November 1, 2010

AASLD: HCV 'Cure' Now on Agenda


By Michael Smith , North American Correspondent, MedPage Today
Published: November 01, 2010

BOSTON -- The possibility of making even the most refractory subtypes of hepatitis C routinely curable is coming closer, a prominent researcher said in this exclusive InFocus interview.
Arun Sanyal, MD, president of the American Association for the Study of Liver Diseases, reviewed some of the new data with MedPage Today North American Correspondent Michael Smith at the association's annual meeting. As part of the discussion, Sanyal explained why he thinks hepatitis C will soon be a "winnable" disease.

Source
Bob Roehr

November 1, 2010 (Boston, Massachusetts) — The investigational protease inhibitor danoprevir, which targets the hepatitis C virus (HCV), combined with the standard of care for HCV infection — peg-interferon alpha-2a and ribavirin — produces rapid and profound reductions in HCV RNA.

Norah Terrault, MD, from the University of California at San Francisco, presented data from a 12-week interim analysis of the ATLAS trial here at The Liver Meeting 2010: American Association for the Study of Liver Diseases 61st Annual Meeting. Last month, Roche, which is sponsoring the study, secured full rights to the compound from collaborator InterMune.

Entry criteria were noncirrhotic treatment-naïve adults (predominately genotype 1 virus) with serum HCV RNA levels of 50 000 IU/mL or more and without advanced fibrosis.

All patients were administered a standard of care regimen of pegylated interferon alpha-2a plus weight-based ribavirin, and were randomized, for 12 weeks, to placebo or 1 of 3 danoprevir groups: 300 mg every 8 hours, 600 mg every 12 hours, or 900 mg every 12 hours. When danoprevir was stopped, all patients continued on standard therapy for an additional 24 or 48 weeks, depending on whether or not they achieved a rapid virologic response

The second part of the study was a planned continuation of danoprevir to week 24, but that "never was undertaken" because of incidents of reversible grade 4 ALT elevations in 3 patients in the 900 mg group, the highest dose of the study, said Dr. Terrault. Patients already enrolled in the 900 mg group were rerandomized to 300 or 600 mg.

The principle measure of efficacy was an undetectable HCV RNA level (<15 IU/mL); measurements were taken at baseline and at weeks 2, 4, and 12. Missing data points were considered to be nonresponders.

Dr. Terrault reported that the interim analysis of those who completed 12 weeks of danoprevir therapy was based on 62 patients receiving 300 mg (93%), 61 receiving 600 mg (94%), and 8 receiving 900 mg (16%).

At week 2, levels of HCV RNA were undetectable in 52% of the 300 mg group, 57% of the 600 mg group, 62% of the 900 mg group, and 0% of the placebo group. At week 4, that progressed to 73%, 86%, 86%, and 7%, respectively; and at week 12, to 88%, 89%, 92%, and 43%.

"In all triple combination arms, there was demonstration of potent antiviral effects that were greater than [peg-interferon alpha-2a] and ribavirin alone," Dr. Terrault summarized.

Viral resistance to danoprevir emerged in the low-dose (300 mg) group in 2 patients at week 2 and in 5 patients at weeks 4 and 12. In the 600 mg group, patients fared better, with 3 developing treatment-emergent resistance by week 12. No patients developed resistance in the highest-dose (900 mg) group, but the cumulative exposure was significantly less because of the emerging toxicity and discontinuation of that dosing regimen. All of the resistance was seen in patients with HCV genotype 1a.

Rates of most common adverse events in the danoprevir groups were at least twice as high as those seen with standard care alone. Often, there was little difference in the incidence of adverse effects with an increase in the dose of danoprevir.

Although the serious adverse event of grade 4 ALT elevation was most likely to occur at the highest dose of the drug (3 incidents) and led to the discontinuation of that dosing, there also was 1 incident among the 60 patients in the 600 mg group. Dr. Terrault said that "modeling the available pharmacokinetics data showed a relationship between danoprevir exposure, specifically AUC and the likelihood of having ALT elevation."

This information has been incorporated into the ongoing Dauphin study, which uses lower doses of danoprevir that are boosted with the pharmaco-inhibitor ritonavir, as is the case with many protease inhibitors used to treat HIV infection. Preliminary work suggests that this might maintain a more steady state of danoprevir in the blood and reduce toxicity.

Hepatologist Scott L. Friedman, MD, from Mount Sinai School of Medicine in New York City, who was not involved with the study, acknowledged that danoprevir, as currently formulated, seems to have a fairly narrow therapeutic window between a dose that is tolerable but can allow for the development of viral resistance and one that results in significant toxicities.

There are a lot of HCV protease inhibitors in development in that space. It is going to be interesting to see "which drugs win the race, in which wave, and in which combination," Dr. Friedman said, quickly adding that he is not about to make any predictions.

Roche is underwriting the study of danoprevir. Dr. Terrault reports receiving grant/research support and serving on an advisory committee or review panel for Roche. Dr. Friedman, who is immediate past president of AASLD, has disclosed no relevant financial relationships.

The Liver Meeting 2010: American Association for the Study of Liver Diseases (AASLD) 61st Annual Meeting: Abstract 32. Presented October 31, 2010.

Source

AASLD: Men Make Better Liver Donors

By Kristina Fiore, Staff Writer, MedPage Today
Published: November 01, 2010
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston.
 
BOSTON -- Men may be higher-quality liver donors than women, potentially a result of differences in life expectancy and causes of death, researchers said here.

Males receiving an organ from females were at an increased risk of graft failure, Norah Terrault, MD, MPH, of the University of California San Francisco, and colleagues reported at the American Association for the Study of Liver Diseases meeting here.

"This likely reflects national gender differences in life expectancy and causes of death," Terrault said during an oral presentation here. "Life expectancy is longer for women, and they're more likely to suffer a stroke, while men are more likely to experience a traumatic incident."

Prior studies have suggested an increased risk of graft loss in gender-mismatched liver transplant recipients.

While donor factors strongly impact outcomes, gender is not currently one of seven major characteristics factored into risk score, which includes age, race, and cardiac or stroke death.

So to evaluate gender differences in donor quality and the effects on the association between donor-recipient gender mismatch and graft loss, the researchers assessed the records of 28,222 patients who had primary single-organ liver transplant in the U.S. between March 1, 2002 and Dec. 31, 2007.

Male recipients were less likely than female recipients to receive a gender-mismatched graft (37% versus 50%, P<0.001).

The researchers found that, in general, recipients of a gender-mismatched graft were at increased risk of graft loss (OR 1.11, 95% CI 1.06 to 1.16, P<0.001).

Yet that relationship appeared to be driven by female-to-male donation.

Compared with male-to-male matched transplants, female-to-male mismatch was associated with a significant 17% higher risk of graft loss and lower graft survival in univariate analyses (95% CI 1.11 to 1.24, P<0.001).

That risk was also significantly higher compared with all other donor-recipient gender pairings, Terrault said.

Women had no significant effects if they received a liver from a man, she said.

Control for multiple significant donor factors, however, completely mitigated the effects of a female-to-male gender mismatched organ.

In fact, Terrault said, female-to-female donation appeared to be protective in that scenario, with a 14% decreased risk of poor outcomes -- further indication that gender is not a direct risk factor for post-transplant outcomes.

She noted that the dominant factors influencing this effect were donor age and donor height. Female donors are, on average, eight years older and 13 cm shorter than men.

They're also twice as likely to die from stroke, while male donors tend to tie in traumatic accidents, indicating male organs may be healthier.

Terrault and colleagues concluded that donor quality differs significantly between men and women, and the donor risk index -- used by hepatologists to predict post-transplant success -- is significantly higher in women.

The differences in donor quality -- rather than donor-to-recipient gender mismatch -- are predictive of graft loss, likely a result of national gender differences in life expectancy and death.

"We need to focus on strategies to reduce the negative effects of unfavorable donor factors on post-transplant outcomes," Terrault said.

The researchers reported no conflicts of interest.

Primary source: American Association for the Study of Liver Diseases

Source reference:
Lai JC, et al "Donor quality differs significantly between female and male donors" AASLD 2010; Abstract 67.

Source

Hepatitis C Treatment: current and future perspectives

Published on: 2010-11-01

Hepatitis C virus (HCV) is a member of Flaviviridae family and one of the major causes of liver disease. There are about 175 million HCV infected patients worldwide that constitute 3% of world's population.

The main route of HCV transmission is parental however 90% intravenous drug users are at highest risk. Standard interferon and ribavirin remained a gold standard of chronic HCV treatment having 38-43% sustained virological response rates.

Currently the standard therapy for HCV is pegylated interferon (PEG-INF) with ribavirin. This therapy achieves 50% sustained virological response (SVR) for genotype 1 and 80% for genotype 2 &3.

As pegylated interferon is expensive, standard interferon is still the main therapy for HCV treatment in under developed countries. On the other hand, studies showed that pegylated IFN and RBV therapy has severe side effects like hematologic complications.

Herbal medicines (laccase, proanthocyandin, Rhodiola kirilowii) are also being in use as a natural and alternative way for treatment of HCV but there is not a single significant report documented yet. Best SVR indicators are genotype 3 and 2, <0.2 million IU/mL pretreatment viral load, rapid virological response (RVR) rate and age <40 years.

New therapeutic approaches are under study like interferon related systems, modified forms of ribavirin, internal ribosome entry site (HCV IRES) inhibitors, NS3 and NS5a inhibitors, novel immunomodulators and specifically targeted anti-viral therapy for hepatitis C compounds. More remedial therapies include caspase inhibitors, antifibrotic agents, antibody treatment and vaccines.

