April 13, 2013

HCV "One-Shot-Cure" ddRNAi Therapy Study Starting

RNAi-based therapeutics company Benitec Biopharma Limited announced Duke Clinical Research Unit, the early phase unit of the Duke Clinical Research Institute (DCRI), in Durham, North Carolina, as a site for its upcoming phase I/II first-in-man trial for TT-034 in Hepatitis C. TT-034 is being developed as a potential "one-shot-cure" for Hepatitis C (HCV).

ddRNAi: expressed RNA interference technology

ddRNAi (DNA-directed RNAi) is a unique platform technology for silencing unwanted or disease-causing genes. In the context of therapy, ddRNAi avoids many of the drawbacks of other gene silencing technologies and produces much longer-lasting effects.
Benitec Biopharma pioneered ddRNAi and was the first company to demonstrate expressed RNAi in human cells. We hold a dominant intellectual property position in RNAi, with over 40 issued global patents for the human use of ddRNAi.

Learn how ddRNAi could target countless human and viral genes. Track our pipeline programs using this exciting technology. View the scope of our patents in ddRNAi. Join us in developing transformational solutions for human health.

SYDNEY and DURHAM, NC - "We are very excited to be working with Duke, a world renowned research institution with significant experience in this area," said Peter French, Ph.D., Chief Executive Officer of Benitec. "The TT-034 trial marks the transition of Benitec to a clinical stage company. We expect that positive results from the trial will provide a value inflection point for the company, and also be a validation for our ddRNAi technology as an effective platform for therapeutics."

The phase I/II clinical trial is an open-label dose escalation study to evaluate the safety and activity of single doses of TT-034 in patients with chronic HCV genotype 1 infection who have failed previous treatments. The trial is expected to involve 14 patients in 5 sequential dose cohorts. Additional consolidation cohorts may be added during the study to confirm the results of the trial. The primary safety endpoints are dose limiting adverse events. The primary activity end points are serum viral load reduction and degree of hepatocyte transduction (measured through liver biopsies). There is a pre-specified interim read on safety and activity within months of trial commencement. The clinical trial is expected to begin enrolling patients during the second half of 2013.

Duke's principal investigator for the study will be Keyur Patel, M.D. Dr Patel has previous experience with oligonucleotide therapeutics in HCV, is a recipient of the prestigious American Association for the Study of Liver Diseases (AASLD) Shelia Sherlock Clinical and Translational Research award and has over 100 citations in peer-reviewed publications.
"TT-034 is a potentially transformative new treatment," Dr. Patel commented. "A therapeutic that could cure an HCV patient with a single injection would obviously be a big step forward compared to even the best treatments that are currently on the horizon, as they all involve comparatively lengthy regimens with a combination of several drugs."

About TT-034: TT-034 is a potentially transformative therapeutic that is intended to provide a "one-shot-cure" for Hepatitis C with a single injection. TT-034 works through RNA interference (RNAi), which is a naturally occurring regulatory process in cells that acts to "silence" genes after they have been transcribed from DNA into messenger RNA. Benitec's proprietary ddRNAi approach involves the introduction of a DNA vector that produces short hairpin RNAs (shRNAs) that are processed by the cell into siRNAs. This approach emulates the cell's own gene silencing mechanism and provides long term activity (months). Moreover, the virus vector used to deliver the TT-034 construct, an engineered non-replicating adeno-associated virus (AAV8), targets almost exclusively liver cells (where HCV replicates). TT-034 is further designed to prevent viral escape through mutations (a major problem for most HCV drugs) by using three different shRNAs to simultaneously target three separate highly conserved regions in the HCV genome. In mice and monkeys, TT0-034 has been shown to transduce 100% of hepatocytes in the liver and provide high shRNA activity for 180 days (the duration of the studies), without adverse effects.

About the Duke Clinical Research Unit: The Duke Clinical Research Unit (DCRU) is a state-of-the-art research facility located within the Duke Medicine campus that provides infrastructure support to sponsors and investigators who are testing new drug candidates and other cutting-edge therapies, or seeking to identify and validate novel biomarkers. The DCRU has more than 20 years of early-phase clinical trial experience and has successfully conducted more than 150 early-phase studies, including 80 phase 1 studies. The experience, support systems and infrastructure of the DCRU enable provision of the highest level of program management and services for early-phase clinical trials, including quality processes, accurate reporting, and regulatory expertise. The DCRU combines the clinical expertise and scientific leadership of one of the most prestigious academic medical centres in the world with the operational capabilities of a full-service contract research organization. The DCRU is part of the Duke Clinical Research Institute. The DCRI is a comprehensive academic research organization and the only one of its kind that can offer all the services of a commercial contract research organization with the academic credibility and expertise of an academic medical center.

About Benitec Biopharma Limited: Benitec Biopharma Limited (ASX Code: BLT), based in Sydney, Australia, has a pipeline of in-house and partnered therapeutic programs based on its patented gene-silencing technology, ddRNAi. Benitec is developing treatments for chronic and life-threatening human conditions. Its most advanced program is TT-034 for the treatment of chronic HCV infection. Benitec has licensed ddRNAi technology to other biopharmaceutical companies who are advancing their programs toward the clinic for applications including HIV/AIDS, retinitis pigmentosa and Huntington's disease. For more information on Benitec refer to the Company's website at www.benitec.com.

Source: PR Newswire


Early Test of Micro-RNA-Targeting Drug Shows Promise Against HCV

Reuters Health Information

Mar 27, 2013

By Gene Emery

NEW YORK (Reuters Health) Mar 27 - The Santaris Pharma drug miravirsen significantly reduced blood levels of hepatitis C virus (HCV) and, in a few cases, kept the virus at undetectable levels 14 weeks after treatment stopped, according to new research funded by the manufacturer.

The study, released online today in the New England Journal of Medicine, was a phase IIa trial that focused on patients with chronic HCV genotype 1 infection and involved a new technique for clearing the virus.

The drug, formerly known by its experimental name SPC3649, blocks the access to microRNA-122 (miR-122), which is active in liver cells and required by the virus to replicate. Similar chunks of microRNA regulate cell activity throughout the body.

When microRNA-122 was blocked, the hepatitis virus couldn't function properly and, in some cases, began to disappear from the blood.

"The reduction in HCV RNA levels was dose-dependent and sustained beyond the administration period for miravirsen," the researchers reported. They said a reduction in HCV RNA of at least 2 log(10) IU/mL occurred in one patient (11%) receiving 3 mg/kg of miravirsen and in six patients each (67%) in the groups receiving 5 or 7 mg, compared to placebo.

"This is a big step forward for hepatitis C but it's a bigger step forward for medicine in general because it's the first study to show that, in humans, blocking microRNA can have good efficacy" with few apparent side effects, said chief author Dr. Harry Janssen of the University of Toronto.

Because cancer, heart, nerve and metabolic diseases may also involve microRNA, he said in a telephone interview from Shanghai, "this study opens up different avenues of treatment for these types of diseases."

Dr. Kenneth Sherman, a hepatitis researcher at the University of Cincinnati College of Medicine who was not involved in the study, told Reuters Health by email that miravirsen "represents an exciting new therapeutic class of drugs for this serious and common liver disease."

"The absence of interactions with other drugs, combined with what appears to be a high barrier to resistance, makes this approach very desirable," he said. Other hepatitis C drugs are being developed, but "these data suggest that miravirsen could play an important role in our future armamentarium against a virus that causes progressive liver disease in millions of people worldwide."

Dr. Janssen's team gave five weekly doses of the drug or placebo to 36 volunteers.

All initially had virus levels ranging from about 5 to 7, using a logarithmic scale. Placebo recipients showed virtually no improvement.

Miravirsen worked better in some volunteers than others, which Dr. Janssen said wasn't surprising.

"The treatment targets the host, not the virus. And in many of these host-targeting treatments you see a heterogeneous response rate," he said.

