::: HCV News :::

June 22, 2006

Graphic hepatitis C ads raise ethical qualms

By John Sullivan
Inquirer Staff Writer

As the head of liver transplantation at Thomas Jefferson University Hospital, Victor J. Navarro has seen many ailing patients with hepatitis C. But they don't look like the man in a half-page, color newspaper ad with a battered and bruised face, his eyes glassy.

"If Hep C was attacking your face instead of your liver, you'd do something about it," the ad reads. "Ready to fight back?"

While Navarro and other experts applaud the ads for raising interest in the viral disease, they think the campaign by drugmaker Hoffmann-La Roche Inc. could cause unnecessary alarm, in part because the vast majority of hepatitis C patients will not die of it.

"It's a marketing tool to make people fearful of hep C," Navarro said.

Roche's drugs, which are improvements over past medications, also work on only half of all patients, and cause considerable side effects. The campaign could leave those who cannot benefit believing they will wind up like the man in the ad.

The ad also is part of a larger marketing effort by Roche to quietly sponsor hep C seminars for the public and support patient groups and many liver physicians. Ethicists say the financing raises questions about whether the advice at such seminars can be objective.

Roche spokesman Mike Nelson said the company was simply trying to get out the word about the disease so more people can be helped. Nelson says nearly 600,000 hepatitis C patients have been diagnosed but haven't been treated, and may not know about the company's current market-leading options: Pegasys (interferon and an antiviral substance) and Copegus (an antiviral).

Nelson also said the ad was meant to be strong "to break through the clutter."

Roche said nearly 56 million people had seen the ad as of April, and more would see the ad in the coming weeks, part of a national blitz Roche launched last year in 250 newspapers, including The Inquirer and Philadelphia Daily News, and seven major magazines, such as Time. The ads also are plastered on 4,000 billboards and in 40,000 posters.

Roche officials would not disclose the cost of the campaign, which will run through July, but such large newspaper ads cost as much as $50,000 a day.

Leonard B. Seeff, who oversees hepatitis research at the National Institutes of Health, originally thought the ad came from an advocacy group.

"I think the ad is awful. Patients with hepatitis C do not look like that," said Seeff, who has been working on a study partly funded by Roche. "On the other hand, if you're trying to get the message across, one way is to make it look bad."

Seeff, who said his opinion did not reflect that of the NIH, said that he also was concerned because only a few people will die from hepatitis C.

"They mostly die from all kinds of things other than chronic liver disease," he said. "They should not think it's a death sentence."

Some doctors and advocates see a strong profit motive behind the campaign. "Ultimately it sells more of their drug," said Sidney M. Wolfe, director of Public Citizen's Health Research Group.

Arthur Caplan, director of the Center for Bioethics at the University of Pennsylvania, said it was not good policy for the United States to rely on companies to sponsor public-health campaigns. Such efforts tend to go to diseases for which companies have developed drugs, while other needy areas are ignored, he said.

Hepatitis C is a viral liver ailment that is the most common chronic blood-borne disease in the country.

The National Institutes of Health estimates that about four million people have hepatitis C in the United States. That number is expected to double in the coming decade as more people learn they are infected.

Many people got the disease from having received tainted blood or organs before adequate tests were developed in 1992. Most new cases are caused by intravenous drug use. A few contract the disease through high-risk sexual behavior, according to the Centers for Disease Control and Prevention.

Most people don't know they've been infected because the disease often doesn't cause symptoms for decades. The only way to confirm a diagnosis is to take a sample of the liver and examine it for scarring.

Only a fraction of those infected - from 1 percent to 5 percent - die of the disease. Yet it remains the No. 1 cause of liver transplants.

About 70 percent to 80 percent of those with the liver disease suffer from a stubborn genetic variant called genotype 1 that resists treatment.

The cocktail of antiviral drugs works in only 30 percent to 40 percent of those cases, and even less often in African Americans, according to the World Health Organization.

For the remaining 20 percent to 30 percent who have genotype 2 or 3, treatment works about 80 percent of the time. Averaging the two groups means that treatment only works in half the cases. Roche claims higher success rates.

While most insurance covers the therapy, uninsured patients must weigh that success rate against the cost, which can run up to $64,000 per year for some genotypes. The drugs are given several times a week, from 24 weeks to 48 weeks.

Still, hepatitis drug sales and advertising have been brisk. Over the last five years, drug company spending to advertise interferon, including Roche's drugs, has jumped from $14 million to $75 million. For Roche's Pegasys, ad spending rose from $30,000 in 2004 to more than $965,000 last year, according to Yardley, Pa.-based Verispan, which tracks pharmaceutical marketing.

The push has paid off. The company sold $1.4 billion worth of hepatitis C drugs, making it a top seller for the firm, according to its 2005 annual report.

Some hepatitis C activists, including those supported by the company, say the ads may seek to take advantage of a small window of opportunity. Roche now controls more than 60 percent of the hepatitis-therapy market, but that could change as other companies win approval for new antiviral treatments due out in coming years.

"We have been advising most people that they should probably wait for the next class of drugs," said Michael Ninburg, president of the National hepatitis C Advocacy Council, who heads the hepatitis Education Project in Seattle, which gets funding from Roche.

Also recommending that are HepTREC, a hepatitis education and support group started by Amy Jessop and a doctor and nurse at Temple University. Roche gave the group more than $250,000 in its first two years.

"I wish that there was public funding that we could turn to," said Jessop, who taught public health at Temple. "But the reality is there is no funding."

Earlier this year, about 15 people sat in a dimly lit auditorium at Graduate Hospital in Center City to hear a lecture on hepatitis C. Jessop told the group that Roche was a sponsor. She never promoted Roche products.

In the crowd sat Marc B. Saxe, a 46-year-old drug counselor from Philadelphia, who was diagnosed with hep C in 1998.

Saxe says he was "freaked out" by the diagnosis and went untreated until last year, about the time the Roche ad first appeared. It has worked, he said.

"I thought it was disgusting," he said of the ad. "But if it gets people to think about it, great."

"I just want to get fixed."

Hepatitis C At a Glance

About 3.9 million Americans are chronically infected with hepatitis C.

Prevalence rates are up to 8 percent to 10 percent of African Americans.

Dialysis patients, hemophiliacs, drug addicts and people transfused with blood before 1990 are particularly affected by the disease.

Injectable drug use remains the main route of transmission.

Sexual transmission is thought to be relatively infrequent.

Of every 100 people infected with hepatitis C:

About 55 to 85 people may develop long-term infection.

70 people might develop chronic liver disease.

5 to 20 people may develop cirrhosis over a period of 20 to 30 years.

1 to 5 people might die from the consequences of liver cancer or cirrhosis.

SOURCES: World Health Organization and the Centers for Disease Control and Prevention

Vertex verges on big time

But hepatitis drug faces competition and some investors wary of stock
By Stephen Heuser, Globe Staff | June 21, 2006

Earlier this year, Joshua Boger , chief executive of Vertex Pharmaceuticals Inc. , stood before several hundred scouts from the country's top mutual funds and drug companies and delivered a piece of news that could make his 17-year-old Cambridge biotech firm profitable for the first time.

An experimental Vertex pill, he said, had dramatic effects in a group of eight patients with hepatitis C, a virus that infects millions of Americans and can lie dormant for years before destroying the liver.

``It's a tremendous responsibility to live up to a molecule like VX-950," Boger told the crowd at the JP Morgan Healthcare Conference . In the shorthand of biotechnology, he meant that he had a drug on his hands that wouldn't just make large amounts of money, but would change society.

In the audience, an investor leaned over to a reporter and whispered: ``He certainly doesn't lack for confidence."

Since news of Vertex's hepatitis drug emerged last year, this company known for its expert chemistry has found itself among the highest fliers in the biotechnology world, soaring from less than $1 billion in market value in early 2005 to nearly $5 billion in March. Yesterday, value had slipped back to about $3.4 billion, after shares closed at $31.18.

Vertex now plans to test its drug in hundreds more people and hopes to file for federal approval in 2008 . If the drug works as well in the larger trial, analysts project it could bring in as much as $2 billion to $3 billion annually -- making it a global blockbuster and vaulting Vertex out of its research-driven niche into a prominent new role carrying the banner for the idea that new science can turn into real profits.

``There's a lot of excitement about Vertex's drug, and rightly so," said Dr. Nezam Afdhal , a liver specialist at Beth Israel Deaconess Medical Center in Boston who helps run one of the company's clinical trials.

But Vertex faces sharp competition from some of the biggest drug makers in the world, who are racing to develop their own hepatitis C treatments. And some investors are eyeing Vertex's stock price warily and asking: Haven't we seen this before?

Hatched in 1989 to exploit the new analytical tools that chemists and biologists were starting to master, Vertex -- like many biotechnology companies -- has survived years of red ink on the promise of a future payday. The company attracted early investors with stories of how its smarter, faster approach to attacking diseases would lead to a rapid flurry of new drug applications. The company was even the subject of a book, ``The Billion-Dollar Molecule," which highlighted the relentless scientific salesmanship of its founder, Boger. Buoyed by a bull market and a biotech boom, its price crested near $100 a share in 2000.

But by 2003, with no significant drugs on the market, its share price had dropped by a factor of 10. The ``billion-dollar molecule," a potential immune-suppressive drug, never materialized. The company has racked up more than $1 billion in losses, and its hepatitis pill won't come to market till 2009 at the earliest.

``I think there are a number of investors who've been burned in the past on Vertex shares, and that's going to make some investors nervous," said stock analyst Joshua Schimmer of Cowen & Co.

Vertex kept itself afloat, however, with a series of science deals with big pharmaceutical companies, helping to defray $200 million in annual research spending, and through a pair of timely debt financings in 2000 that added almost $500 million to its bank account.

Today, the value of the company hangs on its next set of trials for the hepatitis treatment, simultaneous human tests in the United States and Europe. As many as 1,000 people with hepatitis will get the drug, and results are expected to emerge later this year .

