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Alan Franciscus
Editor-in-Chief
January 15th, 2003
Predictors of Fibrosis Progression Identified in Chronic Hepatitis C Infection
The extent of serum aminotransferase elevations and the degree of hepatocellular necrosis and inflammation seen on liver biopsy are the best predictors of fibrosis progression in patients with chronic hepatitis C,
according to a report in the January issue of Gastroenterology (Gastroenterology 2003;124:97-104).
"Fibrosis is the hallmark of hepatic cirrhosis, worsening of which is probably the best surrogate marker for progression of chronic liver disease," Dr. Marc G. Ghany, of the National Institute of Diabetes and Digestive
and Kidney Diseases, Bethesda, Maryland, and colleagues note. They used liver histology to examine the rate and predictors of fibrosis progression in 123 patients with chronic hepatitis C.
The patients underwent two liver biopsies a mean of 44 months apart with no intervening treatment. The team used the histology activity index to grade liver histology and a scoring system of 0 to 6 to stage fibrosis.
Forty-eight of the patients (39%) had worsening fibrosis scores, 46 (37%) exhibited no change, and 29 (24%) showed improvement. Of the 48 patients with worsening fibrosis, 36 (75%) had a 1-point increase and 12
(25%) had at least a 2-point increase in scores. Eleven of the subjects (10%) showed progression to cirrhosis.
"The overall rate of progression was 0.12 fibrosis units per year, a rate that predicts progression to cirrhosis in 50 years if progression was linear," Dr. Ghany and colleagues explain. The rate of progression was
variable. Older patients, patients with higher serum alanine and aspartate aminotransferase levels, and those with extensive degrees of periportal necrosis on initial liver biopsies had higher rate of progression.
"These findings," the investigators conclude, "support the recommendation that patients with normal aminotransferase levels and mild liver histology can safely defer treatment."
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First Monoclonal Antibody in the Clinic to Show Activity against The Hepatitis C Virus
XTL Biopharmaceuticals Ltd. (LSE: XTL) today announces positive clinical data on the antiviral activity and safety of XTL-002, being developed for the treatment of hepatitis C virus (HCV) infections.
Results of the Phase Ia study, which included 15 chronic HCV patients, indicate that HCV viral RNA levels were reduced in over half the patients following a single dose. No serious adverse events were reported. The
single-center study, under the regulation of the United States Food and Drug Administration (FDA) and Ministry of Health, Israel, was designed to test safety, tolerability and efficacy of a single-dose of XTL-002 in
chronic HCV patients. The 15 patients were divided into 5 groups, with each group receiving 0.25, 1.0, 2.5, 10 or 40mg of XTL-002 in a single intravenous infusion. HCV viral RNA levels were measured pre-infusion and
at multiple time intervals following infusion of XTL-002. In 8 out of 15 patients, significant reduction of HCV viral RNA, ranging from 2 to 100 fold, was demonstrated following XTL-002 administration.
XTL-002 is a fully human high-affinity monoclonal antibody which was shown to reduce viral levels of the HCV virus in XTL's proprietary in vivo model, the HCV TrimeraXTL model. This model is being used in conjunction
with a variety of corporate and academic partners to screen and evaluate novel compounds to treat HCV. A peer reviewed scientific article on XTL's HCV TrimeraXTL model was recently published in the Journal of
Infectious Disease.
Professor Eithan Galun, Director, Goldyne Savad Institute of GeneTherapy, Hadassah University Hospital and a principal investigator in the study, commented: "XTL-002 is a promising new therapeutic modality for
treating chronic HCV patients. In addition, XTL-002 could be employed to prevent HCV re-infection in HCV-associated liver transplant patients, where no drug currently exists."
Martin Becker, Ph.D., President and Chief Executive Officer of XTL, said: "XTL is the first company to initiate clinical trials with a monoclonal antibody against HCV. We are pleased that the clinical results with
XTL-002, though early-stage, suggest that XTL-002 is active against the HCV virus. XTL-002 is the most advanced drug in our broad HCV program, which includes multiple drug candidates that are either fully owned
by XTL or co-developed with corporate partners."
Hepatitis C is a major public health concern. The World Health Organization estimates that 170 million people worldwide are chronic States alone. It is estimated that 25-35% of these chronic patients will develop
progressive liver disease including cirrhosis and liver cancer. Hepatitis C is the leading cause of liver transplantation. The Center for Disease Control estimates that in the year 2000, about 10,000 people died in the US
as a result of HCV. It is predicted that by the end of this decade, the number of deaths in the US as a result of HCV will surpass the number of deaths from AIDS.
XTL Biopharmaceuticals develops novel therapeutics to treat life-threatening infectious diseases using fully human monoclonal antibodies and small molecule drugs. XTL's competitive advantage lies in its ability to
leverage both its proprietary human tissue-based in vivo disease models and fully human monoclonal antibodies to validate and develop promising drug candidates. The Company's growing pipeline of therapies,
designed to combat chronic viral infections, drug-resistant bacteria and serious systemic fungal infections, comprises internally developed products as well as those being co-developed with a number of
biopharmaceutical partners. For more information about XTL, visit the Company's web site at www.xtlbio.com
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Roche Fires Next Salvo in Interferon Price War
SCRIP - World Pharmaceutical News
Roche has thrown down the gauntlet to Schering-Plough by pricing Copegus (ribavirin), one component of its newly approved combination treatment for chronic hepatitis C, at 57% of the US price of branded ribavirin,
marketed by ICN Pharmaceuticals.
The move follows last October's US approval of Roche's Pegasys (peginterferon alfa-2a) for hepatitis C monotherapy, when the company said it would provide the product free of charge for three months of therapy for
the first 15,000 patients. Pegasys in combination with Copegus was approved in the US on December 3rd.
The company is trying to overcome the fact that Pegasys is entering the US market two years behind Schering-Plough's competing hepatitis C product, Pegintron (peginterferon alfa-2b), and this is the driving force
behind the company's price-cutting. At the time Pegasys was approved, some analysts forecast an impending price war between the two companies, saying that Schering-Plough could not afford to ignore Roche's
discount.
Nevertheless, the US company has yet to respond with a price cut or other incentive scheme of its own. It markets Pegintron in the US for prescribing together with ribavirin, which it licenses from ICN.
...1998 price
Roche's Copegus price cut will bring the product's US wholesale acquisition cost down to that of branded ribavirin in 1998 - $5.06 per 200mg tablet. For patients infected with genotypes 1 and 4 of the hepatitis C virus,
who are prescribed 1,200mg a day, this translates into a saving of $7,600 for 48 weeks of therapy, the standard treatment duration, the company points out.
The move is not entirely unexpected. In October, Bernstein analysts said that if it was worth 25% of sales (the discount value of the Pegasys three-month free treatment incentive) for Roche to buy market share, it
would be worth that much to defend it. Thus it was unlikely that the company's discount would end at this one offer.
Although analysts widely expected Schering-Plough to respond, saying the company "really could not let this move work", this has not yet happened. A significant loss of market share would spell further trouble for
Schering-Plough. The company recently issued its third profit warning of the financial year after being fined for manufacturing deficiencies and experiencing a drastic sales slowdown when Claritin (loratadine) lost US
patent protection and was switched to over-the-counter.
Roche's pricing move comes shortly after the conclusion of a legal battle with ICN, which has allowed both companies to continue developing and marketing their respective versions of ribavirin. The settlement is
believed to involve a license payment to ICN.
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January 16th, 2003
Many HIV/HCV-Coinfected Patients Have Contraindications for HCV Therapy
By Megan Rauscher
Confirming prior studies, a new study suggests that the majority of patients coinfected with HIV and hepatitis C virus (HCV) are not suitable candidates for HCV treatment with interferon and ribavirin.
The main barriers to HCV treatment in this population--largely minority urban dwellers-- are missed clinic visits, active psychiatric illness, drug and alcohol use, liver disease or other medical illnesses, according to
findings published in the January 1st issue of Clinical Infectious Diseases (Clin Infect Dis 2003;36:97-100)
Team leader Dr. Catherine A. Fleming from Boston Medical Center told Reuters Health: "The bottom line is that this urban population of HIV-HCV coinfected patients have many other medical and social issues that
preclude them from interferon therapy, and that to attempt to overcome this will involve earlier evaluation by specialized multidisciplinary teams."
Among 149 HIV-HCV coinfected patients prospectively evaluated, only 44 (30%) were deemed eligible for HCV treatment. Of these, only 16 (36%) initiated interferon therapy.
The others were considered unsuitable for HCV treatment due to nonadherence with medical visits (23%), active psychiatric disease (21%), drug or alcohol use in the previous 6 months (23%), decompensated liver
disease (12%), advanced HIV disease (13%), and medical comorbidities (8%).
"Successful treatment of HCV in this population involves overcoming these barriers," Dr. Fleming emphasized.
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Highly Active Antiretroviral Therapy and HCV Quasispecies Diversity
There is no immediate effect of highly active antiretroviral therapy on HCV, but immune restoration results in an increase in HCV quasispecies diversity, finds a research team in the January issue of the Journal of
Virology (J Virol 2003; 77(3): 1940-50).
In this study, researchers from California, USA, analyzed the effect of highly active antiretroviral therapy (HAART) on HCV load and quasispecies diversity.
The team assessed patients coinfected with the HIV and HCV. They retrospectively analyzed 3 patient cohorts over a period of 7 to 10 months: Group A was antiretroviral drug naive at baseline, then on HAART for the
remainder of the study. Group B did not receive antiretroviral therapy at any point. Group C was on HAART for the entire course of the study.
The research team analyzed HCV quasispecies diversity by sequencing hypervariable region 1. CD4+-cell count was positively correlated with HCV load, genetic distance, and Ka.
They found no significant change from baseline in any immunologic, virologic, or quasispecies parameter in any of the 3 groups. However, group C showed significantly higher CD4+- and CD8+-cell counts, higher HCV
load, and increased HCV clones, entropy, and genetic distance. The ratio of nonsynonymous substitutions pernonsynonymous site, to synonymous substitutions per synonymous site (Ka/Ks) was also increased in
this group. Furthermore, CD4+-cell count was positively correlated with HCV load, genetic distance, and Ka. Patients infected with HCV genotype 2 or 3 had a significantly higher CD4+-cell count, HCV load, genetic
distance, and Ka/Ks than those infected with genotype 1.
Drs Jennifer Babik and Mark Holodniy concluded, "These results suggest that there is no immediate effect of HAART on HCV but that, with prolonged HAART, immune restoration results in an increase in HCV load
and quasispecies diversity."
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Another Stumbling Block for Schering-Plough
By Ed Silverman, Star Ledger
Shares in Schering-Plough Corp. fell further yesterday as investors digested the news that the beleaguered drug maker faces surprisingly stiff competition to its important hepatitis C treatment. Until now,
Schering-Plough had a monopoly on the market. But since Hoffmann-La Roche Inc. announced pricing for its new hepatitis C product on Tuesday,
Schering-Plough stock has lost 8.5 percent. Yesterday, the shares fell 75 cents, to close at $21.67, on slightly heavy volume. What has Wall Street worried is Roche's pricing - an unexpected 43 percent discount for
the pill contained in the combination therapies both companies are marketing.
