April 23, 2012

Hunter's hidden Hepatitis C epidemic

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DISCRIMINATION: Many myths persist about hepatitis C.

BY JACQUI JONES

24 Apr, 2012 04:00 AM

HEPATITIS C is a hidden epidemic, with one in 100 Hunter residents infected but only a fraction of sufferers seeking treatment, a leading advocacy organisation says.

Hepatitis NSW chief executive Stuart Loveday said discrimination prevented many sufferers from seeking treatment.

Myths persisted about how the virus was contracted, with people believing sharing utensils, laundry, a swimming pool or toilet seat with an infected person put others at risk.

Hepatitis C is a virus contracted through blood to blood contact, usually from sharing needles when injecting drugs, or sharing tattoo and piercing equipment.

It affects the liver, can lead to liver disease or cancer, and is the leading cause of liver transplant.

Hepatitis NSW said that in the Hunter New England Health area, about 9600 people were living with hepatitis C and about 75 per cent of those would develop a chronic illness.

Only 2 per cent to 3 per cent of sufferers nationally were receiving treatment.

Symptoms could delay in presenting, in some cases up to 15 years after infection.

Those infected through blood transfusions, before screening of blood supply was introduced in 1990, were living with the virus.

Mr Loveday said drug therapies were progressing.

Newcastle’s John Hunter Hospital was among the leading treatment centres.

But the latest phase of improved medication was about five years away.

For information phone 1800 803 990 or go to hep.org.au.

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Cleveland Clinic hopes to use more living donors for liver transplants

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Associated Press file
The removal of part of a liver from a living donor is much more complicated anatomically than removing a donor kidney.
Published: Monday, April 23, 2012, 8:15 PM

By Angela Townsend, The Plain DealerThe Plain Dealer

Statistics on living liver donors

Since 1984, the Cleveland Clinic has performed nearly 1,700 liver transplants — more than half of Ohio's total. The University of Cincinnati Medical Center comes in second with 833 liver transplants. University Hospitals Case Medical Center has performed 526 liver transplants.

  • Nationally, just over 100 of the country's 170 transplant centers have liver transplant programs; only one-third have performed more than 50 transplants from living donors.
  • To date, the Cleveland Clinic has transplanted 49 livers from living donors, according to data from the Clinic and the Organ Procurement Transplant Network.
  • Nationally, the number of living donors has dropped over the years. At its peak in 2001, there were 524. The last year in which there were more than 300 was 2005.
  • Less than 4 percent of all liver transplants in 2011 came from living donors.

Source: Cleveland Clinic, Organ Procurement and Transplantation Network

CLEVELAND, Ohio -- After not performing liver transplants from living donors for a year, the Cleveland Clinic has ramped up its program to address a long transplant waiting list. The Clinic's goal for 2012 is to conduct 12 surgeries with living liver donors, at a pace of one a month.

That would be almost as many as the 14 liver transplants using living donors the Clinic did between 2008 and 2010. None of the liver transplants for 247 patients at the Clinic in 2011 involved living donors.

So far this year, four Clinic patients have received a portion of a liver from a living donor, equaling the number in 2010. For the past several years, the Clinic has been the only liver transplant center in Ohio to perform surgery using living donors.

Nearly 17,000 people are currently on the national liver transplant waiting list, 194 of them patients at the Clinic, said Dr. William Carey, director of the Hepatology (Liver) Center in the Clinic's department of gastroenterology.

"Only about one-fourth of patients [on the list] get a transplant every year," said Carey, who also is chairman of the Living Liver Donor Advocacy Team in the Clinic's Digestive Disease Institute. "There is a gap between the need and the reality that is almost exclusively the lack of donors."

Unlike people on the kidney-transplant waiting list who can have dialysis, someone with advanced liver disease who is awaiting transplant has no comparable option, and many are pretty close to death, Carey said. The removal of part of a liver from a living donor is much more complicated anatomically than removing a donor kidney, Carey said.

"This isn't restricted to just one center or one state," Carey said of the scarcity of living liver donors. Part of the decline has stemmed from highly publicized deaths of living donors, he said.

In 2010, two men -- one at the University of Colorado in Denver, the other at Lahey Clinic in suburban Boston -- donating parts of their livers died three months apart as a result of their surgeries. They were the third and fourth recorded deaths since 2000, out of the more than 4,500 living liver donors since 1989.

Those deaths, Carey said, are out of proportion to the relative risk.

"When it hits the news media . . . it does put a damp blanket over people's willingness to step forward and volunteer," he said.

Encouraging liver donors

The Clinic has taken steps to encourage liver donation, including a more user-friendly website, making sure all exam areas have brochures available that explain being a living donor and putting up informational kiosks.

"Volume makes a difference in terms of quality," said Carey, explaining what he calls the Clinic's "self-imposed" goal for 2012. There's no reason why other top transplant centers can't do the same thing, he said.

"There has to be an institutional commitment to get things done," he said. "That's really the only way we're going to make an impact.

"We as [an entire] community need to band together to increase donor-organ awareness," he said.