Of the nine patients who received the lowest dose of 3 mg/kg each week, the five people with the best outcomes also received established treatment with pegylated interferon and ribavirin during the observation period.

At the highest dose of 7 mg/kg, nearly everyone saw some decline in virus levels. Five patients saw their virus levels drop into the undetectable range, but in two of those cases the levels rebounded during the observation period.

Most of those getting 5 mg/kg also had initial reductions and some rebounds. Only one of the nine volunteers in that group ended up with virus levels in the undetectable range.

Taken together, all three treatment groups saw a rebound, with peak effectiveness coming at week seven in the 3 mg/kg group, week 12 in the 5 mg/kg group and weeks eight to 10 for the 7 mg/kg group.

There were no side effects that seemed connected to the treatment.

Problems such as headache and fatigue were experienced by placebo recipients at comparable levels. For example, flu-like symptoms were seen in two patients in the low-dose group, none in the medium-dose group and one in both the high-dose and placebo groups.

No doses were reduced because of side effects.

As seen in previous studies, the drug also produced a gradual and prolonged reduction in cholesterol.

The researchers are currently testing whether it is better to give miravirsen for 12 weeks instead of five.

"All tested strains of HCV depend on miR-122, suggesting that it is a universal HCV Achilles' heel," said Dr. Judy Lieberman of Harvard Medical School and Dr. Peter Sarnow of Sanford University in an online editorial.

Such drugs, alone or in combination, they said, "could provide curative therapy for a large proportion of patients infected with all HCV strains without danger of drug resistance. It could also shorten the treatment time to achieve viral elimination, reduce the rate of relapse, and offer the possibility of interferon-free regimens. Only further clinical trials can determine whether this promise can be met."

SOURCE: http://bit.ly/XfMNEb and http://bit.ly/XfMNEb

N Engl J Med 2013.


Depression in HCV Often Resolves After Interferon Treatment

Daniel M. Keller, PhD

Apr 11, 2013

NICE, France — Depression affects up to 50% of patients with chronic hepatitis C virus (HCV) infection receiving treatment with interferon, but it appears to be self-limiting and does not usually require antidepressant therapy, new research suggests.

A prospective study conducted by investigators at the Clinic for Psychiatry, Clinical Center of Serbia, in Belgrade showed that severe depression occurred in only a small number of patients and that it spontaneously resolved following completion of HCV therapy with pegylated interferon-alfa and ribavirin (peg-IFN+RBV).

According lead investigator Zorana Pavlović, MD, these findings suggest awareness of depression risk in this patient population but not prophylaxis.

The study was presented here at EPA 2013: 21st European Congress of Psychiatry.

Interdisciplinary Management

According to the investigators, treatment with peg-IFN-α in patients with chronic hepatitis C (CHC) is associated with depression more frequently than in patients with other diseases treated with this drug.

To prospectively estimate the prevalence, severity, and course of depression among HCV patients being treated with peg-IFN+RBV, the investigators compared 103 treated patients (aged 18 - 65 years) with a group of HCV-infected patients not receiving therapy, matching the groups by sociodemographic factors.

A diagnosis of depression was established using the Structured Clinical Interview and criteria of the International Classification of Disorders–10. Severity of depression was assessed with the Hamilton Depression Rating Scale, with a score greater than 7 indicating depression (8 - 16: mild; 17 - 24: moderate; ≥25: severe). Treatment lasted 48 weeks, and the mean dose of peg-IFN was 152.6 ± 25.6 μg.

At baseline, the treatment and control groups did not differ in the mean prevalence of depression, but by week 4, depression was evident among treated patients and persisted through week 48 (all P < .05). The greatest prevalence of depression occurred at week 12 in the treatment group, affecting nearly half the patients to some degree.

Table. Prevalence of Depression With Peg-IFN+RBV Treatment (%)


Treatment Week Peg-IFN+RBV Control Patients P-value
0 (baseline) 24.3 21.4 NS*
4 38.8 21.4 < .01
12 49.5 22.3 < .001
24 40.8 22.3 < .01
48 38.8 24.3 < .05
72** 23.3 24.3 NS

* NS = difference not statistically significant

** 24 weeks post-therapy

"Depression spontaneously ameliorated 24 weeks following the completion of peg-interferon-alfa plus ribavirin therapy compared to baseline," Dr. Pavlović reported.

Of treated patients with depression, the majority experienced mild symptoms. At week 12, the point of the highest prevalence of depression, about 28% experienced mild symptoms, and about 22% experienced moderate symptoms.

In the approximately 22% of patients in the control group with symptoms of depression, most of the symptoms were mild. Only a few patients overall had severe depressive symptoms.

Dr. Pavlović strongly recommended an interdisciplinary approach to patients with chronic HCV being treated with peg-IFN+RBV, which would include an infectious disease specialist, a psychiatrist, and a psychologist.

Session chairman Antoine Pelissolo, MD, PhD, professor of psychiatry at Pitié-Salpêtrière Hospital in Paris, France, who was not involved in the study, called the study "well designed" in its comparison of HCV patients receiving peg-IFN+RBV with HCV patients not receiving specific treatment.

He said the therapeutic message is to be aware of the possibility of the development of depression. He agreed with Dr. Pavlović in recommending against prophylactic therapy of depression and advised "very [close] monitoring because some patients are harmed...there could be some problems with suicide attempts in some patients but are very rare."

He pointed out that even patients in the control group had a high level of depression, "but it's not surprising because they have a somatic problem, and there is comorbidity [of depression] with hepatitis."

Dr. Pavlović and Dr. Pelissolo reported no relevant financial relationships.

EPA 2013: 21st European Congress of Psychiatry. Abstract 1680. Presented April 7, 2013.


Hepatitis C Transmission Rare Among Heterosexual Couples

Joe Barber Jr, PhD

Mar 22, 2013

Hepatitis C virus (HCV) transmission appears to be rare among monogamous heterosexual couples, according to the findings of a cross-sectional study.

Norah A Terrault, MD, MPH, from the University of California San Francisco and colleagues published their findings in the March issue of Hepatology.

The authors note that the relationship between sexual activity and HCV transmission has been investigated previously. However, those data lack quantitative risk information that applies to couples in the United States because the studies were performed elsewhere.

"The few prospective cohort studies of monogamous heterosexual couples have reported incidence rates of HCV infection of 0%-0.6% per year in seronegative partners of subjects with chronic HCV infection," the authors write. "In cross-sectional studies, HCV prevalences among partners vary widely (0%-27%) but are < 5% in studies excluding partners with known percutaneous exposures."

In the current study, the authors recruited known anti-HCV–positive individuals and their heterosexual partners between January 2000 and May 2003. All couples had had a monogamous relationship for at least 36 months and at least 3 sexual encounters in the preceding 6 months. The exclusion criteria included a lack of sexual activity, prior organ transplantation, and hepatitis B virus or HIV co-infection.

Among the 500 partners of anti-HCV–positive participants included in the study, 20 (4%) were found to also be anti-HCV positive, 13 of whom were also HCV RNA positive. The 20 anti-HCV–positive couples included 9 couples with concordant genotypes/serotypes, 8 couples with discordant genotypes/serotypes, and 3 couples with indeterminate statuses.

Among the 9 couples with concordant genotypes/serotypes, 3 couples had highly related viral isolates, suggesting viral transmission between the couple. During 8377 person-years of follow-up in this study, the incidence of HCV transmission among couples was 3.6 per 10,000 person-years (95% confidence interval [CI], 0.0 - 7.7).

Additionally, the authors reported an estimated risk per sexual encounter of 1 per 380,000 (95% CI, 1/600,000 - 1/280,000) to 1 per 190,000 (95% CI, 1/1.03 million - 1/100,000).

The limitations of the study included its cross-sectional nature, potential recall bias, and low number of participants.

