Galectin Therapeutics Presents Preclinical Data on the Treatment of Fatty Liver Disease and Fibrosis at EASL

Dec. 16, 2011, 8:00 a.m. EST

NEWTON, Mass., Dec 16, 2011 (BUSINESS WIRE) -- Galectin Therapeutics Inc., the leader in developing carbohydrate-based therapeutic compounds to inhibit galectin proteins, today announced that it presented a poster at the European Association for the Study of the Liver (EASL) Special Conference on Liver Transplantation in Lisbon, Portugal. The data show that galectin inhibitor candidate GR-MD-02 reversed fibrosis in mouse models of steatohepatitis and prevented collagen deposits in groups treated before fibrotic cells were present. The data suggest that patients with non-alcoholic steatohepatitis (NASH), also referred to as fatty liver disease, may benefit from galectin inhibition and that GR-MD-02 could drive in a reduction of steatosis, necrosis, inflammation and collagen deposits. Currently, liver transplantation is the only option for patients afflicted with liver fibrosis or cirrhosis, and many times the condition recurs in the patient's new liver, creating the need for a safer and more efficacious treatment. The data presented provide promising evidence for advancing GR-MD-02 into clinical studies for the treatment of NASH.

"Galectin Therapeutics has previously demonstrated the robust ability of our galectin inhibitor compounds to arrest and reverse liver fibrosis in preclinical studies," said Dr. Peter G. Traber, President, Chief Executive Officer and Chief Medical Officer, Galectin Therapeutics. "We have now expanded that data to include promising results in preclinical models of NASH, offering hope that a new treatment option could be on the horizon and expanding the potential indications for Galectin Therapeutics to pursue in the clinic. The broad effect of GR-MD-02 on all parameters of NASH liver injury, including fat deposition, liver cell death, inflammation, and fibrosis makes this a particularly attractive drug candidate."

The data presented at EASL Special Conference highlight two carbohydrate-based galectin inhibitors, GM-CT-01 and GR-MD-02, in preclinical mouse models of steatohepatitis. Mice are injected with streptozotocin to induce diabetes and then fed a high fat diet. Subsequently, these mice develop fatty liver (steatosis), liver cell death, inflammation between 5 weeks of age, and then, fibrosis by 9 weeks of age. To assess the ability of galectin inhibitors to prevent or reduce fibrosis, mice were separated into early or late treatment groups. Early treatment groups began receiving either GM-CT-01 or GR-MD-02 twice daily at 6 weeks of age, or before fibrosis is evident, until 9 weeks of age. Late treatment groups received either GM-CT-01 or GR-MD-02 twice daily at 9 weeks of age, or when fibrosis is established, until 12 weeks of age. GR-MD-02 demonstrated greater improvements in steatosis, hepatocellular degeneration and inflammation. In the early treatment group, GR-MD-02 prevented the development of collagen deposition, or fibrosis, and was able to completely reverse fibrosis in the late treatment group back to levels of normal mice. GM-CT-01 did show a moderate effect on reducing collagen deposition. Importantly, GR-MD-02 was able to reverse steatohepatitis and fibrosis without having an effect on the diabetic condition of the mice. To view the complete poster presentation, please go to the Galectin Therapeutics' web site at www.galectintherapeutics.com .

About NASH

NASH is a common disease of the liver, affecting 9 to 15 million people in the United States and is characterized by the presence of fat in the liver along with inflammation and damage in people who drink little or no alcohol. Over time, patients with NASH can develop fibrosis, or scarring of the liver, that can lead to cirrhosis, a severe liver disease where transplantation is the only current treatment available. Galectin Therapeutics is developing drug candidates as an alternative to transplantation and lead candidates have reversed fibrosis in preclinical disease models.

About Galectin Therapeutics

Galectin Therapeutics is developing promising carbohydrate-based therapies for fibrotic liver disease and cancer based on the Company's unique understanding of galectin proteins, key mediators of biologic function. We are leveraging extensive scientific and development expertise as well as established relationships with external sources to achieve cost effective and efficient development. We are pursuing a clear development pathway to clinical enhancement and commercialization for our lead compounds in liver fibrosis and cancer. Additional information is available at www.galectintherapeutics.com .

Forward Looking Statements

This press release contains, in addition to historical information, forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements relate to future events or future financial performance, and use words such as "may," "estimate," "could," "expect" and others. They are based on our current expectations and are subject to factors and uncertainties which could cause actual results to differ materially from those described in the statements. Factors that could cause our actual performance to differ materially from those discussed in the forward-looking statements include, among others: incurrence of operating losses since our inception, uncertainty as to adequate financing of our operations, extensive and costly regulatory oversight that could restrict or prevent product commercialization, inability to achieve commercial product acceptance, inability to protect our intellectual property, dependence on strategic partnerships, product competition, and others stated in risk factors contained in our SEC filings. We cannot assure that we have identified all risks or that others may emerge which we do not anticipate. You should not place undue reliance on forward-looking statements. Although subsequent events may cause our views to change, we disclaim any obligation to update forward-looking statements.

SOURCE: Galectin Therapeutics

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EASL: HCV Drug Resistance

This is an excellant article written by Jules Levin of NATAP

from Jules: This is a controversial issue & was at this just completed EASL. Where a number of researchers said flatly 'we will be able to re-use HCV protease inhibitors after patients develop resistance if we wait 2 years for the mutations to disappear & this was pretty much said with regards to telaprevir following the oral presentation by Sullivan of Vertex reporting that mutations mostly disappear after 1.5 years following stopping telaprevir therapy'. This may end up being true but right now this is just a theory without any evidence, no data to support this supposition, it cannot be considered true until a study or real clinical evidence supports this. Until we have data on this question one cannot say flatly patients will be able to re-use a HCV protease after resistance and receive viral load reductions from the drug. Will such a study ever be done, I don't know. There are many other classes of HCV drugs in development so in the future patients ought to be able to switch to a regimen of 2-4 oral drugs with or without peg/rbv without a protease, so the question may be moot. Still I think we need to clarify this. One issue is that the Sullivan study did not use ultra-deep sequencing, which in this study below shows mutations missed by clonal sequencing are picked up by UDS. At baseline before therapy mutations pre-exist, so 2 years later you would expect these same pre-existing mutations to be present but HCV multi-drug therapy suppresses these mutations and SVR still has been achieved evidenced by the studies with telaprevir & boceprevir, but the question is will these mutations be further enriched after failing therapy, will mutations accumulate to a significant degree if a patient remains on failing therapy, will compensatory mutations accumulate, and will these situations persist & affect re-treatment with a PI, I don't know the answer to these questions and I don't think anyone does. Perhaps the prediction that this will not be a problem is correct but we don't know & we have not studied this adequately.

AASLD: Ultra-Deep Sequencing of the NS3 and NS5B Regions Detects Pre-Existing Resistant Variants to Direct Acting Antivirals (DAA) in HCV Genotype 1 Treatment-Naïve Infected Patients - (11/29/10)

"Minority variants resistant to PI or NNI were detected in 3 and 10 subjects respectively at frequencies that ranged from 0.6 to 14%. Concordance between UDPS and molecular clonal sequencing was 87% for MVs detected (by either method) at a level >10%; 68% for MVs detected at a level of 5% to 10%; and 26% for MVs detected at a level of 1% to 5%."

ULTRA-DEEP SEQUENCING OF THE NS3 AND NS5B REGIONS DETECTS PRE-EXISTING RESISTANT VARI- ANTS TO DIRECT ACTING ANTIVIRALS (DAA) IN HCV GENOTYPE 1 INFECTED PATIENTS NAïVE

AASLD ABSTRACT 2010 October

Severine Margeridon4, Sophie Le Pogam2, Tommy F. Liu4, Bozena Hanczaruk3, Todd E. Arnold3, Birgitte B. Simen3, Nancy Shulman1, Robert W. Shafer4, Isabel Najera2; 1Virology - Pharma Research Early Development, Roche Pharmaceuticals, Palo Alto, CA; 2Virol- ogy - Discovery, Roche Pharmaceuticals, Palo Alto, CA; 3454 Life- sciences, a Roche Company, Branford, CT; 4Infectious Diseases and Geographic Medicine, Stanford University Medical School, Stanford, CA

Background: Naturally occurring HCV drug-resistance minority variants (MVs) that are not detectable by standard consensus sequencing may have an impact on the effectiveness of HCV inhibitors. We used ultradeep pyrosequencing (UDPS) and molecular clonal sequencing to assess the prevalence of HCV drug-resistant minority variants to protease (PI), nucleoside ana- log (NA), and nonnucleoside polymerase inhibitors (NNI) in serum samples from DAA-naïve HCV infected subjects.

Methods: Samples were obtained from 39 DAA treatment naive HCV-infected subjects (27 genotype 1a and 12 genotype 1b). Molecular clonal sequencing and UDPS were performed span- ning those regions of the NS3 protease,and of the NS5B poly- merase including amino acid residues known to confer resistance to PIs, NAs and NNIs. The median viral load was 6.6 log10 IU/ml (range 5.1 - 7.6). UDPS was performed using the GS FLX Titanium platform (454 / Roche Life Sciences) at a median coverage per base of ~3,500. MVs for the UDPS were defined as mutations present in ≥0.5% of UDPS reads..whereas for the clonal sequencing analysis, MVs were defined as muta- tions present in ≥1 molecular clone.

