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November 27, 2005
Two Studies Recruiting HCV Patients
Sho-saiko-to is the number one liver remedy in Japan. It has been prescribed to over 1.5 million patients (in Japan, doctors medically prescribe certain natural remedies, just like doctors prescribe pharmaceutical drugs in the U.S.).
Based on the large body of research in Japan, studies are now being conducted by the medical establishment here in the USA with regard to SST and hepatitis C.
Although Sho-saiko-to is considered an herbal supplement (and does not require a prescription in the U.S.) it is being taken seriously enough to warrant medical research.
We have been aware of SST for quite some time now and think highly of the clinical evidence compiled so far. We have also agreed to help Dr. Dan Wen, President of Honso USA (the remedy supplier) to recruit patients for these studies. One is in New York City, the other in San Diego. The details and contact information follow.
Please note, we have nothing to do with enrollment in these trials and are simply passing this information on to you so you can follow up directly with those conducting these studies, if you are interested and able to participate.
Please be sure to read the eligibility criteria in each study and see what criteria they are basing their selections on before contacting them.
If you want more information about Sho-saiko-to, you can go to http://www.sho-saiko-to.com. We provide a more in-depth education about this remedy and the opportunity to purchase the prescription-strength version through that website if you so desire.
Here is the information about the New York trial (along with the request from Dr. Wen for me to get this information out to you).
Hi Ralph,
Thank you very much for agreeing to help spread the word about our New York trial on Hepatitis C. As we have discussed on the phone, our clinical trial at Sloan-Kettering is still enrolling patients. We need help to make the awareness of the trial to patients in New York area and I believe the thousands of hep C patients who are subscribing to your e-newsletter at http://www.hepatitis-central.com would be excited to hear this opportunity. I have also copied this email to Dr. Gary Deng, the Primary Investigator of the trial at Sloan, for his information. The following information about the trial is copied from Sloan-Kettering website at http://www.mskcc.org/mskcc/html/2270.cfm?IRBNO=02-073, from which you can see all eligibility criteria and the contact information.
Sincerely,
Dr. Wen
Phase II Study of Sho-saiko-to in Patients with Chronic Hepatitis C Who Cannot Use Interferon
[Protocol 02-073]
Full Title :
SHO-SAIKO-TO FOR PATIENTS WITH CHRONIC HEPATITIS C WHO ARE INTOLERANT TO OR HAVE CONTRAINDICATION TO INTERFERON-BASED THERAPY: A PHASE II STUDY
Purpose:
Researchers at Memorial Sloan-Kettering Cancer Center are evaluating a Japanese/Chinese herbal medicine called Sho-saiko-to to see if it can help patients with chronic hepatitis C. Chronic hepatitis C may cause inflammation in the liver, which can lead to scarring called fibrosis. In some patients, chronic hepatitis C may result in cirrhosis (severe scarring of the liver), liver failure, and liver cancer.
Standard treatment for chronic hepatitis C includes a drug called interferon, given with or without another drug called ribavirin. Because interferon has a number of side effects, many patients are unable to take it. There are no other proven treatments for chronic hepatitis C.
Sho-saiko-to is an herbal medicine that has been used for many years in Asia to treat liver disease. There is emerging scientific evidence that Sho-saiko-to may benefit patients with hepatitis. The purpose of this phase II study is to determine whether Sho-saiko-to is effective in treating the liver inflammation and injury caused by chronic hepatitis C in patients who cannot take interferon.
Eligibility :
To be eligible for this study, patients must meet several criteria, including but not limited to the following:
· Patients who have received interferon and ribavirin less than 6 months ago will need to wait for a period of time before enrolling in the study. The doctor will make the specific recommendations.
· Patients must be at least 18 years old.
For more information and to see if you are eligible for this study, please contact to Cheryl Co at 212-639-8610.
Here is the information on the San Diego study:
Hi Ralph,
As you can see below, the UCSD group has approved you to proceed with the contact information for enrolling new patients at their site for the trial and the website link for detail. Please use the two clinical trial sites for your communication materials to introduce the need from each site (New York and San Diego) for patients to enroll.
Best regards,
Dr. Wen
Hi Fatma,
We have a good connection to Hepatitis Central. They are able to broadcast any hepatitis C related news to a large body of patients (http://www.hepatitis-central.com/mt/). Currently they are preparing a news piece to include information about the enrollment for the SST study in New York. If you like we can include the UCSD trial information you have posted at the webpage http://health.ucsd.edu/ntrials/031532.htm to help you enrolling patients.
Please confirm with me if we can proceed with this initiative.
Regards,
Dr. Wen
Hi Dr. Wen,
The matter was discussed with Dr. Hassanein and we can confirm that you can proceed with linking the website. Also, please note that Lita Petcharaporn will be the coordinator on the study. Her contact information is below:
Lita Petcharaporn
Phone: (619) 543-7218
Fax: (619) 543-6392
E-mail: lpetchar@ucsd.edu
Thank you,
Fatma
Fatma Barakat
Clinical Research Coordinator
UCSD Liver Center
200 West Arbor Drive
San Diego, CA 92103-8707
Phone: (619) 543-5459
Fax: (619) 543-6392
fbarakat@ucsd.edu
CHSD Clinical Research project
Project Number: 031532
Scientific Title:
Safety and Tolerability of Sho-saiko-to (SST) in Patients with Compensated Cirrhosis Due to Chronic HCV Infection, A Double blinded Phase II Trial
Principal Investigator (ie., Lead Researcher):
Tarek Hassanein, MD
Description:
The purpose of this study is to evaluate the safety and tolerability of an investigational drug called Sho-saiko-to (SST) as well as find out more about preventing a type of liver cancer called Hepatocellular Carcinoma (HCC) from occuring in patients who have Chronic Hepatitis C infection and cirrhosis. SST is a Chinese herbal drug mixture of seven different herbs: Bupleurum Root, Pinellia, Ginger, Scutellaria, Jujube, Ginseng and Licorice.
This is an outpatient study.
Eligibility criteria:
Gender: Both males and females are eligible to participate. Minimum age: 18. Hepatitis C Virus and Cirrhosis
Exclusions (conditions which would prevent a volunteer from participating in this study):
Please contact Fatma Barakat
Location:
UCSD Medical Center, Hillcrest
Compensation:
Study drug will be provided at no cost.
For further information about this study, please contact:
Fatma Barakat
Phone: (619) 543-5459
Posted by Ralph at 02:41 PM --- Printer-friendly version | Comments (0)
November 25, 2005
A Good AASLD Meeting Summary
This is a terrific overview article regarding the AASLD meeting. Liz Highleyman did a fantastic job of condensing the key aspects and announcements.