"In conclusion, HCV transmission by sex from chronically infected persons to their heterosexual partners in a long-term monogamous relationship likely occurs, but is a rare event," the authors write. "Our results provide a basis for specific counseling messages that clinicians can use with their patients. These messages should be qualified given the limitations of the sample size, but they support the current national recommendations that couples not change their sexual practices if they are in a monogamous heterosexual relationship."

The authors have disclosed no relevant financial relationships.

Hepatology. 2013;57:881-889. Abstract


Once-Daily Ribavirin Promising for Hepatitis C

Megan Brooks

Mar 26, 2013

For patients with hepatitis C virus receiving triple therapy, once-daily ribavirin dosing does not increase gastrointestinal adverse effects, and most patients prefer it over twice-daily dosing.

This finding comes from a study presented at the International Conference on Viral Hepatitis (ICVH) 2013 in New York City, which was sponsored by the International Association of Providers of AIDS Care and the Icahn School of Medicine at Mount Sinai.

Ribavirin is approved for twice-daily or divided dosing, but many of the new antivirals in the pipeline for hepatitis C will be taken once daily. "For convenience, we were interested in looking at once-daily ribavirin dosing," said presenter Kian Bichoupan, who is a graduate student at the Icahn School of Medicine at Mount Sinai in New York City.

"The half-life of ribavirin is 2 weeks," he explained, "so there is no reason to suspect there is any difference between taking it once a day or twice a day. Any opportunity that we have to make it easier for patients to take ribavirin would be attractive."

Bichoupan and colleagues conducted a study to assess adverse effects associated with twice-daily and once-daily weight-based ribavirin.

They used a structured interview and reviewed patient medical records to examine ribavirin dosing, changes in dosing over time, dosing preferences, and gastrointestinal (GI) adverse effects such as nausea, diarrhea, and vomiting. "We chose GI side effects because they are known to be more related to ribavirin," Bichoupan explained.

The study cohort consisted of 58 patients receiving telaprevir-based triple therapy and 16 receiving boceprevir-based triple therapy. Mean age was 59 years and time on treatment was about 25 weeks.

Patients can potentially take once-daily ribavirin and have fewer side effects and better adherence.

Adverse events were fairly common; 46% of patients required epoetin alfa for anemia, 9% received transfusions, and 14% visited the emergency department — mostly for anemia-related issues.

However, there was no statistical difference between once-daily and twice-daily ribavirin dosing in the frequency or percentage of patients with GI adverse effects, the investigators report.

GI symptoms were no worse in the once-daily group than they were in the twice-daily group, and most patients preferred taking ribavirin only once a day.

In patients who switched from twice-daily dosing to a lower once-daily dose, the prevalence of nausea, vomiting, and diarrhea was lower, which was "interesting," Bichoupan said.

In addition, this trial confirms what other trials have shown — "that ribavirin dose reductions do not have an impact on sustained virologic response," he noted.

"These results are promising. Patients can potentially take once-daily ribavirin and have fewer side effects and potentially better adherence," Bichoupan said. This is a small observational study, he acknowledged, and a randomized controlled trial is needed to confirm the findings.

Mark Nelson, MD, from Chelsea and Westminster Hospital, London, the United Kingdom, who is also ICVH 2013 conference cochair, told Medscape Medical News that "with the advent of new once-daily therapies, both with and without interferon, and the potential necessity of ribavirin as part of the regimen, the potential for using ribavirin once daily without increase in toxicity should lead to improvements in adherence and the potential, therefore, of even better results than currently seen in clinical practice."

This study was funded by Kadmon Pharmaceuticals. Mr. Bichoupan has disclosed no relevant financial relationships. Coauthor Valérie Martel-Laferrière, MD, from the Icahn School of Medicine at Mount Sinai, was funded by the 2011 AMMI Canada/Pfizer Post Residency Fellowship and the 2012 Grant of the CHUM Foundation. Coauthor Douglas Dieterich, MD, also from the Icahn School of Medicine, reports relationships with Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Merck Sharpe & Dohme, ViiV Healthcare, and AbbVie.

International Conference on Viral Hepatitis (ICVH) 2013: Abstract 30. Presented March 25, 2013.


HCV Clearance Key to Liver Fibrosis Regression

Megan Brooks

Mar 28, 2013

In patients coinfected with human immunodeficiency virus (HIV) and hepatitis C, sustained clearance of hepatitis-RNA after a course of antiviral treatment is "the major" determinant of liver fibrosis regression, according to new research.

The lack of hepatitis C virus treatment increases the "probability of developing advanced liver fibrosis," said study investigator Vincent Soriano, MD, from Hospital Carlos III in Madrid, Spain.

Dr. Soriano presented the findings at the International Conference on Viral Hepatitis 2013 in New York City, which was sponsored by the International Association of Providers of AIDS Care and the Icahn School of Medicine at Mount Sinai.

Dr. Soriano's team studied 498 patients coinfected with HIV and hepatitis C who had undergone longitudinal assessment of liver fibrosis with elastometry (FibroScan).

On the basis of response to peginterferon and ribavirin treatment, patients were categorized into 1 of 5 groups: sustained virologic responders, relapsers, partial responders, null responders, treatment-naïve patients.

Table. Response to Peginterferon and Ribavirin Treatment

Response n %
Sustained virologic responders 138 27.7
Relapsers 40 8.0
Partial responders 61 12.2
Null responders 71 14.3
Treatment-naïve patients 188 37.8

After a median follow-up of 53 months, there was less liver fibrosis progression in the sustained virologic responders (7.2%) than in the relapsers (25.0%; P = .002), the partial responders (23.0%; P = .002), the null responders (29.6%; P < .001), and the treatment-naïve patients (19.7%; P = .002).

In addition, cirrhosis regression was more frequent in the sustained virologic responders (11.0%) than in the null responders (2.8%; P = .04) and the treatment-naïve patients (1.6%; P < .001). Regression to liver fibrosis stage F0 to F2 or a decrease in liver stiffness greater than 30% was more frequent in the sustained virologic responders than in the treatment-naïve patients (21.7% vs 7.4%; P < .001). Median liver stiffness decreased significantly in the sustained virologic responders (P < .001) and increased in the null responders (P = .01).

"This study shows the benefit of the successful treatment of hepatitis C and the benefits on the potential for serious liver disease in the future," conference cochair Mark Nelson, MD, from Chelsea and Westminster Hospital, London, United Kingdom, told Medscape Medical News.

Dr. Nelson added that "this shows the importance of rapid and widespread access to more successful therapies for hepatitis C in reducing the high levels of morbidity and mortality secondary to hepatitis C–associated liver disease in the HIV population."

Dr. Soriano reports financial relationships with Boehringer Ingelheim Pharmaceuticals, Gilead Sciences, Janssen Pharmaceuticals, Merck & Co, and AbbVie. Dr. Nelson reports relationships with Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Merck Sharpe & Dohme, ViiV Healthcare, and AbbVie.

International Conference on Viral Hepatitis (ICVH) 2013: Oral Abstract 8. Presented March 25, 2013.


Hepatitis C Viral Load Fluctuates Without Treatment

Megan Brooks

Apr 04, 2013

Fluctuations in circulating hepatitis C virus RNA could be "clinically meaningful" in a substantial number of patients with chronic infection, and could influence the best time to prescribe antiviral therapy.

"Decisions based on early viral kinetics, such as early stopping rules, may require the testing of baseline specimens collected closest to treatment initiation," said researcher Vincent Soriano, MD, from Hospital Carlos III in Madrid, Spain.

He presented study results at the International Conference on Viral Hepatitis 2013 in New York City, which was sponsored by the International Association of Providers of AIDS Care and the Icahn School of Medicine at Mount Sinai.

Dr. Soriano and his team conducted a retrospective review of longitudinal plasma hepatitis C RNA determinations in 818 consecutive untreated patients with chronic virus seen at a clinic in Madrid. For comparison, the researchers used longitudinal plasma human immunodeficiency virus (HIV) RNA measurements from 333 untreated HIV patients followed at the same clinic.