Results: Plasmid control experiments identified a UDPS error rate of 0.1% - resulting from a combination of PCR and pyrosequencing error. No NA resistance mutation was detected by UDPS nor through molecular clonal sequencing. Minority variants resistant to PI or NNI were detected in 3 and 10 subjects respectively at frequencies that ranged from 0.6 to 14%. Concordance between UDPS and molecular clonal sequencing was 87% for MVs detected (by either method) at a level >10%; 68% for MVs detected at a level of 5% to 10%; and 26% for MVs detected at a level of 1% to 5%.

Conclusions: UDPS is a powerful technique for detecting minority variants within viral quasispecies. Optimization of a number of factors such as amplification error rate, input viral load, and the refining the sensitivity of the technique is ongoing. Comparison of results from molecular cloning and UDPS showed that no nucleoside analogs DRM as detected through either technique. Both techniques, however, detected the most prevalent NNI-DRMs with relative high concordance for MVs present at levels > 5%.

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EASL:Investigational compound PEG-interferon lambda achieved higher response rates with fewer flu-like and musculoskeletal symptoms and cytopenias than PEG-interferon alfa in Phase IIb study of 526 treatment-naive hepatitis C patients

Public release date: 2-Apr-2011

Contact: Cristi Barnett
cristi.barnett@bms.com
609-252-6028
TogoRun

(PRINCETON, N.J., April 2, 2011) – Bristol-Myers Squibb Company (NYSE: BMY) today announced results from the Phase IIb EMERGE clinical trial, in which treatment with the investigational compound PEG-Interferon lambda and ribavirin achieved higher rates of rapid virologic response (RVR) in genotypes 1, 2, 3, and 4, and complete early virologic response (cEVR) in genotypes 1 and 4 than the standard regimen of PEG-Interferon alfa and ribavirin in treatment-naïve patients chronically infected with hepatitis C (HCV). In this study, there were fewer flu-like and musculoskeletal symptoms and cytopenia, as well as fewer interferon and ribavirin dose reductions for anemia in the PEG-Interferon lambda arms up to 12 weeks. Rates of serious adverse events, depression and other common adverse events (incidence ≥10%) were similar across treatment arms up to week 12.

The EMERGE study findings were presented in a late-breaker oral session at the International Liver Congress (ILC), the 46th annual meeting of the European Association for the Study of the Liver (EASL) in Berlin, Germany.

"There is a significant unmet medical need for more therapies that can benefit more hepatitis C patients. This is especially true for patients with HCV genotypes 1 and 4, who generally have lower response rates to treatment with PEG-Interferon alfa and ribavirin than patients with other genotypes," said Stefan Zeuzem, MD, chief of the department of medicine and professor of medicine at the Johann Wolfgang Goethe University Hospital in Frankfurt, Germany. "The EMERGE study results demonstrate that PEG-Interferon lambda may have the potential to help address this unmet need, and support further studies of this new type of investigational interferon."

PEG-Interferon lambda is the first investigational type III interferon. Interferon lambda mediates antiviral activity through a receptor that is distinct from that used by interferon alfa and is present on fewer cell types within the tissues of the body. This restricted distribution of the interferon lambda receptor offers the potential for more targeted delivery of interferon therapy.

Study Results

Viral Response: HCV Genotypes 1 and 4

In this study, HCV genotype 1 and 4 patients treated with PEG-Interferon lambda achieved statistically significant (p<0.05) higher rates of cEVR (primary study endpoint) versus PEG-Interferon alfa at all doses [lambda 240 µg: 56.3% (n=103), lambda 180 µg: 55.9% (n=102), lambda 120 µg: 55.0% (n=100) vs. alfa: 37.9% (n=103)]. These statistically significant (p<0.05) higher viral response rates were seen as early as four weeks of treatment, with greater rates of RVR at the two higher doses of PEG-Interferon lambda (lambda 240 µg: 16.5%, lambda 180 µg: 14.7%, lambda 120µg: 6.0% vs. alfa: 5.8%).

Viral Response: HCV Genotypes 2 and 3

In patients with HCV genotypes 2 and 3, treatment with all doses of PEG-Interferon lambda achieved cEVR rates similar to PEG-Interferon alfa [lambda 240 µg: 83.3% (n=30), lambda 180 µg: 96.6% (n=29), lambda 120 µg: 90% (n=30), and alfa: 86.2%, (n=29)]. Statistically significant (p<0.05) higher rates of RVR were achieved at the two higher doses of PEG-Interferon lambda (lambda 240 µg: 66.7%, lambda 180 µg: 75.9%, lambda 120 µg: 43.3% vs. alfa: 31%).

Safety

In this study, rates of adverse events commonly associated with interferon treatment were lower with PEG-Interferon lambda than with PEG-Interferon alfa. These adverse events included flu-like symptoms (lambda 240 µg: 9.7%; lambda 180 µg: 9.9%; lambda 120 µg: 12.5%; alfa: 42.9%), musculoskeletal symptoms (lambda 240 µg: 14.2%; lambda 180 µg: 14.5%; lambda 120 µg: 18.0%; alfa: 46.6%), neutropenia < 750/mm³ (lambda 240 µg: 0.0%; lambda 180 µg: 0.8%; lambda 120 µg: 0.0%; alfa: 15.2%), anemia with hemoglobin < 10 g/dL (lambda 240 µg: 12.9%; lambda 180 µg: 15.4%; lambda 120 µg: 20.5%; alfa: 43.9%.) and thrombocytopenia < 50K/mm³ (lambda 240 µg: 0.0%; lambda 180 µg: 0.0%; lambda 120 µg: 0.0%; alfa: 14.4%).

The proportion of patients that required interferon dose reductions were: lambda 240 µg: 12.7%; lambda 180 µg: 3.8%; lambda 120 µg: 0.8%; alfa: 18.8%, and the proportion of patients that withheld and/or reduced ribavirin were: lambda 240 µg: 11.2%; lambda 180 µg: 4.6%; lambda 120 µg: 10.2%; alfa: 20.3%. The proportion of patients who required ribavirin dose reductions for anemia were: lambda 240 µg: 0.7%; lambda 180 µg: 1.5%; lambda 120 µg: 2.3%; alfa: 12.8%.

Rates of serious adverse events, depression and other common adverse events (≥10%) were similar across treatment arms. Higher rates of elevated liver enzymes [AST or ALT >5x the upper limit of normal (ULN)] were seen in the highest-dose PEG-Interferon lambda treatment arm compared with PEG-Interferon alfa (lambda 240 µg: 17.4%; lambda 180 µg: 2.3%; lambda 120 µg: 0.8%; alfa: 7.6%), and direct bilirubin was also elevated (>1.2 mg/dL) in the highest-dose PEG-Interferon lambda treatment arm compared with PEG-Interferon alfa (lambda 240 µg: 7.6%; lambda 180 µg: 3.9%; lambda 120 µg: 0.8%; alfa: 0.8%); all resolved spontaneously without sequelae or following interferon dose modification and/or discontinuation.

About the EMERGE Phase IIb Study

The EMERGE study is a two-part, randomized, controlled, multicenter, phase II study of PEG-Interferon lambda in 526 treatment-naïve patients with chronic hepatitis C genotype 1, 2, 3 or 4. Part one of EMERGE was a Phase IIa study, and results were previously presented at The American Association for the Study of Liver Diseases (AASLD) 2010 Liver Meeting. Part two of EMERGE is an ongoing, blinded Phase IIb study designed to evaluate the safety, efficacy, and pharmacokinetics of PEG-Interferon lambda vs. PEG-Interferon alfa, both in combination with ribavirin. The 526 patients were randomized into four dose groups: PEG-Interferon lambda 240 µg (n=134), PEG-Interferon lambda 180 µg (n=131), PEG-Interferon lambda 120 µg (n=128) and PEG-Interferon alfa 180 µg (n=133).

The study will continue for 48 weeks in genotype 1 and 4 patients and 24 weeks in genotype 2 and 3 patients. The primary endpoint of the study is the proportion of patients who achieve complete early virologic response (cEVR).

About PEG-Interferon lambda

PEG-Interferon lambda is the first investigational type III interferon in Phase IIb development for the treatment of hepatitis C. Native human interferon lambda proteins are generated by the immune system in response to viral infection, and signal through a different receptor than native human interferon alfa proteins. Lambda receptors are present on fewer cell types within the human body than alfa receptors. This restricted distribution of the interferon lambda receptor offers the potential for more targeted delivery of interferon therapy.

About Hepatitis C1

Hepatitis C is a virus that infects the liver and is transmitted through direct contact with blood. An estimated 170 million people worldwide are infected with hepatitis C. Twenty percent of people with chronic hepatitis C will develop cirrhosis and, of those, 20 percent will progress to liver cancer. Although there is no vaccine to prevent hepatitis C, it is a curable disease.

###

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com/ or follow us on Twitter at http://twitter.com/bmsnews.

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995, regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that the compound described in this release will move from exploratory development into full product development, that clinical trials of this compound will support a regulatory filing, or that the compound will receive regulatory approval or become a commercially successful product. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2010, in our Quarterly Reports on Form 10-Q, and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise.

