JAMA: Milk Thistle has no effect on serum ALT levels in HCV nonresponders...

Posted on 7/18/12 on the JAMA Network. Further evidence that Milk Thistle and Silymarin have no effect on serum ALT levels in patients with HCV. 

Original Contribution | July 18, 2012

Effect of Silymarin (Milk Thistle) on Liver Disease in Patients With Chronic Hepatitis C Unsuccessfully Treated With Interferon Therapy

Michael W. Fried, MD; Victor J. Navarro, MD; Nezam Afdhal, MD; Steven H. Belle, PhD; Abdus S. Wahed, PhD; Roy L. Hawke, PharmD, PhD; Edward Doo, MD; Catherine M. Meyers, MD; K. Rajender Reddy, MD; for the Silymarin in NASH and C Hepatitis (SyNCH) Study Group
JAMA. 2012;308(3):274-282.

Context:  The botanical product silymarin, an extract of milk thistle, is commonly used by patients to treat chronic liver disease, despite scant and conflicting evidence of its efficacy.

Objective:  To determine the effect of silymarin on liver disease activity in patients with chronic hepatitis C virus (HCV) infection unsuccessfully treated with interferon-based therapy.

Design, Setting, and Participants:  Multicenter, double-blind, placebo-controlled trial conducted at 4 medical centers in the United States. Participants included 154 persons with chronic HCV infection and serum alanine aminotransferase (ALT) levels of 65 U/L or greater who were previously unsuccessfully treated with interferon-based therapy. Enrollment began in May 2008 and was completed in May 2010, with the last follow-up visit completed in March 2011.

Intervention:  Participants were randomly assigned to receive 420-mg silymarin, 700-mg silymarin, or matching placebo administered 3 times per day for 24 weeks.

Main Outcome Measures:  The primary outcome measure was serum ALT level of 45 U/L or less (considered within the normal range) or less than 65 U/L, provided this was at least a 50% decline from baseline values. Secondary outcomes included changes in ALT levels, HCV RNA levels, and quality-of-life measures.

Results:  After 24 weeks of treatment, only 2 participants in each treatment group (P ≥ .99) met the primary outcome measure (3.8% [95% CI, 0.5% to 13.2%] for placebo, 4.0% [95% CI, 0.5% to 13.7%] for 420-mg silymarin, and 3.8% [95% CI, 0.5% to 13.2%] for 700-mg silymarin). The mean decline in serum ALT activity at the end of treatment did not differ significantly (P = .75) across the 3 treatment groups (mean decline, −4.3 [95% CI, −17.3 to 8.7] U/L for placebo, −14.4 [95% CI, −41.6 to 12.7] U/L for 420-mg silymarin, −11.3 [95% CI, −27.9 to 5.4] U/L for 700-mg silymarin); there likewise were no significant differences in HCV RNA levels (mean change, 0.07 [95% CI, −0.05 to 0.18] log10 IU/mL for placebo, −0.03 [95% CI, −0.18 to 0.12] log10 IU/mL for 420-mg silymarin, 0.04 [95% CI, −0.08 to 0.16] log10 IU/mL for 700-mg silymarin; P = .54) or quality-of-life measures. The adverse event profile of silymarin was comparable with that of placebo.

Conclusion:  Higher than customary doses of silymarin did not significantly reduce serum ALT levels more than placebo in participants with chronic HCV infection unsuccessfully treated with interferon-based therapy.

Trial Registration  clinicaltrials.gov Identifier: NCT00680342

Okairos AG begins mid-stage trial of preventative vaccine for HCV...

Posted 3/14/12 via Bloomberg.com .  Swiss company Okairos AG begins mid-stage trial looking a what it hopes to be the first preventative vaccine for the Hepatitis C virus. 

Former Merck Unit Works on First Vaccine for Hepatitis C
By Makiko Kitamura - Mar 14, 2012 1:00 AM PT

Okairos AG, a biotechnology business that Merck & Co. (MRK) sold to venture capital funds in 2007, is seeking to produce the first preventive vaccine for hepatitis C, challenging makers of treatments for the disease.

