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Week Ending: April 16th, 2005
Alan Franciscus
Editor-in-Chief
To download pdf version click here
This Issue:
• Kaiser Downplays Hepatitis Scare
• AIDS Alert After Dental Office Raid
• Management of Community Exposure to HIV, Hep B and Hep C
• Fatty Liver Present in 40% Of HIV/HCV Coinfected Patients: Drug Choice and Weight May Contribute
• Ribavirin Pregnancy Registry Launched
• Sexual Transmission of Hepatitis C Virus between Spouses
• Berg Needle-Exchange Bill Moves On
• Brandywine Business Services Shift Corporate Direction by Acquiring Hepatitis Vaccine Research Entity
• UNM Program Eases Access to Treatment of Hepatitis C
• New Data Calls into Question the "Watch And Wait" Treatment Strategy for Hepatitis C
• HCV Infection May be Concealed Initially, Doctors Warn
• Preventing Variceal Bleeds with Endoscopic Ligation plus Propranolol
• Hep C Therapy Impacts Future Liver Related Morbidity, Mortality and Costs
• Human Genome Sciences Hepatitis C Drug Passes Test
• Valopicitabine Shows Potential Therapeutic Response in the Treatment of Genotype 1 Hepatitis C Patients
• New Data on Most Prescribed Hepatitis C Therapy Pegasys(R) Presented at European Association for the Study of the Liver (EASL) Conference
April 9th, 2005
Kaiser Downplays Hepatitis Scare
SourceURL:http://www.timesheraldonline.com
By MATTHIAS GAFNI, Times-Herald staff writer
There have been "a small number" of positive hepatitis test results from Kaiser patients alerted that unsterilized equipment was used during procedures in South Sacramento and Redwood City, a hospital official said Friday.
So far, no positive results have been found through testing of Vallejo and Vacaville Kaiser patients who were notified of a similar problem, the official added. It was not immediately known how many of the 400 local patients have submitted to the hepatitis tests.
The hospital stressed that any infected patients could have contracted hepatitis before their procedures, which in both Sacramento and Redwood City involved sterilizing malfunctions with certain instruments.
About 1,300 patients were notified in April 2004 in Sacramento, and about 2,100 patients were notified in September in Redwood City that they should get tested for hepatitis A and B, according to Kaiser on Friday. Late Thursday, a Kaiser official told the Times-Herald only 1,500 patients were notified at the Redwood City facility.
Kaiser Permanente officials also clarified that patients notified in Redwood City and Sacramento received gastrointestinal procedures, not hysteroscopy procedures as the hospital first reported Thursday. Scopes used in the GI procedure, in which doctors inspect the intestines for potential digestive tract diseases, were not properly sterilized.
In recent weeks, the female patients of the Vallejo and Vacaville facilities have received similar notifications for improperly sterilized hysteroscopy procedures dating back four years. The hospital said the problem was due to a pre-cleaning of its flexible hysteroscopes used in the women's health departments. Hysteroscopes are used to examine the interior of a woman's uterus for diagnostic purposes.
Kaiser officials said it's too early to tell if any lab tests returned positive for those patients.
"Kaiser Permanente's infection control experts have advised us that our patients are at an extremely low risk for infection, but should be contacted and offered a free screening," the hospital said in a released statement.
So, how many patients tested positive for hepatitis in the Redwood City and South Sacramento facilities?
A Kaiser spokesperson said she doesn't know the number of positive test results, but stressed repeatedly that the infected patients didn't necessarily get hepatitis from their procedures.
"There are some positive tests, which is to be expected," according to Kaiser's statement. "In the population at large there are many people who have a form of hepatitis and don't know it.
"For example, the CDC estimates there are about 1.25 million Americans with hepatitis B, the majority of whom are unaware."
A 35-year-old Vallejo woman, who received a letter asking her to be tested in January, said the last couple months have been traumatic.
The patient, who wished to remain unnamed, said she received a hysteroscopy procedure at the Vallejo medical center in February 2003.
Almost two years later, she said, she received a call from her doctor advising her of the problem. The Vallejo woman was tested Feb. 2 for hepatitis. The results came back negative, she said.
"For about 10 days my husband and I worried that I had contracted something," she said. "I came home hysterical in tears, thinking, 'Oh my God, I'm guaranteed to be positive.' "
Even after testing negative, she said, she's still not feeling comfortable. "Not a day has gone by since then that I haven't thought, 'Hmm, well, Vallejo did the lab work, Vallejo did the results? Who's to say Vallejo didn't fix the results?' " she said. "Kaiser should've offered us patients an outside lab to do the test results through."
Kaiser Vallejo spokeswoman Valerie Roberts Gray said her lab and hospital have an excellent record and doctors would work with anyone with concerns.
"Any members are encouraged to speak directly with their physicians if they have concerns and work with them on a case-by-case basis to alleviate their concerns," Roberts Gray said.
And Kaiser's stressing of the "extremely low risk" of contracting hepatitis has grown old, said the Vallejo patient, telling her doctor after being tested: "If there was such a low probability - I wouldn't be here."
Kaiser discovered the problems in the sterilization methods of the four facilities internally, officials said. "We identified all instances of improper sterilization of scope equipment internally and conducted thorough reviews of sterilization procedures. We had taken steps in all service areas to ensure that this does not occur again," Kaiser's statement said.
The Vallejo and Vacaville facilities halted hysteroscopy procedures in December and began reviewing the equipment and files in order to notify patients who had such procedures done as far back as May 17, 2001.
A Kaiser spokeswoman said she did not know how far back reviews went on the Redwood City and Sacramento facilities.
Kaiser officials said these four facilities were the only ones recognized with these sterilization problems.
-- E-mail Matthias Gafni at mgafni@thnewsnet.com or call 553-6825.
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AIDS Alert After Dental Office Raid
SourceURL:http://www.365gay.com
by 365Gay.com Newscenter Staff
(West Palm Beach, Florida) Health officials in Palm Beach County have issued an emergency appeal for people who were treated in two local dental clinic to get tested for HI/AIDS and hepatitis.
Earlier this week Palm Beach County sheriff's officers and an agent from the Florida Department of Health raided the clinics and home of Kenol Pryam, 60.
Pryam operated clinics in Lake Park and Belle Glade, but it was discovered he does not have a dental license.
A native of Haiti, he is licensed in Florida only as a nursing assistant.
The raid on his offices uncovered what the Sheriff's office said were "unsanitary, deplorable" conditions.
Dr. Jean Malecki, director of the Palm Beach County Health Department said that dental patients may have been exposed to diseases and infections because of his use of unsterilized instruments, some reportedly "sanitized" in a toaster oven.
"This guy had over 300 vials of anesthetic drugs, plus 20 empty vials and 20 or more partially used vials of drugs, all without a license to buy or dispense these drugs," Detective Jim Brown told the Palm Beach Post. "Some of the drugs were imported illegally from South America including Lidocaina."
Dr. Phil Bilger, head of the county health department's division of dentistry, said he is concerned about a "1950s or '60s-era X-ray machine" he saw during the raid.
Bilger said it was unlikely the machine had been properly maintained and periodically recalibrated, as required by state law. Periodic inspections also are required in Florida to avoid the risk of overexposure to X-ray
He is facing six felony charges and authorities say he treated hundreds, possibly thousands of patients over the past few years.
Following his arrest Pryam refused to submit to blood tests for communicable diseases, prompting the health alert.
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April 11th, 2005
Management of Community Exposure to HIV, Hep B and Hep C
SourceURL:http://www.gastrohep.com
A new protocol in the Netherlands has proven effective in referring all people with HIV, Hep B and Hep C exposure outside of hospitals to the municipal health service for treatment, tracing and follow-up, reports this weeks British Medical Journal.
Prophylactic treatment and follow-up after exposure to HIV, Hepatitis B and Hepatitis C outside hospital needs to be improved.
Dr Sonder and colleagues from the Netherlands evaluated the policy on infectious diseases in 2003.
The researchers noted that until 2000, people in Amsterdam could report exposure outside hospital to either a hospital or the municipal health service.
