LiverHope
Volume 5, Issue 4 April 2003
LiverHope
Volume 5, Issue 4 April 2003
Are you newly diagnosed or do you want more information about Hepatitis
C?
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April
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In This Issue
Calendar.............................................................................................. 1
H.I.V.
Lessons Used in Hepatitis C Treatment............................. 1
UTMB to
Launch Revolutionary Program To Screen Drugs..... 3
First Report
on the Antiviral Efficacy of BILN 2061.................... 4
Peg-Intron
Access Assurance Program Ends.............................. 4
Love Your
Liver Walk....................................................................... 5
New Pair of
Shoes............................................................................. 5
Reflexology………………………………………………… 5
NY Times
H.I.V. Lessons Used in Hepatitis C Treatment
No drugs are yet being sold
that specifically treat the hepatitis C virus, but some companies now are
addressing the problem
March 11, 2003
By ANDREW POLLACK
Drugs that interfere with H.I.V. have had a major effect in reducing death and disability from AIDS. Now drug companies are beginning to test the first similar drugs for the hepatitis C virus, which can cause fatal liver disease and has infected far more people than H.I.V.
"If they work, they could have the same impact on H.C.V. that the H.I.V. drugs do," said Dr. Frank Chisari, a professor of virology at the Scripps Research Institute in San Diego.
Hepatitis C is now treated by the combination of alpha interferon, an immune system protein, and a pill called ribavirin. The newest versions of the combination can virtually eliminate the virus in about half of the patients.
But that leaves the other half at the mercy of the virus. Moreover, the treatment has severe side effects that include
anemia, birth defects, flu-like symptoms, depression and even an urge to commit suicide.
"There's a huge need for better drugs, less toxic drugs," said Dr. Michael G. Katze, a professor of microbiology at the University of Washington.
Neither interferon nor ribavirin was specifically designed to attack hepatitis C. Each appears to give a general boost to the immune system to help it attack the virus, though scientists do not fully understand how they work.
But the new hepatitis C drugs entering clinical trials are designed to interfere with enzymes that the hepatitis C virus needs to replicate, like protease and polymerase. Similarly, the AIDS drugs interfere with two enzymes used by H.I.V. to replicate, protease and reverse transcriptase. Some of the AIDS drugs can also be used for hepatitis B but not for hepatitis C, which operates differently.
It will take years to know if the new drugs will work. But scientists are encouraged by a proof of principle reported by Boehringer Ingelheim, a German drug company, at the American Association for the Study of Liver Diseases conference in Boston in November. The company said its experimental protease inhibitor reduced viral levels by a range of a hundredfold to more than a thousand fold in a small number of patients who took the drug for only two days.
"Sort of a hush went over the audience," Dr. Charles M. Rice, director of the Center for the Study of Hepatitis C at Rockefeller University in Manhattan, recalled.
Others are now entering the race. ViroPharma, a biotech company in Exton, PA, announced in January that it had begun a clinical trial of a polymerase inhibitor in partnership with the Wyeth drug company. So did Idenix Pharmaceuticals, a biotech company based in Cambridge, MA. Japan Tobacco reports having a polymerase inhibitor in Phase 2, the middle stage of clinical trials.
Vertex Pharmaceuticals, also of Cambridge, has said it will start a trial later this year of a hepatitis C protease inhibitor and Rigel Pharmaceuticals of South San Francisco, CA, plans to start a polymerase inhibitor trial this year. Isis Pharmaceuticals of Carlsbad, CA, is in Phase 2 trials with a drug that tries to interfere with a different part of hepatitis C.
Hepatitis C has infected about four million Americans and 170 million people worldwide, about four times as many as H.I.V.
Hepatitis C is spread mostly by needles or blood transfusions, rarely sexually. The rate of new infections in this country has dropped sharply to about 25,000 a year since a test to screen donated blood for the virus was approved in 1990. But there are still many people infected before the test was used that have yet to develop symptoms. The Centers for Disease Control and Prevention estimates that the number of deaths from hepatitis C, now 8,000 to 10,000 annually in the United States, could triple by 2010.
But while there are now well over a dozen drugs that directly interfere with H.I.V. enzymes, there are none that work that way for hepatitis C.
Scientists say one reason for the discrepancy is that the hepatitis C virus was identified in 1988, four years after H.I.V. Still, numerous drugs for AIDS were approved within 15 years of its discovery. In contrast, 15 years after the hepatitis C discoveries, the first drugs are only entering clinical trials.
Another reason, some scientists say, is that there has been much more federal financing for H.I.V., which has been considered more of a crisis than hepatitis C and has patients who have fought hard for money for research and treatments. Also, many people with the hepatitis C virus never get sick or do so only 10 or 20 years later.
