July 11, 2010

Individualisation of antiviral therapy for chronic hepatitis C.

J Gastroenterol Hepatol. 2010 Jul;25(7):1206-16.

Teoh NC, Farrell GC, Chan HL.

Gastroenterology and Hepatology Unit, Australian National University Medical School, Canberra Hospital, Garran, Australian Capital Territory, Australia. narci.teoh@anu.edu.au

Abstract

The combination of pegylated-interferon (PEG-IFN)/ribavirin is currently the standard of care antiviral treatment for chronic hepatitis C (CHC), but optimal results require an individual approach. Key issues are to deliver doses that confer optimal antiviral efficacy against hepatitis C virus (HCV) for a time sufficient to minimise relapse. Viral monitoring during therapy guides the subsequent treatment course, particularly HCV RNA results at 4 weeks (rapid viral response [RVR]) and 12 weeks (complete early viral response [cEVR]). There is strong evidence that for most patients with genotypes 2 or 3 HCV infection, RVR allows truncation of treatment to 16 weeks, provided ribavirin dose is weight-based. However, those patients with cirrhosis, insulin resistance/diabetes or older than 50 years need 6-12 months treatment. For "difficult-to-treat" CHC (genotypes 1 and 4), RVR is infrequent (approximately 15% in European studies), but allows treatment to be truncated from 48 to 24 weeks. Without RVR, there is some evidence that longer treatment (72 weeks) improves sustained viral response (SVR). However, "induction dosing" first 12 weeks of PEG-IFN clearly does not improve SVR. To prevent dose reductions and complete therapy, it is critical to detect and treat depression and other disabling side-effects, including judicious use of growth factors for severe anemia or neutropenia and possibly, thrombocytopenia. Another potentially important aspect may be attempts to counter central obesity and insulin resistance, which confer suboptimal antiviral response with any HCV genotype. Treatment partnerships with specialist nurses, psychological therapists and other healthcare workers are also essential for optimal individual management of patients with CHC.

PMID: 20594246 [PubMed - in process]

Source
The Journal of Infectious Diseases 2010;202:000–000
© 2010 by the Infectious Diseases Society of America.
All rights reserved.
0022-1899/2010/20204-00XX$15.00
DOI: 10.1086/654882

MAJOR ARTICLE

Edward L. Murphy 1,2; Junyong Fang 3; Yongling Tu 3; Ritchard Cable 4; Christopher D. Hillyer 5,6; Ronald Sacher 7; Darrell Triulzi 8; Jerome L. Gottschall 9; and Michael P. Busch 2

1 University of California, San Francisco, and 2 Blood Systems Research Institute, San Francisco, California; 3 Westat, Rockville, Maryland; 4 American Red Cross Blood Services, New England Division, Farmington, Connecticut; 5 Emory University and 6 American Red Cross Blood Services, Southern Region, Atlanta, Georgia; 7 Hoxworth Blood Center, Cincinnati, Ohio; 8 Institute for Transfusion Medicine, Pittsburgh, Pennsylvania; and 9 Blood Center of Wisconsin, Milwaukee Wisconsin

Background.
During the period 1992–1993, the prevalence of hepatitis C virus (HCV) antibodies (anti‐HCV) among US blood donors was 0.36%, but contemporary data on the prevalence of antibody to HCV and the prevalence of HCV RNA are lacking.

Methods.
We performed a large, cross‐sectional study of blood donors at 6 US blood centers during 2006–2007. Anti‐HCV was measured with enzyme‐linked immunosorbent assay followed by immunoblot, and HCV RNA was measured with nucleic acid testing. Adjusted odds ratios (aORs) were derived using multivariable logistic regression.

Results.
959,281 donors, 695 had anti‐HCV detected (prevalence, 0.072%). Of those with anti‐HCV, 516 (74%) had test results positive for HCV RNA, and 179 (26%) had test results that were negative for HCV RNA. Compared with the prevalence during the period 1992–1993, prevalence during 2006–2007 was lower and peaked in older age groups. Anti‐HCV was associated with a body mass index (BMI) >30 (aOR, 0.6; 95% confidence interval [CI], 0.5–0.8), and among women, it was associated with higher gravidity (aOR for 5 vs 0 pregnancies, 3.2; 95% CI, 1.9–5.4). HCV RNA negative status was associated with black race (aOR, 0.4; 95% CI, 0.2–0.7), having more than a high school education (aOR, 1.6; 95% CI, 1.1–2.4), and BMI >30 (aOR, 2.4; 95% CI, 1.4–3.9).

