Hepatitis C News; Treatment GT 2 and 3 and Another Tylenol Recall

Shortening of treatment duration in patients with chronic hepatitis C genotype 2 and 3 - impact of ribavirin dose - a randomized multicentre trial

Chronic hepatitis C (CHC) Patients, infected with genotype (GT) 2 or 3 are treated with Peg-IFN and ribavirin (RBV) (800 mg/day) for 24 weeks. Treatment duration can be shortened to 12-16 weeks if a higher dose of RBV (1.000/1.200 mg/day) was used without considerable loss of responsiveness or increased risk of relapse.

Previously we have shown that in patients with CHC, GT 2/3 RBV can be reduced to 400 mg/day if administered for 24 weeks without an increase in relapse rates. Therefore we investigated the efficacy of a reduced RBV dosage of 400 mg/day with shorter treatment duration (16 weeks).

Methods: Treatment naive patients with CHC, GT 2/3 were randomized to receive 180mug peginterferonalpha2a/week in combination with either 800 (group C) or 400 mg/d (group D) for 16 weeks.

The primary endpoint was SVR.

Results: 12 months after the first patient was randomized a inferior outcome of group D as compared to group C was noted, therefore the study was terminated. At study termination 89 patients were enrolled (group C: 31, D: 51).

The SVR rate was statistically different in the two study groups with 51.6% in group C and 28.4% in group D (p=0.038). Patients with low viral load had higher SVR rates (C: 67%, D: 33%) than those with high viral load (C: 33%, D: 21%).

Conclusion: Both treatment duration and the dose of RBV play a major role to optimize outcome of patients with GT3.

If one intends to shorten the treatment weight based RBV dose should be used, if lower RBV doses are used patients should be treated for at least 24 weeks as. A treatment regimen with a reduced RBV dosage and shortened treatment duration is associated with low SVR rates due to high relapse rates.Trial registration: NCT01258101
Author: Andreas MaieronSigrid Metz-GercekThomas-Matthias ScherzerHermann LaferlGabriele FischerMartin BischofMichael GschwantlerPeter Ferenci

Credits/Source: BMC Research Notes 2011, 4:220

NortonPrograms may curb hepatitis C in drug users

By Amy

NEW YORK | Wed Jun 29, 2011 12:01am IST

NEW YORK (Reuters Health) - Programs that give injection drug users clean needles or safer drug substitutes may help cut their odds of contracting the liver infection hepatitis C, a new study suggests.

The hepatitis C virus is passed through contact with infected blood. Health care workers are particularly vulnerable, as are people who get tattoos in unclean environments. But in the U.S., most of the roughly 18,000 new infections each year occur when people who inject opiates, like heroin, share tainted needles or syringes.

Studies have found that clean-needle programs do reduce needle-sharing, and they seem to curb drug users' risk of infection with HIV, the virus that causes AIDS. The same appears true of programs that get addicts into treatment with opiate "substitutes" like methadone, which is taken orally instead of injected.

But there has been little evidence that these programs help cut the spread of hepatitis C.

A problem with the hepatitis C virus is that it's much easier to transmit than HIV. Even a faint amount of blood on a shared needle, for example, might be enough to infect another person.

But the new findings, published in the journal Addiction, suggest that needle and opiate-substitution programs can make a difference in hepatitis C risk, according to senior researcher Matthew Hickman, a professor of public health at the University of Bristol in the UK.

Combining the results from six previous studies of UK programs, Hickman's team found that drug users with the highest "coverage" from clean-needle programs were about half as likely to contract hepatitis C as other users.

Among users who said they got enough clean needles to cover all of their injections, just under 4 percent tested positive for hepatitis C during the studies, which lasted up to a year. That compared with 7 percent of drug users who didn't get clean needles for all their injections.

Similarly, the rate of new hepatitis C infection was 3 percent among drug users who were currently taking an opiate substitute (usually oral methadone), versus 7 percent among those not on treatment.

Drug users participating in both types of programs fared best of all, with a new infection rate of 2 percent.

"The implication is that hepatitis C transmission can be reduced by opiate substitution therapy and needle and syringe programs, especially their combination," Hickman told Reuters Health in an email.

While the study looked only at UK programs, it's likely the results would be similar in other countries, he said.