Author: Saira MunirSana SaleemMuhammad IdreesAaliyah TariqSadia ButtBisma RauffAbrar HussainSadaf BadarMahrukh NaudhaniZareen FatimaMuhammad AliLiaqat AliMadiha AkramMahwish AftabBushra KhubaibZunaira Awan

Credits/Source: Virology Journal 2010, 7:296

Source

Final Results of Clinical Trial on Boceprevir

Presented: Tuesday, 2 November 2010, 9:15 am

BOSTON, Nov. 1, 2010 /PRNewswire/ -- The final results of the RESPOND-2 trial demonstrated that combination therapy with Boceprevir yields higher sustained virologic response (SVR) rates for patients with hepatitis C virus (HCV) genotype 1 who did not respond to or relapsed after treatment with peginterferon alpha 2b and Ribavirin.

"We are excited to have new therapies for treatment of HCV patients who failed to respond to treatment," said Bruce Bacon, MD. "Triple therapy appears to be a significant advance in the fight against hepatitis C."

Three arms were randomly selected from 403 HCV genotype 1 patients who previously failed treatment–partial / non-responders or relapsers:

• Control arm received peginterferon alpha 2b and Ribavirin for 48 weeks

• Second arm received 4 weeks of lead-in therapy of peginterferon alpha 2b and Ribavirin followed by response-guided therapy of peginterferon alpha 2b and Ribavirin combined with 800 mg of Boceprevir three times a day

• Third arm received 4 weeks of lead-in therapy of peginterferon alpha 2b and Ribavirin followed by 44 weeks of peginterferon alpha 2b and Ribavirin combined with 800 mg of Boceprevir

At 24 weeks after conclusion of treatment, the control arm achieved a SVR of 21 percent. Adding Boceprevir to the treatment increased SVR to 59 percent for the second arm and 67 percent for the third arm. It was noted that previous relapsers fared better than nonresponders in all arms. The therapy was well-tolerated, and the most common reason for discontinuing treatment was for patients who still had detectable HCV-RNA at week 12.

"Patients who previously failed to respond to treatment now have a hope for viral eradication," added Dr. Bacon.

Abstract title:
HCV RESPOND-2 Final Results: High Sustained Virologic Response Among Genotype 1 Previous Non-Responders and Relapsers to peginterferon alpha 2b/Ribavirin when Re-Treated with Boceprevir Plus peginterferon alpha 2b/Ribavirin.

About the AASLD

AASLD is the leading medical organization for advancing the science and practice of hepatology. Founded by physicians in 1950, AASLD's vision is to prevent and cure liver diseases. This year's Liver Meeting®, held in Boston, Massachusetts, October 29-November 2, will bring together more than 7,500 researchers from 55 countries.

A pressroom will be available from October 30 at the annual meeting. For copies of abstracts and press releases, or to arrange for pre-conference research interviews contact Gregory Bologna at 703-299-9766. To pre-register, call Ann Haran at 703-299-9766.

Press releases and all abstracts are available online at http://www.aasld.org/.

This release was issued through The Xpress Press News Service, merging e-mail and satellite distribution technologies to reach business analysts and media outlets worldwide. For more information, visit http://www.XpressPress.com.  

Media Contact: Gregory Bologna
703/299-9766
gbologna@aasld.org
Press Room: October 30 – November 2, 2010
Hynes Convention Center, Room 208
Telephone: 617-954-3106

Researcher: Bruce Bacon, MD
Email: baconbr@slu.edu
Phone: 314-577-8764

SOURCE American Association for the Study of Liver Diseases (AASLD)

RELATED LINKS
http://www.aasld.org/

Source

Drug experts say alcohol worse than crack or heroin

By Kate Kelland
LONDON
Mon Nov 1, 2010 10:23am EDT

LONDON (Reuters) - Alcohol is a more dangerous drug than both crack and heroin when the combined harms to the user and to others are assessed, British scientists said Monday.

Presenting a new scale of drug harm that rates the damage to users themselves and to wider society, the scientists rated alcohol the most harmful overall and almost three times as harmful as cocaine or tobacco.

According to the scale, devised by a group of scientists including Britain's Independent Scientific Committee on Drugs (ISCD) and an expert adviser to the European Monitoring Center for Drugs and Drug Addiction (EMCDDA), heroin and crack cocaine rank as the second and third most harmful drugs.

Ecstasy is only an eighth as harmful as alcohol, according to the scientists' analysis.

Professor David Nutt, chairman of the ISCD, whose work was published in the Lancet medical journal, said the findings showed that "aggressively targeting alcohol harms is a valid and necessary public health strategy."

He said they also showed that current drug classification systems had little relation to the evidence of harm.

Alcohol and tobacco are legal for adults in Britain and many other countries, while drugs such as ecstasy and cannabis and LSD are often illegal and carry the threat of prison sentences.

"It is intriguing to note that the two legal drugs assessed -- alcohol and tobacco -- score in the upper segment of the ranking scale, indicating that legal drugs cause at least as much harm as do illegal substances," Nutt, who was formerly head of the influential British Advisory Council on the Misuse of Drugs (ACMD), said in a statement about the study.

Nutt was forced to quit the ACMD a year ago after publicly criticizing ministers for ignoring scientific advice suggesting cannabis was less harmful than alcohol.

The World Health Organization estimates that risks linked to alcohol cause 2.5 million deaths a year from heart and liver disease, road accidents, suicides and cancer -- accounting for 3.8 percent of all deaths. It is the third leading risk factor for premature death and disabilities worldwide.

In an effort to offer a guide to policy makers in health, policing, and social care, Nutt's team rated drugs using a technique called multicriteria decision analysis (MCDA) which assessed damage according to nine criteria on harm to the user and seven criteria on harm to others.

Harms to the user included things such as drug-specific or drug-related death, damage to health, drug dependence and loss of relationships, while harms to others included crime, environmental damage, family conflict, international damage, economic cost, and damage to community cohesion.

Drugs were then scored out of 100, with 100 given to the most harmful drug and zero indicating no harm at all.

The scientists found alcohol was most harmful, with a score of 72, followed by heroin with 55 and crack with 54.

Among some of the other drugs assessed were crystal meth (33), cocaine (27), tobacco (26), amphetamine or speed (23), cannabis (20), benzodiazepines, such as Valium (15), ketamine (15), methadone (14), mephedrone (13), ecstasy (9), anabolic steroids (9), LSD (7) and magic mushrooms (5).

(Editing by Alison Williams)

Source

Two fines for drug company

Kate Hagan
November 2, 2010

DRUG company Roche has been fined $200,000 for offering to fund a nurse's position at a health service - depending on how many patients were treated with its hepatitis C drug Pegasys.

The fine is the maximum under the Medicines Australia code of conduct, which sets standards for marketing and promotion of prescription drugs.

It is one of two $200,000 fines incurred by Roche Products over two separate matters revealed in Medicine Australia's quarterly report for July to September, released yesterday.

A committee found the nurse funding proposal to be a severe breach of the code, and in addition to the fine ordered Roche not to make similar offers in future.

A committee investigating the complaint, made by a health professional, said a letter sent by Roche to the health service ''clearly made an offer of funding that was contingent on the number of patients treated by Pegasys, with a sliding scale of increased funding for more patients treated''.

But Roche argued that ''when [its] employees realised that the proposal could be construed in a way that was contrary to the code, it was withdrawn'', so there was no breach.

The committee disagreed, finding the fact the offer was made was sufficient to breach the code, particularly its requirement that no inducements should be offered that could interfere with a health care professional's independence.

It also noted that the health professional who made the complaint believed the deal had, in fact, been implemented, and said other staff at the health service had the same impression.

Roche was also fined $200,000 in a separate matter, for making misleading claims about its renal anaemia treatment Mircera.

The drug company failed in an appeal against the finding and the fine, which it argued was disproportionate to the seriousness of the breach.

Roche was also ordered to stop using all materials found to breach the code, and to send a correction letter to all health professionals with passwords to its website.

Source

AASLD: Antibiotic Reverses Cognition Loss in MHE

By Michael Smith, North American Correspondent, MedPage Today
Published: November 01, 2010
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine.
 
BOSTON -- In patients with minimal hepatic encephalopathy, an antibiotic appears to reverse difficulties in driving a car associated with the condition, a researcher said here.

Rifaximin (Xifaxan) is most commonly used to treat travelers' diarrhea, but it is also approved for minimal hepatic encephalopathy, according to Jasmohan Bajaj, MD, of Virginia Commonwealth University Medical Center in Richmond, Va.

In a randomized, placebo-controlled, double-blind trial, patients taking the drug did better on simulated driving tasks than those given placebo, Bajaj reported at the annual meeting of the American Association for the Study of Liver Diseases.

Minimal encephalopathy does not lead to overt cognitive dysfunction, but can be shown to exist with neuropsychological tests. It impairs quality of life and has been shown to increase the risk of traffic accidents.

The importance of the study, Bajaj said, is that "it's the first time a cognitive change has resulted in a real-life outcome."

He and his colleagues enrolled 41 patients -- all current drivers -- with minimal hepatic encephalopathy confirmed by a battery of five cognitive tests.

At baseline, the patients were tested using a simulator for driving and navigation skills, with the outcomes being such things as collisions, speeding tickets, and illegal turns, Bajaj said. At the same time, they were given cognitive tests, quality of life was measured using the Sickness Impact Profile, venous ammonia levels were measured, and they were graded on the Model for End-Stage Liver Disease (MELD) score.

The patients were randomly assigned to get rifaximin (at 550 mg a day) or placebo for 30 days, at the end of which time they returned for adherence testing and were given another 30 days of study drug, Bajaj said.

At the end of the eight-week study period, the baseline tests were repeated, including those in the simulator. The primary outcomes were improvements in the driving measures -- speeding, illegal turns, and collisions. Changes in cognition and quality of life were secondary outcomes.