Contacts:
Media: Cristi Barnett, 609-252-6028, cristi.barnett@bms.com
Investors: John Elicker, 609-252-4611, john.elicker@bms.com 

References
1 World Health Organization. Hepatitis C. Available at: http://www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index1.html. Accessed March 9, 2011.

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Breakthrough: Non-Interferon/Ribavirin Regimen Can Cure Hep C

April 4, 2011
by Tim Horn

In what is being heralded as a hepatitis C virus (HCV) treatment research breakthrough, a clinical trial evaluating two oral medications being developed by Bristol-Myers Squibb (BMS) suggests that at least some cases of chronic HCV infection can be cured without the use of either pegylated interferon or ribavirin (IFN/RBV).

The same study, reported Saturday, April 2, at the 46th annual meeting of the European Association for the Study of the Liver (EASL) in Berlin, also appeared to cure 10 people living with HCV treated with a quadruple regimen, consisting of BMS’s BMS-650032 and BMS-790052 in combination with IFN/RBV.

Though a combination of IFN/RBV has long been the standard treatment for chronic HCV infection, both drugs are associated with side effects and neither drug works directly against the virus. The high rate of toxicities, compounded by their indirect mechanisms of action, help explain why current treatment isn’t highly effective in a proportion of people living with HCV, particularly those with hard-to-treat genotype 1 infection.

Direct-acting antivirals (DAAs), drugs that directly target HCV, have been in development for several years. Not only can they potentially maximize treatment responses and reduce the amount of time someone needs to be treated for HCV, but they also have been eyed as a way of treating hepatitis C without the need for either IFN or RBV.

Numerous studies at EASL suggest that DAAs, including protease inhibitors, NS5A inhibitors and polymerase inhibitors, can substantially increase rates of sustained virologic responses (SVRs)—maintaining an undetectable HCV viral load for six months after stopping treatment, or a viral cure—when used in combination with IFN/RBV. Not only did a clinical trial evaluating BMS’s protease inhibitor (BMS-790052) and NS5A inhibitor (650032) add to the encouraging news, but it also demonstrated that two DAAs used together, without IFN/RBV, can cure HCV in some patients.

The Phase II study looked at a cohort of 21 HCV genotype 1 null responders—patients who had very limited responses to previous treatment with IFN/RBV—of whom 19 had an unfavorable IL28B genotype, which predisposes HCV patients to treatment failure. The cohort was divided into two groups: Group A involved 11 patients treated with BMS-790052 plus BMS-650032 without IFN/RB for 24 weeks; Group B involved 10 patients treated with both BMS drugs plus IFN/RBV for 24 weeks.

Nine of the 10 patients treated with quadruple therapy had an SVR after 24 weeks (SVR24), reported Anna Lok, MD, of the University of Michigan Medical Center at Ann Arbor and her colleagues. The one patient who didn’t have an SVR24 was tested again 35 days later and found to have an undetectable HCV viral load, suggesting a possible cure rate of 100 percent in the small number of individuals who received four-drug treatment.

Of particular interest are the results among those treated with the DAAs without IFN/RBV. Four of the 11 patients had an SVR24—among the first individuals in a clinical trial to be successfully cured of HCV without today’s standard-of-care drugs.

In the six patients who saw their HCV viral loads rebound during treatment with the DAAs, IFN/RBV was promptly added. Four of the patients then went on to achieve undetectable HCV viral loads. HCV resistance to both BMS-790052 and BMS-650032 was documented in all six patients who did not respond favorably to DAA therapy alone, though it is not clear what the implications of resistance are for those who potentially require retreatment with these or similar agents.

Many side effects were similar in both groups, including diarrhea, fatigue, headache, fever and difficulty sleeping. Most side effects, however, were mild to moderate in severity, and there were no discontinuations from the study due to adverse events. Moderate-to-severe drops in neutrophils, a type of white blood cell, was documented in six patients in the quadruple-therapy group, compared with no patients in the dual-DAA group.

Lok concluded that quadruple therapy can result in a high rate of cure in this difficult-to-treat population and that, based on the encouraging dual-DAA study results, that HCV infection can be cured without IFN or RBV.

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Also See:
EASL: Quadruple therapy shows 100 percent SVR for HCV patients previously unresponsive to treatment

EASL: Telaprevir Add-On Effective After Initial HCV Therapy Fails

Daniel M. Keller, PhD

April 6, 2011 (Berlin, Germany) — Telaprevir added to standard pegylated interferon alfa-2a/ribavirin (peg-IFN/RBV) therapy for hepatitis C virus (HCV) infection was superior to retreatment with peg-IFN/RBV plus placebo in patients for whom standard therapy had failed in the past, researchers announced here at the European Association for the Study of the Liver (EASL) 46th Annual Meeting.

The safety and tolerability of adding telaprevir were similar to results seen in previous trials. Adverse events leading to permanent discontinuation of the drugs consisted mainly of anemia and rash, and were more prevalent in the telaprevir groups than in the control group.

Standard combination therapy with peg-IFN/RBV fails in approximately 60% of patients with HCV genotype 1, which is one of the more difficult genotypes to eradicate, noted Stefan Zeuzem, MD, chief of the Department of Medicine and professor of medicine at the Johann Wolfgang Goethe University Hospital in Frankfurt, Germany, who presented the study results.

The aim of the Re-Treatment of Patients With Telaprevir-Based Regimen to Optimize Outcomes (REALIZE) trial was to test the addition of telaprevir, a new small-molecule HCV protease inhibitor, to peg-IFN/RBV in 662 patients with HCV genotype 1 for whom peg-IFN/RBV had previously failed to produce sufficient and sustained viral suppression.

The primary objective of this pivotal phase 3 international, multicenter, double-blind, placebo-controlled trial was to compare the proportion of patients achieving a sustained virologic response (SVR) with telaprevir plus peg-IFN/RBV and the proportion achieving an SVR with placebo plus peg-IFN/RBV. All SVRs were below 25 IU HCV RNA (undetectable level).

Patients were divided into 3 categories: null responders did not show at least a 2 log10 drop in serum HCV RNA at week 12 of previous standard therapy; partial responders experienced at least a 2 log10 drop at week 12 of previous therapy but still had detectable HCV RNA in the blood at week 24; and relapsers achieved viral levels below the limit of detection at 42 weeks but then had a recurrence of detectable virus.

The groups were well matched at baseline. Approximately 70% were men, median age was approximately 50 years, 93% were white, HCV RNA was above 800,000 IU/mL in 86% to 89%, and almost 60% were in the advanced stages of disease with bridging fibrosis or cirrhosis (26%). About half were infected with genotype 1a and about half with genotype 1b. About 30% were previous nonresponders, 20% were partial responders, and 50% were previous relapsers.

Patients were randomly assigned to 1 of 3 treatment groups: 266 patients received telaprevir + peg-IFN/RBV for 12 weeks, then placebo + peg-IFN/RBV for 4 weeks (T12/PR48); 264 patients received a lead-in of placebo + peg-IFN/RBV for 4 weeks, then telaprevir + peg-IFN/RBV for 12 weeks (lead-in T12/PR48); and 132 patients received placebo + peg-IFN/RBV for 16 weeks (placebo/PR48).

In these 3 groups, drug doses were as follows: telaprevir 750 mg every 8 hours; peg-IFN 180 µg/week; and RBV 1000 to 1200 mg/day. The groups were followed-up and assessed for SVR at week 72. The primary statistical calculations were on previous relapsers and on previous nonresponders (a combination of previous partial responders and null responders).

Dr. Zeuzem reported that among previous relapsers, 83% to 88% achieved an SVR when treated with telaprevir plus peg-IFN/RBV. Less than 10% of them relapsed by week 72. In contrast, only 41% of previous nonresponders achieved an SVR with telaprevir, but this figure was still a 4-fold increase over the proportion with an SVR when retreated with peg-IFN/RBV and placebo. Overall, about 35% of patients in the 2 telaprevir groups failed to achieve an SVR; those failures occurred mainly among previous partial and previous null responders.

Addition of Telaprevir to Peg-IFN/RBV Enhances SVR Rates

Patient Group T12/PR48, % (n/N) Lead-in T12/PR48, % (n/N) Placebo/PR48, % (n/N)

Previous Relapsers
SVRa  83 (121/145)c  88 (124/141)c  24 (16/68)
Relapseb 7 (10/135)  7 (9/138)  65 (30/46)

Previous Nonresponders
SVRa  41 (50/121)c  41 (51/123)c  9 (6/64)
Relapseb  23 (16/69)  25 (18/72)  33 (3/9)

a SVR assessed 24 weeks after planned treatment completion
b Relapse: detectable virus at week 72 in patients with undetectable HCV RNA at end of assigned treatment
c  P < .001, comparison vs placebo/PR48

"The SVR rates tended to be higher in genotype 1b–infected patients, in particular in prior partial responders and prior null responders," Dr. Zeuzem reported. "The lead-in phase [group] showed numerically slightly higher [SVR] rates in the prior relapsers and the prior nonresponders, but there was an opposite trend for the prior partial responders."

When the data were analyzed by the degree of baseline fibrosis, all subgroups of patients responded better to telaprevir than to peg-IFN/RBV plus placebo. For example, among previous relapsers, 86%, 85%, and 84% achieved an SVR with telaprevir if they had no fibrosis, bridging fibrosis, or cirrhosis, respectively, compared with 32%, 13%, and 13%, respectively, with peg-IFN/RBV plus placebo. The addition of telaprevir added little or no benefit over peg-IFN/RBV alone for previous partial or null responders with cirrhosis.