Conclusions.
Decreasing HCV prevalence is most likely attributable to culling of seropositive donors and a birth cohort effect. We found new associations between anti‐HCV prevalence and gravidity and obesity. Recently discovered genetic factors may underlie differences in HCV RNA clearance in black donors.

Received 3 December 2009; accepted 12 March 2010; electronically published 9 July 2010.

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Man donates part of liver to dad while awaiting second child


Carmela Fragomeni
The Hamilton Spectator
(July 10, 2010 )

Fatherhood has extraordinary meaning in Burlington's Boughan family.

Son Peter, 30, recently donated 70 per cent of his liver to his father Robin, 63. It saved Robin's life.

In a week or two, Peter will become a father again when his wife Jen gives birth to their second child.

"My dad's health was going down quite rapidly and I love my dad," said Peter about undergoing the transplant despite having 15-month-old daughter Leah to care for and another baby on the way.

"I don't think I could live with myself happily if I didn't do anything and I could have made a difference."

Peter, a supply teacher, was the third person tested for suitability. The first, Robin's brother who 21 years ago donated bone marrow to help Robin to fight leukemia, turned out to be a no-go. Same for Robin's daughter.

In all, seven family members, friends and fellow churchgoers at Hamilton's Philpott Memorial had offered part of their liver. Many more in Hamilton, Burlington, the U.S. and Africa offered their prayers after hearing about Robin through friends, family or the church network.

"This is the answer to the prayers of many people," Robin said. "It became a wonder to me to hear from someone that so and so was praying for me.

"The whole thing has an emotion for me that is very gripping. I get very emotional these people would do this for me ... and to think my son would do what he did for me ..."

Robin, a retired teacher and former art department head at Sherwood Secondary in Hamilton, was diagnosed in March 2009 with cirrhosis.

"He doesn't even drink," said his wife Sandy.

Doctors who did the transplant at Toronto General blamed non-alcoholic fatty liver disease. His Hamilton doctors thought it was something else. Whatever the cause, the result was the same: he needed a new liver or he would die.

Robin was put on a list for a transplant this November when his symptoms worsened. He moved up when his kidneys started to fail and water retention bloated him severely. By March 31, doctors bumped another patient out of surgery to make room for Robin's operation because he was too sick to wait anymore.

"It was very stressful," Sandy said. "Because you have both of them in surgery at the same time, on the same day, and they are long surgeries."

Peter's surgery was seven hours, Robin's 13.

"Even though they tell you Peter's healthy, it's still stressful," Sandy said. "He has a wife who's pregnant and a daughter ..."

Both she and Robin urge people to sign their donor card and make their wishes for organ donation clear to their families, especially when it comes to livers.

Once in, liver transplants have the lowest chance of rejection among transplants and 90 per cent of the removed portion used in the transplant grows back within 12 weeks, doctors told them.

"They are looking for liver donors all the time," Sandy said.

From a statistical point of view, the transplant is relatively risk-free, said Robin. Even 80-year-olds can donate because the liver is an organ that regenerates itself.

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Waiting… for a second chance at life

By Cynthia Nelson

This post was written by Trevor Bougill, an intern at Mayo Clinic’s campus in Florida.

*****
Over the past few weeks, the media has been full of reports about renowned musician Gregg Allman of the Southern Rock group, The Allman Brothers Band, who received a life-saving liver transplant at Mayo Clinic. While I’m not a musician – or for that fact, musically inclined in any capacity – I now share something in common with the rock and roll legend: A second chance at life thanks to an organ donation.

It was March 21, 2009 that I learned I had bile duct cancer, or cholangiocarcinoma, a disease that would ultimately necessitate my being placed on the waiting list for a new liver.

As I read about Allman’s surgery, I thought back to my experiences at Mayo Clinic and the uncertainty surrounding organ transplantation. I know first-hand how excruciatingly difficult it is to give up control and just wait and hope for the call to come that an organ is available. It becomes all you think about.