They analyzed 3169 hepatitis C RNA values obtained over 66.2 months and 1998 HIV RNA values obtained over 27.3 months.

Overall, a variation in viral RNA greater than 0.5-log IU/mL occurred more often in hepatitis C specimens than in HIV specimens (44% vs 23%; P < .001). The same was true for variations greater than 1.0-log IU/mL (15% vs 4%; P < .001).

On multivariate analysis, predictors of viral variations greater than 0.5-log IU/mL were lower hepatitis C RNA levels (odds ratio [OR], 0.35; 95% confidence interval [CI], 0.26 - 0.47; P = .001), HIV coinfection (OR, 2.57; 95% CI, 1.56 - 2.68; P < .001), and IL28B-CC alleles (OR, 1.87; 95% CI, 1.28 - 2.74; P = .001).

This study "confirms something that many people knew, that fluctuations in hepatitis C RNA levels are greater and more variable than those of HIV," conference cochair Douglas Dieterich, MD, from the Icahn School of Medicine at Mount Sinai, told Medscape Medical News.

"Using response-guided therapy [RGT] with the new direct-acting antivirals has become the standard of care, and the baseline level of hepatitis C RNA is a very important component of RGT," Dr. Dieterich added. "The timing of treatment to maximize hepatitis C RNA may be a new way to increase treatment success."

Dr. Soriano reports relationships with Boehringer Ingelheim Pharmaceuticals, Gilead Sciences, Janssen Pharmaceuticals, Merck & Co, and AbbVie. Dr. Dieterich reports relationships with Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Genentech, and Novartis Pharmaceuticals.

International Conference on Viral Hepatitis (ICVH) 2013: Oral Abstract 10. Presented March 25, 2013.


Intercept Pharmaceuticals Announces Upcoming EASL Presentation


April 8, 2013

Data Support Strong Statistical Correlation of PBC Biochemical Endpoint With Clinical Outcomes

NEW YORK, April 8, 2013 (GLOBE NEWSWIRE) -- Intercept Pharmaceuticals, Inc. (Nasdaq:ICPT), a clinical stage biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat chronic liver diseases, today announced that an analysis by the Global Primary Biliary Cirrhosis (PBC) Study Group (also known as the PBC Supergroup) confirms that the endpoint used by Intercept in its ongoing Phase 3 POISE trial is strongly predictive of adverse clinical outcomes in PBC patients. The analysis reflects data from more than 2,100 patients. An abstract from the group will be presented at the annual meeting of the European Association for the Study of the Liver (EASL) taking place April 24-28, 2013 in Amsterdam.

The Global PBC Study Group

PBC is an autoimmune chronic liver disease that typically affects women. The disease progresses in patients with an inadequate response to therapy who as a result may require a liver transplant or die. Biochemical assessments of liver function, particularly by measuring plasma levels of alkaline phosphatase (ALP) and bilirubin, are typically used by physicians to diagnose and manage PBC patients. Accordingly, the relationship between these biochemical assessments of liver function and adverse clinical outcomes is highly important in the selection of appropriate endpoints in therapeutic clinical trials.

The Global PBC Study Group is currently comprised of a group of 15 academic medical centers from eight countries that are pooling their data to investigate these relationships. Intercept is sponsoring this independent academic research program but is not involved in the data collection and analysis, which are being conducted by Dr. Henk van Buuren and Dr. Bettina Hansen of Erasmus University Medical Centre in Rotterdam, The Netherlands. The data demonstrate that the primary endpoint being used in Intercept's Phase 3 POISE trial (ALP < 1.67x upper limit of normal and normal bilirubin) is highly statistically predictive of liver transplant-free survival in PBC patients. The risk of adverse outcomes increases from 2-10x in patients with ALP and/or bilirubin levels above these thresholds as compared to patients with biochemical values below them (p < 0.001). Further, the data show that ALP and bilirubin assessed independently are each highly predictive of adverse outcomes.

"This collaborative, international effort has been designed to allow a detailed analysis of both the risks and the natural history of this rare but important disease," noted Dr. van Buuren. "The data show that biochemical assessments predict a patient's risk of requiring a liver transplant or, worse, dying from the disease. More centers have joined the group and we plan to increase the size of the database in the coming months. We believe that we have assembled the largest international PBC study group and database ever, which will prove very useful to both patients and their physicians in the coming years."

Intercept anticipates final data from at least 4,000 patients will be collected and analyzed as part of the study.

About Intercept

Intercept is a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat orphan and more prevalent liver diseases utilizing its expertise in bile acid chemistry. The company's lead product candidate, obeticholic acid, or OCA, is a bile acid analog and first-in-class agonist of the farnesoid X receptor (FXR). OCA is initially being developed for the second line treatment of PBC in patients with an inadequate response to, or who are unable to tolerate, ursodiol (ursodeoxycholic acid), the only approved therapy for this indication. PBC is a chronic autoimmune liver disease that may progress to cirrhosis and liver failure, and it is currently the fifth leading indication for liver transplant in the United States. OCA has orphan drug designation in both the United States and Europe for the treatment of PBC. Intercept owns worldwide rights to OCA outside of Japan and China, where it has out-licensed the product candidate to Dainippon Sumitomo Pharma. For more information about Intercept, please visit the Company's website at www.interceptpharma.com.

Safe Harbor Statement

This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the relationship between ALP and bilirubin and adverse clinical outcomes, the clinical utility of the POISE trial selected endpoints and any potential consensus relating thereto, clinical, preclinical and regulatory developments for our product candidates, the anticipated results of our clinical and preclinical trials and other development activities, and our strategic directives under the caption "About Intercept." These "forward-looking statements" are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: the initiation, cost, timing, progress and results of Intercept's development activities, preclinical studies and clinical trials; the timing of and Intercept's ability to obtain and maintain regulatory approval of OCA and any other product candidates it may develop, and any related restrictions, limitations, and/or warnings in the label of any approved product candidates; Intercept's plans to research, develop and commercialize future product candidates; the election by Intercept's collaborators to pursue research, development and commercialization activities; Intercept's ability to attract collaborators with development, regulatory and commercialization expertise; Intercept's ability to obtain and maintain intellectual property protection for its product candidates; Intercept's ability to successfully commercialize its product candidates; the size and growth of the markets for Intercept's product candidates and its ability to serve those markets; the rate and degree of market acceptance of any future products; the success of competing drugs that are or become available; regulatory developments in the United States and other countries; the performance of third-party suppliers and manufacturers; Intercept's ability to obtain additional financing; Intercept's use of the proceeds from its recently completed initial public offering; the accuracy of Intercept's estimates regarding expenses, future revenues, capital requirements and the need for additional financing; the loss of key scientific or management personnel; and other factors discussed under the heading "Risk Factors" contained in Intercept's annual report on Form 10-K for the year ended 2012 filed with the Securities and Exchange Commission on April 1, 2013, as well as any updates to these risk factors filed from time to time in Intercept's other filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Intercept undertakes no duty to update this information unless required by law.

For more information about Intercept, please contact Mark Pruzanski, M.D., or Barbara Duncan, both of Intercept Pharmaceuticals, at 1-646-747-1000.


Transgene to Present New Data on TG1050 and TG4040 to Treat Chronic Hepatitis B and C at EASL 2013


Strasbourg, April 8th, 2013 - Transgene SA (Euronext Paris: FR0005175080), a biopharmaceutical company that develops targeted immunotherapy products to treat major unmet medical needs in cancer and infectious diseases, today announced that favourable pre-clinical and clinical data on two Transgene products – TG1050 and TG4040 to treat chronic hepatitis B (CHB) and chronic hepatitis C (CHC), respectively – will be presented in oral presentations at this year’s European Association for the Study of the Liver (EASL) Conference (Amsterdam, Netherlands, April 24-28, 2013). The full abstracts are available at http://www.easl.eu.