That increased awareness needs to include a closer tracking of all living donors after surgery, said Donna Luebke of Montville Township in Medina County, who has served as an independent donor advocate to Lorraine Hawks, whose husband, Paul Hawks, died in 2010 during surgery to donate part of his liver to his brother-in-law.

Since 2000, the follow-up on patient conditions has been mandatory for transplant centers, which must report to the United Network of Organ Sharing -- which manages the nation's organ-transplant system -- any problems experienced by living donors for a minimum of two years after surgery.

"There is no safety net for complications afterward," said Luebke, an associate in the Center for BioMedical Ethics at MetroHealth Medical Center. "Kidney donors at least can go on dialysis. But what can you do for a liver donor?"

Montefiore Medical Center in New York City has one of the newer liver transplant programs in the country, performing 65 transplants since its inception in 2008. Two have been from living donors.

"We would like to do about six [living donor transplants] per year," said Dr. Paul Gaglio, medical director of liver transplantation at Montefiore, one of New York's smaller transplant programs.

The target volume of any transplant center is driven not by the desires of those directing the program, but by the number of patients on the waiting list, Gaglio said.

"When we look at the option of living-donor liver transplantation, it's a very thoughtful process," he said. "Is it an appropriate option for the recipient? Is it a safe option for the potential donor? All decisions are made in a way to maximize outcomes and maximize the safety for the donor."

To help liver donors recover, the Clinic has a program that mirrors one begun in 2010 for kidney donors. Donor WIn (Wellness Initiative), helps patients regain their pre-surgery physical condition and activity.

Luebke, who also serves as a board member for Lifebanc, the organ-procurement organization for Northeast Ohio, said more work needs to be done to make available more organs from deceased donors. That means allowing organs to go anywhere in the country where they are needed most, not restricting their use to within their geographic region, whose borders are defined by the United Network of Organ Sharing.

"To me, the living are not the solution to the organ shortage," Luebke said.

When a living donor is the best option

For Roger Hartzell, however, the living -- specifically, his son David -- was the solution.

Hartzell of St. Clairsville (a few miles from the West Virginia border in Belmont County) is recuperating from a transplant performed by Drs. Bijan Eghtesad and Koji Hashimoto in January at the Clinic. David Hartzell, who lives outside of Lima, donated the right lobe of his liver.

Diagnosed in 2004 with liver disease, Roger Hartzell went through two years of testing before discovering cirrhosis that stemmed from his exposure to Agent Orange while serving in the Vietnam War.

The majority of patients who require a liver transplant have cirrhosis, in which scar tissue forms on the liver because of an injury or long-term disease. That scar tissue blocks the normal flow of blood through the liver that is essential for removing toxins.

Cirrhosis is caused by alcohol abuse, drug use and a couple of dozen other causes, including obesity and some inherited diseases.

For a year, a couple of different treatments helped Hartzell. Then he went to the Clinic for an evaluation. Doctors there decided to put him on the transplant waiting list.

A Clinic social worker in the liver-transplant department broached the idea of a living donor to Hartzell and his wife, Jane.

"We only have the one son," she said. The couple's response at the time? "Oh, no. We're not interested in that," she said.

But Hartzell's condition wasn't getting any better.

"I kind of realized that, after being on the list for a while, there weren't enough livers to go around," Hartzell said. His score in the Model for End-Stage Liver Disease system -- used to prioritize people on the waiting list -- wasn't accurately reflecting how sick he really was. Because his score was on the lower end, he wasn't moving up on the list.

"I didn't get really bad until the last year, and then I went down fast," he said, recounting being in and out of the hospital for the better part of a year. "If I didn't get a liver soon, I wasn't going to get one."

The last thing the Hartzells wanted to do, they said, was to put their son, a pharmacist, in harm's way.

"We went back and forth and finally came to the conclusion that David was probably his dad's only hope," said Jane Hartzell.

It took two weeks for Roger to muster up the will to ask David to consider being a donor.

"It is a major, major operation and something could go wrong," he said. "I wasn't really scared for myself. I was more concerned about David."

After listening to his father "hee-haw" around the question during a weekend visit last July, David said he didn't hesitate to say yes.

After tests to establish that father and son were the same blood type, he began the weeks-long process of a medical evaluation, and discussions with the surgeons and other Clinic staff.

"Understanding [the risk] was my biggest question at that point," said David, who exchanged emails and phone calls and spoke face-to-face with Clinic staff about the risks and potential difficulties.

With his questions answered, the surgery went forward.

Drs. Charles Miller, Federico Aucejo and Cristiano Quintini removed the right lobe (the larger of the liver's two lobes) of David's liver for transplant into his father.

David stayed in the hospital for one week. The following week, Roger was cleared to go home.

Both said they are recuperating well, albeit slowly.

Two months after surgery (the costs of both covered by Roger's insurance), David started gradually returning to work. He is exercising again, although nowhere near at his pre-surgery levels.