The researchers found:

• 76% of those getting the drug had fewer total driving errors, compared with 33% of those on placebo (P=0.013)

• 81% of those on the drug had fewer speeding tickets, compared with 33% of those on placebo (P=0.005)

• 62% of those on rifaximin had fewer illegal turns, compared with 19% of those on placebo (P=0.012)

• There was no significant difference in the number of collisions

Participants on rifaximin also had a significantly better increase in cognition and on the psychosocial elements of the Sickness Impact Profile, Bajaj reported.

He said the goal was to increase insight into driving errors, which was best measured by such subtle factors as illegal turns and speeding tickets. In the simulator, he said, a collision stopped the game, with a loud crash, which allowed patients in both groups to gain the same insight.

"Tickets and illegal turns do not come with anything, so the patients have to themselves realize they've gone off," he said.

The findings are important because they appear to demonstrate that some of the cognitive effects of minimal hepatic encephalopathy can be turned back by medication, according to Kevin Mullen, MD, of MetroHealth Medical Center in Cleveland, who moderated the session at which the data were presented.

"Up to now, no one had ever shown reversibility of those driving problems," he told MedPage Today.

Other papers presented at the session, he noted, suggested that the drug could improve survival and slow progression of the disease. But those effects -- as well as the possible cognitive benefits -- are "still up in the air" and need more study.

The study was supported by the NIH and Salix.

Bajaj reported financial links with Salix and Ocera Therapeutics.

Mullen reported financial links with Salix, Ocera, Hyperion, Hoffman LaRoche, and CLDG.

Primary source: American Association for the Study of Liver Diseases

Source reference:
Bajaj JS, et al "Rifaximin improves driving simulator performance in minimal hepatic encephalopathy: A double - blind, placebo - controlled, prospective randomized trial" AASLD 2010; Abstract 22.

Source
Nov. 1, 2010, 3:46 a.m. EDT

HUDDINGE, Sweden, Nov 01, 2010 (BUSINESS WIRE) -- Regulatory News:

Medivir AB (omx:MVIR), the research-based speciality pharmaceutical company focused on the development of high-value treatments for infectious diseases, notes that its development partner, Tibotec Pharmaceuticals, has announced the results of a Week-24 planned interim analysis of the Phase 2 response-guided PILLAR study for TMC435, Medivir's key pipeline asset, a hepatitis C protease inhibitor dosed once-daily. The study was conducted in treatment-naive patients with chronic genotype 1 Hepatitis C virus (HCV) and is part of a late-breaker oral presentation at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston, MA., USA.

Highlights of the data:

79% to 86% of patients were able to stop all therapy at week-24 No relevant differences for adverse events between TMC435 treatment groups and placebo

Commenting on the announcement by Medivir's development partner, Tibotec, Ron Long, Chief Executive of Medivir, said: "We are very pleased to have such exciting TMC435 data presented by our partner, Tibotec, at the AASLD. The data announced shows the significant impact that TMC435 could have on the way we treat hepatitis C."

Please note that Medivir will be hosting meetings for Investors, Analysts and the Media at the AASLD (see end of press release).

Tibotec released the following statement on the results on Saturday 30th October:

Week 24 interim results from phase 2b PILLAR study to be presented as late-breaker at AASLD

-- Data show high antiviral activity, safety and tolerability comparable to placebo --

Boston, MA. Saturday 30th October 2010 -- Tibotec Pharmaceuticals (Tibotec) today will present the results of a Week-24 planned interim analysis of the phase 2 response-guided PILLAR study in treatment-naive patients with chronic genotype 1 hepatitis C virus (HCV) as part of a late-breaker oral presentation at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston, MA., USA.

The results showed that in the four TMC435 treatment groups between 79 and 86 percent of patients were able to stop all therapy at Week-24, according to the response criteria defined in the study protocol. There were no relevant differences for adverse events between TMC435 treatment groups and placebo. TMC435, a hepatitis C protease inhibitor, dosed once daily (q.d.) is being developed jointly by Tibotec Pharmaceuticals and Medivir.

The PILLAR study [Protease Inhibitor TMC435 trial assessing the optimaL dose and duration as once daiLy Anti-viral Regimen] (TMC435-C205; NCT00882908) is an ongoing, five-arm, global phase 2b randomized, double-blind, placebo controlled study in 386 treatment-naive patients. TMC435 was administered in doses of 75mg or 150mg q.d. for either 12 weeks or 24 weeks in combination with 24 weeks of peg-interferon and ribavirin (PR). Patients in the placebo arm receive 24 weeks of placebo plus peg-interferon and ribavirin followed by 24 additional weeks of peg-interferon and ribavirin treatment. The primary endpoint of the study is sustained virologic response at Week-72 (SVR24). The PILLAR study is being conducted in 13 countries in Europe, North America, and Australasia.

Patients receiving TMC435 were allowed to stop all treatment at week 24 when a) HCV RNA levels < 25 IU/mL at week 4 and b) HCV RNA < 25 IU/mL levels at weeks 12, 16 and 20. Patients who did not meet the above response-guided criteria continued with peg-interferon and ribavirin until Week-48. TMC435 demonstrated potent antiviral activity, at week 4 (rapid virologic response (RVR)) and at week 12 (complete early virologic response (cEVR)) HCV RNA was undetectable (<25IU/ml) for the majority of patients. The viral breakthrough rate was 4.9 percent in the TMC435 treatment groups.

"Chronic infection with HCV is a leading cause of cirrhosis, liver cancer, and liver transplantation worldwide" said Dr Michael W. Fried M.D., lead clinical investigator and Professor of Medicine, Director of Hepatology, University of North Carolina at Chapel Hill. "We are extremely encouraged by these data for TMC435."

The goal of HCV treatment is to achieve SVR24, which means the virus remains undetectable in patients' blood six months after they have finished treatment. Patients who achieve SVR are considered cured. The current standard of care for HCV, pegylated interferon combined with ribavirin, may cause debilitating side effects[i] and cures only about half of patients starting therapy for the first time.[1]

The most common adverse events were headache and fatigue, 46 percent and 42 percent in the TMC435 groups and 51 percent and 47 percent in the placebo group respectively. There were no clinically significant differences in frequency of rash, anemia or gastrointestinal events between the TMC435 groups and placebo. Most AEs were mild to moderate in severity. AEs leading to treatment discontinuation were reported in 7.1 percent of patients in TMC435 arms and 7.8 percent in placebo arm.

In laboratory parameters, significant decreases in transaminases (ALT and AST) were observed in all treatment groups. Small and transient bilirubin elevations (direct and indirect) were seen in the TMC435 150mg dose groups.

"With a strong heritage in virology, Tibotec is committed to improving the lives of those impacted by HCV through the development of innovative new treatment regimens," said Greg Fanning PhD, head of hepatitis C research and development at Tibotec. "TMC435 is an important component of our growing HCV pipeline and we are encouraged by the results of the interim analysis presented at the AASLD meeting."

TMC435 is also being studied in HCV genotype-1 treatment-experienced patients who have failed treatment with peg-interferon and ribavirin. The ASPIRE study (Antiviral STAT-C Protease Inhibitor Regimen in Experienced patients; TMC435-C206; NCT00980330) is an ongoing global phase 2b randomized, double-blind, placebo controlled study in 463 patients.

In addition to the late-breaker oral presentation described above, data on TMC435 has been presented in 4 posters at AASLD:

278. "In vitro studies investigating the mechanism of interaction between TMC435 and hepatic transporters." M.T. Huisman

812. "Virologic analysis of genotype-1-infected patients treated with once-daily TMC435 during the Optimal Protease inhibitor Enhancement of Response to Therapy (OPERA)-1 study." O. Lenz

895. "A Phase IIa, open-label study to assess the antiviral activity of TMC435 monotherapy in patients infected with HCV genotypes 2--6." C. Moreno

1873. "Pharmacokinetic-pharmacodynamic analyses of TMC435 in patients infected with Hepatitis C Virus (HCV) genotypes 2 to 6." V. Sekar

About HCV

HCV is a blood-borne infectious disease that affects the liver.1 With an estimated 170 million people infected worldwide1 and three to four million people newly infected each year,2 HCV puts a significant burden on patients and society. Chronic infection with HCV can lead to liver cancer and other serious and fatal liver diseases, and is the most common cause of liver transplant worldwide.3 Discovering and developing new treatments is very important to improving the standard of care for the millions of people living with this disease.

About Tibotec Pharmaceuticals

Tibotec Pharmaceuticals is a global pharmaceutical and research development company. The Company's main research and development facilities are in Beerse, Belgium with offices in Titusville, NJ and Cork, Ireland. Tibotec is dedicated to the discovery and development of innovative HIV/AIDS and hepatitis C drugs, and anti-infectives for diseases of high unmet medical need. Tibotec Pharmaceuticals is a subsidiary of Johnson & Johnson.

[1]World Health Organization (2002). Hepatitis C. Retrieved October 26, 2010 from http://www.who.int/csr/disease/hepatitis/Hepc.pdf

2 Hepatitis C: Global Prevalence. Weekly Epidemiological Record. 1997;72 : 341-8. Retrieved October 26, 2010 from http://www.who.int/docstore/wer/pdf/1997/wer7246.pdf.

3 Roche B, Samuel D., Villejuif, France. Risk factors for hepatitis C recurrence after liver transplantation. J Viral Hepat. 2007 Nov;14. Suppl 1:89-96.

- Ends -

Medivir Activities for Investors, Analysts and the Media at the AASLD:

Medivir will provide an update on the development of TMC435 and the data presented at AASLD on Tuesday 2 November, 2010. The meetings will be hosted by Rein Piir (CFO/IR), Bertil Samuelsson, (CSO) and Asa Rosenquist, (Director).