“We are delighted to have the opportunity to present data at EASL, Europe’s largest liver conference. TG1050 is a novel immunotherapeutic to treat CHB that has shown very promising preclinical results and will soon be moving to early clinical development” stated Philippe Archinard, Chairman and CEO of Transgene. He added: “In addition to the preclinical proof-of-concept data published in September 20121, we have today released supplementary information, obtained in pre-clinical naïve and HBV murine models, on the immunogenicity of TG1050 and its capacity to induce long-term T cell response. This evidence further underlines our belief in the product’s potential to become an important new first in class immunotherapeutic to treat CHB, an area of unmet medical need.”

“TG4040 has recently completed successful phase 2 trial in patients with CHC” stated Nathalie Adda, Chief Medical Officer of Transgene. She added: “Following interim data published in April last year for TG4040 in combination with PegIFNα2a and ribavirin, we report the final results of the phase 2 HCVac trial with sustained viral response at 24 weeks (SVR24) and additional immunogenicity, specific T-cell and humoral responses. The study has demonstrated that pre-treatment with TG4040 has a positive impact on viral response as shown by cEVR and SVR improvement compared to PegIFN alpha 2a and Ribavirin alone. HCV Immunotherapy now could be explored in combination with an IFN-free DAA regimen.”

The oral presentations will take place on Friday, April 26 and Saturday, April 27, 2013.

Friday, April 26, Session entitled: HCV Direct Acting Antivirals (abstract No 62)

Phase 2 HCVac Study of TG4040 immunotherapeutic in combination with PegIFNα2a and ribavirin in genotype 1 CHC treatment naïve patients: SVR24 Final Results

Oral presentation by Pr. Heiner Wedemeyer, Principal Investigator of the HCVac study, University of Hanover, Germany

Session Time: 16:00-18:00

Saturday, April 27, Session entitled: Hepatitis B and D Experimental (abstract No 130)

A Multivalent Adenovirus-Based Immunotherapeutic for Treatment of Chronic Hepatitis B Induces Broad, Robust and Polyfunctional T Cells in Naïve and HBV Tolerant Mice

Oral presentation by Dr. Perrine Martin, Scientific Coordinator of the Hepatitis B Program, Department of Infectious Diseases, Transgene SA.

Session Time: 15:30-17:30

About TG1050

The novel immunotherapeutic product TG1050 developed by Transgene to treat chronic infection by hepatitis B is based on a recombinant non-replicative human adenovirus serotype 5, expressing multiple specific HBV antigens (Core, Polymerase and Envelope) from genotype D. The product has been designed to prime de novo and/or stimulate functional T cells expected to control the HBV replication and to elicit viral clearance.
According to the World Health Organization’s (WHO) estimates, 350 million people are chronic carriers (WHO, 2009) of HBV. Hepatitis B is more common in some parts of the world than others. In China and other parts of Asia, up to 10% of the population is believed to be chronically infected. In addition to the significant burden of disease, CHB is responsible for 1 million deaths each year due to related complications such as liver failure, cirrhosis or hepatocellular carcinoma (liver cancer).

About TG4040

Transgene’s TG4040 vaccine candidate is a recombinant vector based on the MVA virus carrying and expressing three of the major non-structural proteins (NS3, NS4 and NS5B) of the hepatitis C virus (HCV). The MVA vector is a highly attenuated strain of vaccinia virus, which has been tested extensively in humans as a vaccine against smallpox and is known to strongly stimulate innate and adaptive immune responses to antigens.

About TG4040 Clinical Development Program

153 patients in the phase 2 HCVac study were recruited in five countries in Europe, in the United States and in Israel, and were randomized in one control arm (Arm A; 48 weeks of Peg-IFN/RBV) or one of the two experimental arms (Arms B and C). In the Arm B, the TG4040 dosage (subcutaneous injections at the dose of 107 pfu) was administered 6 times and Peg-IFN/RBV was given 4 weeks prior to the initiation of TG4040. In the Arm C, the TG4040 dosage was administered 13 times and Peg-IFN/RBV was introduced 12 weeks after the initiation TG4040. The HCVac trial investigated the efficacy and safety of these two different schedules of TG4040 administration in combination with Peg-IFN and RBV.

About Transgene:

Transgene (NYSE-Euronext: TNG), a member of the Institut Mérieux Group, is a biopharmaceutical company. It creates, develops and manufactures targeted immunotherapeutics for the treatment of cancers and infectious diseases. Transgene’s products are major technological breakthroughs. They use well tolerated viruses to indirectly or directly kill infected or cancerous cells. Its four most advanced products have generated proof of concept data in randomized clinical studies: in lung cancer (TG4010), liver cancer (Pexa-Vec), hepatitis C (TG4040) and HPV-related cervical lesions (TG4001). Transgene has concluded strategic agreements for the development of three of these products: an option agreement with Novartis for the development of TG4010, an in-licensing agreement with US-based Jennerex, Inc. to develop and market Pexa-Vec and a strategic collaboration with EORTC to develop TG4001 in cancer of the oropharynx. Transgene also has a non exclusive agreement with Sanofi/Genzyme for its future commercial production. With 280 employees, it is based in Strasbourg, France, and has operations in Lyon, China and the USA. Additional information about Transgene is available at www.transgene.fr.

Transgene Forward Looking Statements

This press release contains forward-looking statements notably referring to an anticipated future BLA filing date by Transgene. Such anticipated future BLA filing date is based on the current plan of product development and testing. This plan may change in the future and, as such, Transgene could be in a position not to meet the currently anticipated development milestones, including such BLA filing. For further information on the risks and uncertainties involved in the testing and development of Transgene’s product candidates, see Trangene’s Document de Référence on file with the French Autorité des marchés financiers on its website at http://www.amffrance.org and on Transgene’s website at www.transgene.fr .


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Merck to Present New Data on VICTRELIS® (boceprevir) and Investigational Compounds MK-5172 and Vaniprevir for Chronic Hepatitis C Virus at The International Liver CongressTM / 2013 EASL Annual Meeting


Monday, April 8, 2013 10:37 am EDT


Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced today that two analyses of VICTRELIS (boceprevir) and data from Phase II studies of two of Merck’s investigational medicines for chronic hepatitis C virus (HCV) genotype 1, MK-5172 and vaniprevir (MK-7009), will be presented at the 2013 International Liver Congress (EASL) Annual Meeting. The meeting will take place in Amsterdam from April 24-28, 2013.

Key Presentations About VICTRELIS 200 mg Capsules

  • Safety And Efficacy Of Boceprevir/Peginterferon/Ribavirin (Boc/P/R) Combination Therapy For Chronic HCV G1 Patients With Compensated Cirrhosis: A Meta-Analysis Of Five Phase III Clinical Trials, J.M. Vierling et al. Late Breaker. Thursday, April 25, 9:00- 18:00. RAI Convention Centre.
  • Virologic Response Rates Are Similar In Previously Untreated And Previously Treated And Relapsed Patients Receiving Boceprevir Triple Therapy: A Retrospective Analysis. Bacon, B. et al. Poster 791. Friday, April 26, 12:30-14:00. RAI Convention Centre.

Key Investigational Compound Presentations

  • High Sustained Viral Response at 12- and 24-week follow-up of MK-5172 with Pegylated Interferon alfa-2b and Ribavirin (PR) in HCV Genotype 1 Treatment-naïve Non-cirrhotic Patients. Manns, M. et al. Oral Presentation: Friday, April 26, 16:00-18:00, RAI Convention Centre.
  • MK-5172 In Combination With Peg-Interferon And Ribavirin Elicits Limited Resistance While Demonstrating Robust Efficacy In Treatment Naïve Genotype 1 Chronic HCV-Infected Patients. Howe, A. et al. Poster 1197. Saturday, April 27, 12:30-13:30. RAI Convention Centre.
  • Sustained Viral Response And Safety Of MK-7009 In Cirrhotic Treatment-Experienced Patients With Genotype 1 HCV Infection Who Have Failed Previous Pegylated Interferon And Ribavirin Treatment. Rodriguez-Torres, M. et al. Oral Presentation. Saturday, April 27, 8:30-10:30. RAI Convention Centre.