One of the most interesting updates/corrections of known information is the upward measurement of the number of infected persons in the USA. It could be one million more than most commonly estimated.
Hepatitis research reported at liver disease meeting
Liz Highleyman
Treatments for hepatitis B and C continue to improve, with refinements to approved regimens and new experimental agents in the development pipeline, researchers reported at the 56th annual meeting of the American Association for the Study of Liver Diseases, held November 11-15 in San Francisco.
Hepatitis B and C are viral diseases that can cause long-term liver damage including cirrhosis and cancer. The Centers for Disease Control and Prevention estimates that some 75,000 people in the U.S. are newly infected with hepatitis B each year – a number that has declined dramatically since the advent of routine childhood vaccination.
Unlike hepatitis A and B, there is not yet a vaccine for hepatitis C. The National Health and Nutrition Examination Survey found that about 3.9 million people in the U.S. had contracted hepatitis C, but Dr. Brian Edlin from Cornell University presented evidence suggesting this is an underestimate. As a household survey, Edlin said, NHANES does not count several groups that have higher rates of hepatitis C than the general population. These include prisoners (nearly 2 million, with an estimated hepatitis C rate of 32 percent), the homeless (more than 800,000, with an estimated rate of 35 percent), patients in hospitals and nursing homes, and members of the military. Taking these groups together, Edlin estimated that about 1 million more people have hepatitis C than usually reported, for a total of 5 million. Basing public health projections on the lower figure, he warned, "may underestimate the burden of liver disease we will see in coming decades."
Hepatitis C
The hepatitis C virus is spread primarily through contact with blood, and rates are highest among injection drug users. Several studies have shown that sexual transmission between monogamous heterosexual partners is rare, but it appears more common among men who have sex with men and people coinfected with HIV. While outbreaks of sexually transmitted hepatitis C have not been reported in North America, a cluster of more than 200 such cases among gay HIV-positive men in the United Kingdom raises concern.
According to a presentation by Dr. Mark Danta from the Royal Free and University College Medical School in London, a variety of factors related to sexual activity and drug use have contributed to the recent English epidemic. In a case-control study comparing 60 HIV-positive gay men with acute (recently acquired) hepatitis C and 130 matched HIV-positive men without HCV, Danta's team found that the HCV-infected men were significantly more likely to have engaged in unprotected receptive or insertive anal intercourse, fisting, analingus (rimming), use of sex toys, SM, and group sex. Further, the men with hepatitis C were more likely to meet partners in sex clubs, bathhouses, or on the Internet; had more sex partners overall; were more likely to have ever had a sexually transmitted disease; and more often used club drugs including crystal methamphetamine.
While all these factors are linked to higher rates of hepatitis C, Danta said it is "difficult to tease out" how each specifically contributes. He recommended that education about safe sex and drug-sharing practices should be the focus of public health interventions for this population.
At a satellite symposium, HIV specialist Dr. Paul Volberding from the University of California, San Francisco joined several hepatitis experts to discuss similarities and differences between the HIV and HCV viruses and their treatment. Research on hepatitis C is some five to 10 years behind HIV research, Volberding estimated. Hepatitis C researchers are at a disadvantage because HCV cannot be grown in the laboratory, which is important for understanding the virus life cycle and early drug testing (instead, various model systems are used). But patients with hepatitis C enjoy a big advantage: HCV can essentially be eradicated, while HIV persists indefinitely in long-lived memory T-cells.
Current standard treatment for hepatitis C is based on interferon, an injected cytokine (cell messenger chemical) that stimulates the immune response, but future therapies under study directly target HCV. Like current HIV drugs, these new agents will likely be used in combination, since HCV – like HIV – can mutate rapidly and develop drug resistance. But because hepatitis C can be cured in a matter of months or years, there is less concern about long-term side effects such as lipodystrophy.
"This field is getting very lively and will become even more competitive," predicted hepatology researcher Dr. John McHutchinson of Duke University Medical Center in North Carolina.
Indeed, researchers at AASLD presented data on several new candidate hepatitis C drugs. Those furthest along in the pipeline include Idenix Pharmaceuticals' nucleoside analog valopicitabine (NM283) and two HCV protease inhibitors, Shering Plough's SCH503034 and Vertex Pharmaceuticals' VX-950.
Presenting the first data from a phase II trial of valopicitabine, Dr. Christopher O'Brien from the University of Miami reported that 50 percent to 70 percent (depending on dose) of patients with genotype 1 HCV – the hardest type to treat – who did not respond to previous interferon therapy saw an early reduction in HCV viral load after 12 weeks of treatment with the new drug plus pegylated interferon.
"These are promising results, particularly for the many treatment-refractory patients in urgent need of new therapeutic options," O'Brien said.
Dr. Stefan Zeuzem from Germany reported that in a small 14-day study of patients who did not respond to standard treatment with interferon, 60 percent of those receiving the highest dose of SCH503034 three times daily experienced a substantial (at least two logs) reduction in HCV viral load. SCH503034 also showed promising activity when combined with pegylated interferon.
As reported by Dr. Henk Reesink from Amsterdam, in a small early study, all participants with genotype 1 HCV who received VX-950 saw at least a two-log drop in HCV viral load. "As far as I know, this is the most rapid and dramatic response that has been seen with a single agent," he stated.
All three pipeline drugs appear safe, with no serious side effects seen in clinical trials so far. This is reassuring since research on an earlier HCV protease inhibitor, BILN-2061, had to be stopped when it was linked to heart problems in animals. It is too soon to say whether these agents will ultimately produce a cure for hepatitis C (sustained virological response, or continued undetectable HCV viral load six months after the end of treatment). Most experts agree, however, that combinations of antiviral drugs are the wave of the future for hepatitis C therapy.
Posted by Ralph at 06:16 PM --- Printer-friendly version | Comments (0)
November 23, 2005
Shorter Therapy Effective for Genotypes 2 and 3
Genotypes 2 and 3 are much more responsive to current interferon combination therapies. This report details studies that show a shorter course of treatment might be just as effective as longer courses.
Researchers continue to refine treatment protocols for HCV patients.
Short Therapy Regimens Effective for Hepatitis C Virus Genotype 2 and 3: Presented at AASLD
By Crystal Phend
SAN FRANCISCO, CA -- November 21, 2005 -- Hepatitis C infected patients with genotype 2 or 3 may be able to shorten their course of therapy without losing effectiveness, according to a study presented here at the American Association for the Study of Liver Diseases annual meeting (AASLD).