These therapies are essentially two-in-one product kits that also include an injectable medicine. The pricing move surprised patient advocates, who were upset several weeks ago when Roche priced the injectable
product at a level similar to what Schering-Plough charges. By discounting the pill, however, Roche appears to be trying to regain credibility, at least in the eyes of www.hivandhepatitis.com, a Web site devoted to
hepatitis C issues. The pill, which Roche calls Copegus , faces generic competition in a couple of years. But by low balling its price right away, the Web site wrote, Roche may grab market share. That's why Wall
Street is down on Schering-Plough this week. Yesterday, Standard & Poor's noted this is one reason why its outlook for the drug maker, which already lost patent protection on its best-selling Claritin drug, remains
negative.
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January 17th, 2003
Qi Gong May Ease Hepatitis C Effects
The Commercial Appeal (Memphis, TN) via Screaming
Through the simple movements and balanced breathing of the Chinese medicine technique called qi gong, Karen Fann has improved her health and the effects of the liver disease hepatitis C.
Before she was diagnosed with the disease that country music singer Naomi Judd also suffered from, Fann knew something wasn't right. She had started gaining weight, was having panic attacks and often felt tired.
"I didn't know why my metabolism had screeched to a halt," she said.
When she found out she had the liver disease, she started researching ways to control it. Fann and her husband met with a doctor who suggested she take the drug Interferon. She knew that Judd had success with
the drug, but Fann didn't like the side effects. So she decided to take a more natural approach to dealing with her problems.
While on the Internet, she came across an article on acupuncture and Chinese medicine. Fann was interested in what she read and started searching for a doctor in the area. That's when she found the Healing Arts
Medical Group in Memphis. Fann met with Dr. Judi Harrick, who has a doctorate degree in oriental medicine and who started her on herbs such as milk thistle and dandelion root, to help the liver.
She also gave Fann regular acupuncture treatments, had her stop her intake of dairy products and recommended the qi gong class.
Qi gong combines concentration with easy movements and controlled breathing. It is believed that regular practice can reduce stress, pain and the effects of sickness on the body. An article on the Web site
www.acupuncture.com said the exercises are meant to improve health and longevity and "increase a sense of harmony within oneself and in the world."
After participating in qi gong, Fann started seeing improvements in her health. Even her regular doctor was surprised. "My doctor is still scratching his head over this one," she said. "It just relaxes you. It gives you
good energy and boosts your immune system."
Today, Fann continues to have acupuncture treatments about every eight weeks. Part of her improved health regime includes losing 26 pounds through Weight Watchers by walking and changing her eating habits. She
also believes a good attitude helped her heal.
"If you're not positive about what you're doing to promote your own healing, it's not going to work," she said. "I feel better than ever now."
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How Common Is Hepatitis C Infection in People With No Symptoms?
By John C. Martin, hepatitisneighborhood.com
Of the 170 million people around the world with chronic hepatitis C (HCV) infection, edical science has determined through years of research that a certain percentage has no symptoms, even though the virus is
present in their system. But relatively little is known about how common liver damage may be in asymptomatic HCV patients.
Before it became possible to test donated blood for the presence of HCV, many people became infected through blood transfusions. Other ways to spread hepatitis C include sharing infected syringes among illicit drug
users, exposure to blood in the workplace (healthcare workers, firefighters and police officers), and procedures like tattooing, body piercing, or the use of dentistry tools that have not been sterilized.
Mysteries of HCV
Yet, the source of infection is unknown in many people. Although some people with HCV infection become severely ill to the point in which they may need a liver transplant, many remain healthy and have no
symptoms. In people who are infected and asymptomatic, it is not clear how many of those also have liver damage. Knowing the extent of this so-called "silent" liver damage will help physicians determine how
aggressive they should be in testing asymptomatic patients for the possibility of hepatitis C.
So, a group of Italian researchers set out to help clarify the little information that does exist, publishing the results of their study late last year.
Doctors at the University of Padova in Italy examined 4,820 apparently healthy Telecom employees, or their relatives, in northeastern Italy who had been screened for certain cardiovascular risk factors. The scientists
conducted a range of tests in each individual, including checking for alanine aminotransferase (ALT) levels, and conducting a test known as an enzyme-linked immunosorbent assay (EIA).
Effective HCV Testing
EIA tests can detect specific HCV antibodies in infected individuals. The tests can detect more than 95 percent of chronically infected patients, but only 50 percent to 70 percent of acute infections. Tests to determine
alanine aminotransferase levels are also effective in determining whether a person has liver damage, and in most cases, are less expensive. Alanine aminotransferase is an enzyme that is normally present in liver and
heart cells. Elevated levels of ALT in the blood can indicate liver or heart damage, such as in heart attack patients.
In the study, the researchers found that 116 people were positive for the anti-HCV antibody and an additional 85 individuals showed presence of the hepatitis C virus, according to the Italian scientists. They also
reported that enzyme levels were elevated in more than half of the patients. But, 46 percent of those who showed presence of HCV had normal levels of ALT.
Additionally, liver damage was spotted in 61 percent of those who had elevated levels of ALT and showed presence of the virus, which would be expected. But, underscoring the incidence of "silent" liver damage, the
Italian scientists discovered "significant" liver tissue abnormalities in 19 percent of the patients who showed "persistently normal" ALT levels.
Based on those results, the researchers concluded that "hepatitis C is histologically active and progressive in up to 40 percent of asymptomatic persons with HCV infection. The severity of liver disease correlates with
abnormal ALT and increases with age."
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January 20th, 2003
High-Dose Interferon Effective in Patients Coinfected with Hepatitis C
By Michael Greer, Senior Medical Writer of NewsRx.com
Interferon (IFN) treatment may be effective for both HIV and hepatitis C virus (HCV) infection, according to a researcher in Japan.
Working at Ogikubo Hospital in Tokyo, Hideji Hanabusa assessed the efficacy of high-dose IFN therapy in hemophiliacs coinfected with HIV and HCV. IFN-treated patients achieved significant reductions in levels of
both viral pathogens, Hanabusa reported.
A group of 30 patients - 15 coinfected with HIV and HCV and 15 age-matched patients infected with HCV alone - received high-dose IFN-alpha2a therapy for 24 weeks. HIV viral loads dropped from roughly 7410
copies/mL to 320 copies/mL after 2 weeks, according to the report.
Similar effects were seen on HCV viremia. HCV RNA was undetectable after 24 weeks in four of 12 evaluable HIV-positive patients, and in 6 of 15 patients without HIV coinfection, study data showed. Three patients - all
HIV-positive - were forced to discontinue treatment due to IFN-related toxicity. This data is published in Clin Infect Dis 2002 Dec 15;35(12):1527-33.
"Induction therapy and the dose of IFN should be evaluated in combination therapy with IFN and ribavirin," Hanabusa concluded.
Key points reported in this study include:
- Interferon (IFN) treatment may be effective for both HIV and hepatitis C virus (HCV) infection
- IFN-treated patients achieved significant reductions in levels of both viral pathogens
- IFN was well-tolerated
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January 21st, 2003
Tenofovir Shows Activity against Hepatitis B in HIV-Coinfected Patients
Treatment with the nucleotide analogue tenofovir reduces hepatitis B virus (HBV) levels in patients coinfected with HIV, and appears to be equally effective in patients who have and have not been exposed to lamivudine.
The findings are published in the January 3rd issue of AIDS (AIDS 2003;17:F7-F10). As the authors point out, lamivudine is known to be an effective anti-HBV agent in coinfected patients. However, lamivudine-resistant
HBV develops in at least 50% of patients who have been treated for 2 years or longer, so there is a definite need for other anti-HBV agents in this population.
In the current study, Dr. M. Nelson, from The Chelsea and Westminster Hospital in London, and colleagues assessed the outcomes of 20 HIV/HBV coinfected patients who were treated with tenofovir 245 mg daily for 1
year. All of the patients received combination antiretroviral therapy during the treatment period.
The study group included 15 lamivudine-experienced and 5 lamivudine-nave patients. Of the 15 lamivudine-experienced patients, 11 had mutations that conferred resistance to the drug. Patients with such mutations
experienced a more rapid initial fall in HBV DNA levels than patients without such mutations.
During the first 24 weeks of treatment, a median 4 log10 reduction in HBV DNA levels was observed, the authors note. At the same time, ALT levels decreased from 96 to 43 IU/mL. The magnitude of these changes
were similar for patients who had and had not been exposed to lamivudine.
By 52 weeks, HBe-antibody seroconversion had occurred in five patients, the investigators state. Lamivudine resistant mutations were identified in three of these patients.
"These results indicate that 52 weeks of tenofovir in addition to antiretroviral therapy is active against HBV, and it appears to overcome lamivudine resistance," the researchers conclude. "Tenofovir increases the
therapeutic options for HIV-1 and HBV coinfection," they state.
The results are in agreement with those of a smaller pilot study reported last month. In that study, US researchers found that adding tenofovir to the patients' current antiretroviral regimens dramatically reduced HBV
RNA levels.
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UK Hemophiliacs Claim They Were Tested for Hepatitis without Consent
By Richard Woodman
A group representing some of the British hemophiliacs exposed to contaminated blood products in the 1970s and 1980s said on Tuesday that patients had been tested for hepatitis C without their knowledge or
consent.
In a letter to Health Ministers, Haemophilia Action UK said that patients had asked to see their medical records recently in preparation for possible litigation against American plasma companies for contamination with
HIV and hepatitis viruses.
"We were absolutely appalled to find that in the past there has been testing of hemophiliacs for the hepatitis C virus on a national scale without the permission of the patient, and without any pre- or post-test counseling
being offered."
The letter complains that test results were withheld often for several years and that patients were denied the opportunity to make certain life choices, such as taking precautions to ensure that they did not infect their
sexual partners.
"What is truly shocking is that in some cases hemophiliacs have actually been diagnosed with serious conditions related to their hepatitis C infection and were not told of these for many years."
It adds that hundreds of hemophiliacs, who received British government compensation in 1991 for being infected with HIV, had to sign legal waivers promising they would not sue if it was later found that they had
hepatitis C as well.
"Hemophiliacs did not realize at the time that 99% of HIV positive hemophiliacs would test positive for hepatitis C and that the doctors, the solicitors and the Government knew this fact but the only people who didn't
know when signing the waiver were the hemophiliacs!"
In a statement, the Department of Health said: "We are not aware of any complaints to the Department about this either from individual patients or from the Haemophilia Society (the main patient group). We would
however be happy to look into any complaints if they are raised with us."
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HCV infection and Abstinence from Alcohol in Patients with Alcoholic Cirrhosis
Cumulative survival in alcoholic cirrhosis is not influenced by the presence or absence of markers of HCV infection, find researchers in the February issue of the Journal of Clinical Gastroenterology (J Clin Gastroenterol
2003; 36(2): 170-4).
Hepatitis C virus (HCV) infection may be an important cofactor for liver disease in chronic alcoholics.
In this study, researchers from Spain assessed the effect of HCV infection and abstinence from alcohol on survival in a cohort of patients with alcoholic cirrhosis. The research team assessed 213 patients with
alcoholic cirrhosis. Of these, 72 were infected by HCV.
Persistence of alcohol consumption after diagnosis was identified as an independent predictor of poor outcome. Complete alcohol abstinence following diagnosis of alcoholic cirrhosis was recorded in 86 patients.