Meanwhile, Vertex is hiring as fast as any company in Cambridge, planning to grow from about 800 employees at the end of last year to 1,000 by the end of this year. It hires a car fleet to shuttle employees from its Cambridgeport campus to a big chunk of newly occupied lab space in Kendall Square. And in anticipation of a major launch of a product, it has even hired the former marketing manager of Lipitor, the best-selling drug in the world.

It may sound unlikely that an eight-patient test could drive billions in stock-market growth, but that's the nature of the biotechnology industry, in which investors bet not on a company's earnings, but on its potential. One big success can turn a company from a perennial also-ran into a global name.

``I like the idea that Joshua and the management team are really swinging for the fences," said Craig Millian, the former Lipitor marketer who arrived from Pfizer in January.

The hepatitis C virus has emerged in the past few years as a top new target for drug makers. Identified in 1989, it infects people through blood contamination -- injectable drug use and transfusion are the most common means -- and can lurk undetected for years before its liver damage is discovered by a doctor. There is no vaccine.

``When you think about organs you can do without, we still haven't found a way to reproduce the function of the liver," said Raymond Chung , the director of hepatology at Massachusetts General Hospital. ``If you're out of liver, you're pretty much out."

Currently, the disease is treated with a year's worth of injected interferon, which boosts the immune system enough to help about half of those treated with it to clear the virus on their own. It costs $18,000 and has unpleasant side effects, which doctors describe as a terrible flu that can trigger anemia, mood swings, and depression as therapy drags on.

Vertex's pill, by contrast, takes a leaf out of the playbook that was developed to fight HIV: It shuts down a protease, a key enzyme the virus needs to infect the body. Without the protease, the hepatitis C virus can't make the set of protein tools it needs to reproduce itself and hijack other cells.

In the test results disclosed in January, the drug appeared extremely effective in knocking the virus below detectable levels when used in combination with interferon. (If patients' viral levels stay undetectable for long enough, they are considered cured.) In four of eight patients who took Vertex's pill late last year, the hepatitis virus was undetectable within two weeks.

If it shows similar results in the longer trial, it could open the door to a treatment that helps more people, and takes less time, than the current therapy.

It could also open the door to huge growth for whichever drug company gets a product to market first. Global drug giant Schering-Plough is also testing a protease inhibitor, although Vertex's appears to be ahead in effectiveness. Behind them, several other companies have similar drugs in the pipeline, including Bristol-Myers Squibb Co.

It's uncertain whether Vertex's larger trials will replicate impressive early results. Drug resistance and side effects can always crop up in larger and longer trials; an earlier protease inhibitor was pulled by a German drug company after heart problems showed up in animal tests.

But analysts believe that the first company to bring a drug to market will have a chance to set the price -- up to $30,000 for a course of treatment -- and claim a big share of the estimated 8 million patients in the United States and Europe.

``There are obviously no guarantees in drug development, said Schimmer, but Vertex has ``never had a drug that shows such efficacy before. Few companies have."

Vertex does have other products in the pipeline, including a possible pill for rheumatoid arthritis, a cancer treatment being developed with Merck, and a cystic fibrosis pill. But for now it is the hepatitis C pill that has transfixed both doctors and Wall Street.

``This is a drug that we believe is not going to launch quietly. There's going to be worldwide demand, and it's a disaster if you have spectacular results but limited supply," said Boger.

In anticipation, Vertex has already contracted out large-scale manufacturing of the pill, and promises to have produced two tons by the end of the year.

Boger said he is pleased at the prospect that the company he founded could turn the corner to profitability around the time it turns 20.

``To me it's not a surprise that we're 17 years old and in this position," he said. ``That's about how long I thought it would take."

Stephen Heuser can be reached at sheuser@globe.com.

June 20, 2006

Treatment of Acute Hepatitis C

By Liz Highleyman

Past studies have shown that treatment of acute hepatitis C virus (HCV) infection is highly successful; a German study published in 2001, for example, found a sustained virological response (SVR) rate of 98% using conventional interferon monotherapy (Jaeckl 2001). However, many individuals with acute infection will clear HCV spontaneously, so if therapy is started too soon, there is a risk of treating patients who don't need it.

In the May 2006 issue of Hepatology, researchers reported on a study looking at the optimal duration of treatment for acute hepatitis C. The study initially evaluated 161 patients, of whom 30 refused treatment and 29 experienced spontaneous HCV clearance. The remaining 102 patients with persistent HCV were randomly assigned to 1.5 mcg weekly pegylated interferon alpha-2b (Peg-Intron) monotherapy for 8, 12, or 24 weeks.

Results

Using an intent-to-treat analysis, 67.6% patients who received treatment for 8 weeks achieved SVR; the rate was 82.4% after 12 weeks and 91.2% after 24 weeks.

All patients had undetectable HCV RNA 48 weeks after the end of therapy.

Treatment for 8 or 12 weeks was effective for patients with HCV genotypes 2, 3, or 4, but those with genotype 1 required 24 weeks.

Fewer adverse events were observed in patients receiving treatment for 8 or 12 weeks, compared with the 24-week group.

Conclusion

The authors concluded that pegylated interferon monotherapy "effectively induces high sustained virologic response rates in patients with acute hepatitis C virus infection, thus preventing development of chronic hepatitis C." They suggested that treatment duration should be further optimized based on genotype and rapid virological response at week 4.

Treating Acute HCV in Prison

The Hepatology study, and another recent study of HIV/HCV coinfected patients reported in the May 12, 2006 issue of AIDS, demonstrate that treatment of acute hepatitis C can be effective. However, many people with acute HCV infection do not experience symptoms, and most cases of hepatitis C are not identified at this stage.

A study reported in the June 15 issue of Clinical Infectious Diseases suggests that prisons and drug detoxification and treatment center may be appropriate settings for detecting and treating acute HCV infection among injection drug users.

In this study, on-site medical providers at prisons and detox facilities were educated about risk factors for and symptoms of hepatitis, and asked to refer all potential cases to a specialty clinic.

Results

During 30 months of observation, 21 individuals were diagnosed with acute hepatitis C, 3 with hepatitis B, and 1 with hepatitis A.

Of the 21 patients with acute hepatitis C, 19 were identified in prison shortly after incarceration.

Among 17 hepatitis C patients who received follow-up (for a mean 6.3 months), 8 experienced spontaneous HCV clearance.

5 patients with persistent HCV were treated with pegylated interferon monotherapy; 2 of these (40%) achieved SVR.

All patients agreed to receive HIV counseling and testing, as well as immunization against hepatitis A and B.

Conclusion

The authors concluded that, "Incarceration presents a unique opportunity to identify injection drug users with acute HCV infection, to initiate counseling regarding other blood-borne pathogens, and to facilitate immunizations and HCV treatment."

6/20/06

References

SM Kamal, KN Moustafa, J Chen, and others. Duration of peginterferon therapy in acute hepatitis C: a randomized trial. Hepatology. 43(5): 923-931. May 2006.

BH McGovern, A Wurcel, AY Kim, and others. Acute hepatitis C virus infection in incarcerated injection drug users. Clin Infect Dis. 42(12): 1663-1670. June 15, 2006.

E Jaeckel, M Cornberg, H. Wedemeyer, and others. Treatment of acute hepatitis C with interferon Alfa-2b. New England J Med. 345: 1452-1457. November 15, 2001.

Source: http://www.hivandhepatitis.com
Link: http://www.hivandhepatitis.com/hep_c/news/2006/062006_a.html

June 19, 2006

Hep C Stigma

In a world of profitable living, where choices are made purely based on profits alone - the life and existence of a HCV patient is of profit to the pharma/medical community.

When it comes to people outside the medical community, the fear of getting hold of this disease is way too much. Fear of an unknown virus starts with the hatred we all carry for the common flu. It is not easy to inform the common person that Hep C is only transmitted through blood...

A few months back, I read about a school teacher - who developed HCV after a student bit her. That is a very scary prospect, and one can understand the apprehensions of other people.

Social awareness of the disease (No one is at ease with any disease) is the first step in fighting this virus. I believe HCV carriers must reveal the info about their disease to their close relatives, especially the spouse/partner.

There is no point giving the virus to another person.

If children of HCV patients are asked to move out of a school, that's when we know the society has completely failed. The virus would have then succeeded not only in destroying the liver of a person but also the soul of a society.

The compulsion most HCV patients feel about keeping their health status a secret is understandable too. But, then, in the battle against this dreadful virus, a lot of good karma will help a long way.

Good karma being a lot of positive energy.

Some of the relatives and friends might distance from the HCV patient. That also gives us a good idea - who really the best friend is.

There is a certain reality - that the virus resides inside - which cannot be conveniently forgotten.

After almost six months of researching, I am yet to understand what the medical community is doing about HCV. If we have 170 Million people infected with this virus, and if the numbers are increasing... it is time to act - NOW.

Ayurveda has very effective treatment for rejuvenating liver. The roots of Henna has been used in South India as a medicine to cure liver ailments, especially severe jaundice.

More needs to be done about this, a lot more. We all need to do a lot more honest work about HCV, else this virus will be our third world war.

Japan's Hep C Crisis

First ruling near in suit over drug-caused hepatitis C debacle

By YOHEI SEKIand JUN NAGATA

OSAKA (Kyodo) Life changed drastically for Osaka resident Etsuko Morigami in 1987 when she was diagnosed with cirrhosis of the liver, some 13 years after being infected with hepatitis C through a tainted blood-clotting agent given to her while she was giving birth.

Morigami was treated with a blood-clotting product to stop her bleeding when she had her first son, Minoru, now 32.

After contracting cirrhosis, she developed diabetes and kidney damage. Insulin injections three times a day were a must.

"I often went out with my family and I was really in good shape," Morigami, 56, said of the time before the symptoms became severe, looking at the more than 10 kinds of drugs on a table beside her.

Considering her condition, treatment of hepatitis C with interferon, which eliminates the virus but whose side effects are severe, was halted. She developed liver cancer, and a long tube was inserted into her side to kill cancer cells with ethanol.

But she had relapses, with the intervals becoming shorter and shorter. Eventually she had no other option than a partial liver transplant, and Minoru was the donor.

"As you were infected when I was born, I will repay my debt to you," he told her.

Morigami underwent the transplant last June. To prevent rejection, she took an immuno-suppression drug, and to avoid infectious diseases she could not leave home, except to go to the hospital.