The research team stated that if people self-reported to the municipal health service, they were then referred to hospitals for HIV prophylaxis.
The municipal health service handled treatment and follow-up related to Hepatitis B and Hepatitis C and traced sources.
In nearly 75% of cases the municipal health service traced and tested the source of infection – British Medical Journal
The team observed that for cases reported to a hospital, hospital staff often did not trace HIV sources or follow up patients for Hepatitis B and Hepatitis C.
The investigators state that key measures for improvement are required that provide adequate treatment for HIV, Hepatitis B and Hepatitis C for all reported exposures outside hospital.
The researchers report that a new protocol was introduced in January 2000, in which 3 Amsterdam hospitals and the municipal health service collaborated in the treatment and follow-up of exposures outside of hospital.
According to this new protocol, both municipal health service and hospitals can decide whether HIV prophylaxis is necessary and prescribe accordingly.
The researchers report that all people exposed in the community who go to hospitals are subsequently referred to the municipal health service for further treatment and follow-up.
The research team found this protocol to be effective in that most people comply with treatment and follow-up.
When indicated, HIV prophylaxis is started soon after exposure and in nearly 75% of cases the municipal health service traced and tested the source.
Dr Sonder’s team concludes, “Provision of treatment and follow-up in a single place enables tracing and testing sources.”
“Follow-up includes counseling and registration of all reported exposures in Amsterdam, which allows for swift identification of emerging epidemiological trends.”
BMJ 2005: 330: 825-829
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Fatty Liver Present in 40% Of HIV/HCV Coinfected Patients: Drug Choice and Weight May Contribute
source: http://www.aidsmap.com/
Keith Alcorn
Hepatic steatosis, or fatty liver, was present in 40% of a cohort of American patients coinfected with HIV and hepatitis C, researchers from Johns Hopkins School of Medicine report in the April 8th edition of the journal AIDS. The risk of hepatic steatosis was greatest in patients with more advanced liver disease, and in those receiving treatment with stavudine (Zerit) and those suffering from hyperglycemia and/or obesity. Almost half of the patients exposed to a drug combination that included both stavudine and a protease inhibitor had hepatic steatosis.
Hepatic steatosis the accumulation of fatty acids in the liver - occurs frequently in people who are obese and in those with hyperglycemia, hyperlipidemia and/or high alcohol consumption. It also occurs in people with hepatitis C infection and may worsen liver inflammation and fibrosis (Martin-Carbonero 2005).
Dr Mark Sulkowski and colleagues randomly selected 112 patients with HIV/HCV coinfection exposed to at least two years of antiretroviral therapy from the Johns Hopkins University HIV Clinic population. Patients who had already received treatment for hepatitis C were excluded.
Liver inflammation, fibrosis and steatosis were assessed by liver biopsy. Fibrosis was assessed using the Modified Hepatic Activity Index scoring system, and hepatic steatosis was classified on a five point scale (0 no steatosis; 1 steatosis involving <5% of hepatocytes; 2 5-29%; 3 30-60%; 4 >60%).
The patient population selected was predominantly African American (94%), male (64%) and infected with HCV genotype 1 (99%). Twenty-six per cent weighed more than 86kg, 28% had hyperglycemia (glucose > 2.0g/l) and 22% had hypercholesterolemia (total cholesterol >200g/l). Forty-six per cent had been diagnosed with alcoholism previously, although few reported current alcohol use. Seventy-four per cent were taking antiretroviral therapy at the time of biopsy, of whom 86% had been exposed to stavudine. The median duration of NRTI exposure was 5.8 years.
Forty per cent of patients were found to have hepatic steatosis, of whom 22% had grade 1 steatosis, 13% had grade 2 steatosis and 5% had grade 3 steatosis. None had lactic acidosis. There was no difference in the prevalence of steatosis between those patients receiving antiretroviral treatment and those who had stopped treatment.
Fibrosis of MHAI grade 3 or above was present in 36% of patients with steatosis compared to 16% of those without steatosis (p=0.02). Necroinflammatory activity was also more frequent in those with steatosis (p=0.005).
Multivariate analysis showed that hepatic steatosis was independently associated with Caucasian race (OR 11.2), weight > 86kg (OR 3.2), hyperglycemia (OR 3.4) and prior exposure to stavudine (OR 5.1). Hepatic steatosis was not detected in any patient without prior exposure to stavudine plus a protease inhibitor, and was not associated with past alcohol use.
The authors say that their findings are consistent with other cohorts, and that the association with stavudine is presumably due to inhibition of mitochondrial DNA and possible depletion of hepatic mitochondrial DNA.
“These data…suggest that stavudine should be avoided in HIV-HCV coinfected patients with hepatic steatosis,” ther authors state. “If confirmed, our findings suggest that weight reduction and discontinuation of stavudine should be investigated as measures that could reduce hepatic steatosis in affected or at-risk individuals.”
In an accompanying editorial, Spanish coinfection experts Vincent Soriano and Luz Martin-Carbonero note that since only 4 of 112 patients had not received stavudine, and no difference was noted between patients currently receiving the drug and those who had discontinued it, caution should be used in interpretation of these findings.
Whilst experts increasingly support early HIV treatment for coinfected patients in order to limit the impact of immunodeficiency on liver disease, the editorial authors remark that, “depending on the antiretroviral drugs in use, the positive effects of HAART over HCV-related liver disease might be overshadowed by the development of drug-associated liver toxicities…a closer look is warranted.”
References
Martin-Carbonero, Soriano V. Interplay between hepatitis C, liver steatosis and antiretroviral therapy in HIV-infected patients. AIDS 19: 621-623, 2005.
Sulkowski MS et al. Hepatic steatosis and antiretroviral drug use among adults coinfected with HIV and hepatitis C virus. AIDS 19: 585-592, 2005.
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Ribavirin Pregnancy Registry Launched
The Ribavirin Pregnancy Registry is an FDA mandated program to monitor pregnancy exposures to ribavirin. The Registry was implemented in January 2004. Ribavirin is a nucleoside analog used in combination with interferon or pegylated interferon for treatment of chronic hepatitis C (HCV).
What is the Registry?
The Ribavirin Pregnancy Registry is a voluntary, prospective Registry designed to collect observational data on pregnancies and the outcomes following a pregnancy exposure to ribavirin. Ribavirin exposures may be direct, through the pregnant female or indirect, through her male sexual partner.
Why is the Registry important?
The incidence of HCV is highest in the population with reproductive potential (25 – 45 years of age) (CDC, 2001). Therefore, it is possible that inadvertent pregnancy exposures may occur during or following HCV treatment with ribavirin. In addition, it has been shown that significant teratogenic and/or embryocidal effects occurred in all animal species exposed to ribavirin. There are no data to determine if this is also the case in humans. However, ribavirin has been given an FDA Pregnancy Category X, indicating it should not be used in women who are pregnant (and for ribavirin specifically, for 6 months after treatment is stopped or in men whose sexual partners may become pregnant during or for 6 months after treatment is stopped).
It is not possible to study exposures in pregnancy other than monitoring inadvertent exposures. This Registry is the only program expressly established to evaluate first trimester, as well as, later prenatal exposures to ribavirin. Registry data supplement other sources of data and as data accrue, may assist clinicians and patients in weighing risks of ribavirin exposure in pregnancy. The lack of data on ribavirin pregnancy exposures and their outcomes makes such a Registry an essential component of the ongoing risk management program and epidemiologic studies on the safety of this product.
How to participate in the Registry
The Registry will accept prospective reports of pregnancy exposures to ribavirin from health care providers, pregnant patients, or pregnant patient’s male sexual partners. The data collected are minimal and targeted. Data are collected at each trimester and at outcome of pregnancy through the obstetric health care provider and for a live birth for 12 months after birth through the pediatric health care provider. Patient confidentiality is strictly upheld. The Registry assigns ID numbers to follow the pregnant female until a signed authorization for release of medical information is obtained. The Registry also collects “retrospective” information, i.e., reports after the outcome of the pregnancy is known.
How are data collected by the Registry and analyzed and reported?