Yet another factor, some say, is that the Chiron Corporation, the biotech company in Emeryville, CA, that first identified the hepatitis C virus, has demanded too much money for licenses to its patents, discouraging companies from entering the field.
"Chiron has been a little bit like a dog with a bone," said Dr. Donald G. Payan, executive vice president and chief scientific officer of Rigel. "I think they really slowed the field down. A lot of people just didn't want to get into it."
Gilead Sciences, which has developed successful antiviral drugs for H.I.V. and hepatitis B, dropped work on hepatitis C after being sued by Chiron. Vertex, which says it does not violate the patents, is in the midst of a lawsuit.
Robert P. Blackburn, chief patent counsel for Chiron, said the company's patents were available for drug discovery to all comers for a modest upfront fee and royalties if a drug made it to market. He said Chiron took a significant risk in embarking on research to discover the virus and deserved to share in the proceeds from drugs developed by others. "Clearly companies like Vertex would not be working on an H.C.V. drug today but for our inventions," Mr. Blackburn said.
Still, most scientists agree, the biggest obstacle to the development of drugs for hepatitis C has been the inability to grow the virus in the test tube, a fact that makes it hard to study the virus or to test potential drugs. In addition, there are no animals that get hepatitis C except chimpanzees, which are expensive to use in testing.
Scientists have started
to circumvent those problems. In 1999, Dr. Ralf Bartenschlager, then at the
University of Mainz and
now at Heidelberg University in Germany, developed an artificial viral system
known as a replicon. Dr. Rice of Rockefeller University, who was then at
Washington University in St. Louis, improved on it.
The replicon consists of some of the RNA from hepatitis C, including that for the protease and polymerase enzymes. This RNA is put into liver tumor cells that can be grown in culture.
The replicon does not produce complete new viruses. But it does reproduce itself using the protease and polymerase enzymes. So drug companies can use the replicon to test if their protease or polymerase inhibitors seem to interfere with replication of the replicon.
"That's definitely a breakthrough that every group has used," said Dr. Marc Collett, vice president for discovery research at ViroPharma.
As with H.I.V., hepatitis C virus mutates rapidly and is likely to develop resistance to drugs, so combinations of drugs will probably be needed. "No one really knows what it's going to take for the antiviral effect to outrun the resistance effect," said Dr. Nathaniel Brown, vice president for hepatitis clinical research at Idenix Pharmaceuticals.
But, he and others said, hepatitis C may be easier to treat in some ways than AIDS. That is because H.I.V. turns its RNA into DNA, which is incorporated into the chromosomes of cells it infects, making it hard to totally eliminate the virus. But hepatitis C virus does not do that, and the experience with interferon has shown that if the virus can be eliminated, patients can be cured.
Dr. Amy Weiner, director of hepatitis C research at Chiron, is optimistic. "It does appear with the data we have to date that it is possible to cure people with H.C.V., which has never been shown with H.I.V.," she said.
September 24, 2002
University
of Texas Medical Branch at Galveston Public Affairs Office
GALVESTON, TEXAS--With several million Americans now infected by hepatitis C, finding drugs that will fight the deadly virus--which can destroy the liver--has become a medical priority. Scientists at the University of Texas Medical Branch at Galveston (UTMB) will launch a revolutionary effort to identify new treatments for this blood-borne scourge under the terms of a $6.6 million seven-year contract awarded today by the National Institute of Allergy and Infectious Disease (NIAID).
"We'll be screening between one and four thousand antiviral compounds annually to determine which ones have activity against hepatitis C," says principal investigator Nigel Bourne, a senior scientist at UTMB's Sealy Center for Vaccine Development and an associate professor of pediatrics. "For that we'll be using new cell-culture systems to do the first step in identifying novel antiviral agents against hepatitis C."
The cell culture systems being used were developed and patented by two other UTMB scientists working with Bourne on the contract, assistant professor MinKyung Yi and dean of medicine Stanley M. Lemon, director of UTMB's National Institutes of Health Hepatitis C Cooperative Research Center. The new systems build on a breakthrough in hepatitis C research made three years ago, when German scientist Ralf Bartenschlager discovered that a portion of the hepatitis C virus' genetic material known as a replicon could be made to reproduce in a test tube. Prior to Bartenschlager's discovery, researchers had been severely handicapped by the virus' refusal to grow outside a living human or chimpanzee host.