Medivir Conference Call For European Analysts and Investors:

Tuesday, November 2, 2010 at 6.30am EDT / 10.30am GMT / 11.30am CET Please register for the conference call online at: http://invite.taylor-rafferty.com/_Medivir/ConferenceCall

You will receive the dial-in and replay numbers for the conference call following your online registration.

Breakfast Meeting for US based Analysts, Investors and Media at AASLD:

Tuesday November 2, 2010 at 7:00am -- 8.30am EDT (breakfast will be served between 7:00am -- 7.30am EDT)

Venue: Colonnade Hotel, Braemore & Kenmore Room, 120 Huntington Avenue, Boston

Please confirm your participation by registering on-line: http://invite.taylor-rafferty.com/_Medivir/Breakfast/default.htm

For enquiries about the above briefings, please contact: Lindsey Neville at M:Communications on +44 (0)20 7920 2333 or Jason Marshall on +1 212 889 4350 or email Neville@mcomgroup.com

About Medivir

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

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

About TMC435 clinical trial programs

TMC435 is a once daily protease inhibitor jointly developed by Medivir and Tibotec Pharmaceuticals to treat hepatitis C virus infections. TMC435 is currently being studied in three phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215) in genotype 1 (G1) treatment-naive and in G1 patients that failed previous IFN-based treatment. TMC435 is planned to enter phase 3 studies early 2011.

PILLAR Study (TMC435-C205)

TMC435-C205 is an ongoing randomized double-blind global phase 2b study in 386 genotype-1 treatment-naive patients. It evaluates once daily treatment of TMC435 with different doses and durations given in addition to standard of care treatment, consisting of ribavirin and pegIFNalpha-2A.

ASPIRE Study (TMC435-C206)

TMC435-C206 is an ongoing randomized double-blind global phase 2b study in 463 genotype-1 treatment-experienced patients. It evaluates once daily treatment of TMC435 in with different doses of given in addition to standard of care treatment, consisting of ribavirin and pegIFNalpha-2A.

TMC435-C215

TMC435-C215 is an ongoing Japanese phase 2b study in 92 genotype-1 treatment-naive patients. It evaluates once daily treatment of TMC435 with different doses and durations given in addition to standard of care treatment, consisting of ribavirin and pegIFNalpha-2A.

Opera-2 (TMC435-C202)

TMC435-C202 is a completed phase 2a study in treatment-naive genotype 2 to 6 HCV patients. It is a once daily treatment of TMC435 during seven days, at 200 mg. Subsequently, patients could continue with Standard of Care treatment consisting of pegylated interferon and ribavirin upon agreement with the study doctor.

This information was brought to you by Cision http://www.cisionwire.com/

SOURCE: Medivir

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BOSTON, Nov. 1, 2010 /PRNewswire-USNewswire/ -- In a keynote address delivered yesterday afternoon on chronic viral hepatitis, one of the Administration's top health officials provided an outline of the forthcoming HHS "federal action plan" on viral hepatitis and pledged renewed federal leadership to translate this plan into reality. Dr. Howard Koh, U.S. Assistant Secretary of Health at the U.S. Department of Health & Human Services, made the remarks before thousands of liver health experts at the American Association for the Study of Liver Disease (AASLD) 61st annual meeting in Boston.

"NVHR is encouraged that Dr. Koh recognizes that the viral hepatitis battle can only be won with strong and decisive national leadership," said Ms. Lorren Sandt, NVHR Chair and Executive Director of Caring Ambassadors Program, based in Portland, Oregon. "Given all that is at stake, we are eager to review the forthcoming HHS national strategy as soon as possible. Dr. Koh's remarks yesterday were most welcome and stand in stark contrast to this Administration's otherwise lackluster response to this urgent public-health crisis. Chronic viral hepatitis is a winnable public-health battle and it's high time the Administration responded accordingly."

More than 5 million Americans are afflicted with chronic viral hepatitis B or C and an estimated 500 million individuals are infected worldwide. Most Americans afflicted with chronic viral hepatitis are unaware they are infected. Without targeted screening and testing programs for those most at risk, most individuals only become aware of their condition after their infection progresses to liver failure, cirrhosis, or liver cancer. Viral hepatitis is the overwhelming cause of liver cancer, which kills nearly 20,000 Americans annually.

In his remarks, Dr. Koh outlined six key areas that will provide the foundation of the new HHS national strategy. These areas include educating providers; strengthening surveillance; better care, screening, and treatment; encouraging appropriate vaccinations to reduce the incidence of hepatitis B; reducing drug use; and protecting health workers from infections. NVHR continues to have concerns that the Administration's funding levels for state-based viral hepatitis screening and treatment programs are wholly inadequate. In fact, federal funding for 2011 is actually less than it was a decade ago. Meanwhile, this crisis has only worsened.

Ms. Sandt added, "There is a strong expert consensus about what needs to be done to address the chronic viral hepatitis crisis. Thus far, we have lacked the political will. Policymakers face a stark choice: we can either invest the resources now to pay for successful viral hepatitis intervention and treatment or we can pay for failure over the next two decades with billions of dollars in avoidable medical costs and thousands of unnecessary liver transplants and deaths."

NVHR is a coalition of more than 170 public, private, and voluntary organizations dedicated to reducing the incidence of infection, morbidity, and mortality from chronic viral hepatitis that afflicts more than 5 million Americans. http://www.nvhr.org/

SOURCE National Viral Hepatitis Roundtable

RELATED LINKS
http://www.nvhr.org/

Source

Also See:
AASLD President's Choice Lecture: The National Strategy for the Control of Viral Hepatitis and Liver Cancer
Presented: Tuesday, 2 November 2010, 8:00 am

BOSTON, Nov. 1, 2010 /PRNewswire/ -- Researchers studied the treatment of pregnant women with hepatitis B virus (HBV) with Telbivudine in their second to third trimesters. The study concluded that both the mothers benefited from treatment and no transmission of HBV to newborns was detected at 28 weeks postbirth.

The study presenter and co-investigator Calvin Pan, MD, anticipates a "very powerful impact in the field, as hepatitis B is difficult to eradicate and currently there is no treatment modality that can cure the disease. Blocking the vertical transmission from mother to infant will eventually decrease the disease burden in the future generations with the hope to eradicate HBV from the earth."

Current vaccines and HBIG given to a newborn do not work well when the mother has a high viral load and is HBeAg positive. According to Dr. Pan, "Transmission rate to the newborn in this population is about 15 to 30 percent, resulting in a newborn with lifelong HBV infection 90 percent of the time."

For this study, pregnant women with high levels of HBVDNA enrolled in the treatment arm of the study were given 600 mg daily of Telbivudine. All newborns received three doses of hepatitis B vaccine. Patients in the treatment arm achieved sustained virologic response rate (SVR) of 53 percent prior to delivery and 62 percent four weeks after delivery. None of the patients in the control arm achieved SVR at either point.

Only four percent of newborns in the treatment arm tested positive for hepatitis B, whereas 23 percent of newborns from the control group tested positive. None of the patients treated with Telbivudine had to stop treatment due to adverse events. No congenital deformities were observed up to 28 weeks after birth. There were no measurable differences in postpartum health issues for mothers and newborns between the treatment and control groups.

Dr. Pan realizes the limitations of this study: "The infant follow up is limited to 28 weeks after birth. Even though it is good enough to define the failure rate of transmission prevention, the long term safety data for the infant is missing. Hypothetically, antiviral therapy and immunoprophylaxis can be effective in blocking transmission that occurs during late pregnancy or delivery, but the mechanism of intrauterine transmission remains a puzzle. More studies are needed in the field to provide a comprehensive strategy to prevent HBV vertical transmission."

The message he wants to convey is still a positive one and shows a different way of attacking the problem of HBV. "Because we are struggling in combating the pandemic of hepatitis B worldwide, and frustrated in the limited resources we can allocate for treating our patients," said Dr. Pan, "Maybe we should be putting more efforts and allocating more resources on preventing HBV vertical transmission."

Abstract title:
A Prospective and Open-Label Study for the Efficacy and Safety of Telbivudine(Ltd) in Pregnancy for the Prevention of Perinatal Transmission of Hepatitis B Virus (HBV) to the Infants

About the AASLD

AASLD is the leading medical organization for advancing the science and practice of hepatology. Founded by physicians in 1950, AASLD's vision is to prevent and cure liver diseases. This year's Liver Meeting®, held in Boston, Massachusetts, October 29-November 2, will bring together more than 7,500 researchers from 55 countries.

A pressroom will be available from October 30 at the annual meeting. For copies of abstracts and press releases, or to arrange for pre-conference research interviews contact Gregory Bologna at 703-299-9766. To pre-register, call Ann Haran at 703-299-9766.

Press releases and all abstracts are available online at http://www.aasld.org/.

This release was issued through The Xpress Press News Service, merging e-mail and satellite distribution technologies to reach business analysts and media outlets worldwide. For more information, visit http://www.XpressPress.com.

Media Contact:: Gregory Bologna
703-299-9766
gbologna@aasld.org
Press Room: October 30 – November 2, 2010
Hynes Convention Center, Room 208
Telephone: 617-954-3106

Researcher: Calvin Pan, MD
Email: cpan11355@yahoo.com
Phone: 718-888-7728

SOURCE American Association for the Study of Liver Diseases (AASLD)

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http://www.aasld.org/

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Public release date: 1-Nov-2010

Contact: Rebecca Eisenman
newsbureau@mayo.edu
507-284-5005
Mayo Clinic

ROCHESTER, Minn. -- Statistics from the Centers for Disease Control and Prevention (CDC) (http://www.cdc.gov/) rank mortality related to chronic liver disease and cirrhosis as the 12th most common cause of death in adults in the U.S. Using a modified definition that includes diseases such as viral hepatitis, liver cancer (http://www.mayoclinic.org/liver-cancer/) and obesity-related fatty liver disease (liver diseases)(http://www.mayoclinic.org/liver-disease/), Mayo Clinic-led researchers have found that liver-related mortality is as high as fourth for some age groups, and eighth overall. The findings are being presented today at the American Association for the Study of Liver Diseases 61st Annual Liver Meeting (http://publish.aasld.org/thelivermeeting/Pages/default.aspx) in Boston.