But her new liver gradually deteriorated, and the interferon treatments were resumed in February, now that there are more drugs available to control its side effects. Although she has also been diagnosed with lung cancer, it is inoperable.

"There is a time bomb inside you. If it explodes, you will blow up," a group of lawyers said in a statement aimed at trying to explain the plight of patients, many of them unwittingly infected with hepatitis C.

Although initial symptoms may not be critical, the hepatitis will eventually lead to cirrhosis and liver cancer.

"Swift measures should be taken before it is too late," said Morigami, one of the plaintiffs in a damages lawsuit against the government and Mitsubishi Pharma Corp.

Mitsubishi Pharma is the successor of Green Cross Corp., the firm that produced the blood product that caused her hepatitis C infection. The blood product was marketed under the brand name Fibrinogen-BBank.

The Osaka District Court will rule on the suit Wednesday in the first legal judgment involving tainted blood products leading to hepatitis C infections.

Besides the physical effects of hepatitis C, patients face discrimination often born out of ignorance and fear.

At a gathering in Tokyo's political center of Nagata-cho in late May, plaintiffs complained of discrimination and prejudice against them by employers and other sectors of society.

"I may not be employed if I tell (my employer) I am suffering from hepatitis C," a man in his 20s, one of the plaintiffs in a lawsuit filed with the Tokyo District Court, said.

A woman said, "I am hiding my disease because I fear that my children's friends' parents may tell them not to play with my kids."

Hepatitis C is caused mostly by direct infection of the blood and is not transmitted by ordinary social contact, but at the gathering many patients complained of the agony of not being able to tell people they have the disease.

Some reported having been refused dental treatment, and one woman was fired from her job in a company cafeteria. Management told her the disease was infectious.

Since the end of World War II, Japan has suffered several drug-induced disasters, including the childbirth deformities caused by thalidomide in the 1950s and '60s, SMON (a disease similar to polio), another disease caused by defective chloroquine in the 1950s, and the HIV/AIDS outbreak caused by contaminated blood products -- also marketed by Green Cross -- in the 1980s.

"The suffering can be said to be on a historically large scale, but the real situation is not well-known in society," said Kiyohiko Katahira, a professor of health and welfare at Toyo University.

Regarded as the largest of these drug-induced diseases is SMON, caused by the antiflatulence drug chinoform in the 1950s and 1960s, which affected some 10,000 people.

According to Mitsubishi Pharma, the number of patients since 1980 infected with hepatitis C as a result of taking the tainted blood product based on the naturally occurring protein fibrinogen is estimated at 10,000.

But as the product had been sold since its approval by the government in 1964, Katahira said, "The number of victims will be about 30,000 if the average annual number of victims before 1979 is assumed to be the same," making it much larger than the SMON disaster.

There is more than one similarity between this case and the HIV/AIDS fiasco, in which a doctor and a high-ranking official at the old Health and Welfare Ministry were prosecuted for allowing tainted products to stay on the market after being officially warned of their dangers. Victims in both cases have been plagued by discrimination and prejudice, and are waging lawsuits without revealing their real names.

In the case of hepatitis C, only 10 of the 96 plaintiffs across the country have made their real names public.

There are also many other victims who cannot become plaintiffs even if they wanted to, because their medical records have been lost and their link to tainted blood products cannot be proved.

Fibrinogen is a globulin in the blood that aids coagulation, and products containing it were widely used by obstetricians, gynecologists and surgeons. But the U.S. government canceled its approval for such blood products in 1977 because there was a danger that the products, made from donated blood, could be infected.

Despite that, 50,000 to 70,000 packages of the Green Cross product were sold annually between 1980 and 1986. When an epidemic of liver inflammation-infection cases erupted in Aomori Prefecture in 1987 and similar reports continued, Green Cross began to recall the product.

Although the government began to study ways to strengthen the medical examination and treatment system, Norio Hayashi, a professor at the graduate school of Osaka University, said the system is not satisfactory. "Hepatitis C patients are estimated to number 1.5 million in Japan, but there are only some 3,000 liver-specialist doctors," he said.

HCV treatment efficacy can be predicted

New findings in hepatitis C virus described from Canada, Sweden and Austria

Hepatitis Weekly - Jun. 19, 2006

2006 JUN 19 - (NewsRx.com) -- Data on hepatitis C virus are outlined in reports from Canada, Sweden and Austria.

Study 1:
According to scientists from Canada, hepatitis C virus treatment efficacy can be predicted.

"In the past, antiviral therapy has been given to 15% to 30% of patients infected with hepatitis C virus (HCV). The efficacy of therapy has recently improved with the addition of ribavirin and pegylated interferon. The aim of the present study was to identify the clinical, socioeconomic and health-system predictors of antiviral treatment for HCV," wrote M. Witkos and colleagues, University of Toronto. "A retrospective analysis of compensation claims data of patients who acquired HCV through blood transfusions between 1986 and 1990 was performed. The patients consisted of 2456 Canadian HCV-positive individuals."

The researchers wrote, "The authors reviewed narrative comments from physicians, and constructed univariate and multivariate logistic regression models, using receipt of antiviral therapy with interferon or interferon/ribavirin as the primary outcome. Of the 2456 patients, approximately 30% appeared to be eligible, but only 16% received treatment.

"Univariate analyses suggested that the disease severity, age, HIV status and province of residence were associated with the likelihood of receiving treatment (p<.01). The final, multivariable model indicated that in patients with HCV. Intermediate disease severity (eg, fibrosis, p<.0001); middle age (p<.0001); HIV-negative status (p<.0001); and province of residence (Quebec, p<.0001; and Saskatchewan, p<.0001) were independent predictors of treatment."

"Narrative comments of physicians emphasized the importance of age, HIV status and patient preferences in clinical decision-making. Given the efficacy and cost-effectiveness of current antiviral therapy, treatment rates of HCV patients may be suboptimal," reported the authors.

They concluded, "Further work is required to understand barriers to treatment related to geography, organization of medical care, age, medical provider and patient preferences."

Witkos and colleagues published their study in Canadian Journal of Gastroenterology (Predictors of antiviral therapy in a post-transfusion cohort of hepatitis C patients. Can J Gastroenterol, 2006;20(2):107-111).

For additional information, contact M.D. Krahn, University of Toronto, Toronto General Hospital, Department of Health Policy Management & Evaluation, 200 Elizabeth St., EN 14-207, Toronto, ON M5G 2C4, Canada.

Study 2:
According to recent research from Sweden, translation efficiency correlates with therapy outcome in chronic hepatitis C virus (HCV) infection.

"Combination therapy with interferon-alpha (IFN-alpha) and ribavirin (RBV) in chronic hepatitis C demonstrates the best responses against HCV of genotype 3. Still, it has proven to be ineffective in 20-30% of patients infected with this genotype.

"In the present study," wrote A. Yasmeen and colleagues, Karolinska Institute, "we analyzed the translation efficiency mediated by the internal ribosome entry site (IRES) region in HCV genotype 3 genomes isolated from sustained responders (SR) and non-responders (NR), assuming that this may influence the outcome of treatment."

The authors reported, "Pretreatment isolates of genotype 3 from 22 individuals (15 SR, seven NR) were selected for such analyses. The IRES region [nucleotide (nt) 1-407] was cloned into a dual luciferase vector and IRES activity assessed following transfection into various cell lines.

"Low relative translation efficiency was observed for IRES elements derived from SR patients, whereas those of NR patients showed significantly greater translation efficiency (29.7±13 vs 69.4±22; p<.01). Subsequently, the effect of IFN-alpha plus RBV on IRES-driven translation in vitro was determined. A greater suppressive effect was observed on IRES activity isolated from seven SR patients, when compared with seven NR patients."

"IRES efficiency in vitro correlated with treatment response for HCV genotype 3. Further studies are warranted to investigate whether IRES efficiency in vitro, or sequence motifs associated with IRES efficiency, will be worthwhile to explore as prognostic tools for other HCV genotypes in the treatment of chronic HCV infection," the investigators concluded.

Yasmeen and colleagues published their study in the Journal of Viral Hepatitis (Correlation between translation efficiency and outcome of combination therapy in chronic hepatitis C genotype 3. J Viral Hepat, 2006;13(2):87-95).

For additional information, contact M.A.A. Persson, Karolinska Institute, Center of Molecular Medicine, Karolinska Hospital, Department of Medicine, S-17176 Stockholm, Sweden.

Study 3:
According to recent research from Austria, interferon therapy is promising in treatment of chronic hepatitis C.

"Combination anti-viral therapy achieves a sustained virological response (defined as HCV-RNA negativity 6 months after the end of therapy) of 56% of patients with chronic hepatitis C. Little is known about long-term durability of HCV-RNA negativity in patients treated with pegylated interferon."

E. Formann and colleagues, Medical University of Vienna, wrote that the study was done "to evaluate the durability of virologic response in patients with sustained virological response to anti-viral therapy treated at our center."

"A total of 187 sustained virological responses (50% genotype 1, 42% genotype 2 or 3 and 8% genotype 4; 20% with cirrhosis) with a follow-up of >12 months post-therapy were studied. Twelve patients received monotherapy with interferon-alpha2a or -2b. One hundred and seventy-five received combination therapy with ribavirin and standard interferon-alpha (n=73) or pegylated interferon-alpha2a or 2b (n=102)."

"Qualitative serum HCV-RNA was tested by COBAS AMPLICOR HCV test, v2.0. Median follow-up time was 29 months (range 12-172)," explained the authors.

"Recurrence of HCV infection was not observed in any of the 187 sustained virological responders. Ala aminotransferase values were normal in 90% and two patients showed minimal elevation of alpha-fetoprotein levels. No recurrence of HCV infection was seen in any patient."

"Thus," concluded the researchers, "longterm prognosis in chronic hepatitis C patients with a sustained virological response to therapy with pegylated interferon ± ribavirin is promising, but long-term studies need to continue."

Formann and colleagues published their study in Alimentary Pharmacology & Therapeutics (Long-term follow-up of chronic hepatitis C patients with sustained virological response to various forms of interferon-based anti-viral therapy. Aliment Pharmacol Ther, 2006;23(4):507-511).