"We are pleased to present new data on VICTRELIS that will help inform health care professionals as they consider the use of VICTRELIS in appropriate patients," said Eliav Barr, M.D., vice president, Infectious Diseases, Project Leadership and Management, Merck Research Laboratories. "Merck is committed to helping reduce the burden of this serious disease worldwide. We look forward to sharing our new data about VICTRELIS and Merck's investigational medicines for chronic hepatitis C with the global scientific community."

MK-5172 is an investigational, once-daily, oral HCV NS3/4A protease inhibitor currently in Phase II development. Vaniprevir is an oral, twice-daily HCV NS3/4A protease inhibitor in Phase III development in Japan for the treatment of genotype 1 patients.

The abstracts were published today and can be accessed on the EASL website. For program information, please visit http://www2.kenes.com/liver-congress/pages/home.aspx.

Indications and usage for VICTRELIS

VICTRELIS® (boceprevir) is indicated for the treatment of chronic hepatitis C virus (HCV) genotype 1 (G1) infection, in combination with peginterferon alfa and ribavirin (PR), in adult patients (18 years and older) with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy, including prior null responders, partial responders, and relapsers.

The following points should be considered when initiating VICTRELIS for treatment of chronic HCV infection:

  • VICTRELIS must not be used as monotherapy and should only be used in combination with PR.
  • The efficacy of VICTRELIS has not been studied in patients who have previously failed therapy with a treatment regimen that includes VICTRELIS or other HCV NS3/4A protease inhibitors.
  • Poorly interferon responsive patients who were treated with VICTRELIS in combination with PR have a lower likelihood of achieving a sustained virologic response (SVR), and a higher rate of detection of resistance-associated substitutions upon treatment failure, compared to patients with a greater response to PR.

Important safety information about VICTRELIS

All contraindications to PR also apply since VICTRELIS must be administered with PR. Because ribavirin may cause birth defects and fetal death, VICTRELIS in combination with PR is contraindicated in pregnant women and in men whose female partners are pregnant. Avoid pregnancy in female patients and female partners of male patients. Patients must have a negative pregnancy test prior to therapy; have monthly pregnancy tests; and use 2 or more forms of effective contraception during treatment and for at least 6 months after treatment has concluded. One of these forms of contraception can be a combined oral contraceptive product containing at least 1 mg of norethindrone. Oral contraceptives containing lower doses of norethindrone and other forms of hormonal contraception have not been studied or are contraindicated.

VICTRELIS is contraindicated in patients with a history of a hypersensitivity reaction to VICTRELIS. VICTRELIS is contraindicated in coadministration with drugs that are highly dependent on CYP3A4/5 for clearance, and for which elevated plasma concentrations are associated with serious and/or life-threatening events. VICTRELIS is also contraindicated in coadministration with potent CYP3A4/5 inducers, where significantly reduced VICTRELIS plasma concentrations may be associated with reduced efficacy. Drugs that are contraindicated with VICTRELIS include: alfuzosin, carbamazepine, phenobarbital, phenytoin, rifampin, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, St. John’s Wort (hypericum perforatum), lovastatin, simvastatin, drospirenone, Revatio® (sildenafil) or Adcirca®(tadalafil) (when used for the treatment of pulmonary arterial hypertension), pimozide, triazolam, and orally administered midazolam.

Anemia and/or Neutropenia – The addition of VICTRELIS to PR is associated with an additional decrease in hemoglobin concentrations compared with PR alone and/or may result in worsening of neutropenia associated with PR therapy alone. Dose reduction or discontinuation of peginterferon alfa and/or ribavirin may be required. If peginterferon alfa or ribavirin is permanently discontinued, VICTRELIS must also be discontinued. Dose reduction of VICTRELIS is not recommended. VICTRELIS must not be administered in the absence of PR.

Complete blood count (with white blood cell differential counts) must be conducted in all patients prior to initiating combination therapy with VICTRELIS. Complete blood counts should be obtained at Treatment Weeks 2, 4, 8, and 12, and should be monitored closely at other time points, as clinically appropriate. Serious acute hypersensitivity reactions (eg, urticaria, angioedema) have been observed during combination therapy with VICTRELIS and PR. If such an acute reaction occurs, combination therapy should be discontinued and appropriate medical therapy immediately instituted.

The most commonly reported adverse reactions (>35%) in clinical trials in adult patients receiving the combination of VICTRELIS with PR were: fatigue, anemia, nausea, headache, and dysgeusia. Of these commonly reported adverse reactions, fatigue, anemia, nausea, and dysgeusia occurred at rates ≥5% above the rates for PR alone in either clinical study. The incidence of these adverse reactions in previously untreated subjects that were treated with combination therapy with VICTRELIS compared with PR alone were: fatigue (58% vs 59%), anemia (50% vs 30%), nausea (46% vs 42%), and dysgeusia (35% vs 16%), respectively. The incidence of these adverse reactions in previous treatment failure patients that were treated with combination therapy with VICTRELIS compared with PR alone were: fatigue (55% vs 50%), anemia (45% vs 20%), nausea (43% vs 38%), and dysgeusia (44% vs 11%), respectively.

VICTRELIS is a strong inhibitor of CYP3A4/5 and is partly metabolized by CYP3A4/5. The potential for drug-drug interactions must be considered prior to and during therapy.

Please see U.S. prescribing information at: http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_pi.pdf

Merck's Global Commitment to Advancing Hepatitis Therapy

Merck is committed to building on its strong legacy in the field of viral hepatitis by continuing to discover, develop and deliver vaccines and medicines to help prevent and treat viral hepatitis. In hepatitis C, company researchers developed the first approved therapy for chronic HCV in 1991 and the first combination therapy in 1998. In addition to ongoing studies for our marketed and investigational medicines for the treatment of chronic HCV, extensive research efforts are underway to develop additional innovative oral therapies for viral hepatitis treatment.

About Merck

Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebook and YouTube.

Forward-Looking Statement

This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of Merck’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; Merck’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of Merck’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck’s 2012 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

Please see Prescribing Information for VICTRELIS at http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_pi.pdf and Medication Guide for VICTRELIS at http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_mg.pdf.

Revatio® and Adcirca®are trademarks of their respective owners and are not trademarks of Merck & Co., Inc., Whitehouse Station, N.J., USA.
VICTRELIS®is a trademark of Schering Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, N.J., USA.


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Sarra Herzog, 908-423-6154
Carol Ferguson, 908-423-4465
Justin Holko, 908-423-5088


Vertex Enters Agreement with Bristol-Myers Squibb for Phase 2 All-Oral Studies of VX-135 in Combination with Daclatasvir for the Treatment of Hepatitis C


April 5, 2013

-Two Phase 2 studies to evaluate once-daily combination of Vertex's investigational nucleotide analogue VX-135 and BMS' investigational NS5A replication complex inhibitor daclatasvir-

-Study in people with genotype 1 hepatitis C planned to begin in second quarter of 2013-

-Study in people with genotypes 1, 2 and 3 hepatitis C, including people with cirrhosis, planned for second half of 2013-

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced it has entered into a non-exclusive agreement with Bristol-Myers Squibb Company (NYSE: BMY) to conduct Phase 2 studies of once-daily all-oral treatment regimens containing Vertex's nucleotide analogue hepatitis C virus (HCV) polymerase inhibitor VX-135 and Bristol-Myers Squibb's NS5A replication complex inhibitor daclatasvir for the treatment of hepatitis C. As part of the agreement, Vertex plans to conduct two Phase 2 studies of the combination, including an initial study in treatment-naïve people with genotype 1 HCV infection planned for the second quarter of 2013. Vertex plans to begin a subsequent study in treatment-naïve people infected with genotype 1, 2 or 3 HCV, including those with cirrhosis, in the second half of 2013, pending data from the initial study.