"The methodology that the CDC uses to define liver-related mortality is somewhat limited," says W. Ray Kim, M.D., (http://www.mayoclinic.org/bio/11801271.html) a gastroenterologist with Mayo Clinic. "They only look at a certain diagnostic code, and deaths due to other facets of liver disease are not included.

"There are a large number of people with hepatitis C in the U.S. They are getting older and experiencing complications. Also, associated with the 'obesity epidemic,' a large number of individuals have fatty liver disease. Some go on to develop end-stage liver disease, cirrhosis, or liver cancer. In order to discover the true impact of liver disease on the population, we analyzed mortality data using these more comprehensive criteria."

The research team examined data from the CDC's national death registry for deaths among adults during 1979-2006 and compared their results to statistics from the Rochester Epidemiology Project, (http://www.mayoresearch.mayo.edu/rep/) a long-term, collaborative medical records project among health care providers in Olmsted County, Minn.

"We had a good correlation between the national statistics and the Olmsted County mortality data," says Dr. Kim. "Of course, the most common cause of death for adults is cardiovascular disease and cancer. However, we found that liver disease is not far behind in terms of being No. 4 for people between the ages of 45 and 64 years."

Dr. Kim says that obese people and those with hepatitis C need to be watched especially closely for liver disease as part of their overall medical management program. "Liver disease is an important cause of morbidity and mortality in the U.S. -- more than we have recognized in the past -- and as physicians, we need to be aware of that," he says.

###

Co-authors of the study include Sumeet Asrani, M.D.; Patrick Kamath, M.D.; Rachel Pedersen; Jennifer St. Sauver, Ph.D.; and Terry Therneau, Ph.D., all of Mayo Clinic; and Barbara Yawn, M.D., of Olmsted Medical Center in Rochester.

About Mayo Clinic

For more than 100 years, millions of people from all walks of life have found answers at Mayo Clinic. These patients tell us they leave Mayo Clinic with peace of mind knowing they received care from the world's leading experts. Mayo Clinic is the first and largest integrated, not-for-profit group practice in the world. At Mayo Clinic, a team of specialists is assembled to take the time to listen, understand and care for patients' health issues and concerns. These teams draw from more than 3,700 physicians and scientists and 50,100 allied staff that work at Mayo Clinic's campuses in Minnesota, Florida, and Arizona; and community-based providers in more than 70 locations in southern Minnesota, western Wisconsin and northeast Iowa. These locations treat more than half a million people each year. To best serve patients, Mayo Clinic works with many insurance companies, does not require a physician referral in most cases and is an in-network provider for millions of people. To obtain the latest news releases from Mayo Clinic, go to www.mayoclinic.org/news.  For information about research and education, visit http://www.mayo.edu/. MayoClinic.com (http://www.mayoclinic.com/) is available as a resource for your general health information.

Contact:
Rebecca Eisenman
507-284-5005 (days)
507-284-2511 (evenings)
e-mail: newsbureau@mayo.edu

Source

Curing Hepatitis C Will Take More Than New Treatments.

November 1, 2010, 10:23 AM ET
By Jonathan D. Rockoff

At the annual meeting of the American Association for the Study of Liver Diseases that wraps up tomorrow, there’s been lots of talk about the potential for some experimental treatments for hepatitis C.

Pivotal trials have shown that the two therapies farthest along in development — telaprevir from Johnson & Johnson and Vertex Pharmaceuticals, and boceprevir from Merck — are more likely to cure hepatitis C than currently available treatment. There’s widespread anticipation the pills will win FDA approval next year. And they could be followed by the introduction of even more new therapies, the WSJ reports.

Yet the rollout of new medicines won’t be sufficient to wipe out the infectious disease, companies acknowledge. “Just adding a new drug that doubles the cure rate of hepatitis C will not solve the problem,” Camilla Graham, a medical affairs official at Vertex, tells the Health Blog.

One big obstacle: most of those carrying the virus don’t know it. Most estimates say just a quarter of the 4 million infected Americans have been diagnosed. Screening for hepatitis C via a blood test isn’t routine. And the blood-borne disease, which is popularly associated with drug use since it can be spread through sharing of contaminated needles, carries a stigma that can deter people from seeking help.

Another hurdle, doctors say, will be giving the new treatment correctly. The FDA hasn’t signed off on how the new pills would be administered if approved, but doctors expect it’ll be complicated. They anticipate they’ll have to stay on top of the progress of treatment in order to determine its course and duration.

The new pills are “going to increase the cure rate, but at the same time, they are going to add to the chance of side effects, so patients must be vigilant,” says Zobair Younossi, who heads the Inova Health System’s Center for Liver Diseases in Falls Church, Va.

This probably won’t be easy, at least in the beginning, according to doctors. Telaprevir and boceprevir will be used in addition to the antiviral injection and pill currently being given to patients, not in their stead. And those older regimens can produce side effects such as flu-like symptoms and depression.

Addition of a third medicine “makes management slightly more intensive for doctors, and I think the learning curve is going to be steep,” says David Bernstein, chief of gastroenterology and hepatology at North Shore University Hospital and Long Island Jewish Medical Center. He’s been trying to counsel doctors on using the new therapies.

Source
Presented: Tuesday, 2 November 2010, 8:00 am

BOSTON, Nov. 1 /PRNewswire/ -- The Phase 3 results from the ADVANCE study confirm the clinical benefits of telaprevir-based combination therapy regimens. The study reports an improvement in treatment discontinuation rates due to adverse events compared to Phase 2 studies, and demonstrates an increase in sustained viral response (SVR) in patients with hepatitis C virus (HCV). The primary endpoint for this study was SVR 24 weeks after last treatment.

The study was conducted on 1088 treatment-naive HCV patients, all of whom had genotype 1. For the three arms of the trial, one group of patients was treated with 750 mg of telaprevir every eight hours in combination with peginterferon alfa-2a 180 ug/week and ribavirin 1000-1200 mg/day for 12 weeks, while the second group was given the same treatment but for only 8 weeks. Patients in the first group (T12PR) were treated for an additional 12 weeks of peginterferon and ribavirin if HCV RNA was undetectable at weeks 4 and 12, for a total of 24 weeks of treatment, and an additional 36 weeks if HCV RNA was detectable at week 4 or week 12, for a total of 48 weeks' treatment. Patients in the second group (T8PR) were treated with peginterferon and ribavirin for an additional 16 weeks if HCV RNA was undetectable at weeks 4 and 12, and for an additional 40 weeks if HCV RNA was detectable at either week 4 or 12, for a total of 24 or 48 weeks of treatment, respectively. Patients in the control group were treated with peginterferon alfa-2a and ribavirin for 48 weeks.

SVR was 75 percent for those receiving telaprevir combination treatment for 12 weeks, 69 percent for those receiving telaprevir combination treatment for 8 weeks, and 44 percent for those receiving standard of care. Extended rapid virologic response (HCV RNA undetectable at weeks 4 and 12) was attained in 58 percent, 57 percent, and 8 percent, respectively. During the telaprevir/placebo treatment phase, adverse events leading to treatment discontinuation occurred in 7 percent of patients in the arm receiving telaprevir combination treatment for 12 weeks, 8 percent in telaprevir for 8 weeks, and 4 percent in the peginterferon alfa-2a and ribavirin arm.

Abstract title:
Telaprevir in Combination with Peginterferon and Ribavirin in Genotype 1 HCV Treatment-Naive Patients: Final Results of Phase 3 ADVANCE Study

About the AASLD

AASLD is the leading medical organization for advancing the science and practice of hepatology. Founded by physicians in 1950, AASLD's vision is to prevent and cure liver diseases. This year's Liver Meeting®, held in Boston, Massachusetts, October 29-November 2, will bring together more than 7,500 researchers from 55 countries.

A pressroom will be available from October 30 at the annual meeting. For copies of abstracts and press releases, or to arrange for pre-conference research interviews contact Gregory Bologna at 703-299-9766. To pre-register, call Ann Haran at 703-299-9766.

Press releases and all abstracts are available online at http://www.aasld.org/.

Quote from Dr. Jacobson: "This phase 3 trial confirms previous findings that telaprevir confers higher rates of viral cure in patients with the highly prevalent genotype 1 when compared with the current standard of care, with the added advantage of a shorter total duration of treatment in the majority of patients. Although rash and anemia were more common with telaprevir, treatment discontinuation due to side effects was very infrequent and side effects attributable to the drug are reversible. This study, along with others on protease inhibitors at this year's meeting, heralds an exciting new era in HCV therapy in which increasing numbers of patients will be cured and spared the life-threatening risks of advanced liver disease."

Media Contact: Gregory Bologna
703/299-9766
gbologna@aasld.org
Press Room: October 30 – November 2, 2010
Hynes Convention Center, Room 208
Telephone: 617-954-3106

Researcher: Ira Jacobson, MD
Email: imj2001@mail.med.cornell.edu
Phone: 212-726-2115

This release was issued through The Xpress Press News Service, merging e-mail and satellite distribution technologies to reach business analysts and media outlets worldwide. For more information, visit http://www.XpressPress.com.