For additional information, contact P. Ferenci, Department of Internal Medicine IV, Gastroenterology and Hepatology, Medical University of Vienna, Austria, Vienna, Austria.

Sexual Transmission of Hepatitis C

Mike Youle, MBBS

We have spent the last 21 years fighting an emerging epidemic of HIV across the globe with a modicum of success, at least on the treatment front. Highly active antiretroviral therapy (HAART) has now allowed us some breathing room in which to develop better therapies and to address prevention issues that have been rather less successfully tackled in most countries. We have been slow to realize that hepatitis C virus (HCV) represents our next challenge; in fact, surveillance systems are not properly in place in most countries. In the United Kingdom there are an estimated 300,000 HCV cases, over 90% of which are as yet undiagnosed, in comparison to approximately 33,500 people living with HIV, about 30% of whom are undiagnosed. The significance of sexual transmission in the HCV epidemic has been a matter of controversy,^[1] although there is some evidence that it may be an important method of acquisition, at least among men who have sex with men (MSM).^[2]

In a study from a large UK hospital, Browne and colleagues^[3] presented circumstantial evidence that sexual transmission is responsible for an increasing incidence of HCV in HIV-infected individuals. Cases of HCV were identified among individuals with a previously negative HCV antibody result who attended sexual health services between 1997 and 2002. The number of these HCV seroconverters increased from zero during 1997 to 10 during the first half of 2002. A total of 23 cases were seen, of whom only 1 was female, and 21 of these were known to be HIV-infected, including 2 who seroconverted to both viruses concurrently. Although 4 subjects gave a classic history of injection-drug use and needle sharing, 19 did not; these were all MSM, 15 of whom reported recent unsafe sex. Eight subjects in this cohort developed syphilis temporarily associated with HCV seroconversion.

Further details were presented on the 21 subjects known to be coinfected with HIV and HCV. All of the HIV-infected individuals diagnosed with HCV were identified by screening for HCV RNA among those with abnormal liver function, using stored blood samples to try to identify the date of acquisition. Routine antibody tests were also performed which were initially negative, and the median time from detection of HCV RNA to HCV antibody positivity was 4 months (range, 3.0-9.5 months). The rate of diagnosis of HCV among HIV-infected subjects found to have elevated liver function tests increased during the study period from 10.7% to 40%, a statistically significant change (P = .035, Chi-squared test). Among this population of HIV-infected patients with elevated liver function tests, the rate of diagnosis of HCV in 2002 was 5.1 cases per 1000 patient-years (95% confidence interval [CI], 2.2-10.1), which appeared to be significantly higher than the rate in 1997 (0 cases per 1000 patient-years; 95% CI, 0-1.2). This would suggest that the HCV infection burden within the HIV-infected population increased during the study period.

This study raises a concern that the use of HCV antibody tests alone may not be sufficient to identify individuals who acquire HCV with only sexual risk factors or even in low incidence areas, potentially delaying the diagnosis of active infection and thus increasing the risk of onward transmission. The use of stored blood to retrospectively identify HCV seroconversion allows for an accurate identification of time of infection in epidemiologic studies, and further work addressing sexual acquisition is required to identify more clearly the risk factors for transmission as well as the outcomes of these infections. From a public health perspective, more aggressive surveillance studies should be performed, and health promotion messages need to be developed to educate those at risk.

References

Bernard EJ. Sexual transmission of hep C. In: AIDS Treatment Update.
London: NAM Publications. September 2002; Issue 117. Available at: http://www.aidsmap.com/publications/atu/atu117.pdf Accessed December 16, 2002.
Craib KJP, Sherlock CH, Hogg RS, O'Shaughnessy MV, Schechter MT. Evidence of sexual transmission of hepatitis c virus (HCV) in a cohort of homosexual men. Program and abstracts of the 8th Conference on Retroviruses and Opportunistic Infections; February 4-8, 2001; Chicago, Illinois. Abstract 561.
Browne R, Asboe D, Gilleece Y, et al. Increased incidence of HIV-positive individuals with acute hepatitis C due to sexual transmission: a new epidemic? Program and abstracts of the Sixth International Congress on Drug Therapy in HIV Infection; November 17-21, 2002; Glasgow, Scotland. Abstract P283.

June 16, 2006

Herbal solution underway

Herbal solution undergoes Phase II clinical trial for hepatitis C

World Disease Weekly - Jun. 20, 2006

Chronic hepatitis C is associated with significant morbidity (liver cirrhosis and hepatocellular carcinoma) and mortality.

Current treatment is based on interferon and ribavirin. However, treatment options are limited for patients who are not candidates for interferon-based therapy, particularly for those who suffer from HCV genotype 1 infection.

Sho-saiko-to (SST), a standardized herbal formula, is under a clinical phase II trial by a leading New York cancer research institute to determine its effect on hepatitis C patients. The research group reported the preliminary results of 15 patients at the 2nd Society of Integrative Oncology Conference in San Diego on November 10, 2005. This study was titled "Sho-saiko-to for Patients with Chronic Hepatitis C Who Are Intolerant to or Have Contraindication to Interferon-Based Therapy: A Phase II Study."

SST is known to have anti-fibrotic effect by inhibition of lipid peroxidation in hepatocytes and stellate cells in animal studies. It has also been shown to reduce aminotransferase levels and the incidence of hepatocellular carcinoma in hepatitis and liver cirrhosis patients.

According to the design of the clinical trial, 31 patients will receive SST daily for 52 weeks. Fifteen patients have completed the treatment and the preliminary results have been reported. No serious adverse events have been attributed to SST among any patients who enrolled in the trial. Among the 15 patients who completed the study, reductions in alanine aminotransferase (ALT) were observed in 11 patients and aspartate aminotransferase (AST) in 10 patients. In 10 patients, the liver biopsy showed 20% improvement on histological assessment of the liver.

This is consistent with the findings by the Japanese researchers for its anti-inflammatory effect. More interestingly, the majority of the patients whom participated in the clinical trial were genotype 1 infection.

In Japan, over 75% of physicians use at least some of the traditional herbal formulas. Over 1.5 million Japanese patients with hepatitis have been treated with Sho-saiko-to. SST is available in capsules through HepCare Inc., a Phoenix-based company that has licensed the marketing right of SST from Honso Pharmaceutical Co. Ltd., the Nagoya-based Japanese manufacturer of the standardized herbal formula.

This article was prepared by World Disease Weekly editors from staff and other reports. Copyright 2006, World Disease Weekly via NewsRx.com.

June 13, 2006

US scientists isolate liver stem cells

A stable line of human fetal liver stem cells has been isolated and characterized for the first time, U.S. scientists reported on Monday.

The liver stem cells, which have shown the ability to repopulate damaged livers in mice, could be valuable for the treatment of liver diseases in the future, said a research team at the University of Washington.

Their findings appeared in the June 12 issue of the Proceedings of the National Academy of Sciences.

The adult liver contains a reservoir of progenitor cells, which provide the organ with a high regenerative potential. But so far these cells have not been successfully isolated from human livers.

According Nelson Fausto, a professor at the University of Washington who led the study, the researchers derived for the first time progenitor cells from livers in human fetuses of 74 to 108 days.

First, they removed and maintained human fetal livers in culture. Then the researchers treated the colonies with a selective antibiotic, and mechanically isolated stem cells from the liver cells.

Like other stem cells, these liver progenitors displayed the ability for long-term self-renewal, and the capacity to differentiate into multiple cell types.

In laboratory conditions, the liver stem cells can differentiate into not only liver tissue cells (hepatocytes) and bile duct cells, but also fat, bone, and cartilage tissue cells, the researchers said.

When transplanted into mice with damaged livers, the human stem cells survived and repopulated part of the damaged tissue. "They can differentiate into functional hepatocytes in vivo, suggesting liver repopulation potential," the researchers wrote in the paper.

The liver stem cells have durable proliferative capability, according to the researchers. Even after being kept in culture for 6 months, the cells can still be induced to differentiate into functional hepatocytes and biliary duct cells in experiments.

"We anticipate that human fetus multipotent progenitor cells (liver stem cells) will be a valuable tool to study differentiation pathways in the human liver and may have important therapeutic applications in patients with liver failure," the researchers said.

They suggested that other organs, such as the pancreas and the kidney, in human fetuses may have similar stem cells.

"We are also exploring the use of this approach to isolate similar cell populations from other embryonic organs, such as the pancreas and the kidney."

Source: Xinhua

June 09, 2006

We must beat hepatitus C stigma

People at risk include those who have used intravenous drugs, shared spoons, had blood transfusion before 1991, snorted cocaine, had unprotected sex, tattoos or body piercings where non sterile equipment was used.

A man who lived with the Hepatitis C virus for 20 years without knowing it is now at the centre of a campaign to raise awareness about the illness.

Mark McKay, who lives in Newmarket Road, Norwich, was diagnosed with Hepatitis C six years ago, but has no idea how he contracted the virus.

He was horrified when, on his 45th birthday, he received a letter from the Blood Transfusion Service to say it had detected the virus after he had given blood.

Mr McKay, 51, said: “When I first read the letter I did not know too much about Hepatitis C but when I found out later that it was potentially fatal I did get a bit worried. Information is also hard to come by.”

Mr McKay is one of several people with Hepatitis C who have agreed to appear in a national campaign to try to reduce the stigma attached to the virus.

An exhibition featuring giant photographic portraits of people living with Hepatitis C will be launched in Gentleman's Walk, Norwich, from tomorrow and will stay up for two days.

It is part of the Government's new Hepatitis C Action Plan for England launched in March 2005, which aims to improve the prevention, diagnosis and treatment of Hepatitis C.

It is estimated that 200,000 people in England have chronic Hepatitis C infection but the majority are unaware of their condition which can cause serious damage to the liver.

Mr McKay, a business analyst at Norwich Union, said: “I don't have any symptoms at all, but I know there has been liver damage.

“I don't know how I got it. I used to work in operating theatres at a hospital and I may have picked it up from a needle stick injury.”

He said he had agreed to take part in the campaign because he wanted to help raise awareness of the illness.