The team compared the study patients with a reference group consisted of 89 patients with anti-HCV positivity, who had never consumed alcohol. They analyzed survival using the Kaplan and Meier method, and the
predictors of survival using Cox's multiple regression. The research team found that HCV infection was not a determinant factor for survival in alcoholic cirrhosis. Age and Child-Pugh grade at the time of cirrhosis
diagnosis, and persistence of alcohol consumption after diagnosis were identified as independent predictors of poor outcome. Furthermore, the cumulative survival curve in abstinent alcoholics was significantly different
from that of alcoholics who maintained their pattern of alcohol consumption. Additionally, cumulative survival in patients with anti-HCV-positive cirrhosis who stopped drinking after diagnosis was similar to that in
patients with HCV-positive cirrhosis who had never consumed alcohol.
Dr Miguel Serra's team concluded, "Cumulative survival in alcoholic cirrhosis does not seem to be influenced by the presence or absence of markers of HCV infection". "Once liver cirrhosis has been diagnosed in the
alcoholic patient, complete alcohol abstinence should be strongly recommended."
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January 22nd, 2003
Phase I Clinical Studies of Viramidine-A Liver-Targeting Prodrug of Ribavirin
Although ribavirin in combination with interferon has proven reasonably effective in the treatment of chronic HCV, use of the drug is limited by its many toxicities and side effects. Viramidine is a liver-targeting prodrug of
ribavirin. It is efficiently converted to ribavirin by adenosine deaminases and effects similar direct and indirect anti-viral activities as ribavirin.
Pharmacokinetic (PK) studies in monkeys demonstrated that Viramidine is orally absorbed and preferentially taken up by the liver where the majority of the prodrug is converted to ribavirin. Animal toxicology studies
resulted in no clinical side effects and minimal drop in hemoglobin in monkeys dosed at viramidine 600 mg/kg/day for 28 days while greater proportion of animals dosed at ribavirin 300 mg/kg/day experienced greater
decrease in hemoglobin.
The aim of the current study was to characterize the safety and PK profiles of single dosing, the effect of food, and multiple dosing of viramidine in humans.
A rising-single dose (RSD) study to evaluate the safety, tolerability and PK profiles of viramidine at oral doses of 200, 600 and 1200 mg in male adult healthy volunteers (N=8 on viramidine vs. 2 on placebo per dose
group) was conducted.
For the effect of food (FE), 36 adult male subjects were enrolled into 2 groups. Eighteen received viramidine 600 mg after 10-hr fasting and 18 received viramidine after a modified high fat breakfast. Subjects were
crossed over to receive viramidine in reverse fasting/fed condition after a 6-wk washout.
A rising multiple-dose (RMD) study to determine the safety, PK and pharmacodynamics of viramidine at 400 mg BID, 600 mg BID and 800 mg BID for 4 weeks has been initiated in patients with chronic hepatitis C.
RSD and FE study - 57 healthy adult male subjects at mean age of 27.5 years (19-53 yrs) and mean weight of 76.4 kg (51-100 kg) completed the study. All doses of viramidine were safe and well tolerated.
All but one Hepseraerse events (AEs) were mild and comparable between the different dose levels of viramidine. Viramidine was orally absorbed and efficiently converted to ribavirin with Cmax for both compounds at
Tmax of 2.5-3 hrs. Higher AUCs for viramidine-derived ribavirin compared to that of viramidine, by 2-3 folds, at all dose levels were observed.
Both Cmax and AUCs of viramidine-derived ribavirin were proportionally higher with increasing dose. Viramidine was not detectable in RBCs. AUC of viramidine-derived ribavirin in RBCs was about half of that compared
to ribavirin dosing (historical data). Both viramidine and ribavirin were excreted in urine.
Mean AUC and Cmax of viramidine-derived ribavirin were 20% and 40% higher, respectively, after fed than fasting. RMD study is in progress with results available for presentation at AASLD.
Conclusions:
- Single doses of viramidine up to 1200 mg are safe and well tolerated in humans.
- Viramidine is orally absorbed and efficiently converted into ribavirin.
- The linear relationship between Cmax and AUC of viramidine-derived ribavirin with viramidine dose indicates dose proportionality.
- The exposure of viramidine-derived ribavirin to RBC is about half that after ribavirin dosing suggesting a lesser potential in inducing hemolytic anemia than ribavirin.
- The marginal effects of food are not likely to be clinically relevant when the treatment duration is as long as 48 weeks.
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Making the Most of Incremental Advantages in the Hepatitis C Market
By Mary Stuart
Roche is challenging Schering-Plough's hegemony in the hepatitis C market with newly approved Pegasys-Copegus. The trick will be in getting physicians to adopt a second-in-class drug with only marginal
advantages.
Schering-Plough Corp.'s best-selling drug--a combination of PEG-Intron (peginterferon alfa-2b) and Rebetol (ribavirin) for hepatitis C (HCV)--has enjoyed a growing market to itself, with more than $1 billion in
sales. Now, though, Roche is about to challenge Schering-Plough's hegemony by launching its own combination of alfa-interferon plus ribavirin. In December, Roche received FDA approval for combination treatment
Pegasys-Copegus, and earlier this month, it settled a patent dispute with ICN Pharmaceuticals Inc., the first commercializer of ribavirin, putting in place the final piece of the puzzle. (Pegasys was approved as a
monotherapy two months earlier, but the standard of care is to use alfa interferon and ribavirin together; neither drug on its own is highly effective). Now the two players are preparing for battle in a market in which the
stakes are high, and competitive alternatives are still several years away from market.
Most people find out that they have HCV in the course of getting blood tests for other purposes; in the US, an estimated 4 million people are infected. The disease has been transmitted by transfusions of infected blood
that occurred before 1994, when a blood screening test for the disease became available, by infected needles, and by sexual contact. It can remain symptomless for decades, damaging the liver and leading to 10,000
deaths per year.
Eager to help sufferers of the deadly disease, hepatologists put 150,000 patients on Schering-Plough's combination of PEG-Intron and Rebetol (which it had licensed from ICN Pharmaceuticals) within the first year of
its October 2001 launch. But now Roche threatens that franchise.
As the second vendor in, Roche knows its best hope is to demonstrate the superiority of its drug over Schering's, but it's also using aggressive marketing tactics. Roche, after all, has the luxury of watching
Schering-Plough lay the groundwork, so that it can offer refinements. Pegasys and PEG-Intron appear to have similar efficacy. In the most difficult to treat hepatitis C group, heavy patients who have genotype 1(which
comprises 75% of the US patient population), separate studies that demonstrated efficacy in sustaining viral response resulted in 47% efficacy for the Schering-Plough drug combo and 51% for that of Roche; however,
the two regimens have yet to undergo a head-to-head comparison.
So, Roche is aiming for more subtle advantages, such as ease of use and possibly lower side effect profiles. Schering-Plough's drug is administered by weight; it offers five dosage packages, tailored to achieve greater
efficacy for heavy patients and fewer side effects for smaller people. Roche, in contrast, has one dosage form for all, which it claims offers ease-of-use advantages for physicians. Roche also says its drug is more
patient friendly; PEG-Intron comes in a powdered form which needs to be reconstituted by patients using a syringe and two vials. The Roche product comes premixed in one vial.
The Roche combination appears to have a marginally better side effect profile. The comparison, however, may be unfair because in clinical trials, the Roche drug was benchmarked against Schering's older
three-times-a-week Intron, not the current therapy, PEG-Intron, so clinicians will wait to see how this potential difference plays out in clinical practice. If Roche's drug really does have even a slightly improved side effect
profile, that might help it, because side effects are a huge issue with these drugs. Most patients on them experience adverse reactions, including fatigue, aches and pains, fever, chills,vomiting, depression, insomnia,
and even suicidal behavior.
David Bernstein, MD, Chief of Hepatology at North Shore University Hospital in Manhasset, NY, says that given comparable efficacy, side effects and cost, patients and physicians gravitate to the easier-to-use
products. PEG-Intron is slightly more difficult to use but this distinction will disappear in the near future, as both companies are developing prefilled injection pens.
Customized medicine is another of Roche's trump cards. Schering-Plough's labeling, for example, doesn't differentiate among the various HCV genotypes, all of whom are indicated for a 48-week regimen. Roche,
however, took care to structure clinical trials that permitted it to get a labeling for a 24-week regimen of drug therapy for the 25% of patients who are genotypes 2 and 3, compared to a 48-week regimen for genotype 1
patients.
Roche claims this additional labeling allows it to determine earlier the patients who will and won't respond to the drug. Given the horrible side effect profile of these drugs, the ability to shorten a patient's time on them
is a real quality of life advantage. Finally, the shorter courses of therapy will be less expensive.
For Roche, such a strategy puts its strong push into personalized medicine into practice. It has spent several years forging links between its diagnostics and pharmaceutical businesses, with modest gains to show for
it. If it can use its genotyping tests to customize optimal treatment regimens--however crude--and trump the competition, it will be making a point: although customizing therapies according to subsets of patients most
likely to respond to them runs a risk of cutting into revenues, it also gives vendors an edge in a tough marketing challenge.
Roche jump-started its marketing effort with a 15,000 patient giveaway that was fulfilled in November; these patients will get a free three-month supply of the drug. But in mid-January 2003, Roche released a big
marketing gun: it is introducing its formulation of ribavirin, Copegus, at a wholesale price that is 43% less than Rebetol. Thus, although costs are similar for the interferon parts of both companies' regimens, patients on
48 weeks of 1200 mg per day of Roche's ribavirin will save approximately $7,600 over its competitor's version of ribavirin, Roche says. For the future, Roche has shored up another advantage; it has an exclusive license
for levovirin, ICN Pharma's second generation of ribavirin, the first generation of which is teratogenic. Roche's license could potentially preclude Schering-Plough from having access to the newer drug.
Schering-Plough hasn't yet responded to the pricing attack. Already hurting from lower-than-expected prescriptions for Claritin, which recently switched to OTC status, the threat to its largest franchise is serious. For
now, it continues to conduct clinical trials--as does its competitor--that will help it get the most out of its drugs. The FDA-approved drugs are still works in progress, and both competitors are slicing up clinical trials to
identify which sub-groups of patients are the best responders, which drug dosages are optimal for which patients, and both are expanding indications for the drugs. For example, Roche and Schering-Plough are
conducting clinical trials on patients co-infected with hepatitis C and HIV; there is significant overlap in these patient populations. Schering-Plough is evaluating the effects of its drugs as maintenance therapies that
might prevent liver damage, even in patients that don't mount a sustained viral response.
For now, hepatologist Bernstein says, physicians should, and probably will use both companies' drugs, to see which are the most efficacious. In this dire disease with few therapeutic alternatives, physicians will want
to use everything at their disposal, he says
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January 23rd, 2003
Ribapharm Announces Election of Directors. Company Appoints President and CEO
Ribapharm Inc. announced today that its board has elected the following individuals to serve as directors effective immediately: Daniel J. Paracka, Santo J. Costa, Gregory F. Boron and James J. Pieczynski, CPA. Mr.
Paracka was also elected to serve as Chairman.
The new directors join Roberts A. Smith, Ph.D., who continues in his role as a Ribapharm director.