An important aspect of the Registry is the Scientific Advisory Board formed to oversee the Registry data and analysis and presentation of results. The Board is composed of specialists in obstetrics and gynecology, infectious diseases/hepatology, and epidemiology, with ex-officio members from the Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA).
The data are collected through the Registry Coordinating Center (see contact information below). A Registry Interim Report published semiannually, summarizes the aggregate data and is available to interested health care providers.
How does participation benefit me and my patients?
This Registry is the primary source for collecting and evaluating direct or indirect exposures to ribavirin in pregnancy. Your contribution to this collaborative program enables you and your colleagues to assist in this public health initiative and to obtain information on the Registry through the Ribavirin Pregnancy Registry Interim Report published twice a year as data are available.
The success of the Registry relies on participation of patients and health care providers who report ribavirin pregnancy exposures and assist in obtaining pregnancy information through outcome and postnatal information on live birth outcomes.
How can I get more information?
Write, call, or fax at:
The Ribavirin Pregnancy Registry
Research Park; 1011 Ashes Drive; Wilmington, North Carolina 28405
US, Canada (800) 593-2214 (Toll-free phone) (800) 800-1052 (Toll-free fax)
www.ribavirinpregnancyregistry.com
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April 12th, 2005
Sexual Transmission of Hepatitis C Virus between Spouses
SourceURL:http://www.gastrohep.com
April's issue of the American Journal of Gastroenterology reports on the importance of the total number of sexual intercourse in spousal sexual transmission of Hep C and finds that none of the seronegative spouses developed seroconversion during follow-up.
The sexual transmission of Hepatitis C virus is debated.
By excluding other risk factors, the role of sexual intercourse in the transmission may be detected more accurately.
Dr Tahan and colleagues from Turkey screened for prevalence and risk factors for Hepatitis C in the spouses of chronic Hepatitis C patients and followed the seroconversion rate of anti-Hepatitis C negative spouses.
The research team recruited 600 spouses of chronic Hepatitis C patients.
The spouses' Hepatitis C risk factors were questioned and the spouses were tested for anti-Hepatitis C.
Anti-Hepatitis C was found positive in 2% of the spouses - American Journal of Gastroenterology
The team checked the 216 spouses who were anti- Hepatitis C negative on an annual basis for anti- Hepatitis C.
The investigators noted that anti- Hepatitis C was positive in 12 of 600 of the spouses.
Of the 12 anti-Hepatitis C positive spouses, 11 were Hepatitis C-RNA positive.
The researchers also reported that of the anti- Hepatitis C positive and negative spouse groups, the mean age was 52 and 50 years with a mean marriage duration of 1521 and 1532 weeks, respectively.
The number of total sexual intercourse in the 2 groups was 434 and 307, respectively.
In addition, the research team observed that none of the spouses developed anti- Hepatitis C seroconversion during a mean period of 36 months and 258 sexual intercourses.
Dr Tahan concludes, “Anti-Hepatitis C was found positive in 2% of the spouses and none of the seronegative spouses developed seroconversion in the 3 year follow-up period.”
“This is the first study that stresses the importance of the total number of sexual intercourse in sexual transmission.”
“Our results of a special monogamous group with very limited risk factors support the role of number of total sexual intercourse in Hepatitis C transmission.”
“However, the seroprevalence rate of the spouses was still within the upper limit of our country population.”
Am J Gastroenterol 2005: 100(4): 821
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April 13th, 2005
Berg Needle-Exchange Bill Moves On
SourceURL:http://www.eurekareporter.com
A legislative committee approved a bill by Assemblywoman Patty Berg that would make it easier for cities and counties to run needle-exchange programs.
Having been approved by the Assembly Appropriations Committee, Assembly Bill 547 could go before the full Assembly as early as next week.
The Assembly Health Committee approved the bill last week.
AB 547, endorsed by public health officers from around the state, would put an end to a law that requires communities to declare a health emergency every two weeks in order to run a needle-exchange program.
Health experts say the two-week requirement is a waste of time and tends to discourage local governments from operating exchange programs that have been proven effective in slowing the spread of HIV and Hepatitis-C, according to Berg’s office.
The bipartisan bill is being jointly authored by Assemblyman Keith Richman, R-Northridge.
“We should all take our cue from the public health officers on this,” Berg said. “This is a simple, common-sense measure that makes it easier to stop the spread of disease.”
In California, more than 1,800 people die of AIDS annually, and 1,500 new infections occur through syringe sharing among intravenous drug users. Another 5,000 people become infected with Hepatitis-C in the same manner, Berg said.
Providing needle-exchange programs helps slow the spread of disease, helps to prevent transmission to unborn children and provides drug users with important information about treatment for their addiction.
AB 547 is similar to Assembly Bill 2871, which Berg authored last year. That measure, which was approved overwhelmingly in the Legislature, but vetoed by the governor, had support from the California Medical Association, California National Organization for Women, California Nurses Association and the California Primary Care Association.
Berg”s latest measure already has support from 30 lawmakers, all of whom have agreed to co-author the bill.
There are currently 14 publicly run needle-exchange programs in the counties of Alameda, Contra Costa, Humboldt, Marin, Mendocino, Monterey, San Francisco, San Mateo, Santa Clara, Santa Cruz, Sonoma and Ventura, as well as the cities of Berkeley and Los Angeles.
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Brandywine Business Services Shift Corporate Direction by Acquiring Hepatitis Vaccine Research Entity
SourceURL:http://biz.yahoo.com
Press Release Source: Brandywine Business Services, Ltd, Inc
MINNEAPOLIS, MN--(MARKET WIRE)--Apr 13, 2005 -- Brandywine Business Services Ltd, Inc. (Other OTC:BYWN.PK - News) announced today that it has completed the acquisition of Koram Research and Development, South Korea. Koram R&D is a privately held research and development organization possessing patented liposome biotechnology and the exclusive product manufacturing of an oral vaccine for Hepatitis Type B and Type C. As part of the terms of the acquisition, Brandywine has agreed to change its name to TeloVax Corporation.
Mr. David Riggs, the founder of Koram R&D, has agreed to join TeloVax as President and Chief Executive Officer. TeloVax seeks to capture the majority market share of the annual $2B USD worldwide Hepatitis healthcare market opportunity. By leveraging their strategic manufacturing operations located in South Korea, the Company has positioned itself to be the major provider of the worldwide liposome vaccine solution to combat the enormous health care issue caused by Hepatitis Type B and Type C.
Liposome is a microscopic, fluid-filled pouch whose walls are made of layers, identical to the phospholipids that make up cell membranes. Liposomes are used to deliver certain vaccines, enzymes, or drugs (e.g., insulin and some cancer drugs) to the body. When used in the delivery of certain cancer drugs, liposomes help to shield healthy cells from the drugs' toxicity and prevent their concentration in vulnerable tissues (e.g., the kidneys, and liver), lessening or eliminating the common side effects of nausea, fatigue, and hair loss. Liposomes are especially effective in treating diseases that affect the phagocytes of the immune system because they tend to accumulate in the phagocytes, which recognize them as foreign invaders. They have also been used experimentally to carry normal genes into a cell in order to replace defective, disease-causing genes.
TeloVax is currently in the final stages of negotiations with a variety of joint venture initiatives with key strategic partners which will expedite and cost effectively assist the Company to bring biotechnology products to market utilizing Pacific Rim facilities and distribution infrastructures. In addition, the Company is also completing final negotiations with a number of US biotechnology entities to co-develop marketing ventures by addressing contract research and leverage partner licensing agreements. Through these relationships TeloVax believes that it will obtain a unique position to expand market share through product acquisition and development within the global biotechnology industry and pharmaceutical marketplace.
Note Disclaimer: The statements made in this press release contain statements concerning potential developments affecting the business, the prospects, the financial condition and other future aspects of the Company and partners. The actual results of the specifics described in this release, and the Company's operations may differ materially from what is projected in such forward-looking statements. Although such statements are based upon the best judgments of management as of the date of this release, expectations, timing and other significant factors may result in business risks and uncertainties including, without limitation to the company's dependence on third party agreements. The general market conditions, economic factors, the availability of outside capital, receipt of revenues and other technical factors, may also extend beyond the control of the Company. The Company disclaims any obligation to update information contained in all forward-looking statements.