“If you can get people to consider what they have done in the past, they might think it was worth getting tested.

“I would rather know I had it than not know because at least then I can take steps to mitigate it.”

The father-of-three said he was discussing his treatment options at present with his doctors at the N&N because the first treatment he had tried had left him with nasty side effects.

Dr Martin Phillips, consultant gastroenterologist at the Norfolk and Norwich University Hospital, said he was treating more and more patients for Hepatitis C in Norfolk but there were many others who had not been diagnosed.

“I am treating all ages men women and children, but the problem is there are often no symptom until the disease is very advanced,” he added.

People at risk include those who have used intravenous drugs, shared spoons, had blood transfusion before 1991, snorted cocaine, had unprotected sex, tattoos or body piercings where non sterile equipment was used.

But Dr Phillips said the latest treatments had a 50 to 80 per cent success rate in curing it, depending on the type.

He said people who thought they may have put themselves at risk should have a simple blood test at their GP surgery.

For more information ring the Hepatitis C Information line on (0800) 451 451 or go to www.hepc.nhs.uk

Are you campaigning to raise the profile of an illness? Call Evening News health reporter Sarah Hall on 01603 772426 or email sarah.hall2@archant.co.uk

June 08, 2006

Hepatitis C may be the cancer suspect

A new study conducted in Taiwan suggests that the hepatitis C virus is the true culprit behind the nation's rising rates of hepatocellular carcinoma (a common type of liver cancer), debunking theories that the hepatitis B virus was mostly to blame.

The study, entitled Secular trends and geographic variations of hepatitis B and hepatitis C virus-associated hepatocellular carcinoma in Taiwan, was conducted jointly by Chang Gung Memorial Hospital in Kaohsiung, National Taiwan University Hospital in Taipei and Changhua Christian Hospital in Changhua City.

The study reviewed 18,423 hepatocellular carcinoma cases in the country between 1981 and 2001, focusing on Yunlin and Tainan counties, and Chiayi City -- regions where liver cancer is especially prevalent.

Findings show that while the overall mortality rate in patients with liver cancer caused by hepatitis B had dropped, the number of deaths related to the cancer caused by hepatitis C had increased significantly. Specifically, hepatitis C-related hepatocellular carcinoma deaths shot up by approximately 66 percent in Taiwanese males, and deaths doubled for Taiwanese females.

Lu Sheng-nan, a physician at Chang Gung Memorial Hospital said that preventative measures for hepatitis B have been effective; however, more and stronger measures are needed to prevent the spread of hepatitis C, for which no vaccine is currently available.

The virus is transmitted by blood-to-blood contact, usually via intravenous drug injection or transfusions of unscreened blood.

Hepatitis B is usually trans-mitted through exchange of bodily fluids. This includes unprotected sex, blood transfusions and the use of contaminated syringes.

The study is scheduled to be published in the International Journal of Cancer, a prominent medical periodical.

Source: The Taipei Times

June 07, 2006

hepatitis C may be the cancer culprit

The study, entitled Secular trends and geographic variations of hepatitis B and hepatitis C virus-associated hepatocellular carcinoma in Taiwan, was conducted jointly by Chang Gung Memorial Hospital in Kaohsiung, National Taiwan University Hospital in Taipei and Changhua Christian Hospital in Changhua City.

The study reviewed 18,423 hepatocellular carcinoma cases in the country between 1981 and 2001, focusing on Yunlin and Tainan counties, and Chiayi City -- regions where liver cancer is especially prevalent.

Findings show that while the overall mortality rate in patients with liver cancer caused by hepatitis B had dropped, the number of deaths related to the cancer caused by hepatitis C had increased significantly. Specifically, hepatitis C-related hepatocellular carcinoma deaths shot up by approximately 66 percent in Taiwanese males, and deaths doubled for Taiwanese females.

Lu Sheng-nan, a physician at Chang Gung Memorial Hospital said that preventative measures for hepatitis B have been effective; however, more and stronger measures are needed to prevent the spread of hepatitis C, for which no vaccine is currently available.

The virus is transmitted by blood-to-blood contact, usually via intravenous drug injection or transfusions of unscreened blood.

Hepatitis B is usually trans-mitted through exchange of bodily fluids. This includes unprotected sex, blood transfusions and the use of contaminated syringes.

The study is scheduled to be published in the International Journal of Cancer, a prominent medical periodical.

Source: The Taipei Times

June 06, 2006

Is Hepatitis C a luxury?

Interferon Alfa-2B and Rivavirma, both produced in Cuba, are components of Heberviron. The drugt is used not only to combat the causative virus of Hepatitis C in blood but, in the long range, eliminates lesions in the liver and totally cures the disease.

The components of Heberviron were developed and are being produced by Cuba: the Interferon by the CIGB and the Center of Bio-products, and the Ribavirina by the Medicament Research and Development Center and Novatec Laboratories, which demonstrates the integration and cooperation of the institutions in the Scientific Complex.

In the meanwhile, Novartis AG says that it has signed an exclusive worldwide agreement with US biopharmaceuticals company Human Genome Sciences to acquire rights to hepatitis C drug Albuferon.

The investigational drug is expected to enter Phase III clinical trials by the end of 2006, Novartis said.
Under the terms of the agreement, Novartis will make an upfront payment of 45 mln usd, with milestones payable at specific stages of development and sales milestones payable following the drug''s launch.

Novartis and HGS will co-promote Albuferon (albumin interferon alfa-2b) in the US, while Novartis will have exclusive rights to market and promote it in the rest of the world.

The Novartis drug has an albumin prefixed to interferon alfa-2b, which even the Cubans have developed successfully in the fight against the dreadful Hep C Virus.

The western media has been harping about the massive market potential of the new drugs because of the 170 million people infected with HCV. Stocks has been rising and plunging with every detail made available of the research on HCV drugs... it is a scary secnario!

If companies are going to make a fortune out of the misfortune of 170 million people and their families, and if more people in different stock markets around the world are going to speculate and gamble on the stock value of these pharma companies it would only help the rich get richer and meaner.

Out of the 170 Million infected people, how many can actually afford a health insurance or even afford to pay for basic neccessities is something no one has really cared to ask.

Was it the MARKET that determined how we fought against Small Pox, Plague etc?

Anyone who buys a Novartis or Vertex share to make profits out of a HEP C patient is accumulating bad Karma score.

When it comes to medicare and education in a country -- the real profit to that country is a Healthy and Educated population. Outrageous Monetary Profits, by squeezing the ones who want to live without illness and the young ones who want to gain knowledge, is simply unacceptable.

HCV (Hepatitis) is not a luxury that one has to pay for, it is a misfortune that could knock on our doors too.

If the Cubans have got it right and if the drug is working... Thank You Cuba. Wish I could go to Cuba and check it out myself.

June 03, 2006

FAT and HEP C

Obesity and hepatitis C infection act as a one-two punch on the liver, but treating the obesity may also improve the efficacy of antiviral therapy, reported researchers here.

In a review of the effects of obesity on antiviral therapies for hepatitis C (HCV) infection, a Mayo Clinic team found evidence that points to control of obesity as an important therapeutic adjunct.

"Patients who have chronic hepatitis C and are obese are more likely to be insulin-resistant and to have more advanced hepatic steatosis/steatohepatitis and fibrosis," wrote Michael R. Charlton, M.D., and colleagues, in the June issue of Hepatology.

"These latter conditions are independent predictors of non-response to combination therapy with peginterferon alpha and ribavirin [Rebetol], and obese patients are therefore more likely to be non0responders to combination therapy."

"Treatment strategies that focus on improving underlying metabolic factors associated with poor response to combination therapy are thus more likely to overcome the low sustained virologic response," wrote Dr. Charlton and colleagues.

According to the National Health and Nutrition Examination Survey (NHANES) III, about 2.7 million American have chronic HCV infections. Of this population about 20% are obese, putting them at increased risk for steatosis and the progression of fibrosis, the authors noted.

They explored some of the mechanisms whereby obesity and its consequence, the metabolic syndrome, may interfere with antiviral therapies directed against HCV.

For example, among patients with metabolic syndrome, which is associated with non-alcoholic fatty-liver disease, those who also have chronic HCV infections are significantly more likely to develop advanced liver disease than those who are free of HCV infection, and obese patients with chronic HCV are at a greater risk of developing co-existent steatosis and more advanced liver disease.

"Whereas both viral and host factors contribute to coexistent steatosis, clinical factors associated with the metabolic syndrome--including elevated waist-to-hip ratio, the presence of insulin resistance, and diabetes--have been shown to predict more advanced forms of chronic hepatitis C," the investigators wrote.

Obesity also appears to interfere, through a variety of mechanisms, with the efficacy of pegylated interferons plus Rebetol, which is the current gold standard for treating HCV infections, the authors noted.

Three main hypotheses have been proposed to explain how obesity may dampen the effect of antiviral therapy, the authors noted:

Because obesity is an inflammatory condition, it is associated with the release of pro-inflammatory cytokines that may alter the immune response to therapy
Insulin resistance and hepatic steatosis associated with obesity lead to steatohepatitis and hepatic fibrosis, which may in turn interfere with the action of interferons on hepatocytes.
High levels of subcutaneous fat in obese patients may impair absorption of peginterferon alpha by altering lymphatic uptake of the drug, thereby reducing its bioavailability in serum.

The evidence points to control of obesity as an important adjunct to treatment of HCV, the authors said.

"In formulating more effective treatment regimens for obese patients with chronic hepatitis C, it is important to use current knowledge of the metabolic effects of obesity," they wrote. "Thus, the most direct approach is to encourage weight loss and exercise before treatment."

They noted that people who are infected with HCV and who lose weight have been shown to have reductions in steatosis and significant decreases in fibrosis scores and activated stellate cells.

"Recently reported data suggest that treatment with the insulin-sensitizing medications metformin [Glucophage] and the thiazolidinediones (pioglitazone [Actos] and rosiglitazone [Avandia]) reduced serum alanine aminotransferase and histologic features of hepatic steatosis, inflammation, and fibrosis, as well as increased insulin sensitivity, in nondiabetic patients with nonalcoholic steatohepatitis; however, recent human data with metformin do not appear to be as promising," they noted.