According to presenter Olav Dalgard, MD, PhD, Infectious Diseases Specialist, Aker University Hospital, Oslo, Norway, the viral response at week 4 may be a guide to considering shorter treatment.
Two recently published studies found shorter therapy to be effective, but left unanswered which subgroups are less likely to respond, that is, dosing and baseline predictive factors, Dr. Dalgard said during a presentation on November 14th.
To answer those questions, his group used pooled data from two studies involving a total 403 adults with hepatitis C genotype 2 or 3 who were treatment naïve.
The Norwegian study dosed pegylated interferon alpha-2b at 1.5 mcg/kg once weekly with 800 to 1,200 mg of ribavirin for 14 weeks or for 24 weeks if patients had not achieved a response by week 14.
The Italian study followed the same schedule as the Norwegian study, with a slightly lower 1.0 mcg/kg pegylated interferon alpha-2b dose for 12 weeks or 24 weeks for non-responders at week 12.
Patients were tested for virus RNA levels at weeks 4, 12 or 14 and 24.
The 313 patients who achieved a sustained viral response (SVR) were analyzed by subgroup.
Results show a significant difference in the percentage of patients who achieved SVR according to fibrosis score ( 83% with a score of 0 to 2 vs. 67% with a score 3 to 4).
Patients with genotype 2 were significantly more likely to respond than those with genotype 3 (81% vs. 73%).
"In non-rapid viral response patients, 24 weeks of therapy for HCV 2 patients may be satisfactory whereas longer courses should be considered for genotype 3," Dr. Dalgard said.
Patients who had a rapid viral response by week 4 were significantly more likely to have a sustained viral response than those who did not (85% vs. 62%).
Those who had a rapid viral response at week 4 were significantly more likely to have a low fibrosis score (70% 0 to 2 vs. 56% 3 to 4) and to be at the higher 1.5 dose of peginterferon (78% vs. 64%).
Multivariate analysis found that the response at 4 weeks was a significant predictor of sustained response, although genotype, baseline viral load and treatment regimen were not.
Relapse could not be predicted by any baseline characteristic.
"In HCV 2 or 3, viral response at week 4 may reliably guide treatment duration as the majority of rapid responders may safely receive shorter courses of therapy without compromising SVR," the researchers concluded.
[Presentation title: Short-Term Treatment Duration for HCV-2 and HCV-3 Infected Patients with Chronic Hepatitis. Abstract 849]
Posted by Ralph at 01:10 AM --- Printer-friendly version | Comments (0)
November 22, 2005
Vertex Progresses with VX-950
Vertex is the racehorse to watch right now. They are progressing quicky on their preliminary good results.
While it's not yet time to line up for their treatment, we believe theirs will be first to market of the new approaches (although there can still be serious unforseen setbacks).
Vertex Announces Filing of IND in Support of VX-950 Phase II Development in the U.S.
SAN FRANCISCO, Nov. 11 /PRNewswire-FirstCall/ -- Clinical data being presented this week while attending the 56th American Association for the Study of Liver Diseases (AASLD) Annual Meeting confirm that VX-950, an investigational oral hepatitis C protease inhibitor developed by Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX), was well-tolerated and possessed potent antiviral activity in a 14-day study in patients with hepatitis C virus (HCV) infection.
The rapid decline in plasma HCV-RNA levels observed in HCV patients taking VX-950, together with a viral kinetic analysis that projects the potential duration of treatment required to achieve sustained virologic response (SVR), support the evaluation of VX-950 in a novel, three-month combination treatment paradigm.
Vertex also announced today that it has filed an investigational new drug application (IND) with the U.S. Food and Drug Administration (FDA) to support Phase II clinical development of VX-950. "The clinical data demonstrate a swift and dramatic decline in viral levels with VX-950, and provide insight into VX-950's potential to transform future HCV treatment," said Joshua Boger, Ph.D., Chairman, President and Chief Executive Officer of Vertex. "Our clinical development effort is gaining momentum, as indicated by our recent IND submission with the FDA to support the planned initiation before year-end of the first clinical study in what we expect will be a broad Phase II program."
Phase Ib Study Clinical Results: Major Findings Five presentations taking place at the meeting provide a comprehensive analysis of the Phase Ib study of VX-950 given as monotherapy. Results being presented at the conference are from a dose-ranging Phase Ib study of VX-950 dosed in an oral suspension for 14 days in patients with chronic hepatitis C. Dr. Henk Reesink, Principal Investigator for the study, will present the major findings in an oral presentation at the Presidential Plenary Session and at a press conference on Monday, November 14.
In the Phase Ib study, VX-950 in all dose groups exhibited substantial antiviral effects, with 26 of 28 patients receiving any dose of VX-950 achieving more than a 3-log reduction in plasma HCV-RNA within two days. After 14 days, patients in the best dose group (750 mg every 8 hours) achieved a mean reduction in HCV-RNA of 4.4 log10, a 25,000- fold reduction in viral levels. In the trial, VX-950 was well-tolerated. Overall in the Phase Ib study, adverse events observed in patients receiving VX-950 that were considered possibly related to the drug were mild, and generally similar in frequency to events in the placebo group.
The most common adverse events reported in both placebo and VX-950 patients were headache, frequent urination, and gastrointestinal symptoms.(1) In a separate analysis of the Phase Ib trial results to be presented in detail in a poster presentation on Tuesday, November 15, Vertex researchers analyzed the relationship between blood concentrations of VX-950 and antiviral effect over 14 days.
A dose-response was established with higher ranges of VX-950 blood concentrations being associated with a better outcome relative to the responses established at lower blood concentrations of VX-950. The researchers found that the steep decline in plasma HCV-RNA seen in patients during the first two days was correlated closely with total blood concentrations during the first dosing interval, as measured by area under the curve (AUC). In addition, the achievement of a greater than 3.5 log10 reduction in plasma HCV-RNA at day 7 or greater than 4.5 log10 reduction at the end of the full 14 days of treatment was closely correlated with blood concentrations at "trough" (minimum concentration in blood immediately prior to receiving the next dose). Further, these researchers analyzed the viral kinetics to estimate the treatment duration required to achieve viral eradication. In this analysis, researchers projected the continued slope of viral decline that could be expected with dosing beyond 14 days in the patients who achieved HCV-RNA levels below the limit of quantitation at the end of dosing in the Phase Ib study.