SOURCE American Association for the Study of Liver Diseases (AASLD)
RELATED LINKS
http://www.aasld.org/

Source
BOSTON, Nov. 1, 2010 /PRNewswire/ -- Dr. Howard Koh, the 14th Assistant Secretary for Health for the U.S. Department of Health and Human Services (HHS), described the steps the U.S. administration is taking in response to the recent Institute of Medicine (IOM) report on viral hepatitis in his 2010 President's Choice Lecture at The Liver Meeting®, the annual meeting of the American Association for the Study of Liver Diseases (AASLD). Dr. Koh formed and led a U.S. Department of Health and Human Services-wide team that will soon issue a hepatitis action plan that will leverage new funding opportunities and integrate activities throughout HHS to build true systems of care for high-risk individuals.

Additionally, the plan will be used to strengthen partnerships with federal, professional, and patient organizations in an effort to set and implement policies to guide public health and clinical practice. Other goals of the plan will be to harmonize screening guidelines, create new strategies for workforce development, and improve hepatitis B vaccination rates for adults at high risk. Dr. Koh stressed the need for collaboration in addressing the epidemic of hepatitis, including the need to work with state and local health leaders and create stronger links with professional societies such as AASLD. The report will address the need for prevention and building the capacity for reducing the number and incidence of viral hepatitis infections and improving the health of patients and economic consequences of viral hepatitis.

Dr. Koh also praised the recent Trust for America's Health report developed in collaboration with AASLD that translates the IOM report into language that may be used to affect appropriations to support research and health care delivery for liver disease and also to be used in future legislation to make the screening, early detection, and treatment of viral hepatitis a reality.

Viral hepatitis is the fourth leading infectious cause of death, but is virtually unknown to health care providers, the general public, at-risk populations, and policymakers. Individuals with viral hepatitis are at increased risk for liver cancer and chronic liver disease, yet an estimated 70 percent of persons with chronic viral hepatitis do not know that they are infected. In the absence of appropriate treatment, 15 to 40 percent of infected persons will develop liver cirrhosis; viral hepatitis is also the leading cause of liver transplantation in the U.S. In addition, liver cancer rates have tripled over the last several decades in contrast to other types of cancer. Surveillance data suggest that nearly 20,000 people are newly infected with HCV every year.

Recent developments in many health-related areas can potentially contribute to lower rates of chronic hepatitis virus in the U.S. and improve health outcomes for infected persons. The HHS action plan reflects upon feedback received from both experts and the community, and will help HHS improve its existing efforts to prevent viral hepatitis and related disease in the following three ways:

• Establishing priorities for the specific actions that must be taken, assigning lead and partner agencies with responsibility for meeting these priorities

• Helping HHS build prevention and care capacity and improving the efficiency of current efforts through improved coordination of viral hepatitis activities across HHS operating divisions

• Serving as a guide for HHS to engage other governmental agencies and nongovernmental organizations in viral hepatitis prevention and care

This action plan is organized into the following six topic areas, which correspond to IOM recommendations:

• Increasing community awareness and provider education

• Strengthening surveillance for viral hepatitis

• Preventing viral hepatitis associated with injection-drug use

• Preventing viral hepatitis transmission through vaccination

• Preventing health care associated viral hepatitis

• Improving screening, care, and treatment for viral hepatitis

About the AASLD

AASLD is the leading medical organization for advancing the science and practice of hepatology. Founded by physicians in 1950, AASLD's vision is to prevent and cure liver diseases. This year's Liver Meeting®, held in Boston, Massachusetts, October 29- November 2, will bring together more than 7,500 researchers from 55 countries.

A pressroom will be available from October 30 at the annual meeting. For copies of abstracts and press releases, or to arrange for pre-conference research interviews contact Gregory Bologna at 703-299-9766. To pre-register, call Ann Haran at 703-299-9766.

Press releases and all abstracts are available online at http://www.aasld.org/.

Media Contact: Gregory Bologna
703-299-9766
gbologna@aasld.org
Press Room: October 30 – November 2, 2010
Hynes Convention Center, Room 208
Telephone: 617-954-3106

This release was issued through The Xpress Press News Service, merging e-mail and satellite distribution technologies to reach business analysts and media outlets worldwide. For more information, visit http://www.XpressPress.com.

SOURCE American Association for the Study of Liver Diseases

RELATED LINKS
http://www.aasld.org/

Source

Romark Announces Data Presented at AASLD Meeting 2010

Studies highlight important features of nitazoxanide and other thiazolidesas therapeutic agents for chronic hepatitis C

TAMPA, Fla., Nov. 1, 2010 /PRNewswire/ -- Romark Laboratories announced that data from studies of nitazoxanide in hepatitis C are being presented at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), also known as The Liver Meeting® in Boston, October 30 – November 2, 2010.

"The data presented at AASLD provide important support for our ongoing clinical development program for nitazoxanide in chronic hepatitis C (CHC)," said Jean-Francois Rossignol, M.D., Ph.D., Chairman and Chief Science Officer of Romark. "Extensive studies have shown that nitazoxanide does not induce mutations that confer viral resistance – one of the most challenging problems associated with antiviral therapy. Other studies highlight the important role of nitazoxanide in stimulating the interferon signaling pathway and a potential role for nitazoxanide in special populations such as relapsers and liver transplant patients."

Another major finding reported at AASLD is the activity of nitazoxanide-related compounds (called thiazolides) against HCV. Collectively, these studies provide further rationale for the use of nitazoxanide and other thiazolides as part of a new approach to chronic hepatitis C therapy – an approach that focuses on reducing the number of drugs and the toxicities associated with treatment.

Investigators from Georgetown University, the National Institutes of Health, and Mayo Clinic have presented or will present their data on October 31 and November 2. The three presentations are listed and described briefly below:

1. HCV Resistance to Nitazoxanide is not due to Changes in the Viral Sequence. Brent Korba, Microbiology & Immunology, Georgetown Univ. Med. Ctr., Washington, DC. Poster session: Tuesday, November 2, 7:00 am – 12:00 pm.

Dr. Korba reports an extensive series of studies designed to evaluate mechanisms of potential resistance of hepatitis C virus (HCV) to nitazoxanide. These studies show that nitazoxanide does not induce mutations in HCV that confer resistance. Importantly, these findings distinguish nitazoxanide from direct-acting antiviral drugs (e.g., protease and polymerase inhibitors) and other host-targeting anti-HCV agents, such as the cyclophilin inhibitors, where resistance appears to be primarily due to mutations in viral sequences.

2. Augmentation of Interferon Signaling Pathway by Nitazoxanide: A Novel Therapeutic Strategy for Relapsers to Peginterferon and Ribavirin Therapy. Crystal Wang(1), Ziaozhen Zhang(1), Anu Osinusi(1), Henry Masur(2), Dawn Fishbein(3), Shyam Kottilil(1); (1)LIR, NIAID, NIH, Bethesda, MD; (2)CCMD, CC, NIH, Bethesda, MD; (3)SAIC-Frederick, Inc., CMRP in support of CCMD, NIH, Frederick, MD. Poster session: Tuesday, November 2, 7:00 am – 12:00 pm.

This team of researchers from NIH reports that nitazoxanide has potent in vitro anti-HCV activity in the Huh7.5/JFH-1 HCV genotype 2a continuous cell culture system and that the activity is synergistic with interferon. In PBMCs collected from SVR and relapser patients co-infected with HCV and HIV, nitazoxanide significantly enhanced interferon-inducible gene expression. The addition of nitazoxanide to interferon also significantly enhanced interferon-inducible gene expression compared to interferon alone. Importantly, these investigators also report, for the first time, the activity of new nitazoxanide-related compounds (thiazolides) against HCV.

3. Nitazoxanide for the Prevention of Recurrent Hepatitis C Virus Infection after Liver Transplantation: A Pilot Study. Sumeet K. Asrani, Stacy Anderson, Jennie Wilnso, Laura J. Myhre, Julie Heimbach, Walter K. Kremers, Charles B. Rosen, Terry M. Therneau, W. Ray Kim; Mayo Clinic College of Medicine, Rochester, MN. Poster session: Sunday, October 31, 8:00 am – 5:30 pm.

Dr. Kim and his colleagues from the Mayo Clinic have reported results of a pilot study of nitazoxanide in 5 male liver transplant patients who received oral nitazoxanide 1000 mg b.i.d. immediately prior to transplant and for 72 hours thereafter. Each of the 5 patients experienced a decrease in HCV viral load during the first 72 hours. Within 4 days after completing therapy, HCV RNA levels were similar to pre-transplant levels. Nitazoxanide was well tolerated with the primary adverse events being abdominal pain and nausea which resolved. Post-transplant viral kinetics for these 5 patients were similar to a historical control group of 5 transplant recipients, except that there was a greater log drop in nitazoxanide-treated patients within the first 24 hours. The authors concluded that this suggests that peri-transplant induction with nitazoxanide, potentially at a higher dose, may serve as a novel adjunct to other antiviral regimens to prevent HCV recurrence.

About Hepatitis C

Hepatitis C is a blood-borne infectious disease that is caused by the hepatitis C virus (HCV). It is the most common cause of chronic hepatitis in the U.S. and may eventually lead to cirrhosis, liver cancer and liver failure. The disease is transmitted by contact with HCV-infected blood. A large majority of those infected do not show symptoms, but fatigue, abdominal pain and nausea can be common. The current standard treatment of care, peginterferon and ribavirin, is effective in about half of all patients treated. Treatment outcomes vary based on a number of factors including genotype, viral load, genetic factors, stage of liver disease, co-infections and ability to adhere to treatment. According to the Centers for Disease Control, approximately 3.2 million Americans are chronically infected with HCV.