Roger no longer has to use a wheelchair or a walker, and he no longer has to take some of the medicine to deal with the effects of hepatic encephalopathy. That condition, which can occur when the liver is unable to remove toxins in the blood, affects brain function and causes confusion.

That has nearly disappeared.

On Monday, the Hartzells met for lunch before their follow-up appointments at the Clinic.

Father and son each received good reports from their physicians. Roger will return to the Clinic in July. And although David will have his blood tested every three months, his next visit won't be until January.

Before the Hartzells went home, they made one last stop together at the Clinic. They visited a man who, a few weeks after Roger's surgery, also underwent a transplant with a liver from his son.

Source

Capture

04/23/2012 | 02:05am

  • Primary endpoint (efficacy at week-12) met
  • Both faster effect on viral load decrease and significant improvement of viral response over time (week-24) in TG4040 pre-vaccination arm
  • Late-breaker oral presentation at EASL in Barcelona

Regulatory News:

Transgene S.A. (Paris:TNG) (Euronext Paris : FR0005175080) announces today the presentation, during the EASL (European Association for the Study of Liver) congress in Barcelona, Spain, of follow up interim data showing both a more rapid response as well as an improved long term effect on viral load decrease in a combination of TG4040 with PEG-IFN? (pegylated interferon alpha) and ribavirin (the current standard of care) in patients chronically infected with genotype 1 hepatitis C virus.

These data were observed in a randomized phase 2 trial that has enrolled 153 patients (the "HCVac" study). HCVac had three treatment arms: one control arm (Arm A) with the current standard of care alone and two arms (B and C) with a combination of this standard of care and TG4040 delivered in two different administration schedules, including one schedule (Arm C) with pre-vaccination by TG4040 (i.e. TG4040 injected prior to the introduction of PEG-IFN? and ribavirin).

As reported in November 2011 at the AASLD meeting in San Francisco, the primary endpoint of the HCVac study was met in the pre-vaccination arm C with 64% (34/53) evaluable patients having achieved a complete early viral response1 ("cEVR") at week-12 after initiation of treatment with the standard of care compared to 30% (9/30) in the control arm A (p=0.003).

The positive effect of TG4040 pre-vaccination was observed as early as one week after initiation of treatment with the standard of care: the slope of mean viral load decrease was significantly steeper in Arm C (1.4 log10 IU/ml) compared to Arms A and B (respectively 0.9 and 1.0 log10 IU/ml) (p=0.04), meaning a faster viral response in Arm C than in other arms.

When following the viral response at week-24 after the initiation of treatment with the standard of care in the patients evaluable for cEVR (week-12), the responses continue to improve as expected in all arms: 70% in the control Arm A, 67% in the Arm B (initiation of treatment with the standard of care before introduction of TG4040) and 79% (vs. 64% at week-12) in the Arm C.

Preliminary End-of-Treatment Response measurement ("ETR", or viral response measured at the end of 48 weeks of standard of care), is respectively 64% and 56% in Arm A and B. In arm C, 19 out of 19 patients analysed so far are undetectable.

"These data are important for TG4040 as they confirm the efficacy profile of our therapeutic vaccine. As far as we know, they are unheard of for an immunotherapy in HCV and this is one of the reasons why we were invited for a late breaker oral presentation in such a prestigious event" said Philippe Archinard, Chairman and CEO of Transgene. He added: "The benefit seen at week-12 in the pre-vaccination arm is further confirmed at week-24 and the preliminary data of ETR in this arm are also very encouraging".

Data were presented on Saturday April, 21, at the annual meeting of the European Association for the Study of Liver (EASL) in Barcelona, by Pr. Heiner Wedemeyer, MD, of the Department of Gastroenterology, Hepatology and Endocrinology at Hannover Medical School (Germany) and principal investigator of the HCVac study.

Pr. Wedemeyer said: "The data accumulated so far in the HCVac study illustrate the importance of immunity in the treatment of chronic hepatitis C". He added: "The assessment of TG4040 in a combination with directly acting agents (DAA) should be the next development step".

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:

Phase 1

Phase 1 clinical results in 39 treatment naïve genotype 1 HCV patients showed that the product is safe and well tolerated at all dose levels tested. Immunological analyses on 15 treatment naïve patients were encouraging and supported the expected mechanism of action of TG4040 which aims at inducing an effective HCV-specific T cell based immune response, able to control viral replication. Phase 1 data were published in the journal Gastroenterology and reported in Nature Reviews in 2011.

Phase 2

153 patients in the 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) or one of the two experimental arms (Arms B and C). In the Arm B, the TG4040 dosage was administered 6 times and the standard of care was given 4 weeks prior to the initiation of TG4040. In the Arm C, the TG4040 dosage was administered 13 times and the standard of care was introduced 12 weeks after the initiation of treatment with TG4040. The HCVac study is investigating the efficacy and safety of two different schedules of administration of TG4040 administered in subcutaneous injections at the dose of 107 pfu in combination with Peg-IFN and RBV.