The results of this simulation suggest that, with continued steep viral decline on treatment, it may be possible with approximately 12 weeks of treatment to reduce levels of HCV-RNA in patients to less than 10 viral copies (total body viral load). A total body viral load in this range is considered to be what may be required for potential host eradication of infection and achievement of SVR. Vertex is taking the encouraging results of this viral kinetic analysis into account in the design of planned Phase II clinical studies of up to 12 weeks duration.(2)
"The complete data set for the Phase Ib study suggests that VX-950 is well-tolerated and can substantially reduce virus in a 14-day study," said Henk W. Reesink, M.D., Associate Professor of Medicine at Academic Medical Center in Amsterdam. "The results of the blood-concentration versus antiviral effect analysis are encouraging because they indicate that optimal antiviral response could be maintained if certain trough concentrations are achieved. Moreover, the viral kinetic analysis supports the evaluation of VX-950, at doses that maintain the target trough concentration, in a novel treatment paradigm of 12 weeks duration."
Phase Ib Study: Viral Sequencing Results In a further analysis planned for presentation on Monday, November 14, researchers used a novel sequencing approach to analyze the sequences of the HCV NS3 protease gene in samples isolated from patients prior to and following treatment in the Phase Ib study from all dose groups, including suboptimal dose groups.
The relative frequencies of wild-type and variant virus, as well as the sensitivity of variant protease enzymes to inhibition by VX-950 in vitro, were assessed and correlated with the viral load response obtained during dosing with VX-950. Three categories of HCV-RNA response were identified: continued decline (decline in HCV-RNA from day 1 through day 14), viral rebound (increase in HCV-RNA between nadir and day 14), and plateau response (minimal change in HCV-RNA between nadir and day 14). The patients with a continued decline in HCV-RNA had the highest mean trough VX-950 concentration, while the patients with viral rebound had the lowest mean trough blood concentrations. In the group of patients with continued viral decline on treatment, HCV- RNA levels at the end-of-dosing were below the limit of detection (less than 100 IU/mL) of the sequencing assay. At 7-10 days post-treatment, virus could again be isolated. In the post-treatment period, wild-type virus predominated, with some variants detected that displayed a minimally-reduced sensitivity to VX-950 in vitro.
In the other two groups of patients, sequence changes associated with reduced sensitivity to VX-950 in vitro were detected at the end-of-dosing, including some variants with moderately- to highly- reduced sensitivity to VX-950. However, these sequence changes also appeared to result in reduced viral fitness. In particular, the frequency of the variant (A156V/T) with the highest level of reduced drug sensitivity diminished markedly between the end-of-dosing and post-treatment analysis, indicating significantly reduced in vivo fitness relative to wild-type virus. Published in vitro data indicate that the A156V/T variant also retains sensitivity to interferon.(3)
"This is the first study that has attempted to comprehensively characterize HCV protease variants that may emerge during treatment with a potent direct-acting antiviral compound. As expected, selection of certain variants was associated with suboptimal drug levels and a suboptimal initial decline of HCV-RNA concentrations that led to either viral rebound or a plateau in viral response," said Christoph Sarrazin, M.D., Saarland University Hospital, Homburg, Germany, and Study Investigator. "It is encouraging that patients with the highest blood concentrations of VX-950 achieved continuous decline in viral load levels over the entire dosing period, suggesting that achieving sufficient trough concentrations could suppress the viral variants associated with viral rebound. Further, the sequencing results provide a strong rationale for the combination of VX-950 and pegylated interferon to achieve optimal response rates."
Additional Data Presentations Two additional abstracts related to VX-950 will be presented at the conference. In one abstract, researchers showed that despite heterogeneity among viral sequences that could be isolated from patients prior to treatment, all isolates were sensitive to VX-950 in vitro. Minor viral variants that may have existed at a frequency of less than 2 percent would not have been detected with the approach utilized.(4) In another abstract, researchers found that patients receiving VX-950 in the Phase Ib study rapidly achieved substantial reductions in alanine aminotransferase (ALT) levels after 14 days of treatment. In addition, changes in median neopterin levels correlated with decreases in HCV-RNA and ALT during administration of VX-950, suggesting that inhibition of HCV replication by VX-950 may decrease inflammation and tissue damage.(5)
Clinical and Regulatory Milestones Vertex recently announced the initiation of a 14-day Phase Ib combination study of VX-950 and pegylated interferon in Europe, using a new tablet formulation that is expected to achieve significantly higher blood concentrations compared to the oral suspension formulation used previously. Today, Vertex announced the filing of an IND to support Phase II clinical development of VX-950. Vertex also affirmed today that it remains on track to initiate by year-end a 28-day, Phase II combination study of VX-950 and pegylated interferon.
About Hepatitis C Hepatitis C is a liver disease caused by the hepatitis C virus, which is found in the blood of people with the disease. HCV, a serious public health concern affecting 3.4 million individuals in the United States, is spread through direct contact with the blood of infected people. Though many people with hepatitis C may not experience symptoms, others may have symptoms such as jaundice, abdominal pain, fatigue and fever. Hepatitis C significantly increases a person's risk for developing long-term infection or chronic liver disease. It also increases a person's risk of developing cirrhosis and of dying from a long-term infection.
About VX-950 VX-950 is an oral inhibitor of hepatitis C virus protease, an enzyme essential for viral replication. Vertex researchers were the first to solve the three-dimensional crystal structure of HCV protease, and have used structural insights to enable the design of small molecule HCV protease inhibitors, including VX-950. The VX04-950-101 clinical study being reported at AASLD was a dose-range finding study that included three panels of eight healthy subjects each (Part A) and three panels of 12 patients with genotype-1 HCV (Part B). In Part A, subjects were dosed for five days at doses of 450 mg, 750 mg or 1250 mg every eight hours, or placebo. Data from Part A were reported in May 2005 at the Digestive Disease Week meeting. In Part B, patients were dosed for 14 days at doses of 450 mg or 750 mg every eight hours, or 1250 mg every 12 hours or placebo. The objectives of the study were to assess safety, tolerability and antiviral activity in patients with HCV.
About Vertex Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex's product pipeline is principally focused on viral diseases, inflammation, autoimmune diseases and cancer. Vertex co-promotes the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.
Posted by Ralph at 03:34 AM --- Printer-friendly version | Comments (0)
November 19, 2005
Pill Form of Therapy for HCV Coming Closer
This report is an update of therapy progress presented at the AASLD (American Academy for the Study of Liver Diseases).
Three separate approaches are covered.
Yes, progress is being made.
AidsMap, November 18, 2005
Liz Highleyman
The latest data on three experimental hepatitis C drug candidates were presented at the American Association for the Study of Liver Diseases meeting, held November 11-15 in San Francisco. Current standard treatment for hepatitis C is based on interferon, an injected cytokine that stimulates immune response. In contrast, several investigational oral agents work by directly targeting the hepatitis C virus, similar to antiretroviral agents used to treat HIV.