I was placed on the waiting list in June 2009 and every week – week after week – I tried to ignore the emotional angst and remind myself of the solemn assurance that it would happen when it was supposed to.

It was a Tuesday. December first to be specific, early in the afternoon when the phone rang. It was a dreary day, characteristic of the past nine months I had spent cooped up at the Inn at Mayo, waiting. Torrents of despair washed over my mind. I answered the phone with a reticent, frustrated tone.

“Trevor?” Her voice was measured and fastidious. “We think we have a liver for you…”

How hearing those eight words can change your life. The doubt, uncertainty, and despair eradicated. My life was no longer put on hold anymore. My world that I had shutoff from reality reopened.

I had already packed my bag of necessities in advance: New toothbrush, pajamas, blood pressure cuff, a couple books. I was ready to go.

My mother and I arrived at the ER at 4:30 pm. A tech strapped a medical bracelet imprinted with “liver transplant” on my wrist. We were directed to the third floor of Mayo’s hospital, the transplant unit. The nurses escorted us to room 319, my temporary residence for the next week.

I remember looking in the mirror of the bathroom and seeing the whites of my eyes. There was no yellow tint, no evidence of the jaundice that had plagued me for months earlier. Upon first glance, you could not tell I was sick. Although my cheekbones were a little pronounced, I had tried to maintain a healthy weight. I was fortunate enough to still have a full head of hair – the chemo I’d undergone had not ridden me of that.

I lay on the bed in a slightly upright position. A nurse entered the room and gave us a “soft time” of 11 p.m, an estimate of when the surgery would take place. Seven hours, I thought. But then, at that point, what was another seven hours?

The day wore on and finally, she came back. Midnight. It was definite. The surgery was going to happen.

While waiting for the surgery, I was accompanied by Joey and Maggie Shook. Maggie had received a liver transplant two months earlier and Joey was her consummate caregiver. Another liver transplant recipient, Andy Marks joined us. Throughout the arduous wait, Andy had proven to be a constant source of inspiration. He had suffered from the same cancer I had. Both Maggie and Andy were proof that life would continue after this ordeal.

At 10 pm, a short, dark-haired man with thin spectacles appeared. He was dressed in a long white coat that was almost too big for him. I recognized him immediately; it was Dr. Justin Nguyen, the transplant surgeon who would be performing my surgery. His voice was soft and deliberate; slow. He chose his words carefully. He talked about the procedure and asked us if we had any questions. The sagacious man reassured us that everything was going to be fine.

I heard a helicopter hovering above. It was the same noise that I had heard above my hotel room at night for the past eight months. An organ was arriving. Someone’s life was about the change.

I thought I had prepared myself as best as I could for the moment. Anxiety filled my insides. The kind of anxiety one experiences before a big test, except a million times amplified. Life and death anxiety.

The moment had come. Eight months of waiting had culminated to this moment. As I got into a wheelchair, ready to be wheeled to surgery, it hit. I had always tried to distance myself from what the surgery would be like. I tried to remain stoic. But I broke down. Tears of joy (and fear) filled my face. My conscious shuttered. Andy, who had continued to wait with me, placed a hand of reassurance on my shoulder. My mom, by my side, gripped my hand. I gave it a strong squeeze. It was time.

People were everywhere in the operating room. Nurses, anesthesiologists, assistants, doctors. Enough to start a baseball team. I remember the cold. I was shivering. A nurse placed a blanket over my legs while a clear plastic mask covered my nose and mouth. The anesthesiologist told me to relax, to let sleep come. My mind was blank. The wait was over. I was here, on the table, ready.

I spent eleven days in the hospital recovering from the procedure. I dealt with some complications, a stent had to be inserted in my celiac artery due to insufficient blood flow. There is not much I remember about my stay.

When someone has a transplant, they experience a re-birth. Gregg is a week old and I am close to seven months. We are here because of our donors and their families. They saved our lives. How lucky we are. We are forever grateful for their selfless gift.