© Telovax Corporation
This material, or parts thereof may be reused or reproduced for news release purposes only and may not be changed or altered in any manner.
Telovax Corporation, 1401 Marvin Road NE, Suite 307-245, Lacey, WA 98516
Contact Information:
David Riggs
President, CEO
TeloVax Corporation
360-528-2734
http://www.telovax.com
email: new_info@telovax.net
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UNM Program Eases Access to Treatment of Hepatitis C
SourceURL:http://www.rednova.com/
Orlando Velarde is one of 32,000 or more New Mexicans infected with a liver disease called hepatitis C. He learned he had it in 1999, while hospitalized for a blood clot in his arm.
He probably had been sick for two decades. But like many people with hepatitis C, he had no symptoms. Velarde believes he caught the virus through a blood transfusion in 1980 -- long before plasma banks screened for the disease.
Hepatitis C is a leading health concern in New Mexico, where deaths from liver disease and cirrhosis outpace the nation. (Alcoholism contributes to the problem, too.)
Less than 6 percent of New Mexicans with hepatitis C are getting treated. Part of the problem is access.
Velarde understands. To get the regimen of shots and pills, which can last a year, he had to drive from his home in Espanola to Santa Fe. There were no other options at the time.
The side effects alone can be grueling -- fatigue, nausea, pain. Adding a one-hour round-trip drive to that can make it agonizing.
Velarde dropped out of the program. But now he's back on track, because Health Centers of Northern New Mexico in Espanola began offering the treatment last year.
"I am now at seven months and feel good about getting cured," said Velarde, in his mid-40s.
Mainstream medicine offers one treatment for hepatitis C. It cures 50 to 80 percent of cases.
With a three-year grant from the federal government, The University of New Mexico School of Medicine has made treatment more available. Project ECHO, developed by Dr. Sanjeev Arora, educates primary-care physicians on the treatment of hepatitis C and provides weekly support, via telephone, with a broad-based group of specialists at UNM.
Under this telemedicine program, new outlets for care in Northern New Mexico include: Health Centers of Northern New Mexico, Pojoaque Primary Care, Santa Fe Indian Hospital and New Mexico State Penitentiary in Santa Fe. Other locations are: Bernalillo, Albuquerque, Las Cruces and five prisons.
At an open house Thursday, Health Centers of Northern New Mexico will spread the word that treatment is available. "Although not everyone is cured, it helps the liver even if you aren't cured," Bjeletich said.
The treatment isn't free. For uninsured patients, the clinic can bring the cost down to $1,000, using donated services and medicines, she said. Otherwise, insurance usually covers the cost of treatment, minus copays.
Espanola's first patient -- Velarde -- started in August 2004. Now the clinic has six. Patients must be clean from drugs and sober before beginning treatment, Bjeletich said.
The course of therapy lasts six months to a year, depending on what strain of the virus the patient has. Besides taking pills (ribavirin) daily, the patient must self-inject once a week with interferon. Like chemotherapy, the treatment kills infection- fighting blood cells, making patients vulnerable to germs.
New Mexico has lots of deaths related to hepatitis C, according to Arora, though firm numbers aren't available. The disease can lead to cancer of the liver, cirrhosis of the liver and death. For people with significant liver disease, treatment is urgent, he said.
Without medical care, one-fourth of hepatitis C patients develop cirrhosis of the liver -- a condition of irreversible scarring -- within 20 to 30 years of infection, Arora said.
Plenty of others, however, never suffer enough liver damage to endanger their lives. For them, treatment is optional, Arora said. They must decide whether they'd rather live with the fatigue, sleep disturbances, depression and loss of sexual vitality that hepatitis C can cause or endure the side effects of treatment, he said.
Hepatitis C is commonly transmitted through contaminated needles or straws during heroin or cocaine use. But nearly 10 percent of New Mexicans with the virus contracted it through blood transfusion -- a risk that has virtually disappeared, Arora said. Tattoos, especially those made in prison, can be worrisome; the virus can live up to a week in ink.
"There's a stigma attached to hepatitis C that does not need to be there," Bjeletich said. "There's lots of ways to get it."
And to date, there's no vaccine against it.
Hepatitis C: The silent epidemic
Most people infected with hepatitis C have no symptoms. But this disease of the liver can kill you.
In New Mexico, hepatitis C is 20 times more prevalent than AIDS, according to University of New Mexico School of Medicine --Dr. Sanjeev Arora.
The virus is transmitted by blood-to-blood contact.
To find out who is at risk and should take a blood test, Health Centers of Northern New Mexico in Espanola developed a screening tool:
1. Have you ever been diagnosed with hepatitis C? (If yes, stop here.)
2. Have you ever injected yourself with illegal drugs, even one time many years ago?
3. Do you have HIV or AIDS?
4. Did you have a blood transfusion or organ transplant before July 1992?
5. Did you have dialysis or other blood products before July 1992?
6. Are you a chronic hepatitis B carrier?
7. Have you ever snorted cocaine, even once?
8. Do you have tattoos or body piercings?
9. Have you been in jail or prison?
10. Have you had sex with someone who is hepatitis C positive?
11. Have you shared razors, toothbrushes or had blood contact with someone who is hepatitis C positive?
12. Do you drink more than four drinks a day, or have you ever been diagnosed as alcoholic?
The treatment program -- six months to one year of shots and pills -- is not right for everyone. Health Centers of Northern New Mexico offers information to help patients decide if they want treatment.
If you go ...
What: Hepatitis C Awareness Day, including free lunch, risk screenings and information.
When: 11:30 a.m. to 1:30 p.m. Thursday.
Where: Health Centers of Northern New Mexico, 620 Coronado St., Espanola.
Who: Community leaders, relatives of high-risk people, people with hepatitis C.
Follow-up: By appointment only. The Espanola clinic will offer blood testing May 4 to anyone considered at high risk for the disease.
Information: Barbara Bjeletich, 753-7395
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New Data Calls into Question the "Watch And Wait" Treatment Strategy for Hepatitis C
SourceURL:http://www.itnews.it
BASEL, Switzerland,
- New Results Show Treating Early With PEGASYS(R) Combination Therapy Significantly Increases Chance of Achieving a Cure
A study presented today at a major international medical meeting will sound a wake-up call for thousands of hepatitis C patients who are not currently receiving treatment for their disease. New data demonstrate that patients with "normal" liver enzyme levels (alanine aminotransferase (ALT)) who are treated earlier, at a younger age, are much more likely to achieve a sustained virological response (indicative of a cure) than older patients.[i] These findings reinforce the growing body of evidence that the "watch-and-wait" treatment strategy for hepatitis C (HCV) patients may not be the most effective approach. The study was presented at the 40th Annual Meeting of the European Association for the Study of the Liver (EASL) in Paris.
"Many hepatitis C sufferers with so called 'normal' ALT levels are not receiving treatment - either because they have been told they don't require therapy or because they're choosing to wait," said Professor Gane, from Auckland and Middlemore Hepatitis Clinics and the New Zealand Liver Transplant Unit, and lead author of the study. "The results from our study confirm that not only do these patients benefit from PEGASYS combination therapy, they also experience better results when treated at an early age."
ALT is an enzyme used to estimate liver damage and, historically, hepatitis C patients with 'normal' ALT levels have not been treated due to the misconception that 'normal' levels indicated mild disease and that these patients were essentially 'healthy carriers' of hepatitis C. However, the medical community is shifting its thinking as studies reveal that the vast majority of these patients actually have some degree of liver damage and suffer a reduced quality of life compared with uninfected persons. The studies also reveal that these patients benefit from treatment with PEGASYS.[ii] At this time, PEGASYS in combination with ribavirin is the only treatment approved for these patients in Europe.
The Benefits of Treating Young:
Professor Gane's study examined how a patient's age affected their chance of achieving an SVR. Investigators analysed patients aged forty and younger versus those aged over forty. Findings showed that patients treated at a younger age experienced significantly better results, regardless of genotype:
- 54% of genotype 1 patients aged forty or younger treated with 48 weeks of PEGASYS (180 mg/week) plus ribavirin (800 mg/day) achieved an SVR. In contrast, only 34% of similarly-treated patients over forty achieved an SVR.