The Ribapharm board also announced the appointment of Kim D. Lamon, M.D., Ph.D., to the position of President and Chief Executive Officer. Dr. Lamon has more than 20 years of experience in the pharmaceutical,
biotechnology and diagnostics industries, where his teams have been responsible for the development and approval of numerous drugs, including several whose current individual sales exceed $1 billion. Dr. Lamon
most recently served as President of SciPharma Consulting, LLC, a company that provides consulting services to healthcare companies. Dr. Lamon announced that he will be resigning from the board of ICN
Pharmaceuticals, where he currently serves as a director.
Ribapharm noted that its newly reconstituted board has considerable depth in the pharmaceutical, healthcare and biotechnology industries, and significant experience with legal, financial and scientific issues. The new
directors have no prior affiliation with Ribapharm or ICN.
Dr. Lamon commented: "I am honored to be joining Ribapharm, whose outstanding team of scientists have been responsible for the development of ribavirin, the preeminent medicine for hepatitis C. Our strategy going
forward will be to leverage and grow our discovery and development expertise to gain approval of unique medicines of value and other exciting new compounds."
Mr. Paracka has more than 20 years of pharmaceutical experience and an extensive financial controls and management background. He has served on the boards of several pharmaceutical companies, including
chairman of the board for Lidak Pharmaceuticals, and chairman of the finance and executive committees for Celotex Corp. Mr. Paracka's management experience includes senior positions in Rhone-Poulenc Rorer,
where he served as Senior Vice President and Chief Financial Officer; Rorer Group, where he served as Senior Vice President of Finance; and Revlon Healthcare Group (comprised of nine healthcare companies), where
he served as Vice President and Controller.
Mr. Costa has more than 30 years of business experience, including 23 years in the pharmaceutical industry. He recently served as Vice Chairman of Quintiles Transnational Corp, after having spent several years as
President and Chief Operating Officer. He was previously Senior Vice President, Administration and General Counsel of Glaxo Inc. where he also served on the company's board of directors. Mr. Costa sits on the
boards of several pharmaceutical and healthcare companies and has lectured on food and drug law issues and a wide variety of legal and policy issues affecting the pharmaceutical industry.
Mr. Boron has more than 15 years of experience in the healthcare and pharmaceutical industries, having recently been a partner at Boron and LePore Group Companies, a New Jersey-based healthcare
communications, marketing and pharmaceutical services company. There, he also held several senior management positions, including Chief Operating Officer, Chief Financial Officer and Executive Vice President of
Marketing and Sales. Prior to his extensive business experience, Mr. Boron had a distinguished military career, having served as a major in the U.S. Army and on the faculty of the U.S. Military Academy at West Point
and the Royal Military College at Sandhurst, England.
Mr. Pieczynski is a certified public accountant and has nearly 20 years of financial control and management experience, having served in senior capacities in the healthcare and real estate industries, including
President, Chief Financial Officer and Chief Strategic Officer of LTC Properties, Inc. He has also served on the board of directors at LTC Properties. Mr. Pieczynski is currently the Director of Long-Term Care
Investments for CapitalSource Finance.
Dr. Smith has more than 40 years of experience in the pharmaceutical and biotech industries and is a preeminent scientist in the field of virology. He is one of the original scientists who developed the ribavirin molecule
and one of the pioneers in the field of nucleoside analog exploration. Dr. Smith was previously President of Viratek, Inc, and Vice-President, Research and Development of SPI Pharmaceuticals, Inc., both past
subsidiaries of ICN. Dr. Smith also had an illustrious academic career and was Professor of Chemistry and Biochemistry at the University of California at Los Angeles for more than 11 years. Dr. Smith has continued
as a senior scientific advisor and board member since the inception of Ribapharm.
Dr. Lamon is currently a director of Pan Pacific Pharmaceuticals, Inc., and is on the scientific advisory board of VivoMetrics, Inc. He also serves as Adjunct Assistant Professor of Pharmacology at his alma mater,
Thomas Jefferson University School of Medicine. Prior to founding SciPharma in 1999, Dr. Lamon was Corporate Senior Vice President and Group President of Covance Clinical and Periapproval Services, where he had
operating responsibility for the worldwide clinical division of Covance, Inc. He has held senior research and clinical positions at Corning Clinical Laboratories, Corning Life Sciences, Inc., and Rhone Poulenc Rorer (now
Aventis, Inc).
About Ribapharm
Ribapharm is a biopharmaceutical company that seeks to discover, develop, acquire and commercialize innovative products for the treatment of significant unmet medical needs, principally in the antiviral and
anticancer areas.
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InterMune Initiates Phase I Study of PEG-Alfacon for the Treatment of Chronic Hepatitis C Infections
InterMune, Inc. announced today that it has initiated a Phase I clinical study to evaluate PEG-Alfacon, the PEGylated version of Infergen(R) (Interferon alfacon-1), as a potential new treatment for chronic hepatitis C
virus (HCV). InterMune currently markets Infergen, a bio-engineered type I interferon alpha, for the treatment of patients with chronic hepatitis C infections. PEGylation is a technology designed to chemically modify
drugs to decrease dosing frequency and possibly improve drug efficacy and safety.
The Phase I, open-label, dose-ascending study of PEG-Alfacon will enroll approximately 40 healthy volunteers. The study is designed to: i) evaluate the pharmacokinetic and pharmacodynamic characteristics of
PEG-Alfacon; ii) determine the maximum tolerated dose of this new chemical entity; and iii) evaluate its safety. The study is being conducted at a center specializing in pharmacokinetic analyses.
"We anticipate that the introduction of PEG-Alfacon will mark the beginning of a new era of HCV therapeutics where more potent bioengineered compounds are used to combat this disease," said Scott Harkonen,
President and Chief Executive Officer of InterMune. "We look forward to completing this study and plan to initiate a Phase II dose-ranging study by the end of 2003 to further evaluate PEG-Alfacon in patients."
"We believe that the clinical potential of PEG-Alfacon is extremely promising given that Infergen -- the only bioengineered interferon in the hepatitis C market - has been shown to have greater interferon receptor
binding, and better immune activating and viral inhibition capabilities compared to other alpha interferons," said Dr. Curtis Ruegg, Vice President of Pre-Clinical and Process Development at InterMune. "We believe the
advantages of Infergen and pegylation, when coupled, could result in higher response rates with PEG-Alfacon and ultimately a promising new treatment for the more than four million patients suffering from chronic
hepatitis C infections."
About Infergen
Infergen is currently approved for treatment of adult patients with chronic hepatitis C infections, including therapy for patients who have never been treated with interferons and for patients following relapse or
non-response to treatment with certain previous treatments. Please visit www.infergen.com for full prescribing information including the black box warning.
About PEG-Alfacon
PEG-Alfacon is the result of chemical engineering using PEGylation technology to attach a polyethylene glycol (PEG) moiety to the active Infergen molecule. The expected effect of PEGylation is to increase drug
circulation time in the bloodstream, decrease the rate of proteolysis by circulating enzymes, and reduce immunogenicity.
About InterMune
InterMune is a commercially driven biopharmaceutical company focused on the marketing, development and applied research of life-saving therapies for pulmonary disease, infectious disease and hepatology.
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January 24th, 2003
Schering-Plough Drops on $50 Million CEO Parachute
By Ransdell Pierson
Shares of Schering-Plough Corp. fell on Friday, a tumble analysts blamed on concerns about a $50 million retirement package for embattled Chief Executive Richard Kogan, who is slated to give up his post by April.
"It looks like people are fed up with Kogan's pay package," Raymond James analyst Mike Krensavage said.
"Schering-Plough has lost $40 billion in market capitalization in the past two years, so it looks like Kogan is getting over $1 million for every $1 billion they've lost," Krensavage said.
Schering-Plough was down 61 cents, or 3 percent, to $20.07 in heavy midday trade Friday on the New York Stock Exchange, having slumped to $19.50 earlier in the session amid a drop in the overall stock market. A
Schering-Plough spokeswoman declined to comment, citing company policy about not discussing stock moves or analyst remarks.
The Kenilworth, New Jersey-based firm disclosed late Thursday that $24 million of Kogan's retirement package was charged in the company's fourth-quarter expenses and the remainder had been expensed previously.
About $13 million of the package will be basic cash severance, amounting to three times Kogan's annual salary, bonus and benefits. The remainder is from pension, stock awards and stock options, the company said.
Kogan has worked for the company for 22 years, becoming CEO in November 1998. The chief executive of rival Pharmacia Corp., Fred Hassan, is considered a front-runner to replace him in coming months.
Kogan's retirement package comes on the heels of severe problems for the company since early 2001, including quality control deficiencies at its plants that have prompted U.S. regulators to hold up approvals of its
key drugs.
The company's earnings fell 10 percent in 2002 in large part because of the drug-approval delays. The company expects earnings to plunge even more this year -- as much as 30 percent -- due to the patent expiration
last month on blockbuster allergy drug Claritin. It is now being sold for only about $1 a pill without a prescription, barely one-third its former cost.
Moreover, the Securities and Exchange Commission is investigating several private meetings Kogan had with select investors in October just minutes before and during a mysterious three-day sell-off that erased 17
percent of the value of the company's shares.
Another analyst, who asked not to be identified, agreed that investors were reacting negatively to Kogan's "golden parachute."
"Shares are trailing off today on the feeling there's a lack of priorities at Schering Plough -- giving $50 million to a CEO who has become embroiled in disclosure issues and who has shown a lack of control over
manufacturing problems," the analyst said.
Analysts said investors may also be concerned about new rival treatments for hepatitis C made by Swiss drugmaker Roche Holding AG. The U.S. Food and Drug Administration last month approved two Roche drugs
used together against the potentially deadly virus, an interferon called Pegasys and the antiviral pill ribavirin expected to garner combined future annual sales of over $1 billion. They will compete with Schering-Plough's
best-selling products, its own interferon Peg-Intron and much more expensive form of ribavirin against the virus. Fourth-quarter sales of the Schering-Plough drugs leaped 62 percent to $817 million.
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January 25th, 2003
CDC: Prison Action Can Stem Hepatitis
By Daniel Yee, Associated Press Writer
The government said Friday that public vaccination efforts to prevent hepatitis outbreaks should be extended to prisons, a move one expert said could save many lives. "Medical prevention measures can be delivered
effectively in prisons," said Dr. Cindy Weinbaum of the Centers for Disease Control and Prevention. "Prison is a great place for preventing these infections from getting transmitted because it's a venue where we can
vaccinate."
Hepatitis is caused by a virus that attacks the liver. About 1.4 million Americans have chronic hepatitis B conditions and between 125,000 to 200,000 people yearly are infected with hepatitis A.
More than 4 million Americans have chronic hepatitis C infections. Of those, about 39 percent once were in prison, the CDC said. Among the CDC's recommendations, some of which date to 1982 but were
consolidated in Friday's report:
Inmates not previously infected with hepatitis B should be vaccinated because they are in proximity with infected people and those with high-risk behaviors, such as drug use.
Prison guards in frequent contact with blood should be vaccinated against hepatitis B.
High-risk groups, such as men who have sex with men or drug users, should be vaccinated against hepatitis A.
The CDC also suggested hepatitis C tests for intravenous drug users. No vaccine exists for hepatitis C.