About SAEs:

The three cases of severe haematological adverse events, one aplastic anemia and two cases of thrombocytopenia, reported in October 2011, all recovered within 1 to 4 months. A fourth case corresponding to a thrombocytopenia was recorded recently. Of interest, the three cases of thrombocytopenia share all a same class 2 Human Leukocyte Antigen ("HLA") allele. This association is statistically significant and, as these HLA types could be excluded a priori in a new clinical trial, this will be taken into account in future developments of the therapeutic vaccine, should it be combined with standard of care including PEG-IFN?. These adverse events should also have no impact in future developments without PEG-IFN?.

About chronic hepatitis C:

Hepatitis C currently represents a major public health concern. The population chronically infected with HCV in the world is estimated at 170 to 200 million and hepatitis-C-related deaths at approximately 470,000 annually. Peak of prevalence of HCV-related diseases is expected to occur in 2025-2030 in developed countries.

HCV infection leads to liver diseases such as fibrosis, cirrhosis and liver carcinoma, which are the prime indications for liver transplants. The commonly used treatment regimen for patients infected with the HCV genotype 1 (a combination of Pegylated Interferon ? and Ribavirin) is lengthy, often poorly tolerated and effective in only approximately 50% of patients completing therapy. In addition, a substantial number of patients never receive therapy. Therefore, there is a strong medical need for new alternative approaches, including combination therapies.

About Transgene:

Transgene, a member of the Institut Mérieux 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 four compounds in phase 2 clinical development: TG4010 and JX594/TG6006 having already completed initial phase 2 trials, TG4001 and TG4040. 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, Inc. to develop and market JX594/TG6006, an oncolytic virus. Transgene has bio-manufacturing capacities for viral-based products. Additional information about Transgene is available at transgene.fr.

Disclaimer:

This press release contains certain forward-looking statements. Although the company believes its expectations are based on reasonable assumptions, these forward-looking statements are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those anticipated. In particular, the Company's ability to commercialize its first product depends on the continuing success of clinical studies, ongoing financing for further product developments and marketing launch, a positive response from the medical community regarding the product's costs and effectiveness. For a discussion of risks and uncertainties which could cause the company's actual results, financial condition, performance or achievements to differ from those contained in the forward-looking statements, please refer to the Risk Factors ("Facteurs de Risque") section of the Document de Reference prospectus, which is available on the AMF website (http://www.amf-france.org) or on Transgene's website (www.transgene.fr). This press release and the information contained herein do not constitute an offer to sell or a solicitation of an offer to buy or subscribe to shares in Transgene in any country.

1 Limit of detection for the HCV RNA quantification test: 10IU/ml.

Transgene
Philippe Archinard, CEO
Phone: +33 (0)3 88 27 91 22
Stéphane Boissel, Executive Vice President & CFO
Phone: +33 (0)3 88 27 91 02
Elisabetta Castelli, Director IR
Phone: +33 (0)1 44 08 55 05
or
MC Services
Raimund Gabriel
Phone: +49 89 210 228 30
Shaun Brown
Phone: +44 207 148 5998

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Virtual slides reveal disease in 3D

virtualslide

April 23, 2012 in Medical research

(Medical Xpress) -- Computing experts and medical researchers at the University of Leeds have developed a fast, easy-to-use way of studying tissue samples in 3D using ‘virtual’ microscope slides.

The novel digital scanning system produces high-resolution, multicoloured images that can be rotated and examined from any angle.

The new approach is revealing more information about disease processes - information that could be used in future to develop new therapies or explain why conventional treatments are not working. Such 3D views of tissue samples may also eventually play a role in clinical practice, as medical imaging technology provides even higher resolution images of tissue.

Digital 3D reconstruction of tissue has many uses in biological and medical research. Viewing tissue in 3D allows researchers to study its shape in ways that would not be possible with conventional methods. For example, a biologist may want to study the structure of developing organs, a cancer specialist may study the branching of blood vessels supplying a tumour, or a liver specialist may need to understand how this vital organ reacts to damage caused by hepatitis C. All of these require an understanding of the shape of the tissue in three dimensions.

At the moment, hospital pathologists and medical researchers cut tissue samples into ultra-thin slices and examine these by hand, one-by-one, on a microscope. This is a fairly labour-intensive process - a single slide can contain several hundred thousand cells - and the number of slices examined will be limited by the time available. To do a true 3D analysis, users would need to look at 100s of different 2D sections - something that would be prohibitively expensive by hand.

In contrast, the system developed at the University of Leeds requires almost no extra manual input once the tissue has been cut and mounted onto glass slides. An automated system turns batches of the slides into high-resolution digital images, which are then aligned using image registration software. Users can then study these virtual blocks of tissue in 3D and zoom in on particular areas of interest.

The researchers have now tested the system on eight different types of tissue, using more than 13000 virtual slides to create around 400 separate 3D volumes. The system and selected case studies, including examples of liver disease, cancer and embryology, are described in the May issue of the American Journal of Pathology.