The study has its limits. It combined the results of several observational studies, where researchers "observed" groups of injection drug users who chose to use or not use the needle and opiate substitution programs.

Leaving the choice to the individual makes it hard to show that the programs are what caused hepatitis C infection rates to go down. There may be other differences between people who used the programs and those who didn't that would explain the results.

The findings are also based on small numbers, Hickman's team points out. The researchers had usable information on 919 program participants across the six study sites, and there were 40 cases of new hepatitis C infection.

Still, Hickman said the study starts to fill a gap in the knowledge of how well injection drug use programs are working.

In the U.S., new cases of hepatitis C infection have fallen sharply since the 1980s, according to Centers for Disease Control and Prevention. In the early 1990s, doctors found a way to detect the virus in blood, which meant they could make sure it wasn't transmitted in blood transfusions.

But chronic hepatitis C infection, the agency says, remains a major public health problem.

Between 75 and 85 percent of people infected with hepatitis C develop chronic infection, which can eventually cause serious liver diseases like cirrhosis (scarring of the liver) and liver cancer. Hepatitis C presently accounts for about a third of the liver transplants done in the U.S. each year.

An estimated 3.2 million Americans have chronic hepatitis C, about half of whom are unaware of it. (The initial infection most often causes no symptoms.)

There are medications for treating chronic hepatitis C, although they are not effective for everyone and have side effects like fatigue, nausea, headache and sleep problems.

According to Hickman, one question for future studies is whether treating chronic hepatitis C in injection drug users helps reduce transmission.

SOURCE: bit.ly/lMvRUW  Addiction, online May 25, 2011.


Health personnel spread hepatitis

LAHORE,PAKISTAN:  29 June 2011 (IRIN) - A year after Muhammad Ahsan’s elder brother, Muhammad Rafiq, 40, died of hepatitis C, the family has learnt that the widow, Amna Bibi, 35, has also contracted the infection.

“We spent over Rs 150,000 [US$1,764] on my brother’s treatment. The doctors prescribed injections and medicines that were really expensive. How are we to find more money for my sister-in-law and what will become of their three young children if she dies?” asks Ahsan who earns Rs 20,000 (US$235) a month as an office telephone operator, and has two children of his own to support.

Hepatitis is a viral infection spread through the transfusion of blood and body fluids, sexual contact and the use of improperly sterilized instruments. According to the World Health Organization, all five types of the hepatitis virus (A, B, C, D and E) exist in Pakistan.

Hepatitis A and E can be spread through faecal (sewage) contamination of food or drinking water, while B, C and D can be spread through transfusion of blood and body fluids, sexual contact and use of contaminated instruments which are not sterilized properly. While hepatitis A and B have an effective vaccine, the other types have no known vaccine for prevention.

A 2008 study on the prevalence of the disease carried out by the Pakistan Medical Research Council (PMRC), found that 12 million out of a population of 165 million were infected by hepatitis B or C. Mortality rates due to liver failure caused by hepatitis C were also among the highest in the world, according to medical researchers who noted that “Pakistan carries one of the world's highest burdens of chronic hepatitis and mortality due to liver failure and hepatocellular carcinomas.”

The lack of access to medical care for people like Ahsan is a factor in this.

Unsafe techniques

But what is especially alarming is the finding that healthcare practitioners themselves are responsible, in many cases, for the spread of the virus due to unsafe techniques. These include the re-use of syringes and needles. According to the PMRC, nearly 15 percent of paramedics are themselves infected by the hepatitis virus, as are 7.3 percent of nurses, 6.8 percent of doctors and 5.2 percent of medical students based at major hospitals.

The improper disposal of hospital waste adds to the risks. “Sharp waste generated at hospitals and similar settings contribute to a minimum of 20 percent of all infections in the country,” PMRC deputy director Waqaruddin Ahmed said.

“The published literature on the modes of transmission of hepatitis B and hepatitis C in Pakistan implicate contaminated needle use in medical care and drug abuse and unsafe blood and blood product transfusion as the major causal factors,” the researchers noted.

Media reports have suggested one in every 10 Pakistanis suffers from hepatitis B or C, and that the failure to implement laws such as the Safe Blood Transfusion Act of 2002 which puts in place rules for the screening of donated blood, has exacerbated the situation.