- 79% of patients forty or younger with genotype 2/3 HCV achieved an SVR following 24 weeks of the same PEGASYS combination therapy. In comparison, 69% of patients over forty achieved an SVR with this treatment regimen.
"Age is one of the few treatment success factors that a patient has some control over," said Michel Bonjour, President of SOS Hépatites-France and founding member of the European Liver Patients Association. "Patients who choose to undergo therapy early increase their chance of curing themselves of this disease. This especially holds true for those who take the initiative to educate themselves about hepatitis C, and are willing to take charge of their disease."
Today's findings regarding age are consistent with a study presented at the American Association for the Study of Liver Diseases in 2003 which showed that patients with elevated ALT levels also benefit from treatment at a younger age.[iii] Together, these studies show that age is a positive predictor of treatment success regardless of ALT levels.
Is High Patient Weight Really the Culprit?
In addition to learning more about how age affects a patient's chance of eradicating the hepatitis C virus, other factors influencing treatment success are also being carefully scrutinised. Being overweight or obese has been shown in previous studies to reduce a patient's chance of achieving an SVR, irrespective of the pegylated interferon therapy used[iv],[v]. New research presented at EASL shows that poorer treatment outcomes in heavy patients is a result of an array of other patient and disease characteristics.[vi]
"Our goal is to create an accurate profile of the kind of patient that doesn't respond well to treatment, which will then help us determine how we can modify treatment strategies and ultimately, cure more patients," said Professor Mark Swain, from the University of Calgary and lead investigator of the study. "In this analysis, those with a high body weight were also more likely to be male, African American, and have cirrhosis. These are all factors that can decrease a patient's chance of achieving a cure."
Professor Swain and other researchers reviewed data from two multinational trials examining the safety and efficacy of PEGASYS combination therapy for the treatment of hepatitis C. Patients were divided into three groups: patients who weighed less than 65 kg; those weighing between 65 kg and 85 kg; and patients weighing more than 85 kg. Each group was then analysed for additional factors that can influence response to therapy.
"Pointing the finger at a patient's weight as the culprit for poor response is too simplistic," said Professor Swain. "These results show that finding the right treatment solution will require careful consideration and research."
PEGASYS - The Right Solution for More Patients
PEGASYS is the most frequently prescribed pegylated interferon for patients infected with hepatitis C. An extensive clinical study programme has demonstrated its safety and efficacy, particularly for those with difficult-to-treat disease. The benefits of PEGASYS are derived from its unique 40 kilodalton branched PEG molecule that is irreversibly bound to the interferon, and which provides sustained viral control for patients during the full once-weekly dosing interval.
In addition to becoming the first and only treatment approved for hepatitis C patients who are co-infected with HIV, PEGASYS is also the only approved medication in the EU for hepatitis C patients with 'normal' levels of alanine aminotransferases (ALT) - a patient population previously thought not to benefit from treatment. PEGASYS monotherapy has been approved in 112 countries and PEGASYS combination therapy has been approved in 83 countries. It has also been approved in the EU, Switzerland, Hong Kong, New Zealand, Taiwan and Thailand for the treatment of chronic hepatitis B, and is the first and only pegylated interferon with this indication. Roche has recently completed enrolment for an important new study examining the effects of longer treatment duration and/or a high induction dose of PEGASYS in patients who were non-responsive to treatment with pegyinterferon alfa-2b. This study is known as REPEAT - Retreatment with PegInteferon alfa2a in Patients not Responding to prior peginterferon alfa2b/ribavirin combination therapy.
About Roche
Headquartered in Basel, Switzerland, Roche is one of the world's leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As a supplier of innovative products and services for the prevention, diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people's health and quality of life. Roche is a world leader in Diagnostics, the leading supplier of medicines for cancer and transplantation and a market leader in virology. In 2004, sales by the Pharmaceuticals Division totalled 21.7 billion Swiss francs, while the Diagnostics Division posted sales of 7.8 billion Swiss francs. Roche employs roughly 65,000 people in 150 countries and has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai.
All trademarks used or mentioned in this release are legally protected.
Notes for the editor (recent PEGASYS announcements):
•US approval for PEGASYS in HIV-HCV co-infected patients on February 25, 2005.
•EU approval for PEGASYS in HIV-HCV co-infected patients on February 3, 2005.
•EU approval for PEGASYS in HBV on February 25, 2005.
•Swiss approval for PEGASYS in HBV on December 22, 2004.
•EU approval for HCV patients with 'normal' ALT on November 11, 2004.
Further information:
About hepatitis C: http://www.health-kiosk.ch/start_hepa
About Roche in virology: http://www.roche-hiv.com
References:
[i] Gane, E, et al. Age and sustained virological response in patients with persistently `normal' ALT and chronic hepatitis C treated with peginterferon alfa-2a (40KD) plus ribavirin. Presented at 40th Annual Meeting of the European Association for the Study of the Liver, Paris, France, April 13-17, 2005.
[ii] Zeuzem, S. et al. Peginterferon alfa-2a (40 kilodaltons) and ribavirin in patients with chronic hepatitis C and normal aminotransferase levels. Gastroenterology. December 2004. 127(6):1724-1732.
[iii] Foster, G, et al. Treatment of Chronic Hepatitis C With Peginterferon Alfa-2a (40KD) (PEGASYS(R)) And Ribavirin (COPEGUS(R)): Patient Age Has a Marked Influence On The Individual Estimated Probability of Achieving A Sustained Virological Response. Presented at the American Association for the Study of Liver Diseases, 2003.
[iv] Fried, MW et al. NEJM 2002:347;975-82
[v] Manns, MP et al. Lancet, 2001; 358:958-65
[vi] Swain, M, et al. Clustering of poor prognostic factors in patients with chronic hepatitis C.
Presented at 40th Annual Meeting of the European Association for the Study of the Liver, Paris, France, April 13-17, 2005.
Contact:
Janet Kettels, Roche, +41-79-597-82-85;
Joanne Galea, Axon Communications, +44(0)20-8822-6779
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HCV Infection May be Concealed Initially, Doctors Warn
SourceURL:http://www.hepatitisneighborhood.com
by John C. Martin
A new, long-term study of hepatitis C has found that once the virus is transmitted, it can take months for evidence of the virus to appear.1 This initial, acute phase can also be absent any symptoms. Thus, researchers at Johns Hopkins University are stressing the importance of more sensitive tests, like nucleic acid testing (NAT), which are designed to detect the virus' genetic material long before the immune system begins to respond with antibodies.2
According to estimates, nearly 4 million Americans (about 2 percent of the total population) are infected with hepatitis C, 2.7 million of whom have chronic infection. Most of the cases of HCV transmission in the U.S. are due to injection drug use.3
According to the authors of this study, more than two-thirds all cases of acquired HCV infection in the West are connected to illicit drug use. This occurs due to sharing needles or "works" when "shooting" drugs.3
Despite that fact, Andrea Cox, MD, PhD, an assistant professor of Medicine, and her colleagues wrote, "Prospective clinical data regarding the most common mode of HCV acquisition are rare, in part because acute-phase HCV infection is usually asymptomatic."
Evidence of Infection Can Develop Slowly
Based on that, Cox and her team prospectively evaluated the length of time before antibodies to the hepatitis C virus appear in a group of 179 initially infected injection drug users. The patients were enrolled from a larger, unrelated study on HCV incidence and risk factors. Despite counseling about the risks of injection drug use relative to HCV infection, about one-third of them eventually developed antibodies to their HCV infection at the start of the research, an "alarming" number, the investigators noted.
Each patient was interviewed at the beginning of the research about his or her drug use habits, and was classified from lowest to highest risk of contracting HCV. Those at highest risk were individuals who acknowledged daily injection drug use, as well as sharing drug paraphernalia.
Each individual was then evaluated for evidence of HCV once per month throughout the study. Antibody testing was conducted to determine whether those who initially were antibody-negative had become positive. Those who had become antibody-positive then underwent testing to detect HCV RNA, a more sensitive analysis that looks for genetic material associated with the virus.