Dr. Zeuzem noted that adverse events, which occurred at least 10% more frequently in the telaprevir groups than in the placebo group, were fatigue, pruritis, rash, anemia, nausea, diarrhea, and anorectal symptoms (described as pruritis, discomfort, or hemorrhoids).

The majority of adverse effects were grade 1 or 2, with some grade 3 rash in the pooled telaprevir groups. Rash was primarily eczematous, which resolved when therapy ended. Anemia was managed with RBV dose reduction when necessary, which occurred in 25% of the telaprevir-treated patients. Per protocol, erythropoiesis-stimulating agents were not permitted. In the telaprevir groups, 11% to 15% discontinued treatment because of adverse events; in the placebo group, 3% did.

Dr. Zeuzem concluded that "telaprevir/peg-interferon-ribavirin triple therapy was clearly superior to the standard peg-interferon/ribavirin treatment alone" in all 3 treatment-experienced populations."

He said a 4-week lead-in phase with peg-IFN/RBV did not reduce virologic failure or relapse rates and did not improve SVR rates. He noted that the safety of telaprevir was similar to that observed in previous studies. Adverse events, mainly anemia and rash, led to permanent discontinuation of study drugs more frequently in the telaprevir groups than in the control group.

Mark Thursz, MD, professor of hepatology at Imperial College, London, United Kingdom, and vice secretary of EASL, said: "I think these are very responsible conclusions . . . and I feel that the data that are coming out on this particularly difficult-to-treat group of patients — those who had previous treatment and failed — these are really exciting results. Overall, something like 60% of patients were successfully treated [and] reached an SVR in the REALIZE trial." He added that "partial responders [did] so-so; null responders, not so good. This is disappointing but not entirely surprising. They are particularly difficult groups to treat."

Dr. Thursz, who was not involved in the REALIZE trial, said that for patients for whom previous therapy has failed, "now we have treatment options to offer them, assuming that the commissioning authorities will pay for [the drugs] for those who don't pay for their own therapy."

In response to a question from the audience about the rashes and the possibility of Stevens–Johnson syndrome, Dr. Zeuzem said that of the several thousand people exposed to telaprevir, "to the very best of my knowledge, there is only 1 case of Stevens–Johnson syndrome described, but this case occurred after telaprevir was already discontinued, so a causal relationship cannot be justified from this single case. But I know that this single case has made many people very nervous."

Although anemia was more frequent in the telaprevir groups, "we have learned to manage anemia in this group of patients," Dr. Thursz said. "Most patients can tolerate more anemia than the pharmaceutical companies can."

Telaprevir is being developed by Vertex Pharmaceuticals. The US Food and Drug Administration has granted the drug priority review, which is expected on May 23.

Dr. Zeuzem reports relationships with Abbott, Achillion, Anadys, BMS, Gilead, iTherX, Merck, Novartis, Pfizer, Pharmasset, Roche, Santaris, Tibotec, and Vertex. Dr. Thursz has disclosed no relevant financial relationships.

European Association for the Study of the Liver (EASL) 46th Annual Meeting: Opening session. Presented March 30, 2011.

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EASL: Jennerex and Transgene Announce the Presentation of Positive Clinical Data of JX-594 in Patients With Liver Tumors

SAN FRANCISCO and ILLKIRCH, France, April 5, 2011 /PRNewswire/ -- Jennerex, Inc., a private clinical-stage biotherapeutics company focused on the development and commercialization of first-in-class targeted oncolytic products for cancer, and Transgene (NYSE Euronext Paris: FR0005175080), a bio-pharmaceutical company specialized in the development of immunotherapeutic products, today announced that new data from Phase 1 and 2 clinical studies of JX-594 were presented in an oral presentation at the 46th Annual Meeting of the European Association for the Study of the Liver (EASL) over the weekend at the Internationales Congress Centrum in Berlin, Germany.

The data from abstract #LB-283, entitled "JX-594, A Targeted Multi-Mechanistic Oncolytic Poxvirus, is Well-Tolerated and Exhibits Anti-Tumor Activity in Patients with Primary Liver Cancer and Liver Metastases," were presented by Caroline Breitbach, Ph.D., director of translational research.

"We are pleased to present these data on JX-594 at the EASL meeting, as they provide further evidence that both primary liver cancer and metastases to the liver can be treated safely with JX-594, with transient flu-like symptoms being the most common adverse events. Anti-cancer activity continues to be clearly demonstrated in a broad spectrum of common solid tumor types," said David H. Kirn, M.D., president and chief executive officer of Jennerex.

"We look forward to reporting additional clinical results in patients with advanced liver cancer from two ongoing studies—a randomized Phase 2 trial of JX-594 evaluating survival across two dose groups, and a Phase 2 clinical trial evaluating JX-594 in combination with sorafenib," added Philippe Archinard, chairman and chief executive officer of Transgene.

Clinical Results

This presentation highlighted data from 35 patients with either primary liver cancer, known as hepatocellular carcinoma (HCC), or cancer metastases to the liver (including colorectal cancer, melanoma and renal cancer). All patients were given intratumoral (IT) injections (up to eight treatments) over the course of JX-594 therapy. Twenty-three patients (66%) exhibited significant tumor necrosis and responses by modified Choi criteria (decreased tumor density). Choi responses have also been documented in non-injected tumors, consistent with prior data on JX-594. Seven patients (20% of evaluable) also exhibited objective response by Response Evaluation Criteria in Solid Tumor (RECIST) criteria, including two complete responses upon long-term follow-up. Twenty patients (57%) had stable disease as defined by RECIST criteria.

About JX-594

JX-594 is a proprietary, engineered oncolytic virus that is designed to selectively target and destroy cancer cells. JX-594 is designed to attack cancer through three diverse mechanisms of action: the lysis of cancer cells through viral replication, the ablation of the blood supply to tumors through vascular targeting and destruction, and the stimulation of the body's immune response against cancer cells (ie active immunotherapy). Phase 1 and Phase 2 clinical trials in multiple cancer types to date have shown that JX-594, delivered either directly into tumors or systemically, induces tumor shrinkage and/or necrosis and is well-tolerated by patients. Objective tumor response has been demonstrated in a variety of cancers including liver, colon, kidney, lung and melanoma.

Transgene holds an exclusive license to develop and commercialize JX-594 in Europe and neighboring countries. Green Cross Corporation, a leading company in the development, manufacturing, and commercialization of viral vaccines and other biological products, holds an exclusive license to develop and commercialize JX-594 in South Korea, and Lee's Pharmaceutical Ltd. holds an exclusive license to develop and commercialize JX-594 in China.

About Liver Cancer and Hepatocellular Carcinoma (HCC)

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related deaths world-wide with about 660,000 patients dying from the disease annually. Most HCC cases develop on the background of chronic liver cirrhosis; in regions with the highest incidence of HCC, East Asian and African countries, the majority of cases are related to hepatitis B; in developed Western countries and Japan the disease is commonly related to hepatitis C, heavy alcohol consumption and non-alcoholic fatty liver due to metabolic syndromes such as diabetes and obesity. There is accumulating evidence that the incidence of HCC is increasing in Western countries. Despite recent advances, the treatment of advanced HCC remains a significant unmet medical need with a median expected survival under current therapies of less than one year.

About Jennerex

Jennerex, Inc. is a clinical-stage biotherapeutics company focused on the development and commercialization of first-in-class, breakthrough targeted oncolytic products for cancer. The Company's lead product JX-594 is currently in two Phase 2 clinical trials in patients with primary liver cancer—an international, randomized, Phase 2 clinical trial, and a Phase 2 study of JX-594 in combination with sorafenib. Published studies designed to establish optimal dose levels and the safety profile of JX-594 have shown its ability to selectively target and cause destruction of a variety of common cancer types. JX-594 and other product candidates under development are designed to attack cancer tumors through three diverse mechanisms of action: the lysis of cancer cells through viral replication, the ablation of the blood supply to tumors through vascular targeting and destruction and the stimulation of the body's immune response against the cancer. Jennerex is headquartered in San Francisco and has related research and development operations in Ottawa, Canada and Pusan, South Korea. For more information about Jennerex, please visit www.jennerex.com.

About Transgene:

Transgene, a member of the Institut Merieux Group, is a publicly traded French biopharmaceutical company dedicated to the development of therapeutic vaccines and immunotherapeutic products in oncology and infectious diseases, and has five compounds in clinical development: TG4010 and JX594 (TG6006) having completed initial phase II trials, TG4001 in phase IIb trial, TG4040 in phase II trial and TG4023 in phase I trial. Transgene has concluded strategic agreements for the development of two of its immunotherapy products, an option agreement with Novartis for the development of TG4010 to treat various cancers, and an in-licensing agreement with US-based Jennerex Biotherapeutics, Inc., to develop and market JX594 (TG6006), an oncolytic product.