“One of the problems is the widespread belief among patients that injections are more effective than oral medications. People who come to clinics, such as the one I practice at, frequently demand an injection even when pills are available. This contributes to the spread of diseases such as hepatitis, since needles are quite often re-used at some places,” Aziz Ahmed, a doctor in Lahore, told IRIN.

The theft and re-sale of hospital waste, quite often by hospital staff, makes matters worse.

“There are people in this hospital - lab assistants, nurses, cleaners and others who take away used items, such as IV [intravenous] bags, and re-sell them in the market,” a doctor at a government hospital in Lahore, who asked not to be named, told IRIN. “Who knows what illnesses are spreading because of this?”
[This report does not necessarily reflect the views of the United Nations]
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Pharmaceuticals

June 29, 2011, 9:03 a.m. EDT

Research Report on Vertex Pharmaceuticals Inc. and PharmAthene, Inc. - Gaining in the Bio Pharmaceutical Sector

MACAU, Jun 29, 2011 (MARKETWIRE via COMTEX) -- Today, www.EquityMarketsInc.com announced its research report highlighting Vertex Pharmaceuticals Inc . /quotes/zigman/79675/quotes/nls/vrtx VRTX +4.13% and PharmAthene, Inc. /quotes/zigman/1507997/quotes/nls/pip PIP -6.21% . Full content and research is available at www.EquityMarketsInc.com/research.php .


This sector demonstrates renewed investor interest as new and lucrative therapies come to market. The FDA approved the first new drug in 50 years to treat auto-immune disorder lupus in March 2011, and we expect approval of new treatments for Hepatitis C virus around mid-year. The 2010 health care reform act authorized the FDA, will establish a regulatory pathway for approving "biosimilar" drugs, which in turn will increase production and shorten FDA approval times. Longer term, it is expected that a wider acceptance of biomarker research and genetic-targeted clinical studies to help limit expense. It is viewed that therapeutics for cancer and infectious diseases and autoimmune and inflammatory treatments are primary growth areas.

Equity Markets has reviewed Vertex Pharmaceuticals Inc. which is in the business of discovering, developing and commercializing small molecule drugs for the treatment of diseases. The Company is engaged in phase-I clinical trials and/or nonclinical activities with respect to a range of additional drug candidates, including compounds intended for the treatment of hepatitis C virus (HCV) infection, cystic fibrosis (CF) and influenza. In November 2010, the Company submitted a new drug application (NDA), requesting approval to market telaprevir in the United States for the treatment of patients with chronic HCV infection. The full research report on Vertex Pharmaceuticals Inc . /quotes/zigman/79675/quotes/nls/vrtx VRTX +4.13% is available here: www.EquityMarketsInc.com/researchfile4634.php  .

Equity Markets is covering PharmAthene, Inc. as a biodefense company engaged in the development and commercialization of medical countermeasures against biological and chemical weapons. It has five product candidates in various stages of development: SparVax, recombinant protective antigen (rPA) anthrax vaccine; Valortim, a human monoclonal antibody for the prevention and treatment of anthrax infection; Protexia, a recombinant enzyme (butyrylcholinesterase), which mimics a natural bioscavenger for the prevention or treatment of nerve agent poisoning by organophosphate compounds. The full research report on PharmAthene, Inc. /quotes/zigman/1507997/quotes/nls/pip PIP -6.21% is available here: www.EquityMarketsInc.com/researchfile4891.php  .

About Equity Markets Our mission at Equity Markets is to be the best source of content and research, while educating, enlightening and informing investors. Equity Markets combines street smart analysts and professional market researchers to provide investors with detailed company profiles and market coverage.
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R&D Spending In India Is Projected To Mushroom

By Ed Silverman // June 29th, 2011 // 8:00 am

Last year, the pharmaceutical industry spent about $2 billion on assorted R&D activities in India, but that figure is expected to reach a whopping $25 billion by 2025. The reasons are varied, but can be traced to expanding activities by Indian companies, additional government investment and a growing pool of qualified researchers, according to a new report by the Boston Consulting Group.


The optimistic forecast reflects declining R&D productivity in regions where such work has traditionally been conducted, notably the US and Western Europe. Already, the picture is changing. In 2002, pharma spent $25.3 billion in the US, which accounted for 83 percent of the worldwide total. By 2009, that grew to $35.4 million, but represented 76 percent of the total. There were also percentage declines in Western Europe and Japan.