Okairos has begun a mid-stage study, funded by the U.S. National Institutes of Health, of a gene-based vaccine designed to stimulate the body’s immune system to prevent hepatitis C from taking hold, Chief Operating Officer Tom Woiwode said in a phone interview from the company’s Basel, Switzerland, headquarters.

No vaccine exists for hepatitis C, which affects as many as 170 million people globally, putting them at risk of developing liver cancer, according to the World Health Organization. The growing population of patients infected with the virus spurred Gilead Sciences Inc. (GILD)’s decision in November to buy experimental hepatitis C-treatment maker Pharmasset Inc. for $10.8 billion and Bristol-Myers Squibb Co. (BMY)’s acquisition in February of Inhibitex Inc. for $2.5 billion.

“This could change the landscape quite a bit,” said Les Funtleyder, a health-care strategist and portfolio manager at Miller Tabak & Co. in New York. “In theory, if you could vaccinate everyone, you’d need a lot less drug.” Funtleyder said he isn’t aware of any other preventive vaccines in development.
Disease Transmission

Okairos’s vaccine would target those who may be at risk of infection. The disease is most commonly transmitted through contaminated blood transfusions, organ transplants, contaminated syringes and needle-injected drug use, according to the WHO.

Most preventive vaccines stimulate the production of antibodies, molecules produced by the immune system as part of the body’s defenses. Development of Okarios’s vaccine was triggered by studies of patients with early-stage hepatitis C, of whom about 20 percent spontaneously clear the virus and avoid advancing to the chronic phase, Woiwode said.

Researchers have found those patients tend to have a strong response in the blood’s T cells, Woiwode said. Armed with that knowledge, Okairos developed technology that delivers genetic material to stimulate T cells, the white blood cells that help the body fight diseases.

This approach contrasts with most other vaccines, which stimulate an antibody response, Woiwode said.

“We’ve opened up a new path that will allow us to address a number of diseases, hepatitis C being the first one,” he said in the interview yesterday.

Even if a vaccine is approved, medicines are needed to treat patients already infected, Miller Tabak’s Funtleyder said.

Industry Projects
Merck and Vertex Pharmaceuticals Inc. (VRTX) won approval last year for the first new therapies for hepatitis C in almost a decade. Johnson & Johnson (JNJ), a partner in the Vertex drug, is also cooperating with Swedish drugmaker Medivir AB (MVIRB) on a hepatitis treatment. Basel-based Roche Holding AG (ROG) agreed in October to buy Anadys Pharmaceuticals Inc., another maker of experimental medicines for hepatitis C, for about $230 million.

Profectus Biosciences Inc., a Baltimore-based vaccine manufacturer, is also developing a drug that prevents patients with early-stage hepatitis C from advancing to the chronic stage. The company plans clinical trials of the product in 2013.

Investors in Okairos, which is also developing malaria, cancer and flu vaccines, include Boehringer Ingelheim Venture Fund, Life Sciences Partners, Novartis Venture Funds and Versant Ventures. The Swiss company has also received grants from the European Union and the Bill and Melinda Gates Foundation.

The company is in discussions with potential partners for marketing the vaccine, Woiwode said.

“I have no doubt that if this Phase 2 study is successful, there will be no shortage of interest to work with us to bring this to the market globally,” he said.
To contact the reporter on this story: Makiko Kitamura in London at mkitamura1@bloomberg.net

To contact the editor responsible for this story: Phil Serafino at pserafino@bloomberg.net

Committee is split on whether or not to use chimpanzees in US viral drug research...

Acording to an article posted on the Fox News website,guidelines for chimpanzee use in U.S. research are being crafted by committee, however "The committee's 10 members were also split on whether a vaccine intended to prevent or minimize hepatitis C infection would require safety testing on chimpanzees."


First Guidelines for Lab Chimps Drawn Up
By Wynne Parry

For the first time, criteria have been issued on research using our closest relatives in the animal kingdom, chimpanzees.
Guidelines now govern the use of our closest living relatives, chimpanzees, in federally funded U.S. research, and because of them, some biomedical studies are likely to come to an end.