Valopicitabine
Christopher O’Brien from the University of Miami presented the first interim data from an American Phase IIb trial of valopicitabine, or NM283, a nucleoside analogue hepatitis C polymerase inhibitor being developed by Idenix Pharmaceuticals.
The study included 190 patients randomly assigned to receive 800mg valopicitabine monotherapy, one of three doses (400mg, ramped dosing from 400 to 800mg, or 800mg once daily) of valopicitabine plus pegylated interferon alpha-2a (Pegasys) 180mg/week, or pegylated interferon plus ribavirin 1000-1200mg daily; 152 participants completed 12 weeks of treatment. Baseline characteristic were similar in the five arms, with a mean age of about 50 years. By ethnicity, 51-76% were Caucasian, 10-23% were East Asian, 10-23% were Middle Eastern or Indian, and fewer than 2% were African-American.
All were previous non-responders who did not clear hepatitis C with twelve weeks or more of pegylated interferon plus ribavirin, the standard treatment for HCV infection; relapsers were excluded. All had genotype 1 hepatitis C, baseline hepatitis C RNA of at least 100,000 copies/ml, and compensated liver disease.
After twelve weeks, patients in the two higher-dose valopicitabine combination arms achieved significantly greater suppression of hepatitis C RNA compared with the pegylated interferon/ribavirin arm. Hepatitis C viral load declined by 0.78 log10 copies/ml in the valopicitabine monotherapy arm, 1.92 log10 copies/ml in the pegylated interferon/ribavirin arm, 2.22 log10 copies/ml in the 400 mg valopicitabine combination arm, 2.51 log10 copies/ml in the in 400-800 mg valopicitabine combination arm, and 2.77 log10 copies/ml in the 800mg valopicitabine combination arm (p=0.001 for the latter two arms compared with pegylated interferon/ribavirin).
Percentages achieving early virological response (at least a 2-log reduction in hepatitis C virus RNA at twelve weeks) were 5%, 41%, 54%, 71%, and 63%, respectively (p < 0.001 for the latter two arms compared with pegylated interferon/ribavirin). In the 400-800 and 800mg valopicitabine combination arms, 21% achieved at least a 4-log drop in hepatitis C virus RNA compared with 6% in the pegylated interferon/ribavirin arm (p=0.05). Valopicitabine was safe and generally well tolerated, with no dose-limiting adverse events. Among the 50 participants observed for six months, no viral breakthrough or resistance has been detected. “These are promising results, particularly for the many treatment-refractory patients in urgent need of new therapeutic options,” O’Brien concluded.
SCH503034
Stefan Zeuzem from Saarland University Hospital in Homburg, Germany, reported on a Phase Ib study of Shering-Plough’s NS3 serine protease inhibitor, SCH503034. In this international multicentre trial, 61 patients were randomly assigned to receive one of four different schedules of SCH503034 (100, 200, or 400mg twice daily or 400mg three times daily), or placebo, for 14 days. Baseline characteristics were similar across the arms, with a mean age of about 50 years. All patients were non-responders to prior treatment with pegylated interferon plus ribavirin (less than 2-log reduction in hepatitis C virus RNA after twelve weeks of treatment) and had genotype 1 hepatitis C. Participants had baseline hepatitis C viral loads of at least 30,000 copies/mL, mean ALT levels of 82-112 IU/L, and compensated liver disease.
SCH503034 was rapidly absorbed, reaching a maximum concentration at 1-2 hours post-dosing. The most pronounced reduction in hepatitis C viral load was seen in the 400mg three times daily arm, with a mean maximum decline of 2.06 log10 copies/ml from baseline (range 1.1-2.7 log10 copies/ml). The magnitude of hepatitis C viral load reduction was positively correlated with SCH503034 trough level. Participants in all three twice-daily arms experienced smaller hepatitis C viral load decreases than seen in the three times daily group, but still did better than the placebo arm. Sixty percent of patients in the 400mg three times daily arm achieved a maximum hepatitis C viral load reduction of more than 2 log10 copies/ml, compared with 18%, 17%, and 8%, respectively, in the 400mg, 200mg, and 100mg twice daily arms. Conversely, no patient in the 400mg three times daily group had less than a 1-log viral load decrease, compared with 18%, 50%, and 67%, respectively, in the 400mg, 200mg, and 100mg twice daily arms. ALT reduction corresponded with viral load decreases.
Zeuzem also presented data from a second small trial showing that SCH503034 exhibited promising antiviral activity when combined with pegylated interferon in previous non-responders. In this open-label crossover study, all participants received 200 or 400mg SCH503034 monotherapy for seven days, pegylated interferon alpha-2b (Peg-Intron) 1.5 mcg/kg/week for 14 days, and SCH503034 plus pegylated interferon for 14 days, but in different orders (i.e., some started with SCH503034 alone, some with pegylated interferon alone, and some with the combination). The mean hepatitis C viral load decrease was more than 2 log10 copies/ml in both the 200mg and 400mg SCH503034 combination arms, compared with 1 log10 copies/ml in the pegylated interferon monotherapy arm; 40% of patients (4 out of 10) in the 400mg arm achieved undetectable hepatitis C viral load, compared with none of those receiving only pegylated interferon. Zeuzem concluded that combination therapy produced at least an additive decline in HCV RNA.
In both studies, SCH503034 appeared self and well-tolerated at all dose levels. In the monotherapy study, adverse events were mild and similar in the SCH53034 and placebo arms. The adverse event profiles in the second study were similar in the SCH503034 and combination therapy arms, consisting mostly of well-known pegylated interferon side effects. Importantly, in animal and human studies to date, researchers have seen no clinical or histopathological evidence of the type of cardiac toxicity that led to the discontinuation of an earlier hepatitis C protease inhibitor, BILN-2061. While one patient did develop the V170A mutation (shown to cause resistance to SCH503034 in laboratory studies), no phenotypic resistance was observed and no viral rebound was seen during treatment in the 400mg three times daily arm. Phase II studies assessing 24 and 48 week VX-950/pegylated interferon combination therapy are underway.
VX-950
Finally, Henk Reesink from the Academic Medical Centre in Amsterdam reported data from a Phase Ib dose-ranging trial of a second hepatitis C protease inhibitor, VX-950 (Vertex Pharmaceuticals). This study included 36 individuals with genotype 1 hepatitis C, mostly prior non-responders, but also a few treatment-naive patients. Participants were assigned to receive either placebo or an oral suspension of VX-950 as monotherapy, 450 or 750mg every 8 hours (three times daily) or 1250mg every twelve hours (twice daily), for 14 days. Here, too, baseline characteristics were generally similar across the study arms.