Clinical trials will be needed to determine whether treating insulin resistance before or during antiviral therapy could be beneficial, the authors argued.

Other possible means for improving responses to combination therapy with pegylated interferons and Rebetol include longer duration of therapy "and, possibly, higher flat doses, which may counteract the decreased bioavailability of drug and increased resistance to interferon-based therapies," they added.

June 02, 2006

HCV - three more studies

New findings in hepatitis C virus described from the United States, Canada and Germany

World Disease Weekly - Jun. 06, 2006

Data on hepatitis C virus are outlined in reports from the United States, Canada and Germany.

Study 1: According to recent research from the United States, early interferon therapy produces sustained hepatitis C virus (HCV) virologic response.

"Pegylated interferon therapy has not been adequately evaluated in acute HCV infection. This randomized trial assessed the efficacy, safety, and timing of pegylated interferon alfa-2b for treatment of acute hepatitis C," wrote S.M. Kamal and colleagues, Harvard University.

They explained, "One hundred seventy-five patients acutely infected with HCV were screened. Patients whose infection did not spontaneously resolve by week 8 were randomized to once weekly peginterferon alfa-2b monotherapy (1.5 mcg/kg per week) started at weeks 8, 12, or 20 for a duration of 12 weeks. The primary endpoint was undetectable HCV RNA 24 weeks after the end of treatment (sustained virologic response [SVR])."

"All patients were followed for 48 weeks after cessation of therapy. One hundred twenty-nine subjects started treatment at week 8 (group A, n=43), week 12 (group B, n=43), or week 20 (group C, n=43). By using an intent-to-treat analysis, the overall SVR rate was 87%. The SVR rates were 95%, 92%, and 76% with treatment onset at 8, 12, and 20 weeks, respectively. Overall, SVR rates were better for patients infected with genotypes 2, 3, and 4 than those infected with genotype 1.

"Earlier initiation of therapy improved SVR rates for patients infected with genotype 1 with high viral load. Peginterferon alfa-2b was well tolerated. Subjects with SVR maintained undetectable HCV RNA 48 weeks after therapy," wrote the researchers.

The scientists concluded, "Peginterferon alfa-2b monotherapy in acute hepatitis C induces high sustained virologic response rates, prevents chronic evolution, and is well tolerated. Initiation of treatment at week 8 or 12 results in higher sustained virologic rates than initiation at week 20."

Kamal and colleagues published their study in Gastroenterology (Peginterferon alfa-2b therapy in acute hepatitis C: Impact of onset of therapy on sustained virologic response. Gastroenterology, 2006;130(3):632-638).

For additional information, contact S.M. Kamal, Harvard University, Beth Israel Deaconess Medical Center, School of Medicine, Liver Diseases Center, 4 Blackfan Circle, Boston, MA 02115, USA.

Study 2: According to scientists from Canada, hepatitis C virus treatment efficacy can be predicted.

"In the past, antiviral therapy has been given to 15% to 30% of patients infected with hepatitis C virus (HCV). The efficacy of therapy has recently improved with the addition of ribavirin and pegylated interferon. The aim of the present study was to identify the clinical, socioeconomic and health-system predictors of antiviral treatment for HCV," wrote M. Witkos and colleagues, University of Toronto. "A retrospective analysis of compensation claims data of patients who acquired HCV through blood transfusions between 1986 and 1990 was performed. The patients consisted of 2456 Canadian HCV-positive individuals."

The researchers wrote, "The authors reviewed narrative comments from physicians, and constructed univariate and multivariate logistic regression models, using receipt of antiviral therapy with interferon or interferon/ribavirin as the primary outcome. Of the 2456 patients, approximately 30% appeared to be eligible, but only 16% received treatment.

"Univariate analyses suggested that the disease severity, age, HIV status and province of residence were associated with the likelihood of receiving treatment (p<.01). The final, multivariable model indicated that in patients with HCV. Intermediate disease severity (eg, fibrosis, p<.0001); middle age (p<.0001); HIV-negative status (p<.0001); and province of residence (Quebec, p<.0001; and Saskatchewan, p<.0001) were independent predictors of treatment." "Narrative comments of physicians emphasized the importance of age, HIV status and patient preferences in clinical decision-making. Given the efficacy and cost-effectiveness of current antiviral therapy, treatment rates of HCV patients may be suboptimal," reported the authors. They concluded, "Further work is required to understand barriers to treatment related to geography, organization of medical care, age, medical provider and patient preferences." Witkos and colleagues published their study in Canadian Journal of Gastroenterology (Predictors of antiviral therapy in a post-transfusion cohort of hepatitis C patients. Can J Gastroenterol, 2006;20(2):107-111). For additional information, contact M.D. Krahn, University of Toronto, Toronto General Hospital, Department of Health Policy Management & Evaluation, 200 Elizabeth St., EN 14-207, Toronto, ON M5G 2C4, Canada. Study 3: A study from Germany has reported that early monotherapy with pegylated interferon alpha-2b for acute hepatitis C infection leads to high virological response rates.

"Early treatment of acute hepatitis C with interferon alpha-2b for 24 weeks prevents chronic infection in almost all patients. Because pegylated interferons have replaced conventional interferon in the therapy of chronic hepatitis C, the aim of this study was to analyze the efficacy of an early treatment of acute hepatitis C with peginterferon alpha-2b," wrote J. Wiegand and colleagues, Hannover Medical School.

They continued, "Between February 2001 and February 2004, 89 individuals with acute HCV infection were recruited at 53 different centers in Germany. Patients received 1.5 mcg/kg peginterferon alpha-2b for 24 weeks; treatment was initiated after a median of 76 days after infection (range 14-150)."

The researchers explained, "End-of-treatment response and sustained virological response were defined as undetectable HCV RNA at the end of therapy and after 24 weeks of follow-up, respectively.

"In the total study population, virological response was 82% at the end of treatment and 71% at the end of follow-up. Of 89 individuals, 65 (73%) were adherent to therapy, receiving 80% of the interferon dosage within 80% of the scheduled treatment duration. End-of-treatment and sustained virological response rates in this subpopulation. were 94% and 89%, respectively."

"A maximum Ala aminotransferase level of more than 500 U/L prior to therapy was the only factor associated with successful treatment," the scientists explained.

"In acute HCV infection, early treatment with peginterferon alpha 2b leads to high virological response rates in individuals who are adherent to treatment. The high number of dropouts underlines the importance of thorough patient selection and dose monitoring during therapy," concluded the authors.

"Thus," they further noted, "future studies should identify factors predicting spontaneous viral clearance to avoid unnecessary therapy."

Wiegand and colleagues published their study in Hepatology (Early monotherapy with pegylated interferon alpha-2b for acute hepatitis C infection: the HEP-NET Acute-HCV-II Study. Hepatology, 2006;43(2):250-256).

Additional information can be obtained by contacting M.P. Manns, Hannover Medical School, Department of Gastroenterology, Hepatology & Endocrinology, Carl Neuberg Str 1, D-30625 Hannover, Germany.

Keywords: Hannover, Germany, Hepatitis C Virus, Pegylated Interferon, Ribavirin, Viral Clearance, Virological Response Rates.

This article was prepared by World Disease Weekly editors from staff and other reports. Copyright 2006, World Disease Weekly via NewsRx.com.

Hep C - three studies

Data from India, the People's Republic of China and the United States advance knowledge in hepatitis C virus research

Genomics & Genetics Weekly - Jun. 09, 2006

Hepatitis c virus data are the focus of recent research from India, the People's Republic of China and the United States.

Study 1: According to recent research from India, hepatitis C virus (HCV) genotype 3 predominates in north and central India and is associated with significant histopathologic liver disease.

"HCV genotypes help to tailor the treatment response, but their influence on the disease severity and association with hepatic steatosis is not well understood. The prevalence of HCV genotypes and their correlation with the histopathological severity of liver disease and steatosis in Indian patients were studied," wrote S.S. Hissar and colleagues, GB Pant Hospital.

They continued, "HCV-RNA and genotyping was carried out in 398 patients with chronic hepatitis C. Liver biopsy was available in 292 (73.4%) patients. The severity of liver disease was graded on the basis of the histological activity index and the stage of hepatic fibrosis. The patients were categorized as having mild (histological activity index & le;5 and/or fibrosis & le;2) or severe (histological activity index & ge;6 and/or fibrosis & ge;3) liver disease.

"Steatosis was graded in 106 patients as 0 (no steatosis), 1 (<33%>66% of hepatocytes affected). HCV genotype 3 was detected in 80.2% patients (3a:24.4%, 3b:3.3%, 3c:0.5%, 3a/3b:36.7%, and unsubtypable 3:15.3%), genotype 1 in 13.1% (1a:3%, 1b:5.5%, 1a/1b:0.3%, and unsubtypable 1:4.3%), genotype 4 in 3% patients (4a:1.5%,4b:0.3%,4a/4c:0.5%, and un-subtypable 4:0.8%), 2 in 2.5% and mixed genotypes (more than one genotype) in 1.3% of patients."

"The median histological activity index and fibrosis scores were: 5 and 2 in genotype 1; 4 and 2 in genotype 2; 5 and 2 in genotype 3; 7 and 3 in genotype 4; and 5 and 2 in mixed genotypes, respectively. Severe liver disease was present in 17 of 38 (45%) with genotype 1; in 1 of 3 (33%) with genotype 2; in 128 of 236 (54%) with genotype 3; 7 of 10 (70%) with genotype 4; and in 1 of 4 (25%) with mixed genotype. Hepatic steatosis grade & ge;2 was found in 28.1% of genotype 3; 23.5% of genotype 1; 20% of genotype 4; and in none of genotype 2 and mixed genotypes," wrote the researchers.

The authors concluded, "Genotype 3 is the most prevalent genotype in patients with chronic hepatitis C in North and Central India and this is associated with significant hepatic steatosis and fibrosis."

Hissar and colleagues published their study in the Journal of Medical Virology (Hepatitis C virus genotype 3 predominates in north and central India and is associated with significant histopathologic liver disease. J Med Virol, 2006;78(4):452-458).