Tags: Bile Duct Cancer, Liver Transplant, Gregg Allman, Cholangiocarcinoma, Allman Brothers

This entry was posted on July 11, 2010 at 2:54 pm and is filed under Cancer, Education, Employee Stories, Gastroenterology, Media Stories, Patient Stories, Surgery, Transplant, Uncategorized.

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Published: Sunday, Jul. 11, 2010 - 12:00 am

Liver disease is a huge problem worldwide, and one of the contributors is the epidemic of obesity. Persistent obesity often leads to fat deposits and inflammation in the liver, and unchecked inflammation ultimately produces scarring and even cirrhosis.

Perhaps you've thought of cirrhosis of the liver as a drinker's disease; in fact, obesity is now a common cause of cirrhosis. More than 20 percent of all liver disease in the United States is now attributed to non-alcoholic fatty liver disease, also known as NAFLD.

So how do we treat inflammation in the liver when it's caused by fat? The most obvious answer is to lose weight, but for many people this is difficult. Thus, scientists have looked for ways to reduce inflammation in the liver before scarring sets in.

A recently published study in the New England Journal of Medicine suggests that high-dose vitamin E might be one answer.

In this well-designed, two-year study, researchers randomized 247 non-diabetic adults with NAFLD to receive one of three treatments: pioglitazone (an expensive drug used to reduce insulin resistance); vitamin E, 800 units per day; or a placebo. Liver tissue was examined at the beginning and end of the study to look for changes in inflammation and scarring.

The scientists found that both vitamin E and pioglitazone reduced fatty changes and inflammation in the liver, but vitamin E seemed to work better than pioglitazone, and only vitamin E produced significant improvements in scarring. In fact, 43 percent of the patients getting the vitamin E showed benefit. In addition, those people taking the pioglitazone gained weight during this study.

There are no good treatments for NAFLD other than weight loss; based on this study, some researchers believe that everyone with NAFLD should be treated with vitamin E. Vitamin E in high doses like this is probably safe, though there have been some studies suggesting that it may increase the risk of bleeding.

If you have or are at risk of fatty liver disease, first and foremost, we strongly encourage you to do whatever it takes to eat a healthier diet and lose weight. Reducing your intake of animal food and processed food is a great way to start; the website NutritionMD.org is an excellent source of healthy nutrition information and recipes.

If you are overweight or obese, we encourage you to speak with your doctor about your risk of liver disease, and to see if vitamin E supplementation might be right for you.

Read more

Source
Journal of Viral Hepatitis

Early View (Articles online in advance of print)
Published Online: 22 Jun 2010
© 2010 Blackwell Publishing Ltd

A. Brett Hauber 1 , A. F. Mohamed 1 , C. Beam 2 , J. Medjedovic 3* and J. Mauskopf 1
1 RTI International, RTP, NC ; 2 Human Genome Sciences, Inc., Rockville, MD, USA ; and 3 Novartis Pharma AG, Basel, Switzerland

Correspondence to A. Brett Hauber, RTI International, RTI Health Solutions, 3040 Cornwallis Drive, PO Box 12194, Research Triangle Park, NC 27709-2194, USA. E-mail: abhauber@rti.org

*Worked for Novartis Pharma AG while the study was conducted.

KEYWORDS
adherence • conjoint analysis • discrete choice experiment • hepatitis C virus treatments • patient preference

ABSTRACT
Summary. To estimate patient preferences for attributes of hepatitis C virus (HCV) treatment and patients' assessment of the likely effect of treatment attributes on treatment adherence, HCV patients ≥18 years old completed an online survey that included nine 2-alternative choice questions. Each choice question was defined by the probability of sustained viral response (Efficacy), injection frequency (Frequency), duration of flu-like symptoms after every injection (Flu), injection device (Device), average number of days of work missed each week (Lost Work Days), probability of reversible hair thinning while on treatment (Alopecia) and probability of developing clinical depression while on treatment (Depression). We estimated a mean relative importance weight for each attribute. Patients also answered three rating questions to assess the extent to which treatment attributes might affect adherence. Hundred and fifty patients completed the survey. Efficacy was the most important attribute with a mean relative importance weight of 10 [95% CI: 7.9–12.1]. The remaining attributes were ranked in order of importance as follows: Depression (4.4 [95% CI: 3.6–5.1]), Flu Days (Frequency × Flu) (3.7 [95% CI: 2.2–5.3]), Lost Work Days (2.9 [95% CI: 2.3–3.5]), Alopecia (1.3 [95% CI: 0.7–1.9]) and Device (1.2 [95% CI: 0.4–2.0]). Patients with prior treatment experience were less likely to indicate that treatment attributes would affect adherence. Patients also indicated that increases in the number of flu days would increase the likelihood of nonadherence to treatment. Sustained viral response is the most important treatment attribute to patients but treatment side effects might affect treatment adherence.
Received February 2010; accepted for publication May 2010

