apply only as of the date of this press release.

There may be events in the future that the Company is unable to predict accurately, or over which it has no control. The Company's business, financial condition, results of operations and prospects may change. The Company may not update these forward-looking statements, even though its situation may change in the future, unless it has obligations under the Federal securities laws to update and disclose material developments related to previously disclosed information. The Company qualifies all of the information contained in this press release, and particularly its forward-looking statements, by these cautionary statements.

Inhibitex(R) and MSCRAMM(R) are registered trademarks of Inhibitex, Inc.

SOURCE: Inhibitex, Inc.

Inhibitex, Inc.
Russell H. Plumb, Chief Executive Officer, 678-746-1136
rplumb@inhibitex.com
or
The Trout Group
Lee M. Stern, CFA, 646-378-2922
lstern@troutgroup.com

Source

FDA removes full clinical hold on Idenix's HCV drug

Wed Feb 9, 2011 6:12pm EST

* Says to stop development of IDX320

* Says FDA places partial clinical hold on IDX184

* Says HIV drug licensed to Glaxo also put on hold (Adds details)

Feb 9 (Reuters) - Idenix Pharmaceuticals Inc (IDIX.O) said U.S. health regulators have removed the full clinical hold on one of its two experimental hepatitis C drugs, and it ceased the development of the other drug because of a toxicity issue.

In September, the U.S. Food and Drug Administration halted all trials of the experimental drugs after detecting liver function abnormalities in three healthy volunteers during an early-stage study of a combination of the compounds IDX184 and IDX320. [ID:nSGE6860G7]

The company said the observed toxicity in the drug-drug interaction study was likely caused by IDX320.

Idenix, which focuses on treating viral diseases, said the FDA has placed the IDX184 program on partial clinical hold.

It said it expects to initiate a Phase IIb trial of IDX184 in combination with pegylated interferon and antiviral pill ribavirin in the second half of 2011.

The company also said its HIV drug -- licensed to GlaxoSmithKline's (GSK.L) unit ViiV Healthcare -- was placed on a clinical hold by the FDA.

Idenix shares closed at $75.04 Wednesday on Nasdaq. (Reporting by Anand Basu in Bangalore; Editing by Joyjeet Das)

Source
HUDDINGE, Sweden, February 10, 2011 /PRNewswire/ -- Medivir AB (OMX: MVIR), the emerging research-based specialty pharmaceutical company focused on infectious diseases, today announces the start of a phase 1a clinical trial with TMC649128 intended for the treatment of chronic hepatitis C virus infection.

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.

Milestone payment

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."

About Hepatitis C

Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3% 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.

About Medivir's Commitment of the HCV Area

Medivir and Tibotec are also jointly developing the once daily protease inhibitor TMC435 for treatment of hepatitis C virus infections (HCV).

About Medivir

Medivir is an emerging research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development. Medivir has a strong R&D portfolio and has recently launched its first product Xerese(TM)/Xerclear(R). Medivir's key pipeline asset, TMC435, a protease inhibitor, is in phase 2b clinical development for Hepatitis C and is partnered with Tibotec Pharmaceuticals.

Xerese(TM)/Xerclear(R) is an innovative treatment for cold sores, which has been approved in both the US and Europe. It is partnered with GlaxoSmithKline to be sold OTC in Europe and Russia and with Meda AB in North America. Medivir has retained the Rx rights for Xerclear(R) in Sweden and Finland.

For more information about Medivir, please visit the Company's website: http://www.medivir.se/

For more information about Medivir, please contact;

Medivir (http://www.medivir.se/)

Rein Piir, CFO & VP Investor Relations
Mobile: +46-708-537-292
M:Communications

Europe: Mary-Jane Elliott / Amber Bielecka /
Nick Francis
Medivir@mcomgroup.com
+44(0)20-7920-2330

USA: Jason Marshall
+1-212-897-5497

SOURCE Medivir

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