Although replicons do not allow scientists to grow complete infectious virus particles, they do let them study ways to interfere with the virus' ability to reproduce itself and thus prevent it from multiplying. Yi and Lemon's system is faster and easier to use than earlier replicon systems because it relies on a relatively simple enzyme assay rather than the more complicated reverse-transcriptase polymerase chain reaction (RT-PCR) method.
"For screening a large number of compounds, it makes that first step of identifying the ones you want to examine in more detail a lot easier," Bourne says. "It's a lot easier to pick out the trees from the woods, as it were."
Once the enzyme-based replicon system has picked out the most promising compounds from those submitted by industry, academia, and the NIH, a group headed by Richard Pyles of UTMB's Sealy Center for Vaccine Development will test the potential anti-viral agents again, attempting to confirm the results of the first screening and determine whether the compounds are non-toxic to human cells. Finally, Lemon and UTMB researcher Masanori Ikeda will put the most successful compounds through a third screening process to determine the molecular mechanisms involved and the possibility that mutant strains of the hepatitis C virus might develop a resistance to their anti-viral action.
"We hope that the compounds with the best activity and the least toxicity will become the next generation of therapeutics against hepatitis C, which we obviously badly need new drugs to treat," Bourne says.
Story
Courtesy of Newswise.com
Presented at AASLD – November 2002 - Abstract
866
Holger Hinrichsen, I Medizinische
Universitatsklinik, Kiel, Germany; Yves Benhamou, Groupe Hospitalier
Pitié-Salpetrière, Paris, France; Markus Reiser, Medizinische Universitätsklinik,
Bochum, Germany; Roel Sentjens, Academic Medical Center, Amsterdam,
Netherlands; Hemer Wedemeyer, Medizinische Hochschule, Hannover, Germany; Jose
L Calleja, Cimica Puerta de Hierro, Madrid, Spain; Xavier Forns, Hospital
Clinico, Barcelona, Spain; Jens Crönlein, Gerhard Nehmiz, Gerhard Steinmann,
Boehringer Ingelheim Pharma KG, Biberach, Germany
BILN 2061 is a potent and specific inhibitor of the HCV serine protease in-vitro. In a first exploratory trial in patients with minimal liver fibrosis, the effect of a 2-day oral treatment with BILN 2061 on the HCV of genotype 1 was investigated.
In an open, sequential group comparison, 31 patients with HCV genotype 1 and minimal liver fibrosis (determined histologically) were treated with 25, 200 or 500 mg BILN 2061 twice daily over 2 days, given orally as solution with PEG400. In each group, placebo was randomized in the ratio 2:8. Virus load (VL) was measured as HCV RNA by Cobas Amplicor HCV Monitor v2.0.
Mean age of all 31 patients in the 3 groups (including over enrollment of 1 patient with 25mg) was 47± 10 years, 7/31 were female. 14/31 patients were naïve for anti-HCV therapy. All patients completed the study and were followed up for 10-14 days. Viral load decreased by 1 LOG10 unit or greater in 7/9, 8/8 and 8/8 patients, treated with 25, 200 and 500mg, respectively, without difference between naïve and pre-treated patients. No response was seen with placebo.
After end of treatment, viral load returned to baseline levels within 1-7 days. Liver transaminases did not increase during treatment. Vital signs, adverse events, routine laboratory and ECG did not show relevant drug- induced changes. Tolerability was rated “good” by the investigators in all cases.
The authors of this study concluded that BILN 2061, given p.o.(by mouth) over 2 days at 25, 200 or 500mg twice a day, demonstrated antiviral activity against HCV genotype 1 in patients with minimal liver fibrosis. No safety issues were identified among the 25 patients exposed to BILN 2061.
From HCV Advocate Web Site
Peg-Intron Access Assurance Program Ends — Patient Assistance Programs Continue
Schering Corporation is pleased to announce that as of February 18, 2003, the PEG-INTRON Access Assurance program has been eliminated. Patients will now be able to take their prescriptions for PEG-INTRON (peginterferon alfa-2b) Powder for Injection directly to their pharmacy to be filled. Patients will no longer need to contact the Access Assurance program first to receive an Access Assurance ID number.
The PEG-INTRON Access Assurance program was implemented in October 2001 in anticipation of unprecedented patient demand temporarily affecting the supply of PEG-INTRON. Schering Corporation designed the Access Assurance program to ensure that individual patients who begin treatment with PEG-INTRON have uninterrupted access to a full course of therapy, regardless of possible fluctuations in demand for the product.
Schering-Plough has made major investments to increase PEG-INTRON production capacity at its manufacturing facility in Ireland, as well as in manufacturing facilities in Europe and Singapore. This increased production capacity enables us to end the Access Assurance program at this time.