Participants in all VX-950 dose groups showed steep declines in hepatitis C during the first two-to-three days of treatment. All patients receiving VX-950 experienced at least a 2-log viral load decrease from baseline. Most individuals in the three VX-950 arms (26 out of 28) had a maximum hepatitis C viral load decrease of at least 3 log10 copies/ml, and four patients had a greater than 5-log decrease. The 750mg three times daily dose produced the highest VX-950 trough levels and the largest mean HCV RNA decrease: 4.4 log10 copies/ml, or a 25,000-fold reduction. Four patients in this arm had undetectable viral load (below 30 IU/mL) at the end of the treatment period. Hepatitis C viral load also decreased in the other two dose groups, but started to climb again after seven days. VX-950 appeared to work as well in prior non-responders as in naive patients. ALT levels declined during treatment in all dose groups. There were no severe adverse events, dose reductions, or treatment discontinuations. The most commonly reported side effects (headache and diarrhoea) occurred with similar frequency in the VX-950 and placebo arms. As with SCH503034, no cardiotoxicity was observed.
In a companion resistance study presented by Christoph Sarrazin, also from Homburg, researchers sequenced the HCV NS3 gene from 34 patients at baseline, day 14, and day 21-24. Several variants were seen with reduced sensitivity to VX-950, at amino acid positions 36, 54, 155, and 156. A single V36 change conferred minimal resistance, while A156V/T was associated with high-level resistance. These mutations were detected in patients who experienced hepatitis C viral load rebound or plateau rather than continued decline. Variants with reduced sensitivity to VX-950 also had decreased replicative fitness, allowing wild-type hepatitis C virus to re-emerge after treatment discontinuation.
According to Reesink, VX-950 produced “the most rapid and dramatic response” seen to date with a single agent. Based on viral kinetic analysis, he suggested that the drug may reduce hepatitis C to undetectable levels in approximately 12 weeks - substantially shorter than the standard 48 week therapy for genotype 1 hepatitis C. Based on data collected so far, Vertex filed an investigational new drug application with the U.S. Food and Drug Administration on November 11. A 14-day Phase Ib study of a new tablet formulation of VX-950 in combination with pegylated interferon is underway in Europe, and a 12 week combination study is planned for next year.
While all three of these experimental agents look promising, it is too soon to say whether they will ultimately produce sustained virological response. Nevertheless, based on research to date, many experts believe antiviral drugs - potentially in combination regimens consisting entirely of oral agents - are the wave of the future for hepatitis C therapy.
References
O’Brien C. et al. Randomized trial of valopicitabine (NM283), alone or with peg-interferon, vs. retreatment with peg-interferon plus ribavirin (PegIFN/RBV) in hepatitis C patients with previous non-response to PegIFN/RBV: first interim results. 56th Annual Meeting of the American Association for the Study of Liver Diseases, San Francisco, abstract 63186, 2005.
Reesink H. et al. Final results of a phase 1B, multiple-dose study of VX-950, a hepatitis C virus protease inhibitor. 56th Annual Meeting of the American Association for the Study of Liver Diseases, San Francisco, abstract 62580, 2005.
Sarrazin C. et al. Characterization of viral variants in the HCV NS3 protease domain of genotype 1 patients that are selected during 14 days of dosing with VX-950. 56th Annual Meeting of the American Association for the Study of Liver Diseases, San Francisco, abstract 72562, 2005.
Zeuzem S. et al. Anti-viral activity of SCH 503034, a HCV protease inhibitor, administered as monotherapy in hepatitis C genotype-1 (HCV-1) patients refractory to pegylated interferon (Peg-IFN-a). 56th Annual Meeting of the American Association for the Study of Liver Diseases, San Francisco, abstract 67484, 2005.
Zeuzem S. et al. Combination therapy with the HCV protease inhibitor, SCH 503034, plus PEG-Intron in hepatitis C genotype-1 PEG-Intron non-responders: phase Ib results. 56th Annual Meeting of the American Association for the Study of Liver Diseases, San Francisco, abstract 67627, 2005.
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November 16, 2005
Pegasys Shown More Effective In Study
Schering and Roche are taking part in dueling press releases.
Each claiming their solution is better. Either way, they seem to be splitting hairs regarding effectiveness.
There is no clear winner when they keep firing PR salvos back and forth. Who is a patient to believe? How do doctors determine what is best for their patients?
Be sure to stay informed and make as educated a choice as you can.
HEPATITIS C PATIENTS FARE BETTER WITH PEGASYS(R) - STUDY FROM POLAND SHOWS SIGNIFICANT DIFFERENCE IN EFFICACY BETWEEN LEADING TREATMENTS
15-11-2005 06:30
WARSAW, Poland, November 15 /PRNewswire/ -- Early results from a new study comparing the efficacy of the two leading hepatitis C treatments suggests that patients may increase their chance of a cure by more than 10% if they are treated with PEGASYS(R) and COPEGUS(R) combination therapy. The study, presented today at the 56th Annual Meeting of the American Association for the Study of Liver Diseases, is one of the first scientifically rigorous research efforts comparing leading treatments to determine which provides the best solution for patients battling hepatitis C [1].
"Patients and the medical community are understandably anxious to have reliable information regarding what treatment is most likely to provide a cure for hepatitis C," said Dr Andrzej Horban, from Infection Disease Hospital in Warsaw who headed the study. "My colleagues and I wished to undertake a study that would clearly answer this question and use a methodology that would inspire confidence in the results."
To date, there have been a number of comparative studies undertaken, but few if any, have generated results which reflect best practices in clinical research. In fact, a number of studies promoted to the public have been retrospective analyses of small research efforts that were designed to address different research questions altogether.
More PEGASYS Patients Respond After Only 12 Weeks of Treatment
The study was undertaken in Poland and involved more than 200 people infected with hepatitis C. All patients were assigned to be treated with either PEGASYS combination therapy or Peg Intron(R) combination therapy. After 12 weeks of treatment, 85% of the PEGASYS patients were responding to therapy as compared to only 74% of the Peg Intron patients. Response to therapy at 12 weeks (defined as either a significant drop in viral load or eliminating the virus completely) is typically an excellent indicator that a patient will be cured of the disease upon completing the full course of therapy.
Local Patient Groups Respond with Enthusiasm
Mr Jaroslaw Chojnacki - The chairman of the Prometeusze Community - said: "although we are still awaiting the final results of this study, the patient community is very pleased that this study has been undertaken in Poland. The results of this study can help infected people a lot. If we are convinced that someone's odds of beating this disease are increased by 10% because they took this drug, it would be important information for us", he said.