Antibodies May Take Months to Appear
After analyzing all the blood samples, Cox's group estimated the average time from initial infection to the appearance of antibodies was 36 days. However, in one case, antibodies were detected more than a year after infection. However, in no other case were antibodies discovered more than 63 days after HCV was initially contracted, they report.
The researchers also found that blood levels of a liver enzyme that suggest liver disease known as alanine aminotransferase (AL-uh-neen uh-mee-noh-TRANZ-fer-aze) (ALT) climbed four-fold, on average, once the virus was detected in these patients. Evidence of infection preceded increases in ALT in half of the patients and rises in total bilirubin levels in approximately three-quarters of the individuals. However, Cox's team learned that ALT levels were not closely linked with positive HCV RNA tests or in those with persistent viral infection, sex or race of an individual, or the outcome of infection. "That viremia frequently precedes ALT level elevation supports the hypothesis that HCV is not a hepatotoxic virus and that factors that come into effect later, such as immune response, are responsible," the research team wrote.
None of the individuals developed jaundice, confirming the notion that early, acute HCV infection usually lacks obvious symptoms.
Additionally, viral clearance varied from as early as 94 days to greater than one-and-a-half years after initial infection in those who achieved that status.
"The results significantly expand the available data on the dynamics of hepatitis C viremia preceding seroconversion [conversion from being antibody-negative to positive]," Cox and her associates concluded.
The results also stress the significance of reducing the influences that contribute to illicit drug use, as well as ongoing efforts to develop vaccines to prevent chronic HCV infection in that population, Cox's group concluded.
1. Cox AL, Netski DM, Mosbruger T et al. Prospective evaluation of community-acquired acute-phase hepatitis C virus infection. Clin Infect Dis 2005;40:951-8.
2. Challine D, Pellegrin B, Bouvier-Alias M, Rigot P, Laperche L, Pawlotsky JM. HIV and hepatitis C virus RNA in seronegative organ and tissue donors. Lancet 2004 Oct 30;364(9445):1611-2.
3. National Center for Infectious Diseases. Centers for Disease Control and Prevention (CDC). Viral Hepatitis C. Fact Sheet. Available at: http://www.cdc.gov/ncidod/diseases
/hepatitis/c/fact.htm.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
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April 14th, 2005
Preventing Variceal Bleeds with Endoscopic Ligation plus Propranolol
SourceURL:http://www.gastrohep.com/
Both endoscopic variceal ligation alone and in combination with propranolol are effective in primary prophylaxis of variceal bleeding, however, variceal recurrence is lower if propranolol is added to endoscopic variceal ligation, finds this month’s issue of American Journal of Gastroenterology.
The role of propranolol in addition to endoscopic variceal ligation in the prevention of first variceal bleed has not been evaluated.
Dr Sarin and colleagues from India conducted a prospective randomized controlled trial comparing endoscopic variceal ligation with propranolol and endoscopic variceal ligation alone in the prevention of first variceal bleed among patients with high-risk varices.
The researchers randomly allocated 144 consecutive patients with high-risk varices to 2 groups.
Group 1 received endoscopic variceal ligation plus propranolol (n = 72) and group 2 underwent endoscopic variceal ligation alone (n = 72).
The research team undertook endoscopic variceal ligation at 2 week intervals until the varices were obliterated.
In the first group, the investigators administered incremental dosages of propranolol, sufficient to reduce heart rate to 55 beats/min or a 25% reduction from baseline and continued this after the obliteration of the varices.
The endpoints of the study were bleeding and death.
The researchers reported that the 2 groups of patients had comparable baseline characteristics.
At follow-up, 4 patients in the combination group and 11 in the single treatment group had recurrence of varices – American Journal of Gastroenterology
The follow-up time for group 1 was a mean of 13 months and 11 months for group 2.
The team noted that the proportion of cirrhotic and noncirrhotic portal hypertension patients in group 1 was 89% and 11%, respectively, and 88% and 13% in group 2.
The frequency of Child's A was 15 in group 1 versus 18 in group 2, Child’s B was 38 versus 35, and Child’s C compared equally with 19 versus 19.
The investigative team observed that the mean daily propranolol dose achieved in groups 1 was 96mg.
In total, the researchers found that 11 patients had bleeds, with 5 in group 1 and 6 in group 2.
The investigators also reported that all patients bled before the obliteration of varices, the actuarial probability of first bleed at 20 months was 7% in group 1 and 11% in group 2.
The team noted that 6 patients died in the combination group and 8 in endoscopic variceal ligation group.
All deaths in group 1 were reported to be nonbleed-related causes, while in group 2 the deaths were bleed related, with an 8% versus 15% probability of death at 20, respectively.
The probability of bleed-related death was comparable between the groups.
The researchers found that at the end of follow-up, 4 patients in group 1 and 11 in group 2 had recurrence of varices.
In addition, the research team noted side effects on propranolol in 22% patients, and in 8% it had to be stopped, but there were no serious complications of endoscopic variceal ligation.
Dr Sarin’s team concluded, “Both endoscopic variceal ligation plus propranolol and endoscopic variceal ligation alone are effective in primary prophylaxis of bleed from high-risk varices.”
“The addition of propranolol does not decrease the probability of first bleed or death in patients on endoscopic variceal ligation.”
“However, the recurrence of varices is lower if propranolol is added to endoscopic variceal ligation.”
Am J Gastroenterol 2005: 100(4): 797
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Hep C Therapy Impacts Future Liver Related Morbidity, Mortality and Costs
SourceURL:http://www.gastrohep.com
Treatment of the chronic Hepatitis C infected population can eradicate the infection, increase patients' survival and reduce the need for liver transplantation, making this a cost-effective strategy, reports May’s issue of Journal of Hepatology.
Chronic Hepatitis C virus infection is common and often produces a progressive disease.
Some studies suggest that Hepatitis C related complications will increase in the future.
Dr Butia and colleagues from Spain estimated the future morbidity, mortality and costs of chronic Hepatitis C virus infection in a cohort of patients infected by Hepatitis C and evaluated the impact of Hepatitis C virus therapy.
The investigators used a mathematical model to project the Hepatitis C related complications and costs over the next 30 years.
Treating 50% of the population with Hepatitis C will result in a reduction of 26% in morbidity and 20% in mortality – Journal of Hepatology
The researchers examined a cohort of 419,895 infected patients representing the Hepatitis C infected population in Spain.
The team also projected the impact of Hepatitis C virus therapy with peginterferon and ribavirin in this population.
The research team noted that a gradual decline in the infected population is to be expected in the future.
In addition, the researchers reported that the proportion of patients with cirrhosis will increase by up to 14%.
Morbidity associated with Hepatitis C infection will increase by up to 10% by the year 2030 with a subsequent increment in Hepatitis C related costs.
The investigators also found that treating from 10% to 50% of the population with Hepatitis C will result in a reduction of 6% and 26% in morbidity and 4% and 20% in mortality, respectively.
The team observed that the cost per year of life gained ranges from 6078 – for a 29 year old patient to 8911 – for a 59 year old patient.
Dr Butia’s team concluded, “ In the future, Hepatitis C infection mortality, morbidity and associated costs will increase.”
“Treatment of the chronic Hepatitis C infected population can eradicate the infection, increase patients' survival and reduce the need for liver transplantation, making this a cost-effective strategy.”
J Hepatol 2005: 42(5): 639-645
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Human Genome Sciences Hepatitis C Drug Passes Test
SourceURL:http://www.reuters.com/
NEW YORK (Reuters) - Human Genome Sciences Inc. on Thursday said its experimental drug for hepatitis C met its primary goal in a mid-stage trial of patients who had not previously been treated for the liver-damaging virus.
The Rockville, Maryland-based company said the favorable results were seen in a trial of 56 patients with the genotype 1 strain of hepatitis C, the hardest to treat of three main strains, who were given varying doses of its Albuferon injectable drug. The patients had never previously been treated for their condition.