About Nitazoxanide in CHC

Nitazoxanide, the first of a new class of broad-spectrum antiviral drugs called the thiazolides,(1,2,3) is an investigational new drug for CHC. It is a potent inhibitor of HCV in replicon studies,(2) and laboratory studies indicate that it does not induce viral mutations that confer drug resistance.(3,4) Nitazoxanide is synergistic with interferon and direct acting antivirals in replicon studies.(2,5) In a clinical trial of nitazoxanide monotherapy in patients with genotype 4 CHC, 17% (4 of 23) patients achieved sustained virologic response (undetectable serum HCV RNA 24 weeks after end of therapy), with all responders having low baseline serum HCV RNA levels (<400,000 IU/mL).(6) In other clinical trials, the addition of nitazoxanide to peginterferon or peginterferon plus ribavirin was associated with improvement in sustained virologic response rates without increasing the toxicities associated with peginterferon and ribavirin.(7,8) Romark is preparing to initiate phase III clinical trials of nitazoxanide plus peginterferon for treatment of CHC and has recently announced plans to initiate clinical trials of nitazoxanide in combination with IC41, a therapeutic vaccine under development by Intercell AG.

About Romark Laboratories

Romark Laboratories, L.C. (www.romark.com) is a biopharmaceutical company committed to the discovery and development of innovative new small molecules for treating infectious diseases and cancers. The Company is developing a new class of broad-spectrum antiviral drugs called the thiazolides. The first thiazolide, nitazoxanide, is an investigational new drug in late-stage clinical development for the treatment of chronic hepatitis C and influenza. Other new thiazolides are expected to enter clinical development in 2011. Romark markets Alinia® (nitazoxanide) tablets, 500 mg and Alinia® (nitazoxanide) for Oral Suspension, 100 mg/5 mL in the United States.

(1) Rossignol JF. Thiazolides: a new class of antiviral drugs. Expert Opin Drug Metab Toxicol. 2009;5:667-674.

(2) Korba BE, Montero AB, Farrar K, et al. Nitazoxanide, tizoxanide, and other thiazolides are potent inhibitors of hepatitis B virus and hepatitis C virus replication. Antivir Res. 2008;77:56-63.

(3) Korba BE, Elazar M, Lui P, et al. Studies of the potential for hepatitis C virus resistance to nitazoxanide or tizoxanide. Antimicrob Agents Chemother. 2008;52:4069-4071.

(4) Yon C, Viswanathan P, Rossignol JF, Korba BE. Resistance to nitazoxanide is associated with alterations in the host and not the virus in HCV replicon-containing cultures. Submitted for publication.

(5) Korba BE, Elazar M, Liu P, et al. Potential role for nitazoxanide in combination with STAT-C agents for the inhibition of HCV replication without the development of resistance. Hepatology. 2008;48(suppl):356A.

(6) Rossignol JF, Kabil SM, El-Gohary Y, Elfert A, Keeffe EB. Clinical trial: randomized, double-blind, placebo-controlled study of nitazoxanide monotherapy for the treatment of patients with chronic hepatitis C genotype 4. Aliment Pharmacol Ther. 2008;28:574-580.

(7) Rossignol JF, Elfert A, El-Gohary Y, et al. Improved virologic response in patients with chronic hepatitis C genotype 4 treated with nitazoxanide plus peginterferon alfa-2a with or without ribavirin. Gastroenterology. 2009;136:856-862.

(8) Rossignol JF, Elfert A, Keeffe EB. Treatment of chronic hepatitis C using a 4-week lead-in with nitazoxanide before peginterferon plus nitazoxanide. J Clin Gastroenterol. 2010;44:504-509.

SOURCE Romark Laboratories, L.C.

RELATED LINKS
http://www.romark.com/

Source
Nov. 1, 2010, 9:00 a.m. EDT

ABBOTT PARK, Ill. and WATERTOWN, Mass., Nov. 1, 2010 /PRNewswire via COMTEX/ -- Abbott /quotes/comstock/13*!abt/quotes/nls/abt (ABT 51.41, +0.09, +0.17%) and Enanta Pharmaceuticals today announced positive results from a Phase 2 study of ABT-450/r, an investigational, oral protease inhibitor being developed for the treatment of hepatitis C (HCV) infection. Initial 3-day and 4-week results suggest that ABT-450/r (ABT-450 with 100mg of ritonavir to support once-daily dosing) demonstrates potent antiviral activity in treatment-naïve adults. Results show that more than 90 percent of patients (21 of 23) on study drug achieved HCV-RNA levels <25 IU/mL at four weeks. Results were presented today at the American Association for the Study of Liver Disease annual meeting in Boston.

Key findings:

After three days, treatment with ABT-450/r alone resulted in statistically significant, 4-log mean reductions of HCV RNA, across the three dose ranges of ABT-450 (50mg, 100mg, 200mg, once-daily dosing) compared to placebo

At week four, 91.3 percent (21 of 23) of patients receiving ABT-450/r in combination with standard of care (SOC) - pegylated alpha interferon and ribavirin (pegIFN/RBV) - achieved HCV-RNA <25 IU/ml

Safety appears consistent to that expected with SOC

"In spite of the progress that has been made in HCV treatment, limitations in efficacy remain with the current standard of care," Fred Poordad, M.D., chief of hepatology at the Liver Disease and Transplant Center at Cedars-Sinai Medical Center in Los Angeles, and one of the investigators for the study. "The initial results of ABT-450/r in patients with HCV suggest that ABT-450/r has favorable potency in the most common HCV genotype and that ABT-450/r could be an important element in a combination direct-acting antiviral regimen for treatment of HCV."

"Abbott has focused its antiviral research expertise on finding new treatment options for HCV-infected patients that could transform current therapy - by shortening the duration of treatment and increasing cure rates," said Scott Brun, M.D., divisional vice president, infectious disease development, Abbott. "We continue to explore the potential for use of ABT-450/r in a variety of combination regimens."

"We are very encouraged by the 3-day monotherapy and 4-week rapid virologic response results for ABT-450 and we look forward to further clinical results from the program," said Jay Luly, Ph.D, president and chief executive officer, Enanta Pharmaceuticals. "This data is an important step in our HCV program, and for advancing our broader vision to improve patient care in this field."

Study Objectives and Design

The objectives of the 48-week Phase 2 study are to assess the safety, tolerability, pharmacokinetics, and antiviral activity of multiple dose strengths of ABT-450/r in treatment-naïve adults infected with HCV genotype 1, which is the most common and difficult to treat form of the infection in the developed world. Trial endpoints include early virologic response and rapid virologic response. Initial antiviral activity was evaluated via a 3-day treatment period during which ABT-450/r was administered alone. Subsequently, ABT-450/r was administered with pegIFN/RBV (SOC) for 12 weeks, followed by treatment with SOC alone for an additional 36 weeks. Participants are then monitored post therapy for 24 weeks for sustained virologic response.

ABT-450 was discovered as part of an alliance between Abbott and Enanta and is being developed with low-dose ritonavir, which enhances the pharmacokinetic properties of ABT-450, allowing for once-daily dosing. This Phase 2 study also evaluated ABT-333 and ABT-072, two of Abbott's internally discovered compounds that are part of the company's ongoing non-nucleoside polymerase inhibitor development program. The study findings for these two compounds have been submitted for presentation at a future scientific meeting.

About the Hepatitis C Virus

Hepatitis C is a liver disease affecting more than 180 million people worldwide. The virus is primarily spread through direct contact with the blood of an infected person. HCV increases a person's risk of developing chronic liver disease, cirrhosis, liver cancer and death.

Liver disease associated with HCV infection is growing rapidly, and current therapies only cure about half of patients with the genotype 1 form of the virus. Specifically targeted antiviral therapies for HCV, such as protease inhibitors and non-nucleoside polymerase inhibitors, may have the potential to increase the proportion of patients in whom the virus can be eradicated.

About Ritonavir

The use of NORVIR(R) (ritonavir) with ABT-450 for the treatment of HCV is investigational.

NORVIR is in a class of medicines called the HIV protease (PRO-tee-ase) inhibitors. NORVIR is used in combination with other anti-HIV medicines to treat people with human immunodeficiency virus (HIV) infection. NORVIR is for adults and for children age greater than 1 month and older.

NORVIR does not cure HIV infection or AIDS and does not reduce the risk of passing HIV to others. People taking NORVIR may still get opportunistic infections or other conditions that happen with HIV infection. Some of these conditions are pneumonia, herpes virus infections, and Mycobacterium avium complex (MAC) infections.

People should not take NORVIR with certain medicines, as these can cause serious or life-threatening problems such as irregular heartbeat, breathing difficulties, or excessive sleepiness. People should not take NORVIR if they have had a serious allergic reaction to any of its ingredients. Some patients taking NORVIR may develop liver and pancreas problems, which can cause death. Patients may develop large increases in triglycerides and cholesterol, diabetes, high blood sugar, changes in body fat, increased bleeding in people with hemophilia, allergic reactions, and/or changes in heart rhythm. People may develop signs and symptoms of infections that they already have after starting anti-HIV medicines.

Please see the Important Safety Information below for more details, including the potential for serious or life-threatening drug interactions.

Please click here for NORVIR full Prescribing Information.

Globally, prescribing information varies; please refer to your individual country's full Prescribing Information for complete information.

About Enanta

Enanta Pharmaceuticals is a research and development company that uses its novel chemistry approach and drug discovery capabilities to create best in class small molecule drugs in the infectious disease field. Enanta is developing novel protease, NS5A, polymerase, and cyclophilin-based inhibitors targeted against the Hepatitis C virus (HCV). Additionally, the Company has created a new class of macrolide antibiotics, called Bicyclolides, which overcomes bacterial resistance. Antibacterial focus areas include superbugs, respiratory tract infections, and intravenous and oral treatments for hospital and community MRSA. Enanta is a privately held company headquartered in Watertown, Mass. Enanta's news releases and other information are available on the company's web site at http://www.enanta.com/.

About Abbott

Abbott's HCV development programs include its partnership with Enanta Pharmaceuticals to discover protease inhibitors, as well as internal programs focused on additional viral targets, including polymerase inhibitors. Abbott currently has three HCV compounds in clinical trials, including a protease inhibitor, a polymerase inhibitor and an NS5A inhibitor. Abbott is well positioned to explore combinations of these compounds, a strategy with the potential to markedly transform current treatment practices by shortening therapy duration, improving tolerability and increasing cure rates.