"It's critically important that CDC has come out to recommend that inmates be immunized to protect them and the general public from hepatitis A and B," said Alan Brownstein, president and chief executive of the
American Liver Foundation. "This will save many lives among inmates and many lives among those in the public; this is a breath of fresh air."
Weinbaum said each state and prison system will have to decide whether to implement the recommendations.
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January 27th, 2003
HCV/HIV Coinfected Patients Not Candidates for Combo Therapy?
Hepatitisneighborhood.com
Boston researchers have confirmed that people co-infected with both hepatitis C and HIV, the virus that causes AIDS, may not be suitable candidates for HCV therapy with interferon and ribavirin.
"The impetus for this study was the realization that many of the patients we were seeing in our co-infection clinic were not candidates for interferon based therapy despite the increasing access to and benefits of
treatment," said Catherine Fleming, M.D., of Boston Medical Center, and the study's lead investigator, in an interview with Priority Healthcare.
Treatment Barriers
The key barriers to treatment for this group of patients-large minorities who live in urban areas-are missed clinic visits, active psychiatric illness, drug and alcohol use, liver disease, or other medical illnesses, the
researchers conclude.
In the study, Fleming and her colleagues evaluated 180 HCV/HIV co-infected patients to determine whether they were candidates for therapy.
Of the 149 patients who completed the evaluation, they found that only 30 percent were eligible. Of those, just over a third began interferon therapy during the course of the study.
Fleming said that this urban population possesses a range of medical and social issues that prevents its members from being candidates for interferon therapy. Overcoming this challenge will require a multidisciplinary
approach and earlier medical evaluations of these patients, Fleming said.
Of those found unsuitable for treatment, about a fourth failed to visit their physician regularly, 21 percent had active psychiatric disease, a fourth had abused drugs or alcohol in the previous six months, 12 percent had
liver disease, 13 percent were infected with advanced HIV disease, and the remaining patients had other diseases or conditions that were contraindicated in interferon therapy.
"I think that this is a very complex patient population, and that there is no single solution," Fleming told Priority Healthcare. "However, earlier evaluation of hepatitis C in co-infected patients, access to methadone
programs with directly observed therapy, and psychiatry support would all help."
Patient education may also be the key, helping patients who face such challenges to realize the consequences of drug and alcohol abuse, Fleming pointed out.
Prevalence of Co-Infection
It is estimated that more than 500,000 adults in the United States are either infected with HIV, or are living with AIDS. Approximately one-fourth those are also infected with the hepatitis C virus. HCV infection typically
progresses more rapidly to liver damage in HIV-infected people, and may impact the course and management of HIV.
There are several preventative measures that people living with HIV can take to prevent becoming co-infected with hepatitis C, including not injecting or stopping injection drug use, not sharing personal items like
toothbrushes and razors that may be contaminated with blood, and avoiding at-risk behaviors like tattooing and body piercing.
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Healthcare Management Quality Lacking for Chronic Disease Patients
By John C. Martin, hepatitisneighborhood.com
Patient care management falls short when it comes to patients with various chronic diseases, conclude two groups of researchers who conducted a nationwide survey on the issue. The study was published in a recent
issue of the Journal of the American Medical Association.
Researchers at the University of California, Berkeley, and the University of Chicago conducted the poll of physician organizations, asking how often they utilize care management processes, which include the use of
nurse case managers, programs to help patients care for their illness, disease registries, reminder systems, use of guidelines and feedback to physicians on their quality of care.
The scientists found that physician groups, on average, use less than a third (32 percent) of 16 recommended care management processes, and that one in six uses none of them.
"The results suggest that Americans are not receiving care that is as good as it could and should be," said Stephen Shortell, Ph.D., professor and dean of UC Berkeley's School of Public Health, and the study's lead
investigator. "In many ways, physicians are still organized to practice medicine the way they did 100 years ago."
Healthcare Management Quality
The researchers focused primarily on four diseases; asthma, congestive heart failure, depression and diabetes, which account for 140,000 deaths and $173 billion in costs each year in the United States.
They surveyed more than 1,000 medical groups and independent practice associations with at least 20 physician members each. The presidents, chief executive officers or medical directors of each association took
part in telephone surveys from September 2000 to September 2001.
"The processes we studied are known to improve the quality of patient care," said Lawrence Casalino, M.D., assistant professor of health studies at the University of Chicago, and the study paper's lead author. "Our
research indicates that physician organizations are beginning to create effective processes to increase quality, but most still have a long way to go."
Seven out of 10 physician groups surveyed do not keep a list of patients who have serious chronic diseases. Half of the groups reported having no clinical information technology, such as electronic data systems to
track patients illnesses, medications and lab results.
This lack of healthcare management quality has a direct impact on patient outcomes, Shortell explained, in an interview with Priority Healthcare, but acknowledging that more data confirming that association need to
be collected. "The evidence on that isn't as strong as we would all like, and that's one of the additional studies wed like to do, actually," he explained. "But what evidence we have suggests that if patients receive care
from practices that do more of these things that we studied, it's a much higher probability their blood sugar will be in control, their asthma will be in control, they'll have reduced hospitalization, reduced ER visits, and so
on."
The researchers discovered that physician groups are more likely to use organized processes to improve care when they have clinical information technology in place, and are given external incentives such as financial
rewards, public recognition or better contracts with health plans for high quality care.
"Unfortunately, most physician practices don't have a lot of extra resources or capital to invest in electronic medical records, and to hire new types of personnel required to implement team-based care," Shortell
explained.
Incentive Benefits
So, what is the key to helping physicians improve the quality of their care management processes? Casalino and his colleagues found that health plans and large healthcare purchasers---corporate employers and
federal and state governments---that provide external incentives can typically be the motivator. Still, the survey found that as much as a third of physician groups have no incentives to improve quality.
"We know incentives work, but for the most part, they are not being used," said Casalino. "The federal government and large employers have the most leverage to establish incentives. They have the opportunity and the
responsibility to do so. Most Americans probably don't realize that those who purchase health insurance on their behalf are not paying for quality care."
Other Studies
The study comes on the heels of two recent reports from the Institute of Medicine (IOM) that found that the nation's healthcare delivery system falls short in applying new technology and biomedical knowledge safely
and appropriately. The IOM reports blamed a lack of organized process rather than shortcomings in individual physicians for the gap in quality.
The series of reports was the motivation for the latest study, Shortell said. "The impetus was probably the two IOM reports documenting the unnecessary variation of the quality of care we have in this country,
particularly for chronic illness."
The IOM is urging the federal government to spearhead efforts to improve healthcare quality and safety. In addition, it wants health plans, large employers, and government programs such as Medicare and Medicaid to
reward physicians who drive the effort to improve healthcare quality.
There are several public/private incentive programs already in place. In addition to a proposal by Health Secretary Tommy Thompson to launch a federal incentive program, several private sector initiatives are in place in
about two dozen states, Shortell pointed out.
Additionally, several Fortune 500 companies have established successful incentive programs, and Medicare and Medicaid have recently created demonstration projects that reward quality, as well as six California
health plans which have initiated new Pay for Performance initiatives.
"It's not a problem with doctors," Shortell said. "It's a problem with the organization of their practices, and the two big levers are the importance of information technology and the importance of creating some of these
external incentives."
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January 28th, 2003
Nut Allergy Passed Through Liver Transplant
By Stephanie Riesenman
An Australian man who received a liver transplant developed a life-threatening nut allergy apparently passed on through the donated organ, doctors reported Monday.
And while the transfer of an allergy from donor to recipient appears rare, they are suggesting all organ donors be screened for allergies prior to donation.
The liver donor was a 15-year-old boy whose own allergic reaction to peanuts had caused his death. His organs were donated to four different patients, but only the recipient of the liver acquired the nut allergy.
Dr. Tri Giang Phan and colleagues from Royal Prince Alfred Hospital and the University of Sydney report on the case in the January issue of the Archives of Internal Medicine (Archives of Internal Medicine
2003;163:237-239).
"I wouldn't take a liver from a patient who died from a nut allergy," Dr. Patricia A. Sheiner, director of liver transplantation and hepatobiliary surgery for Westchester Medical Center in New York, told Reuters Health.
The surgeons in this case said they did not know the donor had an allergy to nuts prior to performing the operation.
The recipient of the liver was a 60-year-old man with chronic hepatitis B and a liver tumor. A day after he was sent home from the hospital, the man developed a severe allergic reaction after eating cashews. Nuts had
been a regular part of his diet prior to the transplant, causing no problems.
He was taken to a hospital and treated for tightness in his throat, blurred vision, nausea, vomiting and diarrhea. Tests confirmed an allergy to cashews, peanuts and sesame seeds. The patient was sent home with an
epinephrine shot to self-inject in case of a future allergic reaction.
He had to use the shot again 32 weeks after his transplant; this time he was accidentally exposed to peanuts. More tests confirmed antibodies to nuts were present in his system, but in lesser amounts than during his
first bout with anaphylactic shock, or potentially life-threatening allergic reaction.
Two years following his liver transplant, the patient died from complications related to the original liver tumor.
In hopes of determining how the allergy was transferred from organ donor to recipient, the researchers looked at the man's DNA. No donor-specific genes for nut allergy were present in the blood or skin of the liver
recipient.
In the only other reported case of nut allergy acquired from a liver donor, immune system B cells present in the liver were thought to have transferred the allergy.
This case is important for transplant surgeons to consider, said Sheiner.
She noted that she might consider transplanting an organ from someone who was known to have a nut allergy, but the recipient would have to know he or she could become allergic to nuts.
"It doesn't mean it's a bad organ" Sheiner said, "but it probably means that the person receiving it will have to know ahead of time that they'll have to avoid nuts and be willing to do that."
Phan's team notes that "it is possible that reactivity to other allergens such as antibiotics may also be transferred after liver transplantation."
Sheiner said there has not been a case, to her knowledge, where a patient developed an allergy to antibiotics after receiving a liver transplant.
To prevent such potentially serious allergic reactions after liver transplantation, Phan's team recommends that screening for allergies be included in the donor-selection process.
Surgeons in the United States generally conduct a rigorous examination of the donor's health history. Sheiner said that getting a good history of known allergies from the donor's family is a wise addition.
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Albuferon-alpha Well Tolerated, Has Prolonged Half-Life
Immunotherapy Weekly
Human Genome Sciences, Inc., (HGSI) presented the results of 3 phase I clinical trials of its new drugs to an audience of financial analysts and investors at the 21st Annual JP Morgan H & Q Healthcare Conference in
San Francisco.
Results were reported for phase I clinical trials of Albuferon-alpha in adults with hepatitis C, and of BLyS in patients with common variable immunodeficiency (CVID). The company also discussed previously disclosed
results of a phase I clinical trial of Albutropin in adults with growth hormone deficiency, and provided an update on the progress of other drugs in Human Genome Sciences' clinical development pipeline.
During its presentation to the 21st Annual JP Morgan H & Q Healthcare Conference, Human Genome Sciences presented the following data:
Albuferon-alpha phase I clinical trial results:
Results from a phase I clinical trial of Albuferon-alpha, the company's novel long-acting form of interferon alpha, demonstrate that Albuferon-alpha is well tolerated, has a prolonged half-life, and is biologically active in
adults with chronic hepatitis C. Forty-one patients have been treated in the multicenter, open-label, dose-escalation study.