Like many countries in Europe, Poland is actively addressing the potential time bomb that is hepatitis C. Official figures state 1.5% of the population may have the virus. However patient groups and treating doctors believe that the figure is much higher.
Reference:
[1] Berak, H et al. "Randomized, Open Label Trial Comparing efficacy and safety of pegylated interferon alfa 2a vs 2b treatment of patients with chronic hepatitis infected with non 2/3 genetypes - 12 week virological response" Presented at AASLD, 2005.
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November 15, 2005
Weight-based Treatment of HCV
Weight-based dosing has always made sense to us. We don't really understand why Roche has not changed their dosing to weight-based.
Although the difference is subtle, it is certainly significant according to this study.
You must also note, though, that Schering is funding this study. Does bias matter in science? What do you think?
Largest Hepatitis C Trial in U.S. Patients Shows Weight-Based REBETOL in Combination With PEG-INTRON Increases Sustained Response, Lowers Relapse
Final Results of Community-Based WIN-R Study Also Demonstrate Efficacy of Shorter, More Tolerable 24-Week Regimen in Patients With Genotype 2 or 3 Virus
SAN FRANCISCO, CA -- (MARKET WIRE) -- 11/14/2005 -- Final results of the WIN-R trial,(1) the largest hepatitis C study conducted in U.S. patients, showed that weight-based REBETOL® (ribavirin, USP) in combination therapy with PEG-INTRON® (peginterferon alfa-2b) achieved significantly higher rates of sustained virologic response (SVR)(2) and lower rates of relapse compared to the combination therapy using a flat dose of ribavirin. The study also showed that, for patients infected with hepatitis C virus (HCV) genotype 2 or 3, a shorter, 24-week course of therapy was as effective as the standard 48-week course, with better tolerability.
These results from WIN-R (Weight-Based Dosing of PEG-INTRON and REBETOL), a community-based access trial involving more than 4,900 patients at 225 centers across the United States, were reported in an oral presentation today at the 56th annual meeting of the American Association for the Study of Liver Diseases (AASLD).
"These findings help further define optimal therapy for U.S. hepatitis C patients treated in real-world community settings," said principal investigator Ira M. Jacobson, M.D., Vincent Astor Professor of Clinical Medicine at Weill Medical College of Cornell University and chief of the division of gastroenterology and hepatology at NewYork-Presbyterian Hospital/Weill Cornell Medical Center in New York City.
Treating U.S. hepatitis C patients can be especially challenging as they tend to have disease characteristics that are associated with poor response to treatment, including high prevalence of HCV genotype 1, the most difficult type of the virus to treat; high viral load; and advanced liver fibrosis. Other factors such as age, high body weight and African-American ethnicity also have been shown to be associated with poor response.
"Our findings showed that the weight-based dosed combination therapy significantly increased efficacy compared to the flat-dosed ribavirin regimen, especially in more difficult-to-treat patient groups, such as patients with genotype 1 and African-American patients. This confirms what many treating physicians have come to know in their everyday practice and experience," Jacobson said. "Importantly, sustained virologic response rates in this community-based U.S. study were consistent with those seen in the U.S. cohorts of the earlier pivotal studies for the two approved peginterferon combination therapies."(3,4)
Study Design
In the WIN-R study, 4,913 patients were randomized to receive weight-based PEG-INTRON (1.5 mcg/kg weekly) in combination with REBETOL given either as a flat dose (800 mg daily) or a weight-based dose (800 mg, 1,000 mg, 1,200 mg or 1,400 mg daily for body weights of less than 65 kg, 65 to 85 kg, 86 to 105 kg, or 106 to 125 kg, respectively). Patients were treated for 48 weeks (genotype 1) or 24 weeks (genotype 2 or 3). Patients in the treatment arms were evenly matched for gender, age, body weight, genotype, viral load and stage of liver fibrosis.
Key Results
A challenge with conducting large community-based HCV studies such as WIN-R, as opposed to registration trials with their more intensive monitoring capabilities, is the tendency for a high rate of patients to miss their follow-up viral testing (PCR) visit 24 weeks after treatment ends due to the limited ability of many sites to conduct rigorous monitoring of patients once they have received their final treatment dose. In the WIN-R study, 13.1 percent (164/1,256) of patients in the weight-based dose group and 13.7 percent (163/1,193) of patients in the fixed-dose group who were responders at the end of treatment were lost to follow up and subsequently counted as treatment failures under a strict intent-to-treat (ITT) analysis.
Nonetheless, the WIN-R study showed significantly better outcomes for the weight-based combination regimen as compared to the flat-dosed ribavirin regimen, including:
-- Significantly higher SVR overall (44.3 percent vs. 40.6 percent, p=0.01, ITT) and for patients with genotype 1 (34 percent vs. 29 percent, p=0.004, ITT). These SVR rates are consistent with those seen in the U.S. cohorts of the earlier pivotal studies for the two approved peginterferon combination therapies.(3,4)
-- Using an estimated SVR analysis, based on results for patients who had undetectable virus at the end of treatment and were subsequently lost to follow up, SVR was 53 percent vs. 48 percent (p=0.008), respectively, for the weight-based vs. flat-dosed ribavirin groups.
-- Consistent SVR rates were seen across all weight groups for patients in the weight-based dosed regimen compared to the flat-dosed ribavirin regimen where SVR rates declined in the higher weight groups, ranging from 52 percent to 34 percent. Consistent with other U.S. studies, patient weight tended to be high in the WIN-R study, with 45 percent of patients weighing 86 kg (189 lbs) or more.
-- For patients with HCV genotype 2 or 3 virus, a 24-week course of the combination therapy was as effective as 48 weeks, with better tolerability. In the weight-based dose arms, SVR was 68 percent for the 24-week course compared to 60 percent for the 48-week course, with the lower percentage attributable to more missing follow-up data.
-- Lower rates of relapse were seen for patients receiving the weight- based combination therapy compared to the flat-dosed ribavirin regimen, 15 percent vs. 19 percent overall, and 23 percent vs. 29 percent for patients with HCV genotype 1. Relapse is defined as patients with undetectable virus levels at the end of treatment who subsequently had detectable virus at 24 weeks post-treatment.
-- Although there was a higher rate of anemia (hemoglobin < 10 gm/dl) in the weight-based dosing group and more dose reductions (29 percent vs. 23 percent), no difference was seen in the rate of occurrence of serious adverse events between the two groups (12 percent vs. 11 percent) and there were similar rates of discontinuations for adverse events (15 percent vs. 14 percent).