Abbott is a global, broad-based health care company devoted to the discovery, development, manufacturing and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs nearly 90,000 people and markets its products in more than 130 countries. Abbott's news releases and other information are available on the company's Web site at http://www.abbott.com/.

Important Safety Information about Ritonavir

People who have had a serious allergic reaction to NORVIR or any of its ingredients should not take NORVIR. Allergic reactions ranging from hives, asthma, severe breathing issues and mild to severe skin reactions have occurred.

Drug Interactions:

The below list of drug interactions is not complete. Before people take NORVIR, they must tell their doctor about all the medicines they are taking or are planning to take. These include other prescription and non-prescription medicines, and herbal supplements.

People should not take the following medicines with NORVIR because they can cause serious or life-threatening problems such as irregular heartbeat, breathing difficulties or excessive sleepiness: Cordarone(R) (amiodarone); ergotamine, ergonovine, methylergonovine, and dihydroergotamine such as Cafergot(R), Migranal(R), D.H.E. 45(R) and others; Halcion(R) (triazolam); Orap(R) (pimozide); Propulsid(R) (cisapride); quinidine, also known as Quinaglute(R), Cardioquin(R), Quinidex(R) and others; Revatio(R) (sildenafil) only when used for the treatment of pulmonary arterial hypertension; Rythmol(R) (propafenone); Tambocor(R) (flecainide); Uroxatral(R) (alfuzosin hydrochloride); Vascor(R) (bepridil); Versed(R) (oral midazolam); and Vfend(R) (voriconazole).

People should not take NORVIR with St. John's wort (Hypericum perforatum) as this may decrease NORVIR levels and lead to increased viral load and possible resistance to NORVIR or other antiretroviral medicines.

People should not take NORVIR with Mevacor(R) (lovastatin) or Zocor(R) (simvastatin) because of possible serious reactions. There is an increased risk of drug interactions between NORVIR and Lipitor(R) (atorvastatin) and Crestor(R) (rosuvastatin); people should talk to their doctor before they take any of these cholesterol-lowering medicines with NORVIR.

For people taking Viagra(R) (sildenafil), Cialis(R) (tadalafil), or Levitra(R) (vardenafil) with NORVIR, their doctor may lower their dose of these medicines because they may be at risk of side effects such as low blood pressure, visual changes, and penile erection lasting more than 4 hours. People should tell their doctor right away if they experience any of these side effects.

If people are taking Adcirca(R) (tadalafil) for pulmonary arterial hypertension, their doctor may change their dose of this medicine.

Women taking oral contraceptives ("the pill") or using the contraceptive patch to prevent pregnancy should use a different type of contraception since NORVIR may reduce the effectiveness of oral or patch contraceptives.

For people taking Mycobutin(R) (rifabutin), their doctor will lower the dose of Mycobutin.

For people taking Colcrys(R) (colchicine) or Tracleer(R) (bosentan), their doctor will tell them what dose to use.

NORVIR oral solution contains alcohol. People should talk with their doctor if they are taking or planning to take Flagyl(R) (metronidazole) or Antabuse(R) (disulfiram). Severe nausea and vomiting can occur.

Rifampin, also known as Rimactane(R), Rifadin(R), Rifater(R), or Rifamate(R), may reduce blood levels of NORVIR. People should tell their doctor if they are taking rifampin.

Rifampin and saquinavir should not be taken together with NORVIR. People should tell their doctor if they are taking rifampin and saquinavir.

People taking or about to begin using inhaled Flonase(R) (fluticasone propionate), Serevent(R) (salmeterol), or Advair(R) (salmeterol in combination with fluticasone propionate) should talk to their doctor about problems these medicines may cause when taken with NORVIR. Their doctor may choose not to keep them on inhaled Flonase, Serevent, or Advair.

Side Effects (This list is not complete):

Blood tests in patients taking NORVIR may show possible liver problems. People with liver disease such as hepatitis B and C who take NORVIR may have worsening liver disease. Liver problems, including death, have occurred in people who take NORVIR and in people taking Aptivus(R) (tipranavir) with NORVIR. People should tell their doctor right away if they have any of the following signs and symptoms: loss of appetite, yellowing of skin or eyes (jaundice), dark-colored urine, pale-colored stools, itchy skin and/or stomach area (abdominal) pain.

Pancreas problems (pancreatitis), which may cause death, have been reported in some people taking NORVIR. People should tell their doctor if they have nausea, vomiting or abdominal pain as these may be signs of pancreatitis.

Large increases in triglycerides and cholesterol have occurred in some people taking NORVIR. The long-term chance of getting complications such as heart attacks or stroke due to increases in triglycerides and cholesterol caused by protease inhibitors is not known at this time.

Diabetes and high blood sugar (hyperglycemia), changes in body fat, and increased bleeding in people with hemophilia have occurred in some people taking protease inhibitors including NORVIR. People should tell their doctor if they have diabetes or an increase in thirst or urinate often. The cause and long-term effects of body fat changes are not known at this time.

Changes in the electrocardiogram (EKG) can occur when taking NORVIR. People should consult their physician if they experience dizziness, lightheadedness, fainting spells or abnormal heartbeat. People with heart defects or conduction defects should avoid NORVIR.

Immune reconstitution syndrome may occur after starting anti-HIV medicines, including NORVIR. This happens when people develop signs and symptoms of serious infections they already have or had, which may require additional treatment.

The most commonly reported side effects are feeling weak/tired, nausea, vomiting, diarrhea, loss of appetite, abdominal pain, changes in taste, tingling feeling or numbness (in hands, feet or around the lips), headache, and dizziness.

For women who are pregnant or planning to become pregnant, it is not known if NORVIR can harm their unborn baby. Women taking NORVIR while they are pregnant should talk to their healthcare professional about how they can take part in the Antiretroviral Pregnancy Registry. Mothers taking NORVIR should not breast-feed because they may pass HIV on to their baby, or their baby could experience side effects from NORVIR.

The long-term effects of NORVIR are not known at this time.

SOURCE Abbott

Source
Nov. 1, 2010, 7:00 a.m. EDT

Proof of Concept Study to Evaluate INX-189 as Monotherapy and in Combination with Ribavirin
 
ATLANTA, Nov 01, 2010 (BUSINESS WIRE) -- Inhibitex, Inc. /quotes/comstock/15*!inhx/quotes/nls/inhx (INHX 1.99, 0.00, 0.00%) , announced today that it has initiated a Phase 1b, multiple ascending dose (MAD) clinical trial of INX-189, its nucleotide polymerase inhibitor in development for the treatment of chronic infections caused by hepatitis C virus (HCV). The trial, which is being conducted under an IND in the United States, is a double-blind, placebo-controlled, dose escalation study designed to evaluate the safety, tolerability, pharmacokinetics and anti-viral activity of INX-189 administered orally once daily for seven days in treatment naive patients with HCV genotype 1. Each treatment cohort will include 10 patients, eight of which will receive INX-189 and two of which will receive placebo. The first cohort in the Phase 1b study will receive 9 mg of INX-189 once daily. In addition to evaluating INX-189 as monotherapy, the Company plans to evaluate two dose levels of INX-189 administered once daily for seven days in combination with ribavirin, which is one of the drugs currently approved for the treatment of HCV. The dose levels of INX-189 to be evaluated in combination with ribavirin will be determined based upon the results of the monotherapy cohorts.

"The initiation of this proof of concept study in patients with chronic hepatitis C marks an important milestone in the clinical development of INX-189," stated Dr. Joseph Patti, Senior Vice President and Chief Scientific Officer of Inhibitex, Inc. "We believe that dosing INX-189 both as monotherapy and in combination with ribavirin in this study will enhance our ability to assess the anticipated anti-viral synergies of the two agents and allow us to better define the most appropriate doses of INX-189 to evaluate in future clinical trials."

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, and 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. The Company believes that its nucleotides possess several pharmacological advantages over other HCV nucleosides or nucleotides in clinical development, including a more efficient conversion into their active anti-viral form, a more favorable resistance profile, and anti-viral synergy when used in combination with ribavirin. INX-189 is a protide of a 2'-C-methylguanosine analogue, which, based on in vitro data, the Company believes is the most potent HCV nucleotide polymerase inhibitor currently in clinical development. The Company believes that preclinical and clinical studies of INX-189 completed to-date support its potential as a potent, once-daily oral therapy amenable to combination with other anti-virals 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. The Company's clinical stage pipeline includes FV-100, a bicyclic nucleoside inhibitor in Phase II development for the treatment of shingles, and INX-189, a nucleotide polymerase inhibitor in development for the treatment of chronic infections caused by hepatitis C virus (HCV). 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 http://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 plans to evaluate INX-189 as monotherapy for seven days and in combination with ribavirin in the Phase 1b study; that dosing INX-189 in combination with ribavirin will enhance the Company's ability to assess the anticipated anti-viral synergies of the two agents and better define the most appropriate doses of INX-189 to evaluate in future clinical trials; the Company's belief that INX-189 is the most potent HCV nucleotide polymerase inhibitor in clinical development; the Company's belief that its nucleotides possess several pharmacological advantages over other nucleosides or nucleotides in clinical development; and the results of preclinical studies of INX-189 supporting 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 not supporting its further development for lack of safety, tolerability, anti-viral activity, or any other reason, or not demonstrating any significant benefits over nucleosides alone or other nucleotide prodrugs; INX-189 not demonstrating anti-viral activity as monotherapy or any anti-viral synergies with ribavirin in the Phase 1b trial; 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 June 30, 2010, as filed with the SEC on August 12, 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

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