"With more than 170 million people infected worldwide, there is a critical need for new hepatitis C medicines that can offer people simpler and more tolerable treatment regimens that provide high cure rates," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer at Vertex. "These studies with daclatasvir will provide the first opportunity to evaluate VX-135 as part of all-oral regimens in people with multiple hepatitis C genotypes and in people with cirrhosis."

Clinical Development Plans for VX-135 with Daclatasvir

Under the terms of the agreement, Vertex will conduct two Phase 2 studies of VX-135 in combination with daclatasvir. The first study will enroll approximately 20 non-cirrhotic, treatment-naïve people with chronic genotype 1 HCV infection and is expected to begin in the second quarter of 2013. In the second half of 2013, Vertex plans to conduct a subsequent study in approximately 250 treatment-naïve people with chronic genotype 1, 2 or 3 HCV infection, including those with cirrhosis. Each of these studies is expected to evaluate safety, tolerability, pharmacokinetics and viral cure rates (SVR4 and SVR12) of multiple all-oral regimens of VX-135 and daclatasvir dosed once daily, pending regulatory discussions. Vertex will also conduct co-formulation activities to evaluate the potential for development of a once-daily fixed-dose combination regimen. Further clinical development activities beyond the Phase 2 studies are not covered as part of this agreement.

About VX-135

VX-135 is a uridine nucleotide analogue pro-drug designed to inhibit the replication of the hepatitis C virus by acting on the NS5B polymerase. In people with genotype 1, treatment with a 200mg once-daily dose of VX-135 in a 7-day viral kinetic study was well-tolerated, with no discontinuations due to adverse events, and resulted in a 4.54 log10 median reduction from baseline in HCV RNA. Data from a 7-day viral kinetic study of VX-135 in people with genotypes 2, 3 and 4 were consistent with data observed in people with genotype 1 and have been submitted for presentation at a future medical meeting.

Vertex gained worldwide rights to ALS-2200, known as VX-135 in Phase 2 studies, through an exclusive licensing agreement signed with Alios BioPharma, Inc. in June 2011. The agreement also includes a research program that focuses on the discovery of additional nucleotide analogues that act on hepatitis C polymerase. Vertex has the option to select additional compounds for development emerging from the research program.

About Daclatasvir

Daclatasvir is an NS5A replication complex inhibitor that is being extensively studied as a key component of potential DAA-based hepatitis C treatment regimens. Studied in more than 4,100 patients to date, daclatasvir is in Phase 3 development.

Daclatasvir is part of a portfolio of investigational compounds with different mechanisms of action that Bristol-Myers Squibb is developing for the treatment of hepatitis C. These compounds are being studied as part of multiple novel treatment regimens with the goal of increasing SVR rates across diverse patient types and geographies.

About Hepatitis C

Hepatitis C is a serious liver infection caused by the hepatitis C virus, which is spread through direct contact with the blood of infected people and ultimately affects the liver.1 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.1 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.1 Unlike HIV and hepatitis B virus, chronic hepatitis C can be cured.2 If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.3,4

More than 170 million people worldwide are chronically infected with hepatitis C.5 In the United States, up to 5 million people have chronic hepatitis C and 75 percent of them are unaware of their infection.6,7 Hepatitis C is four times more prevalent in the United States compared to HIV.7 The majority of people with hepatitis C in the United States were born between 1945 and 1965, accounting for three fourths of people with the infection.8 Hepatitis C is the leading cause of liver transplantations in the United States and is reported to contribute to 15,000 deaths annually.9,10 By 2029, total annual medical costs in the United States for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.11

About Vertex

Vertex creates new possibilities in medicine. Our team discovers, develops and commercializes innovative therapies so people with serious diseases can lead better lives.

Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, rheumatoid arthritis and other life-threatening diseases.

Founded more than 20 years ago in Cambridge, Mass., we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada. Today, Vertex has more than 2,000 employees around the world, and for three years in a row, Science magazine has named Vertex one of its Top Employers in the life sciences.

Vertex Special Note Regarding Forward-Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, Dr. Kauffman's statements in the second paragraph of the press release and statements regarding Vertex's expectations with respect to the timing and structure of studies evaluating the combination of VX-135 and daclatasvir. While Vertex believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that the initiation of planned studies may be delayed or prevented, that the outcomes of Vertex's planned clinical studies may not be favorable and other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through the company's website at www.vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.


1 Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf Updated June 2010. Accessed September 21, 2012.

2 Pearlman BL and Traub N. Sustained Virologic Response to Antiviral Therapy for Chronic Hepatitis C Virus Infection: A Cure and So Much More. Clin Infect Dis. 2011 Apr;52(7):889-900.

3 Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).

4 Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.

5 Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.

6 Chak, E, et. al. Hepatitis C Virus Infection In USA: An Estimate of True Prevalence. Liver Intl. 2011;1096 -1098.

7 Institute of Medicine of the National Academies. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Colvin HM and Mitchell AE, ed. Available at: http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx Updated January 11, 2010. Accessed September 21, 2012.

8 Centers for Disease Control and Prevention. Recommendations for the Identification of Chronic Hepatitis C Virus Infection Among Persons Born During 1945—1965. Morbidity and Mortality Weekly Report. August 17, 2012; 61(RR04);1-18.

9 Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009;50(6):1750-1755.

10 Ly KN, et al. The Increasing Burden of Mortality From Viral Hepatitis in the United States Between 1999 and 2007. Ann Intern Med. 2012;156:271-278.

11 Pyenson B, Fitch K, and Iwasaki K. Consequences of Hepatitis C Virus (HCV): Costs of a Baby Boomer Epidemic of Liver Disease. Milliman, Inc. May 2009. Available at: http://www.vrtx.com/assets/pdfs/MillimanReport.pdf


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Boehringer Ingelheim to Announce Pivotal Phase 3 Hepatitis C Data at the International Liver Congress


For U.S. Media Only

Ridgefield, CT, April 8, 2013 – Boehringer Ingelheim today announced that data from its pivotal STARTVerso™ 1 Phase 3 hepatitis C clinical trial have been accepted for oral presentation as a late-breaker at the International Liver Congress™ 2013: 48th Annual Meeting of the European Association for the Study of the Liver (EASL), taking place from April 24-28 in Amsterdam, The Netherlands.

The STARTVerso™ 1 trial evaluated faldaprevir (BI 201335), an investigational oral protease inhibitor specifically designed to target and inhibit viral replication in the liver, in combination with pegylated interferon and ribavirin (PegIFN/RBV). The study was conducted in treatment-naïve patients with genotype-1 infection, the most common and one of the most challenging types of hepatitis C to cure.

Further sub-analyses from Boehringer Ingelheim’s interferon-free Phase 2b SOUND-C2 study will also be presented at the Congress. The SOUND-C2 trial evaluated the interferon-free combination of faldaprevir and BI 207127, an investigational non-nucleoside NS5B polymerase inhibitor, plus ribavirin.

Boehringer Ingelheim is developing faldaprevir as a core component of both interferon-based and interferon-free hepatitis C treatment regimens. Through robust science, Boehringer Ingelheim’s goal is to find answers to the ongoing challenges faced by a diverse population of patients with hepatitis C.

The STARTVerso™ 1 abstract can be accessed through the Congress website beginning on April 23 and the SOUND-C2 abstracts can be accessed today.