We would like to take this opportunity to remind you of two unique programs that provide support to hepatitis C patients. The "Be In Charge" program provides support service for hepatitis B patients and hepatitis C patients whose physicians have prescribed Schering products. This program is free of charge and includes toll-free phone access to a nurse counselor 24/7, along with support group referrals and other treatment information. To reach a nurse counselor or to enroll in the program, patients can call 1-888-437-2608.
Schering also sponsors the "Commitment to Care" program, which helps patients identify and access insurance coverage, and provides free Schering products for qualifying patients in the United States. In 2002, the market value of this assistance and treatment, provided to more than 25,000 hepatitis C patients, was more than $100 million. To register for the "Commitment to Care" program, patients can call toll free to 1-800-521-7157.
Patients can also go to http://www.access-assurance.com/ for more information about the elimination of the Access Assurance program. This site includes a set of Frequently Asked Questions.
Press Release from Schering-Plough
|
At A Glance What?The Love
Your Liver Walk is an annual fundraising event for the American Liver
Foundation. Participants gather to
enjoy a morning of food, fun & festivities as they walk around scenic
Hyland Lake. Participants walk to
honor and remember those affected by liver disease. Where? Hyland Lake Park Reserve, Bloomington Edgewood Area When? Saturday May 17th, 2003 Registration: 9:00 Walk Begins 10:00 am Who?All are encouraged to participate;
children, adults, seniors, stroller and wagons are all welcome! This is a casual walk with no fitness
requirements. There is a $25.00 suggested
registration fee. Why?To support the American Liver
Foundation’s mission to prevent, treat and cure hepatitis and other liver
disease through research, education, and advocacy. Funds raised will support research, education, and public
awareness of liver disease and organ donation. How?Form a team or walk as an individual.
It is easy, set a goal for you and your team, and then collect donations from
friends, family and co-workers to support your efforts. It is just that simple. More Information? Contact the Minnesota Chapter of the
American Liver Foundation Amy Nelson,
Chapter Director Phone: 952-892-8441 Website: www.liverfoundation.org (click on the Minnesota Chapter link) |
New Pair of Shoes
Author
Unknown
When I got sober my sponsor told me that I had to be willing to change everything about my life -- everything. So, I wore blue jeans and switched to slacks. I wore western shirts and switched to T-shirts. But the one thing I just couldn't give up was my cowboy boots.
I went to my sponsor and said, "Surely I won't get drunk over a silly pair of cowboy boots. I'm willing to change a lot of things, and if needed I could even give up those boots, but it seems so silly."
My sponsor said, "I don't know how silly it is, or if you'll get drunk over those cowboy boots, but I can tell that you are not 'entirely' willing, though."
"Okay, okay," I said. "I'll prove it to you. I'll give up the boots for 30 days just to demonstrate my willingness to change."
So, I bought a pair of tennis shoes, and after 30 days of not wearing my cowboy boots, wearing tennis shoes instead, the strangest thing happened -- my feet stopped hurting.
That's how it was getting sober and giving up the high life. I never stopped to think that the boots were causing my feet to hurt, or the booze was causing my life to hurt. I got willing to give up the stuff, one day at a time, for 30 days, then 60 days, and then 90 days ... and my life stopped hurting.
And everyday I do something different, some change in some small way. Maybe I just put my socks on different, or drive to work a new way. Everyday, I try to do Little Things in a Big Way so that when Big Things happen I can handle them in a Little Way.
Co-Facilitators
Email: info@liverhope.com
Fax: (763) 566-0589
Website: www.liverhope.com
Helen: (952)
933-0932 – helen@liverhope.com
Pat: (763)
566-3839 – pat@liverhope.com
REFLEXOLOGY Reflexology is
based on a theory that there are areas in the hands and feet that
correspond to every part of the body, including organs and glands, and that
these parts can be affected by massaging the appropriate reflex areas. Reflexology is used to relieve stress
and tension, stimulate deep relaxation, and improve the blood supply to
normalize and balance the entire body.
[1] Susan McCarl CMT, is a graduate of the Sports Massage/Deep Tissue certification program at the Minneapolis School of Massage and Bodywork. She holds a national certification in massage from the National Certification Board for Therapeutic Bodywork and Massage Practitioners. Susan has extensive experience in soft-tissue rehabilitation and chronic pain management. She is also trained in reflexology, a therapy that has a long history of bringing balance within via reflex points that form a “map” of the body on the feet. Susan incorporates her sense of energy flow into all of her work but as a certified Reiki Master, she aids in bringing healing energy into blocked or depleted areas. Susan sees her role in massage and bodywork as a partner in the maintenance of well being.