Transgene has bio-manufacturing capacities for viral-based products. Additional information about Transgene is available on the internet at http://www.transgene.fr/

Cautionary note for Transgene regarding forward-looking statements

This press release contains forward-looking statements referring to the joint clinical testing and development and commercial potential of JX-594. Clinical testing and successful product development and commercialization depend on a variety of factors, including the timing and success of future patient enrolment, the risk of unanticipated adverse patient reactions, regulatory approval and the level of demand for the product by the medical community. Results from future studies with more data may show less favorable outcomes than prior studies, and there is no certainty that product candidates will ever demonstrate adequate therapeutic efficacy or achieve regulatory approval or commercial success. In addition, forward-looking statements regarding product development, testing and marketing costs are by the nature subject to uncertainties as a result of unforeseen difficulties and expenses which may arise, and future product development costs may exceed current expectations. For further information on the risks and uncertainties involved in the testing and development of Transgene's product candidates, see Transgene's Document de Reference on file with the French Autorite des marches financiers on its website at http://www.amf-france.org/ and Transgene's website at http://www.transgene.fr/.

SOURCE Jennerex, Inc.

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EASL Issues Clinical Practice Guidelines for Management of HCV

Daniel M. Keller, PhD

April 4, 2011 (Berlin, Germany) — Here at the opening session of the European Association for the Study of the Liver (EASL) 46th Annual Meeting, new guidelines were announced to help healthcare providers, patients, and interested individuals make decisions about the management of patients with acute and chronic hepatitis C virus (HCV) infections.

The guidelines encompass all aspects of the diagnosis and treatment of chronic HCV infection and address the use of diagnostic, therapeutic, and preventive techniques. They are the fifth in a series that the EASL has issued for liver diseases.

As evidenced by a wealth of clinical trial presentations that are being made here at the conference on new drugs in development to treat HCV, it is expected that many more treatments will be licensed in the next few years.

However, the guidelines issued here are restricted to therapies that have been approved at the time of publication. EASL has committed to update the guidelines on a regular basis upon approval of additional therapies.

Antonio Craxi, MD, professor of gastroenterology and internal medicine at the University of Palermo in Italy, and director of gastroenterology and hepatology at the university's Academic Department of Internal Medicine, coordinated the development of the guidelines. He discussed them in a news conference and said that part of the rationale for them is to set standards of diagnosis and treatment for specific patient profiles. They were developed by an expert panel that reviewed the scientific literature on the subject through December 2010. If clinical data were unavailable, expert experience and opinion were included.

The guidelines comprise sections on diagnosis, therapy, follow-up to therapy, measures to improve treatment success rates, and factors to consider when deciding on retreatment if therapy has failed.

Dr. Craxi emphasized that history and physical examination of the patient must be part of diagnosis, and that diagnosis cannot rely solely on serology that identifies anti-HCV antibodies or the level of HCV RNA in the blood.

"We had to . . decide on a very crucial point — whether a biopsy was still necessary to assess the severity of liver disease," Dr. Craxi said.

Although biopsy remains the reference method for assessing the degree of fibrosis, most patients dislike it, and it carries risk for complications. "It won't be acceptable to have a liver biopsy as a prerequisite for all treatment," he said, noting that it can usually be dispensed with for HCV genotypes 2 and 3, which are easier forms of the virus to eradicate with current therapy. And a biopsy is not always necessary for the more difficult-to-treat genotypes 1 and 4, since other methods such as transient elastography (FibroScan) and serum biomarkers are available to determine the degree of liver fibrosis.

Eradication of HCV Infection Is Therapeutic Goal

Eliminating virus from the body can prevent complications such as fibrosis, cirrhosis, liver cancer, and death. The desired end point of therapy is a sustained virological response, determined by undetectable HCV RNA in the blood 24 weeks after the end of therapy, Dr. Craxi noted.

The current standard approach is treatment with a combination of pegylated interferon alfa plus ribavirin. The University of Palermo investigator said large studies have shown that the 2 commercially available pegylated interferons are equivalent, and neither is recommended over the other.

He pointed out that the new guidelines consider the virological response to pegylated interferon/ribavirin to guide therapy, taking into account the speed of response and the degree of viral suppression. "For the first time, there is a clear statement that patients with a rapid response and with genotype 1 can be treated for 24 weeks [and that treatment can be extended] beyond 24 weeks for patients who have a delayed viral response."

Separate decision maps in the published guidelines, which will appear in the Journal of Hepatology, delineate response-guided therapy for genotypes 1 and 4 and for genotypes 2 and 3.

Previous American guidelines were issued more than 5 years ago, Dr. Craxi noted, and they did not involve response-guided therapy. Additionally, ribavirin dosage adjustment according to patient weight is now recommended, since heavier weight adversely affects the response to therapy.

The expert panel made recommendations for the follow-up of untreated patients with or without cirrhosis and for the retreatment of patients for whom previous therapy failed. Dr. Craxi said that patients with resistant disease might respond to some of the new small-molecule drugs currently in development, and it might be worthwhile to delay treatment for some of them until the new drugs are available, depending on their current state of health.

Mark Thursz, MD, EASL vice secretary and professor of hepatology at Imperial College, London, United Kingdom, noted that not recommending a liver biopsy for every patient is an important development for patients. "It's no longer necessary for every patient. In fact, it's probably only appropriate when there's a doubt about the contribution of different diseases," such as heavy alcohol consumption and HCV, or obesity and HCV. Response-guided therapy can also be positive for patients, sparing some of them unnecessary adverse effects if they can be treated for a shorter time. It should have a positive economic impact, as well, he noted.

Dr. Thursz said he reviewed the guidelines before publication but was not involved in their development.

Dr. Craxi reports receiving research support and lecture fees from, and taking part in clinical trials for, Roche, MSD, Siemens, and Abbott. Dr. Thursz has disclosed no relevant financial relationships.

European Association for the Study of the Liver (EASL) 46th Annual Meeting: Opening session. Presented March 31, 2011.

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Download PDF: Management of Hepatitis C Virus Infection 1.41 mb

EASL: Abbott and Enanta Present Positive 12-Week Results and 3-Day Resistance Data From Phase 2 Study of ABT-450/r for Treatment of Hepatitis C

ABBOTT PARK, Ill., and WATERTOWN, Mass., April 4, 2011 /PRNewswire/ -- Abbott (NYSE: ABT) and Enanta Pharmaceuticals today announced 12-week 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. Study results show that 92 percent (22 of 24) of patients taking ABT-450/r once daily, combined with standard of care, achieved complete early virologic response (HCV RNA levels <25 IU/mL) at 12 weeks. Results were presented at the European Association for the Study of Liver Disease (EASL) annual meeting in Berlin.
Key findings:

• At week 12, 92 percent of patients receiving ABT-450/r (ABT-450 with 100 mg of ritonavir to support once-daily dosing) in combination with standard of care (SOC) – pegylated interferon alpha and ribavirin (pegIFN/RBV) – achieved HCV RNA <25 IU/mL

• In a separate analysis of 3-day resistance data, ABT-450/r dosed at 200/100 mg appeared to more consistently suppress the emergence of ABT-450-associated resistant variants than the 50/100 mg and 100/100 mg doses

• Previously presented 3-day and 4-week results from the study had suggested the ABT-450/r demonstrated significant antiviral activity in treatment-naive adults

• After three days, treatment with ABT-450/r alone resulted in 4-log (10,000-fold) mean reductions of HCV RNA, across the three dose ranges of ABT-450 (50 mg, 100 mg, 200 mg, once-daily dosing)

"A significant number of HCV patients are unable to begin treatment with peginterferon and ribavirin, and for those that do begin treatment, more than 50 percent will not be cured," said 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. "These results suggest that ABT-450/r could be an important component in combination therapy approaches to treating HCV."

"Abbott is working to transform treatment options for patients with HCV infection by investigating ways to simplify treatment and increase cure rates," said Scott Brun, M.D., divisional vice president, infectious disease development, Abbott. "We will continue to explore the use of ABT-450/r and our other investigational HCV treatments in a variety of patient populations and combinations, with and without pegylated interferon alpha."

"We continue to be encouraged by the results for ABT-450/r and the potential it holds for treatment-experienced and treatment-naive patients with HCV," said Jay Luly, Ph.D., president and chief executive officer, Enanta Pharmaceuticals.

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-naive 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.

In the trial, the most common adverse events reported in subjects receiving ABT-450/r in combination with pegIFN/RBV were headache, fatigue, insomnia and depression. A similar proportion of subjects reported at least one adverse event in all treatment groups, including placebo.

ABT-450 is being developed with low-dose ritonavir, which enhances the pharmacokinetic properties of ABT-450, allowing for once-daily dosing. The use of ritonavir 100 mg with ABT-450 for the treatment of HCV is investigational.

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.

Ritonavir Use in Treatment of HIV

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

Ritonavir does not cure HIV infection or AIDS and does not reduce the risk of passing HIV to others. People taking ritonavir 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.

Ritonavir Safety in Treatment of HIV

Patients should not take ritonavir with certain medicines, as these can cause serious or life-threatening problems such as irregular heartbeat, breathing difficulties, or excessive sleepiness. Patients should not take ritonavir if they have had a serious allergic reaction to any of its ingredients. Some patients taking ritonavir 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. Patients may develop signs and symptoms of infections that they already have after starting anti-HIV medicines.

For more information, please see the Important Safety Information and full Prescribing Information for ritonavir.

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, nucleoside(tide) 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 four HCV compounds in phase 2 clinical trials, including a protease inhibitor, two polymerase inhibitors 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.

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/.