DIGITAL OBJECT IDENTIFIER (DOI)
10.1111/j.1365-2893.2010.01343.x About DOI
 
Source
SUMMARY: HIV/HCV coinfected individuals who achieve undetectable hepatitis C virus (HCV) RNA in their blood plasma following successful pegylated interferon plus ribavirin treatment for acute or chronic hepatitis C were found to have no signs of residual HCV genetic material in their peripheral blood immune cells, indicating true eradication or cure, according to a report in the June 1, 2010 issue of AIDS.

By Liz Highleyman

Even with the most successful antiretroviral therapy (ART), HIV only can be suppressed to an undetectable level in the blood and other tissues, while viral genetic material remains in latent reservoir cells including CD4 T-cells. Some past studies have found that this is also the case for HCV, but others have been unable to detect replication-capable virus, suggesting that hepatitis C treatment represents a true "cure."

To shed further light on this issue, Emma Page from the Chelsea and Westminster NHS Foundation Trust in London and colleagues looked at HCV RNA persistence in peripheral blood mononuclear cells (PBMCs) of HIV/HCV coinfected individuals who had cleared HCV from their blood plasma. PBMCs are specific types of immune system blood cells in the peripheral circulation, including lymphocytes, monocytes, and macrophages.

This prospective cross-sectional study included 26 HIV positive individuals who had previously been infected with HCV but currently had undetectable plasma HCV viral load:
  • 6 had spontaneously cleared HCV without treatment;
  • 10 had achieved sustained virological response (SVR) -- or continued undetectable plasma HCV RNA 6 months after completion of treatment -- following 24 weeks of pegylated interferon plus ribavirin for acute hepatitis C;
  • 10 had achieved SVR following standard pegylated interferon plus ribavirin treatment for chronic hepatitis C.
The researchers collected blood samples to test for HCV genetic material in both serum and PBMCs. Intracellular HCV was extracted using the QIAamp RNA Blood MiniKit. Reverse transcriptase PCR was performed using a modified COBAS TaqMan HCV test.

They found that none of the participants showed any evidence of HCV RNA persistence in their either serum or their peripheral blood cells.

"Our findings lend support to the view that clearance of HCV RNA from serum in HIV/HCV coinfection indicates eradication from PBMCs," the study authors concluded. "Thus, absence of serum HCV RNA 6 months after the end of therapy can be used as a marker of treatment success for interferon-based therapies."

However, they added, "the advent of small molecule HCV inhibitors may require us to rethink our definitions of response and cure," referring to direct-acting antiviral agents such as HCV protease and polymerase inhibitors currently in development.

Investigator affiliation: Chelsea and Westminster NHS Foundation Trust, London, UK.

6/25/10

Reference
EE Page, A Cox, A Atkins, and MR Nelson. Clearance of hepatitis C virus RNA from serum in HIV/hepatitis C virus coinfection indicates eradication from peripheral blood mononuclear cells. AIDS 24(9): 1267-1271 (Abstract). June 1, 2010.

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By GENE MARCIAL

Posted 7:30 AM 07/07/10

It seems like the growing ranks of emerging biotechnology companies are always behind the eight ball in building up their financial resources to fund extensive research and clinical studies for novel therapies. The fountain of innovative drugs for Big Pharma, biotechs usually seek the help of financiers, venture capitalists and the like. But biotechs that are well on the road to advanced development of drugs resort to another funding strategy: Striking partnerships with large drugmakers.

One such company is Achillion Pharmaceuticals (ACHN), which had raised some $27 million last year but now needs a partner to advance development of its three products. One of them is a possible next-generation drug to fight chronic hepatitis C virus, an inflammation of the liver that has infected some170 million people worldwide.