"Up until now, the use of 3D imaging technology to study disease has been limited because of low resolution, and the time and difficulty associated with acquiring large numbers of images with a microscope," said lead investigator Dr. Darren Treanor, pathologist at the University of Leeds and the Leeds Teaching Hospitals NHS Trust. "Our virtual system means that users can look at the shape and structure of cells and the 'micro-architecture' of blood vessels and tumours on large tissue samples. This can all be done without input from computing specialists."

"Having a 3D view can often make a real difference," said Dr Derek Magee, from the University of Leeds' School of Computing who developed the software behind the system. "For instance, if you want to understand how a system of blood vessels supplying a tumour connects up, you really need to see that in 3D, not as a series of separate 2D sections."

The work was funded by the National Cancer Research Institute informatics initiative, Leeds Teaching Hospital Trust Research and Development, National Institute for Health Research, West Yorkshire Comprehensive Local Research Network, and UK Department of Health.

More information: "Towards Routine Use of 3D Histopathology As a Research Tool," by N. Roberts, et al. (DOI: http://dx.doi.org/ … .2012.01.033) will appear in the American Journal of Pathology, Volume 180, Issue 5 (May 2012).

Provided by University of Leeds (news : web)

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PRESS RELEASE

April 23, 2012, 10:00 a.m. EDT

Designation could open pathway to expedited approval of platform protein delivery technology and additional market exclusivity

MISGAV, Israel & SAN FRANCISCO, Apr 23, 2012 (BUSINESS WIRE) -- Medgenics, Inc., the developer of a novel technology for the sustained production and delivery of therapeutic proteins in patients using their own tissue, today announced that it has filed for Orphan Drug Designation with the U.S. Food and Drug Administration (FDA) for INFRADURE(TM) for the treatment of hepatitis D. INFRADURE is based on Medgenics' proprietary tissue-based Biopump(TM) platform technology, which uses the patient's own tissue to continuously produce and deliver therapeutic proteins, such as interferon-alpha for use in the treatment of hepatitis.

Orphan Drug Designation carries multiple benefits, including the availability of grant money, certain tax credits and seven years of market exclusivity, as well as the possibility of an expedited regulatory process.

This application for Orphan Drug Designation follows Medgenics' recent submission of an Investigational New Drug (IND) application to the FDA for a Phase IIb anemia trial in dialysis patients using EPODURE(TM), a different implementation of the same Biopump platform that produces erythropoietin (EPO).

Marlene Haffner, M.D. MPH, former Director of Orphan Products Development at the FDA, and regulatory advisor to Medgenics said, "INFRADURE's application for the treatment of hepatitis D appears to meet the key criteria required for Orphan Drug Designation by the FDA, as the number of U.S. patients with this disease is estimated to be considerably fewer than 200,000. Furthermore, preclinical data support that INFRADURE has a reasonable rationale for treatment of the disease based on its potential ability to continuously delivery interferon alpha, the current standard of care for hepatitis D that is administered by years of repeat injections. Should Orphan Drug Designation be granted, the regulatory approval route for INFRADURE for the treatment of hepatitis D could be significantly expedited."

This Orphan Drug Designation filing marks the first application for Medgenics' Biopump technology seeking an expedited regulatory pathway in the U.S. Obtaining Orphan Drug Designation could potentially allow for substantially smaller pivotal clinical trials, as compared to a more wide-spread disease. This could lead to more immediate access of the treatment to a patient population in need. Medgenics expects to receive the FDA's initial response to the filing before the end of this quarter, and believes Orphan Designation could be confirmed during the third quarter.

Bruce Bacon, M.D., past President of the American Association for the Study of Liver Disease and a recognized global expert in hepatitis who serves on Medgenics' Strategic Advisory Board, commented, "The current treatment for hepatitis D requires years of weekly injections of interferon alpha, which leads to patient discomfort and substantial compliance challenges. Oral antiviral treatments have proven to be ineffective. INFRADURE is intended to be implanted infrequently, with a single administration potentially replacing many months of weekly injections. This could offer a safe and efficacious treatment that could greatly improve patient compliance. Medgenics' treatment is potentially a game changer not only as a treatment for hepatitis D, but also as a key element in the treatment of various other forms of hepatitis worldwide."

"Our application for Orphan Drug Designation for hepatitis D demonstrates Medgenics' commitment to the treatment of hepatitis. Obtaining Orphan Drug Designation could be the most rapid route for us to bring our Biopump technology to the U.S.," stated Andrew L. Pearlman, Ph.D., President and Chief Executive Officer of Medgenics. "We recently submitted an IND application with the FDA for a Phase IIb anemia trial for EPODURE, a version of the Biopump which produces a different protein, EPO, and have received approval in Israel to commence a Phase IIa trial for that same indication. We are very encouraged with the momentum we are building in 2012 as these important clinical advancements reflect the progress that various applications of our platform technology are making through regulatory approval processes as we continue to build shareholder value."