For additional information, contact S.K. Sarin, GB Pant Hospital, Department of Gastroenterology, Room 201, Academy Block, New Delhi 110002, India.

Study 2: Research from the People's Republic of China has documented that combination therapy is influenced by fatty liver in chronic hepatitis C (CHC).

"Hepatic steatosis is a histological feature in patients with CHC and adversely affects the virologic response rates to anti-hepatitis C virus (HCV) therapy. The aim of this study is to investigate whether the fatty liver and related factors have impact on the efficacy in CHC treated with peginterferon and ribavirin, and the associations between HCV genotyping and fatty liver," wrote J. Wu and colleagues, Harbin Medical College.

They continued, "Ninety-eight patients received subcutaneously 180 mcg peginterferon alpha-2a once a week plus ribavirin. HCV genotypes and the levels of plasma insulin of patients were measured. Fatty liver was detected by B ultrasound. The body mass index (BMI), waist-to-hip ratio (WHR) and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated."

The researchers wrote, "Among 98 CHC patients, 38 (38.8%) were infected with genotype 1; 44 (44.9%) with genotype 2; 13 (13.3%) with genotype 3; 3 (3.0%) with indeterminate genotype. The prevalence of fatty liver was 10.5%, 11.4%, 38.5% in patients infected with HCV genotype 1, 2, 3, respectively, which suggested that the distribution of fatty liver in different HCV genotypes was imbalanced (chi2=6.758, p=.034).

"In univariate analysis, the efficacy of combination therapy was significantly associated with BMI (p=.011), WHR (p=.024), the levels of plasma insulin (p=.001), genotype (p=.036), presence of fatty liver (p=.028), treatment dosage and duration (p=.012) and HOMA-IR (p=.002). With binary logistic regression analysis, the plasma insulin levels and HOMA-IR showed independent predictors to the efficacy of antiviral therapy."

"The prevalence of fatty liver in HCV genotype 3 was markedly higher than that of other genotypes. The BMI, WHR, the levels of plasma insulin, genotype, presence of fatty liver, treatment dosage and duration and HOMA-IR were associated with the sustained virologic response," the authors reported.

They concluded, "The level of plasma insulin and HOMA-IR were independent factors for predicting effect of antiviral therapy."

Wu and colleagues published their study in Liver International (Effects of fatty liver and related factors on the efficacy of combination antiviral therapy in patients with chronic hepatitis C. Liver Int, 2006;26(2):166-172).

For additional information, contact S. Chen, Harbin Medical College, Affiliated Hospital 2, Department of Infectious Disease, Harbin 150086, People's Republic of China.

Study 3: According to researchers from the United States, intrahepatic cytokine expression is downregulated during hepatitis C virus HCV/HIV co-infection.

"HIV co-infection is associated with reduced HCV treatment response rates and accelerated HCV-related liver disease. Cytokines play an important role in regulating hepatic inflammation and fibrogenesis during chronic HCV infection, yet the roles of HIV and/or its therapies on cytokine expression are unknown," wrote J.T. Blackard and colleagues, Massachusetts General Hospital.

"Total RNA was extracted from liver biopsies of 12 HCV monoinfected and 14 HCV/HIV co-infected persons. We used real-time PCR to quantify cytokines that contribute to innate and adaptive immune responses, including IFNalpha, IFNgamma, TNFalpha, TGFbeta1, IL-2, IL-4, IL-8, IL-10, and IL-12p40. Positive- and negative-strand HCV RNA levels were quantified using a molecular beacon approach."

The researchers wrote, "Detection of positive-strand HCV RNA was 100% in both groups; negative-strand HCV RNA was detected in four (33%) HCV mono-infected persons and in nine (64%) HCV/HIV co-infected persons."

"Median strand-specific HCV RNA levels were not significantly different between the two groups. Detection rates of cytokine mRNAs were lower for the HCV/HIV co-infected group compared to the HCV mono-infected group; the detection rates for TNF alpha, IL-8, and IL-10 were statistically significant."

"Overall, cytokine mRNA quantities were lower for HCV/HIV co-infected compared to HCV monoinfected persons, with the exception of TGFbeta1," reported the authors.

They concluded, "These data suggest that a defect in cytokine activation may occur in HCV/HIV co-infected persons that limits efficient clearance of HCV from the liver."

Blackard and colleagues published their study in the Journal of Medical Virology (Intrahepatic cytokine expression is downregulated during HCV/HIV co-infection. J Med Virol, 2006;78(2):202-207).

For additional information, contact R.T. Chung, Massachusetts General Hospital, Gastrointestinal Unit, GRJ 825, Boston, MA 02114, USA.

Keywords: Boston, Massachusetts, United States, AIDS, Antiretroviral Therapy, Hepatitis C Virus, Human Immunodeficiency Virus, HIV, Cytokines, Downregulation, Co-Infections, RNA.

This article was prepared by Genomics & Genetics Weekly editors from staff and other reports. Copyright 2006, Genomics & Genetics Weekly via NewsRx.com.

PegIntron & Ribavirin experience

Debbie, a resident of Peoria, Arizona, United States - writes in her blog Chronic Hepatitis C:

DARE I ASK, WHAT'S NEXT?

What a mind-blower! To discover that my treatment was actually working and killing me, at the same time. What the hell is that? How truly ironic this whole situation is. Just what exactly am I supposed to do now? Wake up everyday knowing that a deadly virus is slowly destroying my liver, and there is nothing I can do? I guess so. Oh what the hell! I can not change one single thing or a moment, can I? On the other hand, that damn treatment is over and I am starting to recover.

I had two attempts at the PegIntron & Ribavirin cocktail, over the past two years. As for me, I AM DONE!! I will never go through this again, nor will I ever put my husband and family through this. It is just not worth the pain and suffering we all had to endure. As most all of you know from my past blogs, "I HATE NEEDLES, remember? I knew, that you would! Well, my abhorrence for needles, has only gotten worse from the treatment; (weekly routine blood labs, 12 blood transfusions in 5 months, 2 weekly injections, etc.,) and just the thought of needles makes my skin crawl. I guess the 48/wk treatment wasn't the best option for me, but it was the only option I had or have even now.

I am not quite sure how I feel, at the moment. I have been struggling with many issues. My sister is in grave health back east. I moved out west 18 months ago and have been unable to return for a visit. I can not recall a time when I have been away for so long without seeing them. THIS ONE IS FOR MY BROTHER-IN-LAW,(who reads my blog): "Hey Dan, Love you, Take Care!" My sister is far worse than I. My chronic hepatitis C has been a cake walk, compared, to what she has to endure, and what she will be going through the rest of her life, as well.

In life you never know what each day holds, or what each hour may bring, and how each second, our lives hang in the balance. There are so many things that are out of our control, and there are times when great pain, suffering, despair and heartache, strikes all of our lives. All we truly have is this moment, right here, right now. As for anything else, well, I guess that remains to be seen. Does't it?

June 01, 2006

Hepatitis C calls top 700 in day

Alert: if you have HEP C, please inform the same to your dentist and all other healthcare workers.

The hepatitis C virus is blood-borne

More than 700 patients of a former Gwynedd health care worker diagnosed with hepatitis C called a special hotline for advice on its first day.

About 5,000 patients have been sent letters with the phone number, and 400 people have now booked blood tests for hepatitis C and B and HIV.
Five of the 47 special clinics set up for blood testing were fully booked.
But the National Public Health Service for Wales has stressed the risk to patients is "very small indeed".

The NPHS discovered that the member of staff, who was understood to have worked at a dental surgery, had hepatitis C in October. Free testing is being offered to some 5,000 patients who may have concerns. The confidential hotline for patients to book blood tests was opened on Wednesday, and 717 people called on the first day.

Special blood testing clinics are being held around Gwynedd between 5 June and 17 July. Dr Sandra Payne, regional director for the NPHS for Wales, said: "Our lines are very busy and I am grateful to patients for the understanding they are showing.

"People are understandably concerned and I would like to emphasise that the risk of patients getting hepatitis C, hepatitis B or HIV is very small indeed."

Vertex Pharmaceuticals - 23 May 2006

Vertex Pharmaceuticals Initiates the First of Two Major Phase II Studies of VX-950 in Treatment-Naïve HCV Patients

- PROVE 1 & PROVE 2 Studies Expected to Enroll 580 Patients -

Cambridge, MA, May 23, 2006 –– Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today reported that it has initiated PROVE 1, a major Phase II study of VX-950, an investigational oral hepatitis C virus (HCV) protease inhibitor. In addition, the Company today announced it expects to initiate PROVE 2, a second major Phase II study in June. The studies will be conducted in the United States and Europe as part of a global Phase II development program for VX-950. Together, the two studies are expected to evaluate sustained viral response (SVR) rates in 580 treatment-naïve patients infected with genotype 1 HCV.

Vertex’s global Phase II development program in treatment-naïve patients has three objectives: to evaluate the optimal SVR rate that can be achieved with VX-950 therapy in combination with the current standard of care, to evaluate the optimal treatment duration for VX-950, and to evaluate the role of ribavirin in VX-950-based therapy. In addition to these two major studies, Vertex expects to begin additional clinical studies of VX-950 in the second half of the year, including a Phase IIb study in patients who failed prior standard of care treatment. Vertex anticipates this Phase IIb study to enroll approximately 400 patients. By the end of the first quarter of 2007, Vertex expects to have enrolled approximately 1,000 patients in clinical trials of VX-950.

“PROVE 1 is the largest clinical study to date of an HCV protease inhibitor in triple combination therapy in a treatment-naïve patient population, and provides us with the first opportunity to assess the potential to enhance sustained virologic response rates with a shortened treatment duration with VX-950, along with peginterferon and ribavirin,” said John McHutchison, M.D., Duke University and Lead Investigator for the PROVE 1 study. “Throughout this Phase II study, we will further develop a clinical and safety database and increase our experience with VX-950 among clinicians and patients.”