The primary purpose of the phase I clinical trial is to determine the safety, tolerability and pharmacokinetics of Albuferon-alpha in adults with chronic hepatitis C who have failed previous interferon alpha treatments.
Pharmacodynamics, immunogenicity, and biological activity data also were evaluated. Ninety-three percent of the patients (38 of 41) participating in the trial were infected with hepatitis C virus (HCV) genotype 1, which
accounts for nearly 70% of all HCV infections in the United States and is generally regarded as the most difficult HCV genotype to treat.
On average, patients participating in the study had been treated previously for approximately 12 months with interferon alpha or pegylated interferon alpha, either alone or in combination with ribavirin. The protocol called
for patients to be given either single doses of Albuferon-alpha subcutaneously, or 2 doses of Albuferon-alpha subcutaneously 14 days apart, at 7 micrograms (microg), 20 microg, 40 microg, or 80 microg.
Results show that Albuferon-alpha is well tolerated, has a prolonged half-life, and is biologically active in adults with chronic hepatitis C. There were no drug-related serious adverse events or discontinuations.
Albuferon-alpha remains in the blood substantially longer than is reported for recombinant interferon alpha and pegylated interferon alpha. At 80 microg, Albuferon-alpha exhibited a mean half-life of up to 157 hours. This
compares to a half-life of 70 to 90 hours reported for Pegasys, and a half-life of 35 to 40 hours reported for Peg-Intron. No patient developed an immune response against Albuferon-alpha.
The level of the enzyme known as 2', 5'-oligoadenylate synthetase (OAS) in peripheral blood cells is a biological marker for the activity of interferon alpha. Albuferon-alpha was found to be biologically active and capable
of inducing prolonged elevations of 2', 5'-oligoadenylate synthetase mRNA. The elevations in 2', 5' OAS mRNA were sustained for up to 28 days following a single injection of Albuferon-alpha. Levels of alanine
aminotransferase (ALT), an enzyme, which is elevated by liver cell injury, were reduced substantially in some patients. Furthermore, even at the low doses evaluated, the HCV viral load was reduced in some patients.
Albuferon-alpha was found to be biologically active and capable of inducing prolonged elevations of 2', 5'-oligoadenylate synthetase mRNA. The elevations in 2', 5' OAS mRNA were sustained for up to 28 days following
a single injection of Albuferon-alpha.
Interim data on the Albuferon-alpha phase I study were presented at the American Association for the Study of Liver Diseases (AASLD) meeting in November 2002. Human Genome Sciences is continuing to evaluate
Albuferon-alpha's safety, tolerability, and pharmacology at higher doses, in single-dose and repeat-dose cohorts, under an amended protocol designed to seek the maximum biological response that can be achieved at
a tolerable dose.
BLyS phase I clinical trial results:
A phase I clinical trial to evaluate the safety and pharmacology of BLyS (B-lymphocyte stimulator) in patients with common variable immunodeficiency (CVID) is complete. The primary endpoint of the multicenter,
open-label, dose-escalation study was safety. Pharmacokinetics, immunogenicity, and the effects of BLyS on peripheral B cell representation and serum immunoglobulin concentration also were evaluated. Results
demonstrate that BLyS is safe and well tolerated. There were no drug-related serious adverse events or discontinuations. BLyS is a novel protein discovered by Human Genome Sciences that stimulates immune
system cells called B cells to mature into plasma B cells, which produce antibodies.
BLyS also is the subject of an ongoing phase I clinical trial to evaluate its potential as a treatment for an immune disorder known as immunoglobulin-A (IgA) deficiency. The phase I study in IgA deficiency continues to
enroll patients.
Albutropin phase I clinical trial results and next steps:
A phase I clinical trial of Albutropin, Human Genome Sciences' novel long-acting form of human growth hormone, is complete. The primary purpose of the multi-center, open-label, dose-escalating phase I clinical trial
was to determine Albutropin's safety and tolerability in adults with growth hormone deficiency. Pharmacodynamic, immunogenicity, and biological activity also were evaluated.
Forty-two patients were given either single doses of Albutropin subcutaneously at 10 microg/kg, 30 microg/kg, or 60 microg/kg, or 2 doses of Albutropin subcutaneously at 60 microg/kg 7 days apart. The results show
that Albutropin is biologically active and well tolerated. There were no drug-related serious adverse events or discontinuations. Albutropin remains in the blood substantially longer than is reported for recombinant native
human growth hormone. No patient developed an immune response against Albutropin.
The level of insulin-like growth factor-1 (IGF-1) in serum is a robust surrogate marker for the biological activity of human growth hormone. Albutropin was found to be biologically active and capable of restoring IGF-1
levels to within the normal range in a dose-dependent manner. Sixty-four percent of patients (9 of 14) responded who received single doses of Albutropin at 60 microg/kg, and 66% of patients (6 of 9) responded who
received 2 doses of Albutropin 7 days apart at 60 microg/kg. Drug responses were defined in the trial as at least a 50% increase over baseline to within the normal range of IGF-1 levels. The IGF-1 responses were
durable, lasting from 5 to 6 days following each injection of Albutropin. These data were first reported in October 2002 at a joint meeting of the Growth Hormone Research Society and the International Society for
Insulin-like Growth Factor Research.
Phase I results showed that patients who responded to a single 60 microg/kg dose of Albutropin and patients who responded to 2 60 microg/kg doses of Albutropin administered 7 days apart experienced prolonged
elevations of IGF-1 to within the normal range. The IGF-1 responses were durable, lasting from 5 to 6 days following each injection of Albutropin. The positive results from this initial phase I study of Albutropin provide
Human Genome Sciences with the safety, dosing, and biological activity data needed to support advancing Albutropin into the next phase of clinical development.
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Ribapharm Executives Resign Amid Dispute with ICN
By Doug Macron
Ribapharm Inc. said on Wednesday that its senior executives and most of its board members have resigned their positions, settling a dispute over its future with majority stockholder and former parent firm ICN
Pharmaceuticals Inc.
In April last year, ICN publically floated about 20% of Ribapharm as part of a long-planned restructuring. While ICN has maintained that it will spin off the remaining 80% it still holds to Ribapharm shareholders, it has
yet to do so.
Ribapharm publicly announced in late December that it had requested reassurances from ICN that the 80% stake would in fact be sold off, a protective measure industry insiders say was taken in response to ICN's
secret plans to buyback Ribapharm's outstanding stock at a discount to its initial public offering price of $10 per share.
ICN, which said it had lost confidence in Ribapharm's leadership, then moved to oust all but one of Ribapharm's board members. Shortly thereafter, ICN filed for and won a restraining order preventing Ribapharm's board
from making decisions outside the normal course of business, barring the board from issuing new shares, taking on debt, acquiring or selling businesses, or entering new licensing arrangements.
In response, Ribapharm CEO Dr. Johnson Lau, CFO Thomas Stankovich, and general counsel Roger Loomis said they would resign if ICN proceeded with its board reorganization effort.
On Wednesday, ICN and Ribapharm said that these executives, along with the four board members ICN was looking to remove, had tendered their resignations. Losing no time, Ribapharm announced on Thursday that
Dr. Kim Lamon has left his role as ICN board member and taken over as Ribapharm's president and CEO, and that four new board members have been appointed.
SG Cowen analyst Ian Sanderson sees the resignations as a total victory for ICN, clearing out any opposition to the Ribapharm repurchase, which he believes is motivated by ICN's desire to regain the royalty revenues
from the lucrative hepatitis C treatment ribavirin in order to pay down its significant debt.
ICN developed ribavirin and later licensed it to Schering-Plough Corp. Ribapharm took the rights to the ribavirin royalties, which were $186.4 million in the first three quarters of last year, when it was created.
"The best source of cash flow for [ICN] is the ribavirin royalty stream," Sanderson told Reuters Health. "And the only way to gain full control over that royalty stream and the spending against it is to regain control of
Ribapharm."
"Because they are the 80% shareholder, they, in realistic terms, can kind of do what they want with Ribapharm," he said. "The independent directors on the Ribapharm board were...looking to protect the interest of the
minority shareholder."
During mid-afternoon trading on the New York Stock Exchange, shares of Ribapharm fell $0.05 to $6.40, while shares of ICN climbed $0.29 to $11.30.
The dispute with Ribapharm marks just the latest upheaval at ICN. In June 2002, ICN's founder and former CEO Milan Panic left the company after he lost an acrimonious proxy battle with dissident investors looking to
gain control of the company's board.
Six months later, ICN and Panic agreed to pay $1.5 million to settle US Securities and ExchangeCommission allegations that they mislead the public in 1994 and 1995 over the development of ribavirin.
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Infections in Newly Freed Inmates Are a Rising Concern
By Fox Butterfield, The New York Times
Marva Johnson was thrilled when her longtime boyfriend, Randy Vallad, was paroled from prison in 1999.
They went back to living together, and once when he had a bad cut on his head, she took care of him. She was splattered with his blood, but the couple did not think anything of it at the time.
It was not until Mr. Vallad was sent back to prison in 2001 for a parole violation that he was accidentally shown his Michigan Department of Corrections medical records. They reported that Mr. Vallad had tested
positive for hepatitis C, a blood-borne virus that can cause potentially fatal liver disease, when he was first admitted to prison years before.
''They knew and didn't tell him,'' Ms. Johnson, 33, said today in this small city in central Michigan. ''As a result, they also let him infect me.'' For the past 11 months she has been taking a powerful, enervating course of
drugs for hepatitis C.
Such cases are becoming increasingly common across the nation, as jails and prisons have become giant incubators for some of the worst infectious diseases. According to a study released today at a conference
sponsored by the federal Centers for Disease Control and Prevention, at least 1.3 million inmates released from jail or prison in 1996 were infected with hepatitis C. That was 29 percent of the 4.5 million cases
nationwide.
Similarly, newly released inmates accounted for 35 percent of the 34,000 Americans with tuberculosis in 1996, the study found. And newly released inmates accounted for 13 to 17 percent of Americans infected with
H.I.V. or AIDS, the study estimated.
The problem has become so acute that health care officials and prisoner rights groups are calling for widespread testing of prison populations for hepatitis C and faster treatment of prisoners.
''This is a public health problem that has been growing and growing, but we are reluctant to do anything about it because these are bad guys,'' said Dr. Robert Greifinger, a former chief medical officer for the New York
State Department of Correctional Services and the author of the study, which was commissioned by Congress and prepared for the Justice Department.
The Centers for Disease Control held a conference of prison medical officers in San Antonio devoted to the issue last weekend. During the conference, the centers said that public vaccination efforts to prevent hepatitis
outbreaks should be extended to prisons.
The centers also issued new guidelines urging states to test all prisoners with a history of intravenous drug use and other risky behavior for hepatitis C. Sharing needles and unprotected sex are common ways the virus
is spread.
The problem is not that large numbers of prisoners are contracting hepatitis C while incarcerated, experts say. Most were infected years before. The experts say the high rate of communicable diseases among inmates
is a critical issue for two reasons: the danger inmates pose of infecting others when they are released, and the opportunity to treat them that is largely being wasted.