Stem Cells

The promise of stem cell-based gene therapy
Will depend on novel gene delivery tools

New Rochelle, NY, June 29, 2011—Sophisticated genetic tools and techniques for achieving targeted gene delivery and high gene expression levels in bone marrow will drive the successful application of gene therapy to treat a broad range of diseases. Examples of these cutting-edge methods are presented in a series of five provocative articles in the latest issue of Human Gene Therapy, a peer-reviewed journal published by Mary Ann Liebert, Inc. (http://www.liebertpub.com/ ). The articles are available free online at www.liebertpub.com/hum

Barese and Dunbar highlight the advances in gene marking techniques that are enabling selection and targeting of specific immune cell populations for cell and gene therapy. The success of marking studies will help optimize gene transfer for immunotherapeutics and improve patient survival, conclude the authors in the review article "Contributions of Gene Marking to Cell and Gene Therapies."

Giordano et al. explore the use of PCR and next-generation DNA sequencing methods to identify specific gene products that are associated with successful long-term transfer of therapeutic genes to bone marrow. They report their findings in the research article entitled "Clonal Inventory Screens Uncover Monoclonality Following Serial Transplantation of MGMTP140K-Transduced Stem Cells and Dose-Intense Chemotherapy."

As a model for therapeutic gene delivery to bone marrow and peripheral blood cells to treat lysosomal storage disorders, Walia et al. describe successful gene replacement in a primate model of Farber disease. The study, "Autologous Transplantation of Lentivector/Acid Ceramidase-Transduced Hematopoietic Cells in Nonhuman Primates," reports the ability to replace acid ceramidase (AC) gene activity and reduced ceramide levels in blood cells transduced with the AC gene.

Hunter et al. present a study that compares the use of a human gene promoter with a mouse promoter-enhancer for achieving high levels of gene expression in a dog model of leukocyte adhesion deficiency type 1. "Gene Therapy for Canine Leukocyte Adhesion Deficiency with Lentiviral Vectors Using the Murine Stem Cell Virus and Human Phosphoglycerate Kinase Promoters" describes the study results.

Evidence to support the effective use of chromatin insulators—a class of DNA regulatory elements—to improve the expression and safety of gene transfer vectors is the focus of the Methods Review by David Emery entitled "The Use of Chromatin Insulators to Improve the Expression and Safety of Integrating Gene Transfer Vectors."

"Bone marrow-directed gene therapy was the first model considered in the treatment of genetic diseases and remains one of the most successful models in terms of clinical efficacy," says James M. Wilson, MD, PhD, Editor-in-Chief, and Director of the Gene Therapy Program, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia.

###

Human Gene Therapy, the Official Journal of the European Society of Gene and Cell Therapy, British Society for Gene Therapy, French Society of Cell and Gene Therapy, German Society of Gene Therapy, and five other gene therapy societies is an authoritative peer-reviewed journal published monthly in print and online that presents reports on the transfer and expression of genes in mammals, including humans. Related topics include improvements in vector development, delivery systems, and animal models, particularly in the areas of cancer, heart disease, viral disease, genetic disease, and neurological disease, as well as ethical, legal, and regulatory issues related to the gene transfer in humans. Complete tables of content and a free sample issue may be viewed online at www.liebertpub.com/hum

Mary Ann Liebert, Inc. is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Tissue Engineering, Stem Cells and Development, and Cellular Reprogramming. Its biotechnology trade magazine, Genetic Engineering & Biotechnology News (GEN), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 60 journals, books, and newsmagazines is available at www.liebertpub.com.

Mary Ann Liebert, Inc. 140 Huguenot St., New Rochelle, NY 10801-5215 http://www.liebertpub.com/
Phone: (914) 740-2100 (800) M-LIEBERT Fax: (914) 740-2101

FDA

J&J recalls more Tylenol Extra Strength pills


On Tuesday June 28, 2011, 8:01 pm EDT


FORT WASHINGTON, Pa. (AP) -- Johnson & Johnson on Tuesday announced another Tylenol recall due to a musty moldy odor linked to a trace chemical.

The company's McNeil Consumer Healthcare unit is recalling one product lot of Tylenol Extra Strength Caplets made in February 2009 and distributed in the U.S. The recall totals 60,912 bottles, each of which has 225 caplets.