VX-950 Program Update
PROVE Studies
The two studies announced today are the initial studies in a program of the “Investigation of HCV Protease Inhibition for Viral Eradication” (PROVE). The PROVE 1 and PROVE 2 studies have been designed as major, complementary studies to be conducted in the United States and Europe that will evaluate the ability of VX-950 to achieve SVR with short duration combination therapy. Following consultations with regulatory authorities in the U.S. and Europe, trial designs have been completed. Vertex expects the PROVE 1 and PROVE 2 studies to enroll 580 patients at more than 55 centers worldwide. Vertex expects that these studies, taken together, will provide a substantial evaluation of the potential of VX-950-based therapy to achieve SVR.

PROVE 1 Study in the U.S.
Vertex has initiated in the U.S., a four-arm, 260-patient Phase II study of VX-950 known as PROVE 1. The first dosing of patients will occur in June. The primary objective of this study is to assess the proportion of patients in each study arm who achieve SVR, defined as undetectable (less than 10 IU/mL, as measured by the Roche TaqMan® assay) HCV RNA 24 weeks after the completion of dosing. In the study, there will be an initial randomization of 80 patients equally across all four treatment arms. There will be a second randomization of an additional 180 patients across three treatment arms focused on 24 and 48 weeks of therapy. The study will be conducted in approximately 35 centers in the U.S. The study arms include:

12 weeks of therapy, with VX-950 dosed at 750 mg every eight hours (q8h) in combination with standard doses of pegylated-interferon (peg-IFN) and ribavirin (RBV); or
24 weeks of therapy, with VX-950 dosed at 750 mg every eight hours (q8h) in combination with standard doses of peg-IFN and RBV for 12 weeks, then continuing for another 12 weeks with peg-IFN and RBV alone; or
48 weeks of therapy, with VX-950 dosed at 750 mg every eight hours (q8h) in combination with standard doses of peg-IFN and RBV for 12 weeks, then continuing for another 36 weeks with peg-IFN and RBV alone; or
A control arm with peg-IFN and RBV dosed for 48 weeks

Patients in the 12 and 24-week treatment arms who achieve a rapid viral response (RVR) defined as undetectable (less than 10 IU/mL) viral levels by the end of week 4, and who maintain this status through to either week 10 or 20 respectively, will stop all treatment at the 12 or 24-week time point and will be followed post-treatment to evaluate whether they achieve SVR. Patients in these treatment arms who do not meet the RVR criterion will continue on peg-IFN and RBV for a total duration of 48 weeks. The 48-week treatment arm that contains VX-950 will evaluate whether 36 weeks of additional treatment with peg-IFN and RBV adds substantially to the SVR rate compared to 12 weeks of additional treatment with peg-IFN and RBV.

PROVE 2 Study in Europe
In June, Vertex will initiate in Europe, a four-arm, 320-patient Phase II study of VX-950, known as PROVE 2. The primary objective of this study is to assess the proportion of patients in each study arm who achieve SVR, defined as undetectable (less than 10 IU/mL) HCV RNA 24 weeks after the completion of dosing. In the study, 320 patients will be randomized equally across all four treatment arms, providing a total of 80 patients per arm. The study will be conducted in more than 20 centers in Europe. The study arms include:

12 weeks of therapy, with VX-950 dosed at 750 mg every eight hours (q8h) plus a standard dose of pegylated-interferon (peg-IFN); or
12 weeks of therapy, with VX-950 dosed at 750 mg every eight hours (q8h) plus standard doses of peg-IFN and ribavirin (RBV); or
24 weeks of therapy, with VX-950 dosed at 750 mg every eight hours (q8h) plus standard doses of peg-IFN and RBV for 12 weeks, then continuing for another 12 weeks with peg-IFN and RBV alone; or
A control arm with peg-IFN and RBV dosed for 48 weeks

As in the PROVE 1 study, patients in the 12 and 24-week treatment arms who achieve a rapid viral response (RVR) defined as undetectable (less than 10 IU/mL) viral levels by the end of week 4, and who maintain this status through to either week 10 or 20 respectively, will stop all treatment at the 12 or 24-week time point and will be followed post-treatment to evaluate whether they achieve SVR. Patients in these treatment arms who do not meet the RVR criterion will continue on peg-IFN and RBV for a total duration of 48 weeks. The 24-week treatment arm will evaluate whether 12 weeks of additional treatment with peg-IFN and RBV adds substantially to the SVR rate compared to 12 weeks of VX-950 in combination with peg-IFN and RBV.

Additional Studies
In addition, Vertex expects to further broaden the VX-950 development program to evaluate VX-950 in other treatment regimens and patient populations. In the second half of the year, Vertex plans to initiate a Phase IIb study in patients who failed prior standard of care treatment. Vertex anticipates this Phase IIb study to enroll approximately 400 patients. The Company also expects to begin a multi-dose, drug-drug interaction study of VX-950 and low-dose ritonavir in the second half of this year. By the end of the first quarter of 2007, Vertex expects to have enrolled approximately 1,000 patients in clinical trials of VX-950.

“In clinical trials to date, VX-950 has consistently demonstrated rapid and dramatic reductions in HCV RNA levels,” said John Alam, M.D., Executive Vice President of Medicines Development and Chief Medical Officer for Vertex. “We believe the 2006 global Phase II program will establish VX-950’s clinical profile by answering key questions about SVR rates, treatment duration and the role of ribavirin. We will receive the first clinical data from this global Phase II program starting in Fall 2006.”

Data Presentations for VX-950
On May 21, 2006, Vertex announced results for a 28-day, Phase II study of VX-950 in combination with peg-IFN and RBV at the Digestive Disease Week® (DDW®) Conference in Los Angeles, California, which showed that plasma HCV RNA levels were below the limit of detection (10 IU/mL) in 12 of 12 patients at the end of 28 days of treatment with VX-950 in combination with peg-IFN and RBV. Researchers also reported that 11 of these patients continued to have no detectable virus in their blood at the end of 12 additional weeks of follow-on peg-IFN and RBV dosing. On April 29, 2006, at the 41st Annual Meeting of the European Association for the Study of the Liver (EASL), Vertex presented initial results for a 14-day, Phase Ib study of VX-950 and peg-IFN, which showed that at day 14, the majority of patients (6 of 8) receiving the combination had HCV RNA levels below the limit of quantitation (30 IU/mL), and 4 of 8 patients had HCV RNA levels below the limit of detection (10 IU/mL). Researchers reported for the first time at EASL that 8 of 8 patients who received VX-950 and peg-IFN in combination for 14 days had no detectable virus in their blood at the end of 12 additional weeks of peg-IFN and RBV dosing.

About Hepatitis C
Hepatitis C is a liver disease caused by the hepatitis C virus, which is found in the blood of people with the disease. HCV, a serious public health concern affecting 3.4 million individuals in the United States, is spread through direct contact with the blood of infected people. Though many people with hepatitis C may not experience symptoms, others may have symptoms such as jaundice, abdominal pain, fatigue and fever. Hepatitis C significantly increases a person’s risk for developing long-term infection, chronic liver disease, cirrhosis or death. The burden of liver disease associated with HCV infection is increasing, and current therapies provide sustained benefit in only about 50% of patients with genotype 1 HCV, the most common strain of the virus.

About Vertex
Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company’s strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex’s product pipeline is principally focused on viral diseases, inflammation, autoimmune diseases and cancer. Vertex co-promotes the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.

Lexiva is a registered trademark of the GlaxoSmithKline group of companies.
TaqMan® is a registered trademark of Hoffman-La Roche Inc.

Safe Harbor Statement
This press release may contain forward-looking statements, including statements that (i) Vertex expects to have the first clinical data from this Phase II program beginning in the fall of 2006; (ii) planned studies will build extensive clinical activity and safety experience with VX-950 among clinicians and patients; (iii) the PROVE 1 study will begin dosing patients in June; (iv) the PROVE 2 study will be initiated in June; (iv) the PROVE 2 study will be initiated in June; (v) Vertex will initiate later in 2006 a Phase II study of VX-950 in approximately 400 patients who have failed prior HCV therapy; and (vi) by the end of the first quarter of 2007, Vertex expects to have enrolled approximately 1,000 patients in clinical trials of VX-950. While management makes its best efforts to be accurate in making forward-looking statements, such statements are subject to risks and uncertainties that could cause Vertex’s actual results to vary materially. These risks and uncertainties include, among other things, the risks that clinical trials for VX-950 may not proceed as planned due to technical, scientific, or patient enrollment issues, or disagreements with regulatory authorities over trial design or other matters, that the scale and scope of future clinical and nonclinical studies may change and will be determined in significant part by data collected in ongoing and future trials, that further clinical studies of VX-950 may not reflect the results obtained in early clinical and nonclinical studies, that ongoing nonclinical studies, including toxicology studies, will yield currently unanticipated negative outcomes that could adversely affect planned clinical trials, that results from the Company’s clinical trials commenced during 2006 will be insufficient to support a Phase III program without additional trials and consequent delay in the timetable for potential approval, and other risks listed under Risk Factors in Vertex’s form 10-K filed with the Securities and Exchange Commission on March 16, 2006.

Conference Call and Webcast: PROVE Study Update
Vertex Pharmaceuticals will host a conference call today, May 23, 2006 at 9:00 a.m. EDT to review the VX-950 global Phase II program. This call will be broadcast via the Internet at www.vrtx.com in the investor center. Alternatively, to listen to the call on the telephone, dial (800) 374-0296 (U.S. and Canada) or (706) 634-2224 (International). Alternatively, Vertex is providing a podcast MP3 file available for download on the Vertex website, www.vrtx.com.

The call will be available for replay via telephone commencing May 23, 2006 at 12:00 p.m. EDT running through 5:00 p.m. EDT on May 30, 2006. The replay phone number for the US and Canada is (800) 642-1687. The international replay number is (706) 645-9291 and the conference ID number is 9742527. Following the live webcast, an archived version will be available on Vertex’s website until 5:00 p.m. EDT on June 6, 2006.

Vertex Contacts:
Lynne Brum, Vice President, Strategic Communications, (617) 444-6614
Michael Partridge, Director, Corporate Communications, (617) 444-6108
Lora Pike, Manager, Investor Relations, (617) 444-6755
Zachry Barber, Senior Media Relations Specialist, (617) 444-6470