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EASL: Avalanche of hepatitis C products on the way

World News April 04, 2011
Ian Mason in Berlin

Having had no new drugs for hepatitis C since ribavirin’s approval more than a decade ago, doctors will shortly be spoilt for choice.

A wave of new products are emerging from R&D pipelines, with more than 30 companies developing scores of novel antivirals. At the European Association for the Study of the Liver (EASL) annual congress in Berlin, which ended yesterday (April 3), Mark Thursz of Imperial College, London and vice-secretary of EASL reviewed what to look out for.

The two front runners are both protease inhibitors (PIs) - Victrelis (boceprevir) from Merck & Co and telaprevir from Vertex, Tibotec and Mitsubishi Tanabe Pharma. Launches of both drugs are expected this year and snapping at their heels are second generation PIs such as Boehringer Ingelheim’s BI 201335 – an oral once-daily offering which has just moved into Phase III and been fast-tracked by the US Food and Drug Administration.

Boceprevir is given three times a day; telaprevir every eight hours. Asked how clinicians would choose between the two PIs, Prof Thursz said that although there was no head-to-head data, the products differed in their side effect profiles: “With boceprevir there is more anaemia and dysgeusia (foul taste in the mouth) and with telaprevir, the main side effect is a rash which some patients may not be able to tolerate.”

'Remarkable' results

Overall, he said that results with the new PIs were “remarkable”, offering unprecedented levels of sustained virological response, however the drugs still need to be given against a relatively toxic ‘back-bone’ of pegylated interferon-alfa plus ribavirin. For him, the "light at the end of the tunnel" would be an interferon-free regimen, such as combination therapy with a PI plus an NS5b-polymerase or NS5a inhibitor.

Boehringer’s HCV polymerase inhibitor BI 207127 has been FDA- fast-tracked in combination with the German firm’s aforementioned BI 201335. Bristol-Myers Squibb is trialling its PI, BMS 650032, in combination with the NS5A inhibitor BMS 790052 – albeit in a quadruple regimen with PEG-IFN/ribavirin.

Prof Thursz sounded a note of caution about potential resistance to PIs. “We are going to face a problem with resistant variants,” he said. “These new drugs will need to be handled by specialists who have some understanding of these patterns of resistance and their future implications.”

Patients not getting proper treatment

He concluded that despite ‘fantastic’ new drugs upcoming for hepatitis C, they would have little impact on the global burden of this potentially eradicable disease unless health policies change (up to 170 million people are estimated to be infected with the virus). France has the highest rates of treatment in the European Union, but even there only 16% of hepatitis C patients currently receive treatment. “In the UK, I am embarrassed to say, only 3% of our hepatitis C patients receive treatment. We cannot expect to have much of an impact if we do not screen and treat patients and get rid of the virus,” he said.

In other presentations, early data from Phase I trials of an HCV vaccine were unveiled. Two studies flagged by EASL reported high immunogenicity and good safety profile for a novel T-cell vaccine based on adenovirus vectors (abstracts 750 and 2104). The therapeutic vaccine is being developed by a team at the University of Oxford, UK.

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EASL: Quadruple therapy shows 100 percent SVR for HCV patients previously unresponsive to treatment

April 02, 2011

Berlin, Germany, Saturday 02 April 2011: Exciting new data presented today at the International Liver CongressTM 2011 show that quadruple therapy in chronic hepatitis C (HCV) patients suppressed the emergence of resistant variants and resulted in a 100% rate of sustained virological response - undetectable HCV RNA - 12 weeks after treatment (SVR12).1

In the quadruple therapy study, HCV patients were given four drugs in combination; pegylated Interferon-alpha (PegIFN-alpha); ribavirin (RBV); and two different direct-acting antivirals (DAAs) BMS-650032 (an HCV NS3 protease inhibitor) and BMS-790052 (an HCV NS5A replication complex inhibitor).

The current standard of care (SoC) for HCV therapy is PegIFN-alpha plus RBV – a dual therapy. The addition of DAAs (currently in phase-III clinical trials) marks the next step in treatment evolution – a triple therapy. However, the new data presented today suggests that quadruple therapy could be the next generation of treatment for chronic HCV patients.

Professor Heiner Wedemeyer, EASL'S Secretary General, said: "Quadruple therapy is possibly the future of HCV treatment; this study goes a way to confirming that. While it's expected that the first DAAs and triple therapy will be approved for use later this year, quadruple therapy appears to have a more profound effect on virological response, with less of a resistance problem."

The study may also provide new hope for a growing number of HCV patients who cannot be effectively treated for chronic hepatitis with current treatments.

The Phase-IIa trial looked at a cohort of 21 HCV genotype 1 null responders (patients who have failed to respond to previous treatment), of whom 19 had an unfavourable IL28B genotype, which predisposes HCV patients to treatment failure.

Only about 30% of null responders to PegIFN-alpha/RBV treatment achieve sustained virological response (SVR) when retreated with PegIFN-alpha/RBV plus telaprevir, demonstrating a high unmet medical need.1

More information: 1. Lok A et al. Quadruple therapy with BMS-790052, BMS-650032 and peg-IFNRBV for 24 weeks results in 100% SVR12 in HCV genotype 1 null responders. Abstract presented at The International Liver CongressTM 2011. http://www1.easl.eu/easl2011/program/Orals/418.htm

Provided by European Association for the Study of the Liver

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--------------------------------------------------------------------------

EASL 46th Annual Meeting
March 30th - April 3rd 2011
Berlin, Germany
 
Quadruple Therapy With BMS-790052, BMS-650032 and Peg-IFN/RBV for 24 Weeks Results in 100% SVR12 in HCV Genotype 1 Null Responders: "HCV infection can be cured without interferon & ribavirin: 2 orals BMS790052+BMS650032"

Reported by Jules Levin
EASL 2011 April 2 Berlin Germany

Presented by Anna Lok

from Jules of NATAP: this is the biggest story & news to come out of this meeting, needless to say, and the biggest advancement in medicine in 50 years. In this study 4/11 null-responders receiving BMS-790052 (NS5A inhibitor) + BMS-650032 (protease inhibitor) alone for 24 weeks achieved SVR12 & SVR24. The presentation says "HCV infection can be cured without interferon & ribavirin". BMS-790052 & BMS-650032 with peg/RBV for 24 weeks: 10/10 patients achieved SVR12 & 9/10 achieved SVR24: "QUAD therapy can result in a high rate of cure in this difficult to treat population" (1 patient < LLOQ at week 24 post treatment undetectable on retesting 35 days later). This is the proof of concept we have been waiting for that at least some patients can be cured without peg/rbv, now these are the hardest to treat patients null-responders.

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EASL: Entry inhibitors show promise as drugs with new MOA for treatment of HBV and HDV infection

Public release date: 2-Apr-2011
Contact: Travis Taylor
easlpressoffice@cohnwolfe.com
44-784-306-9451
European Association for the Study of the Liver

First new hepatitis B and D treatment for many years

Berlin, Germany, Saturday 02 April 2011: Promising new viral hepatitis data presented today at the International Liver CongressTM show that entry inhibitors --a new mechanism of action for drugs to treat viral hepatitis -- could provide the first new hepatitis B and hepatitis D treatments for many years.1,2

Most current approved therapies directly target viral replication (e.g. nucleotide/side analogues), and can lead to the development of viral resistance or viral rebound after the end of treatment. Entry inhibitors prevent the virus from entering the cell and forming a stable replication complex, limiting the issue of viral rebound and resistance development.

Professor Heiner Wedemeyer, EASL's Secretary General, commented: "The current treatments available for hepatitis B & D are limited. These novel drugs are the first promising treatments for many years. The shift in the mechanism of action of these drugs from inhibiting the virus's replication directly to inhibiting its entry into the cell, and thus its replication – means they are less likely to produce viral resistance; a huge problem faced by many of today's clinicians."

One study1 showed that treatment of ex-vivo liver cells with synthetic anti-lipopolysaccharide peptides (SALPs) during and prior to HBV infection was highly effective and dose dependent in inhibiting infection – reducing markers of HBV infection (e.g. HBV RNA, HBV antigens) in the concentration range of 4-5 µg/mL by 90% and 0.5-2 µg/mL by 50%.

The study also demonstrated that SALPs showed activity against other viral (e.g. HIV, herpes) and microbial (e.g. peritonitis, colitis and pneumonia) infections. Therefore, SALPs represent a very promising therapeutic strategy to treat viral hepatitis infection and concomitant bacterial infection – which often leads to life threatening systematic complications.

Other studies2,3 illustrated the enormous value of the chimaeric mouse model of chronic HBV and HDV infection for the preclinical evaluation of antiviral drugs. The study demonstrated that the HBV entry inhibitor Myrcludex-B was able to completely block the spread of HBV from cell to cell and to prevent de-novo HDV infection of human hepatocytes.

Professor Wedemeyer commented: "Although there are 35 million people around the world with HDV infection there is currently little to offer them therapeutically. I am therefore delighted to see these new drug developments."

###

Notes to Editors

About EASL

EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.

EASL's main focus on education and research is delivered through numerous events and initiatives, including:

• The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide

• Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year

• Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology

• Journal of Hepatology published monthly

• Participation in a number of policy initiatives at European level

About The International Liver CongressTM 2011

The International Liver Congress™ 2011, the 46th annual meeting of the European Association for the study of the Liver, is being held at the Internationales Congress Centrum, Berlin, Germany from March 30 – April 3, 2011. The congress annually attracts over 7,500 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field.