Albuferon is a laboratory-altered form of interferon-alpha, a standard treatment for hepatitis C. But unlike standard interferon treatments that must be injected once weekly, researchers said the Phase II trial indicated Albuferon is highly effective with injections only every two to four weeks.
Patients taking the two highest doses of the drug saw their levels of virus decline by over 99.9 percent 28 days after treatment began. That satisfied the trial's primary goal of showing at least a 99 percent reduction in virus, meaning a reduction to undetectable levels, after four weeks.
The company said 69 percent of patients in those two high-dose groups achieved the 99 percent reduction of virus after four weeks. Undetectable virus levels after 42 days were seen in 23 percent of the same patients.
Swiss drugmaker Roche sells the most popular interferon, called Pegasys, which is taken with a pill called ribavirin to treat the often-deadly virus. Schering-Plough Corp.'s interferon, called Peg-Intron, is also taken alongside ribavirin.
Those standard combo treatments are considered the best available therapies for the virus, but use of them for up to 48 weeks only knocks down the virus to undetectable levels in about 42 percent of patients with genotype 1, Human Genome Sciences said.
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Valopicitabine Shows Potential Therapeutic Response in the Treatment of Genotype 1 Hepatitis C Patients
SourceURL:http://www.rxpgnews.com
By Idenix Pharmaceuticals
Idenix Pharmaceuticals, Inc. (Nasdaq: IDIX - News), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral and other infectious diseases, today announced preliminary phase IIa clinical trial data for valopicitabine (NM283) in treatment naive genotype 1 hepatitis C patients.
In this phase IIa clinical trial, 9 patients receiving the combination of valopicitabine and pegylated interferon have reached 24 weeks of treatment, and achieved a mean reduction in serum HCV RNA of 4.5 log10, or more than 99.99 percent. These data will be presented at the 40th Annual Meeting of the European Association for the Study of the Liver (EASL) in Paris, France on Sunday, April 17 at 12:00 p.m. Central European Time (CET) by Nezam Afdhal, M.D., of Harvard Medical School.
In January, Idenix reported 12-week data on 12 patients receiving valopicitabine plus pegylated interferon combination therapy. Of the 12 patients previously reported, nine patients have now reached 24 weeks of combination treatment and have experienced substantial additional antiviral response. In eight out of the nine patients, levels of virus have decreased to below 600 IU/mL, which is the lower quantification limit of the Amplicor(TM) PCR assay, an assay typically used by physicians to monitor the effectiveness of hepatitis C treatment. Six of the nine patients achieved undetectable levels of virus utilizing the real-time TaqMan® PCR assay, an assay with a high level of sensitivity, which has a detection limit of 10 IU/mL.
"This is the first time that we are seeing 24-week data for an antiviral drug directly targeting a specific enzyme of the hepatitis C virus," said Nezam Afdhal, M.D., a principal investigator in the phase IIa valopicitabine trials and Chief of Hepatology at Beth Israel Deaconess Medical Center in Boston and Associate Professor at Harvard Medical School. "These preliminary data are promising and suggest that direct antiviral drugs, such as valopicitabine, could set a new treatment standard in hepatitis C, by offering hepatitis C patients, particularly patients infected with HCV genotype 1, potentially improved clinical benefit with fewer side effects."
Clinical Trial Design: A total of 30 patients in the phase IIa clinical trial were enrolled and randomized to one of two treatment arms so that 18 patients receive the combination of valopicitabine and pegylated interferon and 12 patients receive valopicitabine monotherapy. Patients on combination treatment receive a titrating dose of valopicitabine once a day up to 800 mg by day 8 and then continue this dose throughout the treatment period. Additionally, a Peg-Intron® dose of 1.0 mcg/kg is administered once a week starting on day 8. Enrolled patients are treatment naive, HCV genotype 1, with baseline viral load greater than 5 log10 IU/mL and alanine aminotransferase (ALT) levels less than 5 times the upper limit of normal. With the agreement of the clinical trial investigators and submission of protocol amendments to the United States Food and Drug Administration (FDA), Idenix has extended the treatment duration of this clinical trial from the initially planned 28 days, to 12 weeks, then 24 weeks and finally to 48 weeks based on the interim results.
Clinical Trial Results: Of the 30 patients enrolled, one has recently begun treatment, 25 have reached 12 weeks of treatment and four patients discontinued treatment prior to week 12. Two of these withdrawals were interferon-related, one patient consented only to participate in the initial 28-day clinical trial and one was lost to follow-up. Results for the group that have reached 12 weeks of treatment are consistent with the previously announced 12-week findings reported in a company press release on January 10, 2005. The updated 12-week data demonstrate a mean HCV RNA reduction from baseline of 3.01 log10 IU/mL, or 99.9 percent, for the 16 patients in the combination treatment group, and 0.87 log10 IU/mL, or 86.5 percent, for the 12 patients in the valopicitabine monotherapy group.
To date, 10 patients have reached 24 weeks of treatment. Nine patients in the valopicitabine plus pegylated interferon treatment group have completed 24 weeks of treatment. The mean HCV RNA reduction from baseline for those patients was 4.5 log10 IU/mL, or more than 99.99 percent. One patient in the monotherapy group continued treatment after week 12, and after 24 weeks of treatment experienced an HCV RNA reduction from baseline of 1.9 log10 IU/mL. Six of the nine patients receiving the combination treatment achieved virus levels below the level of detection by real-time PCR, an assay with a high level of sensitivity (<10 iu ml/)
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April 15th, 2005
New Data on Most Prescribed Hepatitis C Therapy Pegasys(R) Presented at European Association for the Study of the Liver (EASL) Conference
SourceURL:http://biz.yahoo.com
- Roche continues pioneering research to enhance treatment for hepatitis C patients -
PARIS, April 15 /PRNewswire/ -- New Pegasys® (peginterferon alfa-2a) data, including exploration of factors associated with treatment response in hepatitis C patients, were revealed in 33 oral and poster presentations at the 40th Annual Meeting of The European Association for the Study of the Liver, April 13 - 17, in Paris, France.
Pegasys and Copegus® (ribavirin, USP), are approved by the U.S. Food and Drug Administration for the treatment of chronic hepatitis C and are the only combination regimen FDA-approved for the treatment of chronic hepatitis C in patients coinfected with hepatitis C and HIV.
Hepatitis C is a blood-borne virus that chronically infects an estimated 2.7 million Americans. The virus is a leading cause of cirrhosis and liver cancer and is the number-one reason for liver transplants in the U.S.
According to the Centers for Disease Control, approximately 1.25 million Americans are chronically infected with hepatitis B, a virus that can be transmitted through sexual contact and contact with infected blood.
Data from several Pegasys studies will be presented and discussed at the meeting, including:
Hepatitis C
1. The Influence of Cumulative Peginterferon Alfa-2a (40 KD) and Ribavirin (RBV) Exposure on Sustained Virological Response (SVR) Rates in Patients with Genotype 1 Chronic Hepatitis C (Viral Hepatitis: Hepatitis C Clinical Poster Session; 4/15/05)
This analysis of pooled data from two phase III trials looked at the relationship between cumulative ribavirin exposure (total drug administered) and the desired outcome (sustained virological response, or SVR) in 569 chronic hepatitis C patients treated with Pegasys and ribavirin. The analysis found that as the cumulative dose of ribavirin decreased, SVR rates also decreased. Sixty-six percent of patients who took greater than 97 percent of the recommended ribavirin dose achieved an SVR compared to only 33 percent in patients who took less than 60 percent of the recommended ribavirin dose.
2. Age and Sustained Virological Response in Patients With Persistently 'Normal' ALT and Chronic Hepatitis C Treated With Peginterferon Alfa-2a (40KD) Plus Ribavirin (Viral Hepatitis: Hepatitis C Clinical Poster Session; 4/15/05)
A retrospective analysis of 422 chronic hepatitis C patients with persistently 'normal' ALT levels showed that younger patients had higher response rates to Pegasys and Copegus treatment compared to older patients. In the study, patients were divided into two groups based on age (<40 or >40), and were treated for 24 or 48 weeks. The study found that 54 percent of patients in the younger group achieved an SVR compared to 34 percent of those in the older group.