"A Partnership or Two"?

"We are in the midst of doing several [Phase 2 clinical trials] for our products, so we have been in advanced talks with several of the major global pharmaceutical companies for almost a year now to forge one or two partnerships," says Michael D. Kishbauch, Achillion's president and CEO. He expects that sooner rather than later "we will sign a partnership or two" to fund the clinical studies and complete development of its hepatitis programs, a potentially multibillion market.

Major pharmaceuticals that are involved in or plan to participate in developing new treatments for hepatitis include Pfizer (PFE), Merck (MRK), Bristol Myers-Squibb (BMY), GlaxoSmith, (GSK) Novartis (NVS), Roche (RHHBY) and Abbott Laboratories (ABT). Kishbauch declines to identify which of the companies he's in discussions with because "our negotiations are in a very advanced and delicate stage right now."

Several of the drugmakers want to partner with Achillion on all three of its products. Those are ACH-1625, a potential next-generation treatment for chronic hepatitis C virus that some analysts expects will be the "best-in-class" treatment; ACH-1095, an "NS4A antagonist" also for fighting the hepatitis virus; and ACHN-2684, a molecule that targets NS3 protease found to be effective against a broad range of natural hepatitis variants.

However, Kishbauch says he would prefer having different partners for each of the drugs to make sure they all get all the attention and support they require. He's negotiating for a guarantee that the partners will advance the products to a level equal to standard-of-care products.

Once-a-Day Dosing

Some analysts believe Achillion's hepatitis drugs would be superior to products now in the market, such as interferon and Vertex Pharmaceutical's (VRTX) Telaprevir, which is being marketed by Johnson & Johnson (JNJ). The demonstrated potency and safety of Achillon's ACH-1625 looks very good," says Jason Kolbert, analyst at National Securities, who rates Achillion's stock, now at $2.20 a share, a buy. It's down from its 52-week high of $3.89 reached on Dec. 16, 2009. "I believe the best is ahead for Achillion because of its strong hepatitis program," says Kolbert.

In the recent IB clinical trials on ACH-1625, safety and tolerability in patients continued to be excellent, notes Kolbert. And the trials also showed "meaningful reductions in the key pharma paradigm for antiviral therapy," he adds. Telaprevir requires twice-a-day dosing, he notes, while ACH-1625 needs only once-daily dosing.

Kolbert says when the Phase 2 clinical trials for ACH-1625 get under way -- and when clinical studies for the two other drugs start next year -- "Achillion's stock will see a sharp rise in valuation."

Edward Nash, senior analyst at Roth Capital Markets, says with the data he has seen on ACH-1625, the drug has a "strong chance of being as potent as, if not more than, Telaprevir." Importantly, he adds, the dosing schedule and better side-effect profile make Achillion a "very attractive partner candidate for the big pharmaceuticals."

Multibillion-Dollar Market

Achillion's clinical performance with ACH-1625, says Nash, should attract investors looking to be involved in the important fight against hepatitis C virus. He rates the stock a buy with a 12-month price target of $12. If that price objective looks mighty high, it isn't when you consider the multibillion dollar hepatitis market and the probability that Achillion will find a partner or two to move its potential winners to market.

The three largest institutional investors in Achillion are Janus Capital Management, which owns a 12.95% stake; Clarus Ventures, with 11.39%; and Wellington Management with 6.12%. Janus and Wellington bought more shares, and none sold stock as of Mar. 31, 2010.

Tagged: biotech, biotech stocks, biotechnology, biotechnology stocks, drugmakers, hepatitis, hepatitis c, pharma, pharmaceutical stocks, pharmaceuticals

See full article from DailyFinance

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Hepatitis C Treatments in Current Clinical Development

Alan Franciscus
Editor-in-Chief

To download pdf version click here

There are many compounds being studied to treat hepatitis C. A number of compounds for these targets are in early “test-tube” development or pre-clinical “animal” development phases. Most of these compounds, however, will never make it to trials in humans (clinical studies). In fact, only one in 1,000 compounds makes it to human testing. Of those drugs that make it to human testing only 1 in 5 will receive FDA marketing approval. Therefore, every effort has been made to focus this list only on treatments that are known to be in current or very near to active clinical development in human subjects.