References

1. Lucifora J et al. Novel peptide-based microbiocides inhibiting hepatitis b virus entry by preventing virus interaction with the cell surface. Abstract presented at The International Liver CongressTM 2011. http://www1.easl.eu/easl2011/program/Orals/338.htm

2. Lutgehetmann M et al. Block of hepatitis delta infection by the entry inhibitor myrcludex b in upa mice: establishment of an efficient mouse model for human HBV/HDV infection. Abstract presented at The International Liver CongressTM 2011. http://www1.easl.eu/easl2011/program/Orals/390.htm

3. Ben M et al. Administration of the entry inhibitor Myrcludex-B after establishment of Hepatitis B Virus infection prevents viral spreading among human hepatocytes in uPA mice. Abstract presented at The International Liver CongressTM 2011. http://www1.easl.eu/easl2011/program/Orals/337.htm

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EASL: Idera Pharmaceuticals Presents Data from a Phase 1 Clinical Trial of IMO-2125 in Treatment-Naïve Genotype 1 HCV Patients at EASL 2011

April 02, 2011 03:30 AM Eastern Daylight Time

- Phase 2 clinical trial expected to begin in second quarter 2011-

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Idera Pharmaceuticals, Inc. (Nasdaq: IDRA) announced today the presentation of data from a four-week Phase 1 clinical trial of IMO-2125 in combination with ribavirin in treatment-naïve patients chronically infected with hepatitis C virus (HCV) genotype 1. During the four weeks of treatment, IMO-2125 in combination with ribavirin was well tolerated and produced clinically meaningful antiviral activity. IMO-2125 is a Toll-like Receptor 9 (TLR9) agonist that stimulates production of natural interferons and other antiviral cytokines. The presentation (Abstract #1209), entitled “IMO-2125 plus ribavirin gives substantial first-dose viral load reductions, cumulative antiviral effect, is well tolerated in naïve genotype 1 HCV patients: a Phase 1 trial”, was made at the 46th Annual Meeting of the European Association for the Study of the Liver (EASL) being held in Berlin, Germany from March 30 – April 3, 2011. The presentation provided additional detail from the trial for which interim data was announced in December 2010.

“This study provides several key results that support our IMO-2125 development program,” said Robert Arbeit, M.D., Vice President of Clinical Development at Idera. “First, IMO-2125 in combination with ribavirin had substantial antiviral activity in treatment-naïve patients. This antiviral activity was associated with decreases in serum liver enzyme levels over the four-week course of treatment. Second, IMO-2125 was well tolerated, and demonstrated important safety features in comparison to Pegasys® used in the control arm. These included shorter duration of flu-like symptoms and minimal hematologic toxicity, with no IMO-2125-treated patients developing neutropenia requiring intervention or platelet levels below lower limits of normal.”

Dr. Arbeit continued, “We are preparing to initiate a 12-week Phase 2 clinical trial of IMO-2125 plus ribavirin in treatment-naïve genotype 1 HCV patients in the second quarter of 2011. We expect to use data from that study to select dosages for subsequent clinical trials of IMO-2125 in combination with ribavirin and a direct acting antiviral agent.”

"We have now completed Phase 1 clinical evaluation of IMO-2125 in both treatment-naïve and null-responder HCV patients and have established that its immune stimulation mechanism of action provides clinically meaningful antiviral activity and is well tolerated,” said Tim Sullivan, Ph.D., Vice President of Development Programs and Alliance Management at Idera. "By the end of this year we expect to have completed chronic nonclinical safety studies to support further clinical development of IMO-2125 as an immune modulatory component of HCV therapy.”

"Our objective is to develop a novel immune modulator for the treatment of HCV as a potential alternative to pegylated interferons,” said Sudhir Agrawal, D.Phil., Chairman and Chief Executive Officer at Idera. “We have confirmed the intended mechanism of action of IMO-2125 and are very pleased with its safety profile and antiviral activity in both null-responder and treatment-naïve HCV patients. We look forward to initiating the Phase 2 clinical trial, which we expect will provide the additional data needed to advance the clinical development of IMO-2125 and support studies in combination with direct-acting antiviral agents.”

Phase 1 Clinical Trial in Treatment-naive HCV Patients

Study Design:

In this Phase 1 clinical trial, treatment-naïve genotype 1 HCV patients received IMO-2125 by subcutaneous injection over four weeks in combination with daily oral administration of standard, weight-based doses of ribavirin in one of four treatment regimens of 12 patients each. The four regimens of IMO-2125 were 0.08, 0.16, and 0.32 mg/kg once weekly and 0.16 mg/kg twice weekly. In addition, 12 patients received Pegasys® plus ribavirin. Study endpoints of safety and antiviral activity were measured through Day 29. Upon completion of the four weeks of protocol-specified treatment, all patients received follow-on treatment with Pegasys® plus ribavirin. Under the trial protocol, final safety and antiviral assessments were taken at Day 59, four weeks after the follow-on treatment with Pegasys® plus ribavirin was initiated.

Study Results:

Patient Population

All patients were Caucasian, except one Asian patient in the 0.16 mg/kg/week IMO-2125 group; all were infected with HCV genotype 1. Additional demographic and baseline data are summarized in the following table.

Safety

• IMO-2125 was well tolerated at all dose levels in combination with ribavirin over four weeks of treatment, with no treatment-related serious adverse events and no treatment discontinuations. The most common adverse events observed in the IMO-2125 regimens were mild to moderate flu-like symptoms and injection site reactions.

• Flu-like symptoms. Among patients who received IMO-2125, flu-like symptoms consisted primarily of fever and chills with onset within approximately eight hours of dosing and of brief duration, typically lasting less than one day. In contrast, the observations for the patients receiving Pegasys® who experienced flu-like symptoms were consistent with the extensively published experiences showing that flu-like symptoms generally include malaise and fatigue, have delayed onset at one or two days after dosing, and often last two days or more.

• Neutropenia. Neutropenia (absolute neutrophil count (ANC) <1000/mm3) with IMO-2125 plus ribavirin treatment was infrequent, occurring in five of 48 patients, or 10%, at some point during the four-week treatment period. Neutropenia in patients treated with IMO-2125 plus ribavirin was transient; no patients required intervention and at Day 29 no patients had ANC <1000/mm3. Neutropenia was more common with Pegasys® plus ribavirin treatment, occurring in seven of 12 patients, or 58%. Two of these patients, or 17%, required intervention for their neutropenia and at Day 29 two additional patients had ANC <1000/mm3.

At Day 29, all 48 patients who had received IMO-2125 initiated standard of care treatment with Pegasys® plus ribavirin. At Day 59, six of these patients, or 13%, had neutrophil counts less than 1000/mm3.

• Thrombocytopenia. On Day 29, all patients treated with IMO-2125 plus ribavirin had platelet counts of 145,000/mm3 or greater. Three of the 12 patients, or 25%, treated with Pegasys® plus ribavirin had platelet counts at or below 130,000/mm3 on Day 29.

At Day 29, all 48 patients who had received IMO-2125 initiated standard of care treatment with Pegasys® plus ribavirin. At Day 59, 13 of these patients, or 26%, had platelet counts at or below 130,000/mm3.

Liver Enzyme Normalization

• Serum liver enzyme levels, AST and ALT, are generally elevated in chronic hepatitis C patients. Treatment with all dose levels of IMO-2125 plus ribavirin led to progressive reductions in group means of AST and ALT to within normal limits by the end of the fourth week of treatment. Similar reductions in AST and ALT levels were observed in patients receiving treatment with Pegasys® plus ribavirin.

Effect on HCV RNA Viral Load

• Viral load reduction after first dose. IMO-2125 at all dose levels induced declines in viral levels at 48 hours after the first dose. The mean viral load reductions at 48 hours after the first dose with the 0.16 mg/kg once-weekly, 0.32 mg/kg once-weekly and 0.16 mg/kg twice-weekly IMO-2125 regimens were -2.5, -1.3, and -1.6 log10, respectively. The mean viral load reduction for patients treated with Pegasys® plus ribavirin at the same time point was -1.4 log10.

• Viral load reduction after four weeks. Antiviral response was variable within all treatment groups, including Pegasys® plus ribavirin. At Day 29, in each of the IMO-2125 treatment groups at 0.16 mg/kg/week or higher and in the Pegasys® plus ribavirin group, some patients achieved greater than 4 log10 reductions in viral load and some failed to achieve even a 1 log10 reduction.

Mean viral load reductions from baseline at the mid-week evaluation in the fourth week of treatment with the 0.16 mg/kg once-weekly, 0.32 mg/kg once-weekly and 0.16 mg/kg twice-weekly IMO-2125 regimens were -3.4, -2.0, and -3.3 log10, respectively. The mean viral load reduction for patients treated with Pegasys® plus ribavirin at the same timepoint was -3.8 log10.

Mean viral load reductions from baseline at Day 29 with the 0.16 mg/kg once-weekly, 0.32 mg/kg once-weekly and 0.16 mg/kg twice-weekly IMO-2125 regimens were -1.7, -0.6, and -2.4 log10, respectively. The mean viral load reduction for patients treated with Pegasys® plus ribavirin at Day 29 was -3.4 log10.