"We are eager to pursue this niche opportunity in hepatitis D, which would use a similar INFRADURE approach to that we will employ in treating hepatitis C in a Phase I/II study in Israel that is scheduled to commence in the third quarter of 2012 pending final regulatory approval. Receiving Orphan Drug Designation for our INFRADURE Biopump in the treatment of hepatitis D could lead not only to an expedited approval route based on clinical studies of moderate size for this specific rare indication, but could also represent a significant advancement of our entire portfolio of treatments. Such an approval may serve to pave the way for a more rapid pace at which our platform protein delivery technology can move through the FDA approval process for other multibillion-dollar clinical indications," added Dr. Pearlman.

About Hepatitis D

According to the U.S. Centers for Disease Control and Prevention, hepatitis D, also known as "delta hepatitis," is a serious liver disease caused by infection with the hepatitis D virus (HDV), which is an RNA virus structurally unrelated to the hepatitis A, B or C viruses. Hepatitis D, which can be acute or chronic, is not common in the United States. HDV is an incomplete virus that requires the helper function of the hepatitis B virus (HBV) to replicate and only occurs among people who are infected with HBV. HDV is transmitted through percutaneous or mucosal contact with infectious blood and can be acquired either as a co-infection with HBV or as a super-infection in persons with HBV infection. There is no vaccine for hepatitis D, but it can be prevented in persons who are not already HBV-infected by administrative of the hepatitis B vaccination. Hepatitis D infects about 15 million people worldwide.

About Medgenics

Medgenics is developing and commercializing Biopump(TM), a proprietary tissue-based platform technology for the sustained production and delivery of therapeutic proteins using the patient's own skin biopsy for the treatment of a range of chronic diseases including anemia, hepatitis, and hemophilia, among others. Medgenics believes this approach has multiple benefits compared with current treatments, which include regular and costly injections of therapeutic proteins.

Medgenics has three long-acting protein therapy products in development based on this technology:

-- EPODURE(TM) to produce and deliver erythropoietin for many months from a single administration, has demonstrated elevation and stabilization of hemoglobin levels in anemic patients for six to more than 36 months in a Phase I/II dose-ranging trial, and is about to commence a Phase IIa safety/efficacy trial in dialysis patients in Q2 2012 in Israel. An IND has been filed with the U.S. Food and Drug Administration to initiate a Phase IIb study to evaluate the safety and efficacy of EPODURE in the treatment of anemia in dialysis patients in the U.S.

-- INFRADURE(TM) for sustained production and delivery of interferon-alpha for use in the treatment of hepatitis is awaiting final approval of two Phase I/II trials in Israel in hepatitis C, slated to commence Q3 2012.

-- HEMODURE(TM) for sustained production and delivery of clotting Factor VIII therapy for the sustained prophylactic treatment of hemophilia is now in development.

Medgenics is focused on the development and manufacturing of its innovative Biopumps, aiming to bring them to market via strategic partnerships with major pharmaceutical and/or medical device companies.

In addition to treatments for anemia, hepatitis and hemophilia, Medgenics plans to develop and/or out-license a pipeline of future Biopump products targeting the large and rapidly growing global protein therapy market, which is forecast to reach $132 billion in 2013. Other potential applications for Biopumps include multiple sclerosis, arthritis, pediatric growth hormone deficiency, obesity and diabetes.

Forward-looking Statements

This release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and as that term is defined in the Private Securities Litigation Reform Act of 1995, which include all statements other than statements of historical fact, including (without limitation) those regarding the Company's financial position, its development and business strategy, its product candidates and the plans and objectives of management for future operations. The Company intends that such forward-looking statements be subject to the safe harbors created by such laws. Forward-looking statements are sometimes identified by their use of the terms and phrases such as "estimate," "project," "intend," "forecast," "anticipate," "plan," "planning, "expect," "believe," "will," "will likely," "should," "could," "would," "may" or the negative of such terms and other comparable terminology. All such forward-looking statements are based on current expectations and are subject to risks and uncertainties. Should any of these risks or uncertainties materialize, or should any of the Company's assumptions prove incorrect, actual results may differ materially from those included within these forward-looking statements. Accordingly, no undue reliance should be placed on these forward-looking statements, which speak only as of the date made. The Company expressly disclaims any obligation or undertaking to disseminate any updates or revisions to any forward-looking statements contained herein to reflect any change in the Company's expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based. As a result of these factors, the events described in the forward-looking statements contained in this release may not occur.

SOURCE: Medgenics, Inc.

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You are receiving this message as a subscriber to the FDA hepatitis electronic list serve. The purpose of the list serve is to relay important information about viral hepatitis-related products and issues, including product approvals, significant labeling changes, safety warnings, notices of upcoming public meetings and alerts to proposed regulatory guidances for comment.

Please do not reply to this message.

On April 20, 2012, FDA updated the Victrelis (boceprevir) label to include drug-drug interactions between Victrelis and Norvir (ritonavir) in combination with the HIV protease inhibitors Reyataz (atazanavir), Prezista (darunavir), and Kaletra (lopinavir/ritonavir) The main changes to the label are highlighted below. Other changes were made to the Medication Guide to reflect the new interaction data.