When a company is ready to proceed to clinical trials, it files an Investigational New Drug Application (IND) with the Food and Drug Administration (FDA). Most clinical trials are designated as phases I, II, or III, and sometimes IV based on the type of questions that the study is seeking to answer.

Study Phases
  • In Phase I clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
  • In Phase II clinical trials, the study drug or treatment is given to a larger group of people (100-300) to evaluate safety, optimal dose, and may include some information on the drug’s effectiveness. Most drugs that enter phase II studies do not progress on to phase III studies. This is because the drug is being tested in more people for a generally longer period of time so lack of effectiveness and a better picture of the effectiveness emerges.
  • In Phase III studies, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
  • In Phase IV studies, the drug is already on the market for a particular indication, but is now being tested to answer questions about sub-populations of the same condition it is approved to treat, or for a different indication, use, or disease.
The testing of new drugs is a long process that typically takes about 12 years from pre-clinical testing to FDA approval and marketing to the general public.

Fast Track Status:
A drug can be granted fast track status by the Food and Drug Administration to help facilitate the development and to expedite the review process of new drugs that have the potential to address an unmet medical need for serious or life-threatening conditions such as hepatitis C.

Orphan Drug Status:
A status given to a certain drug by the Food and Drug Administration to encourage the development of drugs that are necessary, but are too expensive or unprofitable to develop under regular circumstances. Drugs being developed to treat orphan diseases (low prevalence in the population) offer tax reductions and marketing exclusivity for the drug manufacturer (up to 20 years).

For more information about clinical trials for the treatment of hepatitis C go to http://www.clincaltrials.gov/.

STAT-C Combinations

HCV Inhibitors

Drugs ( General)

Interferons

Vaccines in Development

Anti Cancer Drugs

Adjunct Therapies

Clinical trials on Hold

Clinical Trials that Have Been Cancelled

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Disease detection in the palm of your hand

Published: July 9, 2010 at 2:40 PM

ALBUQUERQUE, July 9 (UPI) -- University of New Mexico researchers brought sci-fi technology to the doctor's office by creating a device that can diagnose a number of ills in seconds.

Best of all, researchers said, the hand-held "biosensor" eliminates the need for expensive and time-consuming tests, The Albuquerque Journal reported Friday. And it runs on AA batteries.

Researchers determined biosensor can identify hepatitis B and C, HIV, hantavirus, flu, and other viral and bacterial pathogens, said David Larson, vice president for research at UNM Health Sciences Center and the project's lead researcher.

The biosensor can test blood, saliva, urine or any other water-based compound, Larson said, returning results in a few minutes to as soon as five seconds.

The device's ability to detect blood-borne illness would be a godsend during disasters, such as the Jan. 12 earthquake in Haiti where health officials needed to quickly identify safe blood donors, Larson said.

"In a situation like Haiti, you can't easily test someone's blood for infection, and you can't ship blood units in and out of the area," Larson said.

R&D Magazine Thursday recognized the biosensor as one of the 100 most technologically significant new products of the year, the Journal said.

Source
Harald Farnik, Christian M. Lange, Christoph Sarrazin, Bernd Kronenberger, Stefan Zeuzem, Eva Herrmann

Received 17 February 2010; received in revised form 17 June 2010; accepted 18 June 2010. published online 30 June 2010.

Accepted Manuscript

Abstract

Background & Aims:
Clinical trials have provided conflicting results about whether extended duration of treatment with pegylated interferon-alfa (pegIFN-alfa) and ribavirin (more than 48 weeks) improves rates of sustained virologic response (SVR) in patients infected with hepatitis C virus (HCV) genotype 1 that have a slow virologic response. We performed a meta-analysis to determine the overall impact of extended treatment, compared to standard treatment, on virologic response rates in these patients.

Methods:
We performed a literature search to identify randomized controlled trials (RCT) that included mono-infected, treatment-naive patients infected with HCV genotype 1; data were compared between slow responding patients treated with pegIFN-alfa-2a/b plus ribavirin for 48 weeks and those that received extended treatment (as much as 72 weeks). Endpoints included SVR rates, end-of-treatment response and relapse rates; they were calculated as meta-analysis of data with binary outcome according to the DerSimonian-Laird estimate.