• Prognostic factors affecting antiviral activity. Uneven distribution of negative prognostic factors, such as IL28B CT or TT genotype, high baseline IP-10, and age, contributed to the variability in antiviral activity across the treatment groups. Additional data on IL28B genotype are being collected.

See Table 2

Authors of the presentation and study investigators include Dominique Guyader, M.D., of Universite de Rennes, France, Pavel Bogomolov, M.D., of the State Institution Moscow Region named after M.F. Vladymirsky, Moscow, Russia, Zhanna Kobalava, M.D., of GOUVPO Russian Peoples’ Friendship University (City Clinical Hospital #64), Moscow, Russia, Valentin Moiseev, M.D., of GOUVPO Russian Peoples’ Friendship University (City Clinical Hospital #3), Moscow, Russia, Janos Szlavik, M.D., of Szt László Hospital, Budapest, Hungary, Béatrice Astruc, M.D., of Biotrial, Rennes, France, Istan Varkonyi, M.D., of Kenezy Hospital, Debrecen, Hungary, Tim Sullivan, Ph.D., Kerry Horgan, Alice Bexon, MBChB, and Robert Arbeit, M.D., of Idera Pharmaceuticals.

About IMO-2125

IMO-2125, a Toll-like Receptor (TLR) 9 agonist, is a novel immune modulator being developed as a component of treatment for chronic hepatitis C virus (HCV) infection. IMO-2125 is designed to stimulate the immune system, causing the body to generate natural interferons and other antiviral cytokines. IMO-2125 has been evaluated in a Phase 1 clinical trial in null-responder HCV patients as monotherapy for 4 weeks and in a Phase 1 clinical trial in treatment-naïve HCV patients in combination with ribavirin for 4 weeks.

About Idera Pharmaceuticals, Inc.

Idera Pharmaceuticals develops drug candidates to treat chronic hepatitis C virus infection, autoimmune and inflammatory diseases, cancer, and respiratory diseases, and for use as vaccine adjuvants. The company's proprietary drug candidates are designed to modulate specific Toll-like Receptors, which are a family of immune system receptors. Idera's pioneering DNA and RNA chemistry expertise enables us to create drug candidates for internal development and generates opportunities for multiple collaborative alliances. For more information, visit http://www.iderapharma.com/.

Idera Forward Looking Statements

This press release contains forward-looking statements concerning Idera Pharmaceuticals, Inc. that involve a number of risks and uncertainties. For this purpose, any statements contained herein that are not statements of historical fact may be deemed to be forward-looking statements. Without limiting the foregoing, the words "believes," "anticipates," "plans," "expects," "estimates," "intends," "should," "could," "will," "may," and similar expressions are intended to identify forward-looking statements. There are a number of important factors that could cause Idera's actual results to differ materially from those indicated by such forward-looking statements, including whether results obtained in preclinical studies and early clinical trials such as the studies and trials referred to in this release will be indicative of results obtained in future clinical trials; whether products based on Idera's technology will advance into or through the clinical trial process on a timely basis or at all and receive approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies; whether, if the Company's products receive approval, they will be successfully distributed and marketed; whether the Company's collaborations will be successful; whether the patents and patent applications owned or licensed by the Company will protect the Company’s technology and prevent others from infringing it; whether Idera's cash resources will be sufficient to fund the Company's operations; and such other important factors as are set forth under the caption "Risk Factors" in Idera's Annual Report on Form 10-K for the year ended December 31, 2010 which important factors are incorporated herein by reference. Idera disclaims any intention or obligation to update any forward-looking statements.

Pegasys® is a registered trademark of F. Hoffmann-La Roche Company.

Contacts
Idera Pharmaceuticals, Inc.
Teri Dahlman, 617-679-5519
E-mail: tdahlman@iderapharma.com
or
MacDougall Biomedical Communications
Chris Erdman, 781-235-3060
E-mail: cerdman@macbiocom.com

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EASL: New data show non-alcoholic fatty liver disease will reach epidemic status in the US

Public release date: 2-Apr-2011
Contact: Dimple Natali
easlpressoffice@cohnwolfe.com
44-797-160-8315
European Association for the Study of the Liver

Berlin, Germany, Saturday 02 April 2011: According to new data presented today at the International Liver CongressTM, the United States (U.S.) could soon be faced with an epidemic of Non-Alcoholic Fatty Liver Disease (NAFLD)1, one of the major contributing factors of chronic liver disease (CLD), considered as one of the major causes of morbidity and mortality worldwide. The study highlights that if the current rates of obesity and diabetes continue for another two decades, the prevalence of NAFLD in the US is expected to increase by 50% in 2030.

The study analysed pre-existing clinical survey data over a 10 year period (1988-1994, 1999-2004 and 2005-2008), which included 39,500 adults from three survey cycles. Over the three cycles the prevalence of NAFLD doubled from 5.51% to 11.0% respectively. Furthermore, during the first survey cycle (1988-1994) 46.8% of all CLD's was related to NAFLD but by 2005-2008 this had increased to 75.1%. In addition, the prevalence of obesity and diabetes, the two key risk factors for NAFLD also steadily increased.

Mark Thursz EASL's Vice Secretary commented: "Non-alcoholic fatty liver disease is fast becoming one of the top concerns for clinicians due to the obesity epidemic and it's potential to progress to advanced liver disease which significantly impacts on overall liver-related mortality. This data highlights a serious concern for the future, and the enormous increasing health burden of NAFLD. If the obesity epidemic is anything to go by, the U.S. NAFLD epidemic may have a ripple effect worldwide. It is imperative that health systems continue to drive effective educational programmes to reinforce awareness among the general public to alert them of the risks of obesity and promote the importance of diet and exercise".

NAFLD is the term used to describe fat build-up in liver cells in people who do not drink alcohol excessively and is the most common persistent liver disorder in Western countries with an estimated overall prevalence of 20-30%.2

NAFLD encompasses a spectrum of liver disease associated with insulin resistance, diabetes and obesity and as such people most at risk of NAFLD are those who are obese, have insulin resistance associated with diabetes, high blood pressure and cholesterol.3

###

Notes to Editors

About EASL

EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.

EASL's main focus on education and research is delivered through numerous events and initiatives, including:

• The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide

• Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year

• Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology

• Journal of Hepatology published monthly

• Participation in a number of policy initiatives at European level

About The International Liver CongressTM 2011

The International Liver Congress™ 2011, the 46th annual meeting of the European Association for the study of the Liver, is being held at the Internationales Congress Centrum, Berlin, Germany from March 30 – April 3, 2011. The congress annually attracts over 7,500 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field.

References

1. Younossi Z et al., The Changing Face of Chronic Liver Disease (CLD) in the United States: The Rising Epidemic of Non-Alcoholic Fatty Liver Disease (NAFLD). Presented at The International Liver CongressTM 2011. http://www1.easl.eu/easl2011/program/Orals/204.htm

2. Understanding and Preventing the Progression of Liver Disease in Non-Alcoholic Fatty Liver Disease (NAFLD). Fatty Liver Inhibition of Progression (FLIP) http://www.flip-fp7.eu/. Accessed March 2011.

3. Fatty Liver. Patient UK. Available at http://www.patient.co.uk/doctor/Steatohepatitis-and-Steatosis-(Fatty-Liver).htm. Accessed March 2011.

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EASL: First Vaccine for Viral Hepatitis C Could Become a Reality

ScienceDaily (Apr. 1, 2011) — Early data from phase I trials of an HCV vaccine presented April 1 at the International Liver Congress show encouraging results, with high immunogenicity and good safety profile.

In the first study, a therapeutic T-cell vaccine, based on novel adenoviral vectors was used on a small population of treatment naive patients with chronic genotype 1 HCV infection. Intra-muscular vaccination was administered 2 or 14 weeks into a 48-week course of treatment with Peg-IFNa2a/ribavirin. 50% of vaccinated patients had CD4+ and CD8+ HCV specific T-cell responses as detected by ELISpot at 2-8 weeks post boost, showing a strong immunogenicity for the vaccine. Local and systemic adverse events to vaccination were mild, with no evidence of liver immunopathology (measured by liver transaminase levels).

The second study looked at the potential for a prophylactic vaccine based on similar novel adenoviral vectors technology (replicative-defective human Ad6 and a novel simian AdCh3 vector that encode 1985 amino-acids derived from the NS3-5 region of a genotype-1b strain). 27 healthy volunteers were vaccinated following a double prime, heterologous boost strategy. The vaccine induced polyfunctional CD4+ and CD8+ T cells responses which were maintained up to 52 weeks post prime. Overall vaccination was very well tolerated with mild/moderate local and systemic reactions and no serious adverse advents.

Professor Heiner Wedemeyer, EASL's Secretary General commented: "Vaccines are an exciting area of research now with the potential to add to the range of treatments available for patients with chronic viral hepatitis. These are early data but results are very encouraging indeed and as experts, we look forward to more scientific evidence being made available to support this new technology as a future treatment option as well as potentially preventing infection."

Previous research and data presented at the International Liver Congress shows that vaccination with adenoviral vectors induced highly potent and durable T-cell responses in healthy human and that similar vectors may prevent chronic infection in animals.3 This is the first time the immunogenicity and safety of vaccination was tested on HCV patients and healthy subjects.

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