3. Clustering of Poor Prognostic Factors in Patients with Chronic Hepatitis C (Viral Hepatitis: Hepatitis C Clinical Poster Session; 4/15/05)
An analysis of 2,404 patients from two multinational, randomized, controlled phase III studies showed that a cluster of poor prognostic characteristics, and not weight alone, may explain why lower response rates to therapy are observed in heavier patients, irrespective of the pegylated interferon therapy used. Patients were divided into three weight categories: <65 kg, <65-<85 kg, >85 kg. As previous studies with both pegylated interferons have shown, the patients in the highest weight category experienced lower SVR rates than lighter weight patients. The heaviest patients were also more likely to be male, black, cirrhotic, and infected through intravenous drug use, which are characteristics that are typically associated with lower treatment response rates.
About Pegasys
Pegasys, a pegylated alpha interferon, and Copegus, an oral antiviral medication, were approved by the FDA in December 2002 for use in combination for the treatment of adults with chronic hepatitis C who have compensated liver disease and have not previously been treated with interferon alpha. Patients in whom efficacy was demonstrated included patients with compensated liver disease and histological evidence of cirrhosis. In addition, Pegasys is the only pegylated interferon approved by the FDA for use alone and in combination with Copegus for the treatment of chronic hepatitis C in patients coinfected with hepatitis C and HIV who are clinically stable (e.g., antiretroviral therapy not required or receiving stable antiretroviral therapy).
Roche filed a submission with the U.S. Food and Drug Administration in 2004 to market Pegasys for the treatment of hepatitis B. Action on the submission is expected in 2005.
About Roche - More Than a Century in the U.S. and the World
Founded in 1896 and headquartered in Basel, Switzerland, Roche is one of the world's leading innovation-driven healthcare groups. Its core businesses are pharmaceuticals and diagnostics. Roche is one of the world's leaders in diagnostics, the leading supplier of pharmaceuticals for cancer, as well as a leader in virology and transplantation. As a supplier of products and services for the prevention, diagnosis and treatment of disease, the Group contributes on many fronts to improve people's health and quality of life. Roche employs roughly 65,000 people in 150 countries, including approximately 15,000 in the United States.
Roche's U.S. operations celebrate their American Centennial in 2005. In another milestone this year, Roche was named in January to Fortune magazine's list of Best Companies to Work for in America. One of an increasingly rare breed of major healthcare companies that still bear their original name, Roche today has more than a dozen U.S. sites located in California, Colorado, Indiana, New Jersey and South Carolina, as well as in Puerto Rico. Roche has alliances and research and development agreements with numerous partners, including majority ownership interests in Genentech and Chugai. Roche's Pharmaceuticals Division offers a portfolio of leading medicines in therapeutic areas including cancer, HIV/AIDS, hepatitis C, transplantation, dermatology and influenza. Roche's Diagnostics Division supplies a wide array of innovative testing products and services to researchers, physicians, patients, hospitals and laboratories world-wide. For further information, please visit our worldwide and U.S. websites (Global: http://www.roche.com and U.S.: http://www.roche.us).
Facts About Pegasys (Peginterferon alfa-2a) in Combination with Copegus
PEGASYS, alone or in combination with COPEGUS®, is indicated for the treatment of adults with chronic hepatitis C virus infection who have compensated liver disease and have not been previously treated with interferon alpha. Patients in whom efficacy was demonstrated included patients with compensated liver disease and histological evidence of cirrhosis (Child-Pugh class A) and patients with HIV disease that is clinically stable (eg, antiretroviral therapy not required or receiving stable antiretroviral therapy).
Alpha interferons, including PEGASYS® (Peginterferon alfa-2a), may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Therapy should be withdrawn in patients with persistently severe or worsening signs or symptoms of these conditions. In many, but not all cases, these disorders resolve after stopping PEGASYS therapy (see CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and ADVERSE REACTIONS in complete product information).
Use with Ribavirin. Ribavirin, including COPEGUS®, may cause birth defects and/or death of the fetus. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin causes hemolytic anemia. The anemia associated with ribavirin therapy may result in a worsening of cardiac disease. Ribavirin is genotoxic and mutagenic and should be considered a potential carcinogen (see CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and ADVERSE REACTIONS in complete product information).
PEGASYS is contraindicated in patients with hypersensitivity to PEGASYS or any of its components, autoimmune hepatitis, and hepatic decompensation (Child-Pugh score greater than 6; class B and C) in cirrhotic CHC monoinfected patients before or during treatment. Pegasys is also contraindicated in hepatic decompensation with Child-Pugh score greater than or equal to 6 in cirrhotic CHC patients coinfected with HIV before or during treatment. PEGASYS is also contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurological and other complications in neonates and infants, which are sometimes fatal. PEGASYS and COPEGUS therapy is additionally contraindicated in patients with a hypersensitivity to COPEGUS or any of its components, in women who are pregnant, men whose female partners are pregnant, and patients with hemoglobinopathies (eg, thalassemia major, sickle-cell anemia).
COPEGUS THERAPY SHOULD NOT BE STARTED UNLESS A REPORT OF A NEGATIVE PREGNANCY TEST HAS BEEN OBTAINED IMMEDIATELY PRIOR TO INITIATION OF THERAPY. Women of childbearing potential and men must use two forms of effective contraception during treatment and during the 6 months after treatment has concluded. Routine monthly pregnancy tests must be performed during this time. If pregnancy should occur during treatment or during 6 months post-therapy, the patient must be advised of the significant teratogenic risk of COPEGUS therapy to the fetus. Healthcare providers and patients are strongly encouraged to immediately report any pregnancy in a patient or partner of a patient during treatment or during 6 months after treatment cessation to the Ribavirin Pregnancy Registry at 1-800-593-2214.
Chronic hepatitis C (CHC) patients with cirrhosis may be at risk of hepatic decompensation and death when treated with alpha interferons, including PEGASYS. Cirrhotic CHC patients coinfected with HIV receiving highly active antiretroviral therapy (HAART) and interferon alfa-2a with or without ribavirin appear to be at increased risk for the development of hepatic decompensation compared to patients not receiving HAART. During treatment, patients' clinical status and hepatic function should be closely monitored, and PEGASYS treatment should be immediately discontinued if decompensation (Child-Pugh score greater than or equal to 6) is observed.
The most common adverse events reported for PEGASYS and COPEGUS combination therapy observed in clinical trials (N=451) were fatigue/asthenia (65%), headache (43%), pyrexia (41%), myalgia (40%), irritability/anxiety/nervousness (33%), insomnia (30%), alopecia (28%), neutropenia (27%), nausea/vomiting (25%), rigors (25%), anorexia (24%), injection site reaction (23%), arthralgia (22%), depression (20%), pruritus (19%) and dermatitis (16%). The adverse event profile of coinfected patients treated with PEGASYS and COPEGUS was generally similar to that shown for monoinfected patients. Events occurring more frequently in coinfected patients were neutropenia (40%), anemia (14%), thrombocytopenia (8%) weight decrease (16%) and mood alteration (9%).
Serious adverse events included neuropsychiatric disorders (suicidal ideation and suicide attempt), serious and severe bacterial infections (sepsis), bone marrow toxicity (cytopenia and rarely, aplastic anemia), cardiovascular disorders (hypertension, arrhythmias and myocardial infarction), hypersensitivity (including anaphylaxis), endocrine disorders (including thyroid disorders and diabetes mellitus), autoimmune disorders (including psoriasis and lupus), pulmonary disorders (dyspnea, pneumonia, bronchiolitis obliterans, interstitial pneumonitis and sarcoidosis), colitis (ulcerative and hemorrhagic/ischemic colitis), pancreatitis, and ophthalmologic disorders (decrease or loss of vision, retinopathy including macular edema and retinal thrombosis/hemorrhages, optic neuritis and papilledema).
Contacts:
Pamela VanHouten
Roche
(973) 562-2231
pamela.vanhouten@roche.com
David Freundel
Manning Selvage & Lee
(212) 468-3982
david.freundel@mslpr.com
Source: Roche
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