Results:
Six randomized controlled trials assessed the benefits of extended treatment with pegIFN-alfa-2a/b and ribavirin in treatment-naive patients with HCV genotype 1 that were slow responders (n=669). The extended treatment significantly improved SVR rates in slow responders, compared to the standard of care (14.7% increase in overall SVR, 95% confidence interval: 4%–25.5%, P =0.0072). Rates of viral relapse were significantly reduced by extended treatment but end-of-treatment response rates were similar. The frequency of voluntary treatment discontinuation, but not of serious adverse events, was significantly increased by extended therapy.

Conclusions:
Extending the duration of treatment with pegIFN-alfa-2a/b and ribavirin in patients with HCV genotype 1 and a slow response to therapy improves the rate of SVR.

Keywords: antiviral therapy, individualized treatment, treatment duration, EOT

No full text is available. To read the body of this article, please view the PDF online.

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Saturday, July 10, 2010 - 9:45pm

RIVERDALE -- "There's a strong possibility that in two or three months, I won't be here no more."

Bob Leggett, 55, sits in a brown recliner, an oxygen tube running along the floor, his swollen legs propped on the foot rest.

Bob is dying.

He needs a liver transplant. Soon.

He is currently ineligible for Medicaid and Medicare and Bob and his wife, Roma, can't afford the $140,000 they would need as a down payment to begin the process of paying for a transplant themselves.

Bob contracted hepatitis C. They don't know when or where. Their best guess is an infected blood transfusion from an operation more than 15 years ago, but it might have been from one of his amateur tattoos.

Whatever the cause, he began having symptoms and was diagnosed a year-and-a-half ago. Now he has cirrhosis.

"Six months ago, he was a big, burly mean sucker. Look at what it's done to him," Roma said, looking at her husband.

Because of the cirrhosis, Bob's body is retaining fluid. His stomach is distended and his feet are puffy, making it difficult and dangerous for him to get out of his chair and walk.

Bob had to quit work as a truck driver more than a year ago. He lost insurance and Roma applied for Medicaid several times, but problems kept cropping up. He was finally approved and had two months of Medicaid coverage until he began receiving disability payments.

That was when Medicaid said he was making too much money to qualify. Roma has severe arthritis and between the two, they get $2,800 a month in disability.

The letter they received said the limit was $1,200.

They have applied for Medicare, but must wait two years on disability before it takes effect. Roma said Bob doesn't have two years. Without a transplant, he probably will not make the four months until their 16th anniversary.

There is not anything Medicare or Medicaid can legally do under the circumstances, said Mike Fierberg, regional spokesman for the Centers for Medicare & Medicaid Services (CMS).

The only way to bypass the two-year waiting period for Medicare after getting disability is to have end stage renal disease (kidney failure) or Lou Gehrig's disease (ALS), he said. Fierberg said he doesn't know why those are the only two exemptions, but it is specified by law.

He said nobody at CMS likes it, but they can't change it. An attempt to change the length of the waiting period was originally included in the recently passed health care reform bill, but the provision failed.

So now the Leggetts wait, playing a cruel game that is robbing Bob of the years he could have.

"I would have stayed driving truck until I was 62 or 65, retired and then taken my little guy, my grandson, and gone fishing."

Roma said it's hard to see her husband, once a strong man with a scrappy streak, barely able to move around their mobile home.

Bob is the kind of man to help anyone without a thought for himself, she said.

It's tough for the hard-working man to be idle, and even harder for him to handle what his illness has done to his family. Bob said it's especially hard on his daughters because their mother died two months ago and their brother two years before that.

He takes 10 prescriptions daily, one of which is $1,300 a month. He's been hospitalized several times. The high medical costs meant they sold their house and moved to a trailer park.

"I just want to make sure the best I can that she (Roma) has a good place to go," he said.

"He's just a good ol' teddy bear really," she said, tears in her eyes.

Roma said she doesn't know if they will get help. She'll keep fighting for it, just in case. If nothing else, she hopes it makes people more aware of how the system works, so they will fight to change it.

For now they play a waiting game, hoping for a miracle that may never come.

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