In fact, nearly all research using chimpanzees to develop drugs or answer other questions with medical applications for humans should end, according to a committee charged with establishing the first set of criteria for research on chimpanzees. The committee released its report Thursday (Dec. 15).

Research into genetic or behavioral questions — such as looking for insight into human behavior by studying how chimpanzees help one another out, or searching for the genetic underpinnings of language — are acceptable, or could become so with only minor modifications, according the committee convened by the National Academy of Sciences.

These types of projects are typically less invasive than biomedical research, which could involve, for instance, infecting chimpanzees with a virus.

For example, in behavioral research, chimpanzees — which, like humans, are social — must live with others, and may not be anesthetized by being shot with a dart. However, chimpanzees can be trained to offer their arms to have blood drawn or accept anesthesia so they can be examined, according to the committee.

New principles

The criteria for both types of research are based upon three general guidelines: The knowledge gained by the research must be necessary to advance public health; the research cannot ethically be done on a human being, or is not possible on another animal or in something that is not a living organism; and the chimpanzees used in the research must be given appropriate places to live.

In practice, this means the National Institutes of Health (NIH) will not award any new grants for research until an assessment process is in place, and a project-by-project review will be conducted to determine if ongoing research fits the criteria, said NIH Director Francis Collins, who accepted the committee's recommendations.

"Chimpanzees are our closest relatives in the animal kingdom, providing exceptional insights into human biology, and the need for special consideration and respect," Collins said in a statement on Thursday.

He estimated that about 37 research projects might be affected, and that, of these, about half may not be continued.

These criteria will only apply to research projects that receive some kind of NIH support, including animals used by private groups but housed using federal money, according to committee member Warner Greene, a virologist at the University of California, San Francisco.

The exceptions

Although the committee did not review projects, it did provide two examples of biomedical research that met its criteria to continue, at least temporarily.

Research using chimps to study monoclonal antibodies was given a temporary reprieve to avoid substantially slowing research. Monoclonal antibodies are similar to the regular antibodies your immune system produces, but they are designed to target specific molecules. They are used to treat a variety of conditions, including cancer and autoimmune disorders.

The committee's 10 members were also split on whether a vaccine intended to prevent or minimize hepatitis C infection would require safety testing on chimpanzees.

"I think the committee accurately identified the few biomedical topics for which continuing involvement of chimpanzees is essential," said Joseph Erwin, a primatologist who specializes in the care of captive primates and the neurobiology of aging.

Erwin, along with many others, presented his views to the committee during its deliberations.

"If research is done in humane ways under good conditions with consideration for the animals, I don't see why anyone should be against it," Erwin said. "People who oppose all animal research seem not to be aware that scientific research can be done without harming or hurting animals. In fact, that is the only kind of study I find acceptable."

A future of chimpanzee research?

But Theodora Capaldo, president of the New England Anti-Vivisection Society/Release & Restitution for Chimpanzees, said she believes the new guidelines mean an end to all work with chimpanzees, including those typically considered less invasive, such as for instance, a behavioral study involving an MRI scan.

"If that criteria is scrupulously applied, it is an end to chimpanzee research. We do not believe there are any projects out there that can meet that criteria," Capaldo said.

Even though the committee did leave the door open to future testing on chimpanzees, biomedical research on chimpanzees is on its way out, said Andrew Rowan, chief scientific officer of the Humane Society of the United States.

"Biomedical and research technology has changed dramatically in the last 25 years. What was necessary in 1980 is no longer necessary today, and what is necessary today will no longer be necessary in 2020," Rowan said.

The use of cell cultures — when cells are grown without an organism — allows researchers to generate higher volumes of data under more easily controlled conditions and have replaced animals, including chimpanzees, in labs, Rowan said.

"Chimpanzees deserve greater moral consideration than we are currently giving them. It is going to come to an end, the question now is when," Rowan said.