McNeil said it has received a small number of reports about the pills' odor, which has been linked in past J&J recalls to the presence of trace amounts of "2,4,6-tribromoanisole." TBA is a byproduct of a chemical preservative sometimes used on shipping pallets.

Besides causing an unpleasant odor, TBA has been associated with temporary and non-serious gastrointestinal symptoms.

Since September 2009, New Brunswick, N.J.-based Johnson & Johnson has had about two dozen recalls of prescription and nonprescription medicines, replacement hips, contact lenses and diabetes test strips, including tens of millions of bottles of children's and adult Tylenol and Motrin.

The reasons have ranged from metal and other contaminants, to nauseating odors and packaging issues. Joint replacement systems so painful they required corrective surgery were also recalled, as were contact lenses that irritated eyes, along with potentially contaminated syringes full of the antipsychotic drug Invega.

The high-profile lapses have tugged at J&J's revenue, profit and stock price, as well as its once-stellar reputation. J&J has said that it has inspected more than 100 plants around the world and invested millions to improve the quality of its manufacturing and satisfy federal regulators, who have three of its factories under scrutiny.

The product lot number for the recalled Tylenol Extra Strength product can be found on the side of the bottle label -- it is ABA619 300450444271.

Customers should stop using the product from the lot immediately and contact McNeil at http://www.tylenol.com/  or by calling 1-888-222-6036 for instructions on receiving a refund or product coupon.


FDA-Approved Diabetes Simulator Commercially Available


Released: 6/29/2011 12:05 AM EDT

Source: University of Virginia

Newswise — June 29, 2011 — A computer-based diabetes simulation tool developed by University of Virginia researchers is now commercially available, thanks to a partnership with the Charlottesville-based medical research firm The Epsilon Group. The simulator is the only protocol that has been accepted by the U.S. Food and Drug Administration as an alternative to animal testing of Type 1 diabetes control strategies.

Boris P. Kovatchev and Marc D. Breton of the U.Va. Center for Diabetes Technology developed the simulator in collaboration with Claudio Cobelli and Chiara Dalla Man at the University of Padova, Italy. The U.Va. Patent Foundation granted Epsilon, a division of Medical Automation Systems Inc., an exclusive license to the technology in April.

"It takes a tremendous amount of time and resources to conduct animal testing for clinical trials, often only to find that a treatment doesn't work," said Miette H. Michie, interim executive director and CEO of the U.Va. Patent Foundation. "Through their innovative diabetes simulator, Drs. Kovatchev and Breton and their collaborators have provided an FDA-accepted substitute for animal trials, allowing effective treatments to reach the market – and start impacting patients – much sooner."

The simulator uses a software algorithm to model the human metabolic system. Based on patient data from 300 children, adolescents and adults with Type 1 diabetes, the algorithm uses 26 different parameters to mimic human metabolism at the individual level, through several distinct patient profiles. Within these individual profiles, variables such as diet, exercise behavior and insulin intake can be manipulated to test the accuracy or effectiveness of a new product under varying conditions – or to compare it to existing products.

According to the researchers, this technology is an improvement over other simulators, which provide only average or group-level results.

"This simulator allows 'in silico' pre-clinical experiments to be conducted at the level of an individual, revealing inter-personal differences due to treatment," said Kovatchev, director of the diabetes technology center at U.Va. and an internationally renowned diabetes technology scientist.

Kovatchev and Breton are researchers in the U.Va. School of Medicine's Department of Psychiatry and Neurobehavioral Sciences. Kovatchev holds a joint appointment in the School of Engineering and Applied Science's Department of Systems and Information Engineering and was named U.Va. Patent Foundation's 2011 Edlich-Henderson Inventor of the Year for the development of novel computational methods that have advanced the state of diabetes research.

Approximately 60 academic and industrial sites are already using a test version of the simulator for research purposes.

Kurt Wassenaar, Epsilon CEO, said that computational modeling can help improve and accelerate new products for diabetes care. "We are very enthusiastic about the opportunity to build and provide a robust commercial version of the model technology to the diabetes research and disease management community," he said.

The simulator project has been funded by the Juvenile Diabetes Research Foundation and the National Institute of Diabetes and Digestive and Kidney Diseases. A patent on the simulator is pending.