Dr. Greifinger said that Americans tended to forget that most inmates eventually return home. In 2000, about nine million people were released from jail and prison, according to Allen J. Beck, of the Bureau of Justice
Statistics, the statistical arm of the Justice Department.
In a sign that the problem is getting more attention, the C.D.C. made public Dr. Greifinger's report today. It had been given to the Justice Department in March 2001, Dr. Greifinger said, but never before released to the
public.
In a separate action, the American Civil Liberties Union and two dozen other organizations interested in prison conditions issued a call today for a Congressional investigation into the state of medical care in jails and
prisons.
''Correctional systems have buried their heads in the sand because they don't want to know how many prisoners have hepatitis C ,'' said Eric Balaban, a staff lawyer with the National Prison Project of the A.C.L.U.
Russ Marlin, a spokesman for the Michigan Department of Corrections, said, ''We are treating hepatitis C in accordance with federal guidelines.''
He said that Michigan did not do blood tests of all incoming inmates or all those who engage in risky behavior. ''Our position is that indiscriminate testing is not useful,'' he said. In addition, it would cost $200 million to
test and treat all suspected cases of hepatitis C among Michigan inmates, he said. Even more important, he said, is that the drug treatment -- a combination of interferon and ribarvin given over a 6 to 12 month period --
is very toxic.
Mr. Marlin said he had no information on why Mr. Vallad was not told he had tested positive for hepatitis C and could not release it even if he did because of the confidentiality of prisoners' medical records.
Mr. Vallad, was originally convicted for fleeing the police when he was stopped for driving with a suspended license. It was not the last of his problems. Today, the police raided the trailer where he lives with his sister
and brother, looking for drugs.
It was a bad tip from an informant, the police later said, and they found no drugs. But they detained Mr. Vallad anyway.
Steven Croley, a lawyer for Mr. Vallad and Ms. Johnson, said Mr. Vallad had stumbled on the information that he had tested positive for hepatitis C when he asked to see some of his private medical records compiled
by doctors while he was out of prison. At the time, in 2001, Mr. Vallad had just been sent back to prison because of a urine test that showed evidence of drug use, a violation of his parole. But the records he received
accidentally included pages of his prison medical file reporting on a blood test he had been given during his first admission in 1998.
At the bottom of one page was the notation '' Hepatitis C -- Positive.''
''I said, wait a minute, what's this?'' Mr. Vallad recalled. He called Ms. Johnson, who went for a test and discovered she was also infected.
Mr. Vallad, now 42, was never offered any treatment inside prison for hepatitis C. His level of infection has steadily gone up and his health has deteriorated, Mr. Croley said.
Mr. Croley said he will soon bring suits against the Michigan Department of Corrections on behalf of Mr. Vallad and Ms. Johnson.
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January 29th, 2003
CDC Recommends Hepatitis C Testing for All Prison Inmates with History of Injection Drug Use
hivandhepatitis.com
The CDC recommended last week that every state administer hepatitis C tests to all prison inmates who have a history of injection drug use, which is a common route for transmission of the virus, the Philadelphia
Inquirer reports.
The CDC also set guidelines for educating and treating prisoners with the virus and outlined the care prisons should provide to inmates with the disease. While the CDC cannot mandate policy for prisons, the agency
can make recommendations that will influence how states "wrestle with the explosion" of hepatitis C in prisons. The complete CDC Guidelines are available online: http://www.cdc.gov/mmwr/PDF/rr/rr5201.pdf
According to the CDC, the testing recommendations would "catch most cases" of hepatitis C among prison inmates. Of the estimated one million infected prisoners released annually, it is unknown how many have
been informed of their hepatitis status; depending on the state, 16% to 41% of prisoners are infected.
Of the approximately three million people with chronic hepatitis C in the United States, 39% will go through prisons and corrections facilities each year, putting the facilities "on the front lines for screening, counseling
and treating the disease," according to the CDC. The agency did not recommend that entire prison populations be tested for the virus, an issue of "intense debate" because of the cost (Philadelphia Inquirer, 1/24/03).
New Jersey has estimated that a state program to pay for hepatitis C tests and treatment for prison inmates will cost between $4.5 million and $8 million this year. Pennsylvania estimates that its hepatitis C tests for
more than 1,000 inmates will cost approximately $6 million.
In addition, if inmates are screened for the virus, more are likely to qualify for medication; annual treatment can cure 50% of cases, but can cost up to $25,000 a year. Cindy Weinbaum, a CDC hepatitis specialist who
prepared the recommendations, said that federal law requires states to treat sick inmates and that some prison officials argue that funds are not available for treatment, but she added that "[denying treatment that
would be a standard of treatment on the outside would not be acceptable."
The CDC this week is hosting a conference in San Antonio, Texas, to address management of hepatitis C in prisons.
'Giant Incubators'. The New York Times today (January 28, 2003) examines how jails and prisons are becoming "giant incubators" for several of the "worst infectious diseases." According to a CDC-sponsored study
released today, at least 1.3 million people released from incarceration in 1996 were infected with hepatitis C, or 29% of the 4.5 million cases of hepatitis C nationwide. Further, the study estimated that newly released
inmates accounted for 35% of the 34,000 Americans diagnosed with tuberculosis in 1996, and between 13% and 17% of all Americans infected with HIV/AIDS. "This is a public health problem that has been growing
and growing, but we are reluctant to do anything about it because these are the bad guys," Dr. Robert Greifinger, author of the study and former chief medical officer for the New York state Department of Correctional
Services, said. The study was commissioned by Congress and prepared for the Justice Department, according to the Times (Butterfield, New York Times, 1/28/03).
January 30th, 2003
Adherence and Mental Side Effects During Hepatitis C Treatment
Researchers from Germany find no increased risk for interferon alpha-induced mental side effects in psychiatric patients, if interdisciplinary care and antidepressant treatment are available.
Psychiatric disorders or drug addiction are often regarded as contraindications against the use of interferon alpha (IFN-alpha) in patients with chronic hepatitis C.
In this study, a research team obtained prospective data on adherence to, efficacy, and mental side effects of treatment with IFN-alpha. They assessed different psychiatric risk groups and compared these with
controls.
Their findings are published in the February issue of Hepatology (Hepatology 2003; 37: 443-51)
The team included 81 patients with chronic hepatitis C and psychiatric disorders (n = 16), methadone substitution (n = 21), former drug addiction (n = 21), or controls without a psychiatric history or drug addiction (n =
23) in there study. Study subjects were treated with a combination of IFN-alpah-2a 3 MU 3 times weekly and ribavirin (1000 to 1200 mg/d). In the psychiatric group, more patients received antidepressants before and
during treatment with interferon alpha.
The team found that sustained virologic response did not differ significantly between subgroups. In addition, no significant differences between groups were detected with respect to IFN-alpha-related development of
depressions during treatment. The researchers found that, in the psychiatric group, significantly more patients received antidepressants before and during treatment with IFN-alpha. However, none of the patients in the
psychiatric group had to discontinue treatment because of psychiatric deterioration.
Overall, 43% of patients with former drug addiction dropped out of the study, compared with 18% in the psychiatric group, 14% in the methadone group, and 13% in the control group.
Dr Martin Schaefer's team concluded, "Our data do not confirm the supposed increased risk for IFN-alpha-induced mental side effects and dropouts in psychiatric patients if interdisciplinary care and antidepressant
treatment are available".
"Preexisting psychiatric disorders or present methadone substitution should no longer be regarded as contraindications to treatment of chronic hepatitis C with IFN-alpha and ribavirin in an interdisciplinary setting."
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Hepatitis B Vaccine in Babies Born to Carrier Mothers
A 3-dose hepatitis B vaccination regimen is effective in protecting newborns of carrier mothers from infection and chronic carriage, find a research team in the January issue of the Journal of Viral Hepatitis (J Viral
Hepatitis 2003; 10(1): 23-30).
In this study, researchers from Hong Kong, China, evaluated the long-term efficacy of a childhood hepatitis B vaccination program.
A total of 112 newborn babies of hepatitis B carrier mothers were given hepatitis B immune globulin (HBIG) and a 10g 3-dose regimen of plasma-derived vaccine. These were administered at a conventional (0, 1, 6
months), delayed (2, 3, 8 months) or accelerated (0, 1, 2 months) schedule.
The babies were followed up to determine their anti-HBs status over a 16-year period.
The 3 schedules to be equally effective in preventing chronic infection. The research team found that upon completion of the vaccination schedules, 93% developed antibody against surface antigen (anti-HBs)
seroconversion. This rate fell to 33% at year 16.
The team also found the 3 schedules to be equally effective in preventing chronic infection, with a protective efficacy of 89% from hepatitis B surface antigen (HBsAg) carriage, compared with historical control. However,
study subjects on the delayed schedule had a slightly higher seroconversion rate over time. They were better able to maintain an anti-HBs level of > 100 iu/l.
The team found that overall, a quarter of study subjects demonstrated evidence of exposure to the virus. They were positive for antibody against core antigen or HBsAg, or mounting a rise in anti-HBs during the
follow-up period.
Dr Young's team concluded, "A 3-dose hepatitis B vaccination regimen is generally effective in protecting newborns of hepatitis B carrier mothers from infection and chronic carriage".
"Booster is not needed even after 16 years of monitoring."
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January 31st, 2003
Aethlon Medical Reports Hepatitis-C Blood Studies
Aethlon Medical Inc. (OTCBB:AEMD) today announced that initial pre-clinical human blood studies of the company's new HCV-Hemopurifier(TM) have documented a consistent ability to remove 58 percent of
Hepatitis-C virus (HCV) from infected blood in two hours.
The data was presented at the "International Conference on Dialysis V" which ends today in Miami, Florida. The data compares favorably with Aethlon's lead product AEMD-45, which is a HIV treatment
Hemopurifier(TM) that is able to remove 55 percent of HIV from human blood in three hours and in excess of 85 percent in 12 hours.
"This data helps substantiate the clinical expectation that our Hemopurifier(TM) treatment platform can be effective for numerous disease states," said James A. Joyce, Chairman and CEO. "Our data becomes
especially important when considering the magnitude of HIV and HCV infections and the reality that both viruses can mutate to defeat current drug therapies."
According to the Centers for Disease Control (CDC), over 200 million people worldwide are infected with the Hepatitis-C (HCV) virus. In the United States, HCV has become the most common chronic, blood-borne
disease with nearly 4 million infected. Chronic and progressive Hepatitis C, which represents 80-90 percent of all cases, has significant morbidity and mortality rates, and is the leading cause of liver disease and
transplantation.
Richard Tullis, Ph.D., chief scientific officer at Aethlon stated, "This is a significant advance in Aethlon's virus treatment platform. The possibility now exists that we will be able to deliver a medical device that can
simultaneously treat both HIV and HCV infections, a factor that could be crucial for the large population of patients that are infected with both diseases."