Section 7: Drug Interactions was updated to include information regarding the following drug-drug interactions

Atazanavir/ritonavir: Concomitant administration of boceprevir and atazanavir/ritonavir resulted in reduced steady-state exposures to atazanavir and ritonavir. Coadministration of atazanavir/ritonavir and boceprevir is not recommended.

Darunavir/ritonavir: Concomitant administration of boceprevir and darunavir/ritonavir resulted in reduced steady-state exposures to boceprevir, darunavir and ritonavir. Coadministration of darunavir/ritonavir and boceprevir is not recommended.

Lopinavir/ritonavir Concomitant administration of boceprevir and lopinavir/ritonavir resulted in reduced steady-state exposures to boceprevir, lopinavir and ritonavir. Coadministration of lopinavir/ritonavir and boceprevir is not recommended.

Ritonavir: When boceprevir is administered with ritonavir alone, boceprevir concentrations are decreased.

Section 12: Clinical Pharmacology was updated to include the magnitude of interaction between boceprevir and HIV protease inhibitors.

Victrelis is a protease inhibitor for the treatment of HCV infection and manufactured by Schering Corporation, a subsidiary of Merck & Co

The complete, revised label will be posted soon at Drugs@FDA.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration

If you are interested in receiving information about a broader range of FDA topics, consider subscribing to the FDA Patient Network News, a twice monthly newsletter containing FDA-related information on a variety of topics, including new product approvals, significant labeling changes, safety warnings, notices of upcoming public meetings, proposed regulatory guidances and opportunity to comment, and other information of interest to patients and patient advocates.

Public release date: 22-Apr-2012

Contact: Phyllis Picklesimer
p-pickle@illinois.edu
217-244-2827
University of Illinois College of Agricultural, Consumer and Environmental Sciences

URBANA – University of Illinois scientists report that soy protein may significantly reduce fat accumulation and triglycerides in the livers of obese persons. And they've discovered why it happens: soy restores partial function of that organ's key signaling pathway.

"Almost a third of American adults have fatty liver disease, many of them without symptoms. Obesity is a key risk factor for this condition, which can lead to liver failure," said Hong Chen, a U of I assistant professor of food science and human nutrition.

Fat is metabolized in the liver, and in obese persons, the transport of fat to adipose tissue can slow down to the point that the liver becomes a dumping ground for excess fat, she said.

"When fat accumulates in an organ that's not supposed to store fat—like the liver, that organ's vital function can be dangerously compromised," she noted.

Adding soy protein, in such sources as tofu and soy yogurt, appears to alleviate some of the stress on fatty livers, she said.

Chen's study compared fat accumulation in the livers of lean and obese rats, which were assigned to either a diet containing casein, a milk-based protein, or a diet containing soy protein isolate, for 17 weeks after weaning. The researchers found that diet had no effect on the liver profiles of lean animals.

But obese rats fed soy showed a 20 percent reduction in triglycerides and overall fat accumulation in the liver, leading Chen to believe that soy protein could be used to alleviate the symptoms of fatty liver disease.

Further, the scientists discovered that soy protein isolate partially restored the Wnt/β-catenin signaling pathway, a crucial player in fat metabolism.

"In many obese persons, there's a sort of traffic problem, and when more fat can make its way out of the liver, there is less pressure on that organ," she said.

The scientists verified the involvement of this pathway by doing in vitro cell culture studies.

Graduate student Dan Zhou found the results especially interesting because of their practical implications. "It's exciting to think that adding soy protein to their diets might help people who have fatty liver disease," she said.

###

The research will be presented at April's Experimental Biology meeting. Co-authors are Dan Zhou and Huan Wang of the U of I and Jeremy Davis and William Banz of Southern Illinois University. The study was funded by the Illinois Soybean Association and Solae, Inc.

Source

ACH

April 23, 2012

NEW HAVEN, Conn., April 23, 2012 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today provided clarification with respect to end of treatment (EOT) data from segment 2 of its Phase 2a trial of ACH-1625 that was presented during the 47th Annual Meeting of the European Association for the Study of the Liver (EASL) International Liver Congress 2012 in Barcelona, Spain on April 21, 2012.

In this study, 58 patients were randomized to receive ACH-1625 at a once daily dose of 200 mg, 400 mg, or 800 mg in combination with pegylated interferon and ribavirin (P/R) for twelve weeks. At of the time of the poster presentation, a total of 22 patients had completed 12 weeks of ACH-1625 plus P/R followed by 12 weeks of P/R as per response guided treatment (RGT.) All (22/22, or 100%) patients had undetectable levels of HCV RNA at the end of the 24 weeks of treatment.

EOT was defined in the EASL poster presentation as any patient who returned for an EOT visit, which also included those patients who withdrew from the study prior to week 12. The additional EOT data is defined as patients who achieved extended rapid virological response (eRVR) and received a total of 24 weeks of therapy consisting of 12 week of ACH-1625 plus P/R followed by 12 weeks of P/R alone.

The rapid virological response (RVR) at week 4, cEVR at week 12 and EOT results for all patients returning for an EOT visit (30 patients) presented in the poster, as well as detailed results for patients who received a total of 24 weeks of therapy consisting of 12 weeks of ACH-1625 plus P/R followed by 12 weeks of P/R alone, are provided in the table below.