Oral Presentation
Study Lead Author Presentation Details
STARTVerso™ 1
P. Ferenci
Embargoed until April 23 at
12:00PM CET (6:00AM ET)

Poster Presentations
Title Lead Author Presentation Details
An analysis of response rates
by fibrosis stage in patients
treated with faldaprevir,
BI 207127 and ribavirin in the
SOUND-C2 study

S. Zeuzem
Abstract number 1227

Date: Sat. April 27
Time: 9:00 AM - 6:00 PM.
CET (3:00 AM - 12:00 PM ET)

Poster Session: P03-08d,
Category 08d: Viral Hepatitis C:
Clinical (new compounds,

ITPA gene variants predict
haemolytic ribavirin induced
anaemia in patients treated
with the interferon-free
regimen of faldaprevir,
BI 207127 and ribavirin in

T. Asselah
Abstract number 1186

Date: Sat. April 27
Time: 9:00 AM - 6:00 PM
CET (3:00 AM - 12:00 PM ET)

Poster Session: P03-08d,
Category 08d: Viral Hepatitis C:
Clinical (new compounds,
The relationship between
sustained virological response
and plasma concentrations of
faldaprevir or BI 207127 in HCV
GT1-infected patients in
S. Olson Abstract number 1212

Date: Sat. April 27
Time: 9:00 AM - 6:00 PM
CET (3:00 AM - 12:00 PM ET)

Poster Session: P03-08d,
Category 08d: Viral Hepatitis C:
Clinical (new compounds,

About Boehringer Ingelheim in Hepatitis C Virus (HCV)
In partnership with the scientific community, our clinical trial program is rigorously designed to find answers to the challenges that HCV patients face, including those who are the most difficult to treat. Our pivotal HCV clinical trials for faldaprevir and BI 207127 are comprised of two multi-trial programs, STARTVerso™ and HCVerso™.

Faldaprevir, also known as BI 201335, is an investigational, oral protease inhibitor that is specifically designed to target viral replication in the liver. STARTVerso™ 1 is the first of an ongoing multi-study Phase 3 trial program that is evaluating faldaprevir combined with PegIFN/RBV. Three additional STARTVerso™ trials in treatment-naïve, treatment-experienced and HIV co-infected patients with chronic genotype-1 HCV are near clinical completion. BI 207127 is an investigational NS5B non-nucleoside polymerase inhibitor that has shown the potential to eliminate interferon from HCV treatment when combined in a regimen with faldaprevir and RBV. Phase 2 trials of this interferon-free regimen have been completed and Phase 3 HCVerso™ trials are now underway. As part of our long-term commitment to HCV, the company is exploring other combinations of investigational HCV compounds that work in different ways. The recent collaboration of Boehringer Ingelheim with Presidio Pharmaceuticals, Inc. for a Phase 2 clinical study investigating an interferon-free, all-oral combination is part of the company’s continued commitment to discover and develop innovative options for the treatment of HCV.

Faldaprevir and BI 207127 are investigational compounds and not approved by the FDA. Their safety and efficacy have not been established.

Hepatitis C is a blood-born infectious disease and a leading cause of chronic liver disease, transplant and failure that affects as many as 150 million people globally. In the United States, an estimated 4.1 million Americans have been infected with HCV, of which approximately 3.2 million have chronic HCV infection. Since 1999 there has been a significant increase in deaths due to chronic HCV, accounting for 15,000 deaths in the United States in 2007.

About Boehringer Ingelheim Pharmaceuticals, Inc.
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.

The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 145 affiliates and more than 42,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

As a central element of its culture, Boehringer Ingelheim pledges to act socially responsible. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim’s endeavors.

For more information, please visit http://us.boehringer-ingelheim.com and follow us on Twitter at http://twitter.com/boehringerus.


New Drug Application has been filed with FDA for Simeprevir (TMC435) for combination treatment of adult patients with genotype 1 chronic hepatitis C


28-Mar-13 Stockholm, Sweden — Medivir AB (OMX: MVIR) today announced that a new drug application (NDA) has been filed with the U.S. Food and Drug Administration (FDA) seeking approval for simeprevir. The filing is based on phase III data in treatment-naïve and treatment-experienced patients with compensated liver disease.

The filing of a regulatory application in the US triggers a milestone payment of €10m to Medivir.
Simeprevir is jointly developed by Medivir and Janssen Pharmaceuticals, Inc. (Janssen), and is an investigational NS3/4A protease inhibitor, administered as a 150 mg capsule once daily with pegylated interferon and ribavirin for the treatment of genotype 1 chronic hepatitis C in adult patients.

“The filing in the U.S. is a very important milestone for simeprevir, the hepatitis C patients and for Medivir as a company. In addition it triggers a € 10m milestone payment to us, which strengthens our solid financial situation even more.” comments Maris Hartmanis, CEO of Medivir.

The regulatory submission for simeprevir is supported in part by data from three pivotal phase III studies: QUEST-1 and QUEST-2 in treatment-naïve patients and PROMISE in patients who have relapsed after prior interferon-based treatment. In each study, participants were treated with one 150 mg simeprevir capsule once daily for 12 weeks plus pegylated interferon and ribavirin for 24 or 48 weeks. Primary efficacy data from the phase III studies will be presented at different upcoming medical meetings.

For more information please contact:
Rein Piir, EVP Corporate Affairs & IR
Office: +46 8 546 831 23
Mobile: +46 708 537 292.

About Simeprevir

Simeprevir, an investigational next generation NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB, is currently in late phase III studies as a once-daily capsule (150 mg) taken in combination with pegylated interferon and ribavirin for the treatment of genotypes 1 and 4 HCV.

Global phase III studies of simeprevir include QUEST-1 and QUEST-2 in treatment-naïve patients, PROMISE in patients who have relapsed after prior interferon-based treatment and ATTAIN in null-responder patients. In parallel to these trials, phase III studies for simeprevir are ongoing in treatment-naïve and treatment-experienced HIV-HCV co-infected patients, HCV genotype 4 patients and Japanese HCV genotype 1 patients. Janssen recently announced the submission of a new drug application for simeprevir in Japan for the treatment of genotype 1 hepatitis C.

Simeprevir is being studied in phase II interferon-free trials with and without ribavirin in combination with:

· Janssen’s non-nucleoside inhibitor TMC647055 and ritonavir in treatment-naïve genotype 1a and 1b HCV patients;

· Gilead Sciences, Inc.’s nucleotide inhibitor sofosbuvir (GS-7977) in treatment-naïve and previous null-responder genotype 1 HCV patients; and

· Bristol-Myers Squibb's NS5A replication complex inhibitor daclatasvir (BMS-790052) in treatment-naive and previous null-responder genotype 1 HCV patients.

In addition, Janssen has a non-exclusive collaboration with Vertex Pharmaceuticals to evaluate in a phase II study the safety and efficacy of an all-oral regimen of simeprevir and Vertex’s investigational nucleotide analogue polymerase inhibitor VX-135 for the treatment of HCV. As a first step, Janssen Pharmaceutical Inc. will conduct a drug-drug interaction (DDI) study with simeprevir and VX-135.

We also recently announced plans to initiate a phase II trial of an investigational interferon-free regimen with simeprevir, TMC647055 and Idenix’s IDX719, a once-daily, pan-genotypic NS5A inhibitor, with and without ribavirin.

For additional information about simeprevir clinical trials, please visit www.clinicaltrials.gov.

About Hepatitis C

Hepatitis C, a blood-borne infectious disease of the liver and a leading cause of chronic liver disease and liver transplants, is a rapidly evolving treatment area with a clear need for innovative treatments. Approximately 150 million people are infected with hepatitis C worldwide, and 350,000 people per year die from the disease.

About Medivir AB

Medivir is an emerging research-based pharmaceutical company focused on infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company’s key pipeline asset is simeprevir, a novel protease inhibitor in late phase III clinical development for hepatitis C that is being developed in collaboration with Janssen R&D Ireland.

Medivir has also a broad product portfolio with prescription pharmaceuticals in the Nordics.

For more information about Medivir AB, please visit the Company’s website: www.medivir.co

Medivir is a collaborative and agile pharmaceutical company with an R&D focus on infectious diseases and a leading position in hepatitis C. We are passionate and uncompromising in our mission to develop and commercialize innovative pharmaceuticals that improve people’s lives.