About Aethlon Medical
Aethlon Medical develops therapeutic devices that treat HIV/AIDS, Hepatitis-C (HCV) and other infectious diseases. In pre-clinical testing, Aethlon has published that AEMD-45, its lead product for treating HIV, is able
to remove 55 percent of HIV from infected human blood in three hours and in excess of 85 percent in 12 hours. Aethlon has also documented that AEMD-45 removes up to 90 percent of toxic viral proteins that deplete
immune cells during the equivalent of a one-hour treatment. The AEMD-45 therapeutic device, like all product offerings from Aethlon Medical, is developed from an expansive platform technology known as the
Hemopurifier(TM), which employs a proprietary method to increase the capability of FDA cleared artificial kidneys (dialysis cartridges) to remove targeted intoxicants from the blood. In the case of AEMD-45, dialysis
cartridges are modified to mimic the immune system's response to clear infectious virus from circulation before healthy cells are infected. AEMD-45 is designed to fill the urgent need for new treatments that are
effective in reducing viral load, decrease the likelihood of treatment resistance and treat without the toxic side-effects associated with AIDS drugs. For more information, visit the company's Web site at www.AethlonMedical.com.
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Paying for the Pegylated Interferons plus Ribavirin: Access at What Price?
By Ronald Baker, PhD. HIVandHepatitis.com
Almost everyone agrees that the introduction of the pegylated interferons (Pegasys and PEG-Intron), especially in combination with ribavirin, has resulted in improved responses to HCV therapy and a higher standard of
care for the treatment of chronic hepatitis C.
For many individuals living with this debilitating disease, pegylated interferon/ribavirin combination therapy has translated into increased "cure" rates, increased survival and an improved quality of life.
Unfortunately, access to this new and improved standard of care for HCV infection is extremely limited by the cost of the therapy. Unlike un- or under-insured HIV patients, who have access to the AIDS Drug
Assistance Program (ADAP), a federal- and state-funded program that provides them access to the latest and best antiretroviral drugs, HCV patients with low and limited incomes find themselves unable to pay for the
pegylated interferons and ribavirin.
Following is a chart of the pricing for the two pegylated interferons, combination therapy with the pegylated interferons plus ribavirin and for compounded ribavirin. First published on HIV and Hepatitis.com on 1/15/03,
this chart was prepared by Brian Klein of the Hepatitis C Action and Advocacy Coalition in San Francisco (HAAC-SF).
PRICING CHART
Unless otherwise noted, prices listed are average wholesale price (AWP) or estimated AWP for approximate retail price comparisons for one month -28 day- standard supply for the average American patient (genotype
1 high viral load). Other patient (genotypes non-1 and/or low viral load) may see lower costs based on dose and/or duration of treatment:
| Ribavirin |
Dosage |
Price |
| Fisher's SPS compounded |
(800/1200mg) |
$ 168/ 252 |
| Copegus |
(800/1200mg) |
$ 708 / 1063 |
| Rebetol |
(800/1200mg) |
$1236 / 1855 |
| |
| Pegylated Interferons |
Dosage |
Price |
| Pegasys |
(180mcg) |
$1455 |
| PEG-Intron |
(150mcg) |
$1491 |
| |
| HCV Comb. Treatments |
Time period |
Price |
| Pegasys + Copegus (1200mg) |
(month/annual--48weeks) |
$2518/ 30,216 |
| PEG-Intron + Rebetol (1200mg) |
(month/annual -48 weeks) |
$3346/ 40,152 |
Pharmaceutical Pricing Primer
Wholesale Acquisition Cost (WAC)-"The Wholesale Price"-- is the quoted price a pharmaceutical company charges drug wholesalers. Brand drug makers tend to quote WAC prices as it is more under their control
and tends to make their drug appear lower in cost. Most drug makers though, offer wholesalers contracts that discount off the WAC. This discounting is where real pricing competition between drug makers occurs and
can often be one reason why one drug may be accepted on a drug formulary as opposed to another. Drug A may have a lower published WAC, but Drug B might be discounted more. The usual game is to price at
whatever the best paying customers will bear, knowing you will discount to the rest.
Average Wholesale Price (AWP)-"The Retail Price"-- is an industry average of what wholesalers charge retail pharmacies for a drug. Discounting contracts often apply here well, including to government (i.e. VA,
Medicaid/Medi-Cal, ADAP) managed care and private insurance payers. AWP tends to be around 25% above WAC. With all the confusing discounting that happens in the industry, AWP becomes, in effect, similar to
the Manufacturer's Suggested Retail Price (MSRP) for any other non-drug product sold like clothing, a car, or food products. Almost no one really pays it, but it is useful for making retail price comparisons.
How to Pay for Pegylated Interferon and Ribavirin
The AIDS Treatment Data Network (ATDN) offers the following information on the available options to pay for pegylated interferons/ribavirin combination treatment:
Medicaid - The federal insurance program for the poor and disabled is required to cover all FDA-approved treatments. Currently, all 50 Medicaid programs cover Peg-Intron and ribavirin. New York and Puerto Rico are
the only two Medicaids that does not currently cover Pegasys. Check with your Medicaid for eligibility criterias.
ADAP - Currently, only Seven ADAPs (AIDS Drug Assistance Programs) cover Peg-Intron and ribavirin for people co-infected with HIV and HCV. They are: Connecticut, Delaware, New Hampshire, New Jersey,
Massachusetts, Wisconsin and Virginia. In addition, New York and California cover ribavirin and Intron A (standard interferon) but not Peg-Intron. New Hampshire, New Jersey, Massachusetts, Mississippi and
Wisconsin also covers Pegasys. For eligibility criterias, See the Access Project database. People who live in states where the ADAP does not cover HCV treatment can apply to the programs listed below.
Schering's "Commitment To Care" Program for Peg-Intron and Rebetol (ribavirin) - Thisprogram will help you identify ways to get the drugs paid for. If your private insurance does not cover the drugs, and you do not
qualify for Medicaid, or your ADAP does not cover Peg-Intron and Rebetol, Schering will supply a full 48-week treatment of the drugs for free. Eligibility ranges between 200% to 300% of the Federal Poverty Level
(Currently $17,720 and $26,580 annual income for an individual, respectively), depending on where you live. Call 1-800-521-7157 to enroll.
Everyone, regardless of the ability to pay, must still register with Schering's "Access Assurance Program" in order to get Peg-Intron. However, the previous supply shortage has now been resolved and there is no longer
a waiting list to get the drug. Schering plans to phase this program out as soon as they are certain there will be no supply problems. The phone # for Access Assurance is 1-800-437-2608, or go to
www.access-assurance.com.
Roche's Pegasys is available by prescription with no registration requirements Patients who make less than 300% of the Federal Poverty Level ($26,580 annual income for an individual) and have no other medical
coverage, or if their state's Medicaid does not yet cover Pegasys, are eligible for Roche's Patients' Assistance Program by calling Pegasys' reimbursement Hotline 1-800-387-1258. Roche claims no one on Medicaid
will be turned down if their state has not yet added Pegasys to the Medicaid formulary.
Compounded Ribavirin - Compounded ribavirin is still available for patients, healthcare providers, and payers to consider. Compounding pharmacies throughout the country provide ribavirin at about $150-$225 a month
for an 800-1,200 mg daily dose. If you don't have a local pharmacy that can make compounded ribavirin, there are some that can send the drug to you by mail order.
Recently, Fisher's Specialty Pharmacy Services, one of the first and most reputable providers of high quality, low cost compound ribavirin, after 3 and a half years of no price increase, has raised its price on ribavirin
from $1.25/capsule ($210/month) to $1.50/capsule ($252/month) for 1200 mg/day dose. They continue to work with patients who have limited resources when possible. This is one company that has gone out on a limb
to try to meet patient needs and keep prices as affordable as possible. This current price is still 86% below Rebetol and from a small independent company that has continued to meet and exceed requirements of its
quality control. Not all compounding/specialty pharmacies can do that.
To reach Fischer's, call toll free (888) 347-3416, web address: www.spsdrug.com . Other local specialty or compounding pharmacies to consider are available as well.
People who choose HCV treatment should consider all their options for ribavirin in their contacts with their healthcare providers. It's best to shop around to consider the price, quality and flexibility of brand and
compound sources and to utilize insurance, government programs and pharmaceutical patient assistance programs when qualified.
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Predicting Survival in Patients with Excessive Alcohol Intake and Cirrhosis
In patients with cirrhosis and excessive alcohol intake, age, liver failure, GI bleeding, and viral B or C infection are independent prognostic markers, find researchers in the February issue of Liver (Liver 2003; 23(1): 45).
In this study, researchers from France evaluated 5-year survival predictive factors in hospitalized patients with excessive alcohol intake and cirrhosis.
They included a multivariate analysis the severity of the liver disease, GI bleeding, viral B or C infection, smoking status, presence of alcoholic hepatitis at inclusion, and abstinence from alcohol during follow-up.
The research team performed a non-concurrent cohort study.
- They included 122 patients with excessive alcohol intake and cirrhosis, who were followed-up for at least 5 years, or until death.
- Throughout the course of the study, 2 patients were lost to follow-up.
- Overall 5-year survival rate was 43%.
- The research team found that the 5-year survival rate was 43% overall.
- However, in Child-Pugh classes A, B, and C survival rates were 66%, 50%, and 25%, respectively.
Using multivariate analysis, the team found that age, Child-Pugh score, GI bleeding, presence of HBs Ag and/or anti-HCV, smoking, absence of histologically proven alcoholic hepatitis, and persistent alcohol intake
were associated with an increased risk ratios of death.
Dr Pessione's team concluded, "In hospitalized patients with excessive alcohol intake and cirrhosis. . . age, liver failure, gastrointestinal bleeding, concomitant viral B or C infection and persistent alcohol intake are
independent poor prognostic markers".
In addition, "Smoking may contribute to the aggravation of cirrhosis".
However, "Alcoholic hepatitis, being a potentially reversible cause of liver failure, has a favorable prognostic significance".
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February 3rd, 2003
Artificial Liver Finds Success in Two Patients
From PR Newswire via Screaming Media
As part of a national study, University of Pittsburgh Medical Center (UPMC) researchers used an experimental artificial liver assist system that helped stabilize two patients who were in acute liver failure and close to
death until donor organs were available for transplantation. Both received successful transplants and are doing well.
One patient received a liver transplant and the second patient received a five-organ transplant that included the liver, small bowel, stomach, pancreas and duodenum. She is the first patient to be supported with the
device for acute liver failure and then to receive a multivisceral transplant.
UPMC is one of 12 centers participating in a multi-center Phase II trial to evaluate the safety and effectiveness of the ELAD(R) (Extracorporeal Liver Assist Device) Artificial Liver system developed by VitaGen
Incorporated of La Jolla, Calif., to temporarily support patients in fulminant hepatic failure, acute liver failure that has a sudden onset. The company hopes to enroll 30 patients in the study. Of 19 that have been enrolled
so far, 13 have been supported with the device, say company officials.
UPMC participated in the company's Phase I trial as well. According to VitaGen, 12 of 15 (80 percent) of the ELAD-treated patients in that trial involving six centers had positive outcomes -- either they were
successfully bridged to transplantation or their livers recovered and transplantation was not necessary. Five of nine (56 percent) of the control group patients, who received standard medical treatment for fulminant
hepatic failure, were transplanted or recovered.
The ELAD is an external device that works in a similar fashion to kidney dialysis, whereby waste products are removed from the blood. A pump pushes the patient's blood through a catheter into a large filter that
separates blood cells from plasma, creating what is called ultrafiltrate. The ultrafiltrate in turn passes through cartridges containing a cultured human cell line and is then returned through another catheter back to the
patient.
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