 

ACH-1625
Segment 2: 12-week treatment
duration assessments
200 mg
n=19
400 mg
n=20
800 mg
n=19
RVR (HCV RNA < 25 IU/mL week 4), % (n) 79% (15/19) 89% (16/18) ** 90% (17/19)
cEVR (undetectable week 12), % (n) 100% (18/18) * 94% (15/16) ** 100% (19/19)
EOT Visit (including patients who withdrew) (undetectable) *** % (n) 86% (6/7) 69% (9/13) 100% (10/10)
Reasons for discontinuation include: *200 mg 1 patient withdrew for unrelated AEs at Week 5. **400 mg 1 patient withdrew consent at Week 9, 1 patient moved at Week 2, each were undetectable at the time of withdrawal; 2 patients withdrew for unrelated AEs, one before Week 4 and one before Week 12. ***EOT denominator includes only patients who returned for their end of treatment visit.
Patients who achieved eRVR and received 12 weeks of ACH-1625 and P/R followed by 12 weeks of P/R 200 mg 400 mg 800 mg
Undetectable, % (n) 100% (5/5) 100% (7/7) † 100% (10/10) †
† Two patients in both the 400 mg and 800 mg dose groups had week 4 RVR (HCV RNA < 25) with remaining patients below lower limit of detection.

Michael Kishbauch, President and Chief Executive Officer, commented, "We are providing these results as we recognized that some of the data was not clear at our poster session at EASL. We remain both happy and encouraged with the continued potency of ACH-1625, including the 100% response for all patients who completed a full 24 week regimen, and we hope that this clarification provides additional transparency with respect to the ACH-1625 data."

About ACH-1625

ACH-1625 is a Phase 2 pan-genotypic HCV protease inhibitor designed and synthesized based on crystal structures of enzyme/inhibitor complex. ACH-1625 is an open chain, non-covalent, reversible inhibitor of NS3 protease. In preclinical studies, ACH-1625 demonstrated high potency, unique pharmacokinetic properties and an excellent safety profile at high drug exposures. ACH-1625 has demonstrated rapid and extensive partitioning to the liver, as well as high liver/plasma ratios. ACH-1625 has shown low single-digit nanomolar potency that is specific to HCV. It is equipotent against HCV genotypes 1a and 1b at IC50 of approximately 1nM. ACH-1625 has shown clinical antiviral activity against genotypes 1 and 3. Fast Track status was granted to ACH-1625 in 2012 for the treatment of chronic HCV.

About HCV

The hepatitis C virus is the most common cause of viral hepatitis, which is an inflammation of the liver. It is currently estimated that more than 170 million people are infected with HCV worldwide including nearly 4 million people in the United States, more than twice as widespread as HIV. Three-fourths of the HCV patient population is undiagnosed; it is a silent epidemic and a major global health threat. Chronic hepatitis, if left untreated, can lead to permanent liver damage that can result in the development of liver cancer, liver failure or death. Few therapeutic options currently exist for the treatment of HCV infection. The current standard of care is limited by its specificity for certain types of HCV, significant side-effect profile, and injectable route of administration.

About Achillion Pharmaceuticals

Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. Achillion's proven discovery and development teams have advanced multiple product candidates with novel mechanisms of action. Achillion is focused on solutions for the most challenging problems in infectious disease including hepatitis C and resistant bacterial infections. For more information on Achillion Pharmaceuticals, please visit www.achillion.com or call 1-203-624-7000

Forward-Looking Statements

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other important factors that could cause actual results to differ materially from those indicated by such forward-looking statements, including statements with respect to the potency, safety, tolerability, effectiveness and other characteristics of ACH-1625. Among the factors that could cause actual results to differ materially from those indicated by such forward-looking statements are risks relating to, among other things Achillion's ability to: replicate in later clinical trials positive results found in earlier stage clinical trials of ACH-1625 and its other product candidates; advance the development of its drug candidates under the timelines it anticipates in current and future clinical trials; obtain necessary regulatory approvals; obtain patent protection for its drug candidates, and the freedom to operate under third party intellectual property; establish commercial manufacturing arrangements; identify, enter into and maintain collaboration agreements with appropriate third-parties; compete successfully with other companies that are seeking to develop improved therapies for the treatment of HCV; and raise the substantial additional capital needed to achieve its business objectives. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2011 and its subsequent SEC filings.

In addition, any forward-looking statement in this press release represents Achillion's views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. Achillion disclaims any obligation to update any forward-looking statement, except as required by applicable law.

CONTACT:

Company Contact: Glenn Schulman Achillion Pharmaceuticals, Inc. Tel. (203) 752-5510 gschulman@achillion.com

Investors: Mary Kay Fenton Achillion Pharmaceuticals, Inc. Tel. (203) 624-7000 mfenton@achillion.com

Media: Christin Culotta Miller Ogilvy PR

Tel. (212) 880-5264 christin.miller@ogilvy.com

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