WIN-R Study
Serving with Dr. Jacobson as co-principal investigator of the WIN-R study is Dr. Robert S. Brown Jr., associate professor of clinical medicine at Columbia University College of Physicians and Surgeons; and chief of clinical hepatology and medical director of the Center of Liver Disease and Transplantation at NewYork-Presbyterian Hospital/Columbia University Medical Center. Drs. Jacobson and Brown are also co-directors of NewYork-Presbyterian Healthcare System's Liver Clinical Trials Network (LCTN).
Dr. Jacobson also is medical director of the Center for the Study of Hepatitis C, a unique interdisciplinary center established jointly by The Rockefeller University, NewYork-Presbyterian Hospital and Weill Cornell Medical College in New York City.
WIN-R is an investigator-initiated clinical study supported by Schering-Plough Corporation and monitored by Schering-Plough Research Institute as part of a post-marketing commitment to the U.S. Food and Drug Administration (FDA). PEG-INTRON and REBETOL are registered trademarks of Schering-Plough.
About Hepatitis C
Hepatitis C is the most common blood-borne infection in America, affecting approximately 4 million people or about one in every 50 adults. Chronic hepatitis C can cause cirrhosis, liver failure and liver cancer. It has been estimated that at least 20 percent of patients with chronic hepatitis C develop cirrhosis, and a smaller percentage of patients with chronic disease develop liver cancer. Patients with chronic hepatitis C and related cirrhosis are 100 times more likely to develop liver cancer than uninfected persons.(5) About half of all cases of primary liver cancer in the developed world are caused by hepatitis C, and hepatitis C related liver disease is now the leading cause for liver transplants.(6)
About New York-Presbyterian Hospital/Weill Cornell Medical Center
The New York-Presbyterian Hospital/Weill Cornell Medical Center, located in New York City, is one of the leading academic medical centers in the world, comprising the teaching hospital NewYork-Presbyterian Hospital and its academic partner Weill Cornell Medical College. NewYork-Presbyterian/Weill Cornell provides state-of-the-art in-patient, ambulatory, and preventive care in all areas of medicine, and is committed to excellence in patient care, research, education, and community service.
References
1. Jacobson I, Brown Jr. R, Freilich B, Afdahl N, Kwo P, Santoro J, Becker S, Wakil A, Pound D, Godofsky E, Strauss R, Bernstein D, Flamm S, Bala N, Araya V, Davis M, Monsour H, Vierling J, Regenstein F, Balan V, Dragutsky M, Epstein M,. Herring RW, Rubin R, Galler G, Pauly MP, Griffel LH, Brass CA, the WIN-R Study Group. Weight based ribavirin dosing (WBD) increases sustained viral response (SVR) in patients with chronic hepatitis C (CHC): final results of the WIN-R study, a U.S. community-based trial. Oral presentation at: 56th Annual Meeting of the American Association for the Study of Liver Diseases, San Francisco, CA, Nov 11-15, 2005.
2. Sustained virologic response (SVR) is defined as undetectable virus (HCV-RNA) levels in the blood at 6 months after the end of therapy.
3. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001 Sep 22;358(9286):958-65.
4. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, Haussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002 Sep 26;347(13):975-82.
5. Ince N, Wands JR. The increasing incidence of hepatocellular carcinoma. N Engl J Med 1999 March 11;340:10.
6. Centers for Disease Control and Prevention. Recommendations for prevention and treatment of hepatitis C virus (HCV) and HCV-related chronic disease. MMWR Weekly Report 1998 Oct. 16;1.
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November 11, 2005
HCV Vaccine Progress
The development of a HCV vaccine is very exciting, even to patients already infected. Although the vaccine will not help them direcly, it shows definite progress in understanding and outsmarting this virus that is known to be difficult to combat due to its rapid mutation.
If they are making progress with a vaccine, progress for better treatment must be close behind.
Major Milestone Reached In Hepatitis C Vaccine Program
Select Vaccines (AUSTRALIA)
November 11, 2005
11 November 2005: Melbourne-based biotechnology company, Select Vaccines Ltd (ASX:SLT), today announced positive results from its first pre-clinical studies of a potential vaccine against hepatitis C.
The results followed nine months of animal studies and represent a major advancement of the hepatitis C vaccine program.
Managing Director of Select Vaccines, Dr Martin Soust, said "We obtained good results in our early studies in the laboratory and in a pilot study and, on the strength of these results, we initiated a dose ranging study in mice."
"We observed very strong immune responses after just one small dose of less than one microgram of this hepatitis C vaccine," said Associate Professor David Anderson, Chief Scientific Officer with Select Vaccines.
Hepatitis C specific antibodies were produced by all 46 animals injected with the hepatitis C vaccine, even at the lowest dose studied which was 0.2 micrograms. There was also the induction of significant levels of hepatitis C specific T cells, which suggests the vaccine may promote better overall control of infection.
An immune response of this strength in mice suggests a very strong likelihood that a similarly strong response will be produced in a larger animal species that will be studied in the next round of investigations.
The results exceeded the company's expectations and suggest that the prospects of developing a human vaccine with a good safety profile are excellent.
"The commercial potential of a vaccine against hepatitis C is substantial. Globally, there are almost 300 million people currently infected with hepatitis C and up to 10 million new infections each year. The market for a vaccine against hepatitis C has been estimated to be worth more than $US500 million. The company is pursuing the development of this vaccine as there is currently no vaccine available" said Dr Soust.
"The next steps in our hepatitis C vaccine program are very clear," Anderson said. "We plan to undertake further studies in larger animals and to produce purified injectable material under GLP conditions for use in a preclinical toxicology study before moving into a phase I clinical trial." Professor Anderson explained.
Select Vaccines is developing the hepatitis C vaccine with its proprietary vaccine technology that employs virus-like particles to generate a protective immune response against infection. The platform technology involves producing virus-like particles into which specific vaccine antigens of interest, in this case an envelope protein from hepatitis C virus, have been inserted.
"We have been waiting for the outcome from these initial animal studies before considering a very substantial longer-term commitment to vaccine development. With this proof of the VLP platform in hand we have a very strong indication that we may be able to develop vaccines against other infectious diseases and we will look to accelerate and expand our work accordingly." said Dr Soust.
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November 09, 2005
Your Results May Vary For HCV Treatment
According to this study, actual treatment results may be only half as good as touted. Doctors tend to trust the numbers presented by the pharaceutical companies. The pharmaceutical companies have a vested interest in presenting the best numbers they can find.
Patients may be unpleasantly surprised with the actual results.
Hepatitis C Often Untreated and Outcomes Lag behind Trials in Clinical Practice: Presented at ACG
By Paula Moyer
HONOLULU, HI -- November 9, 2005 -- When patients with hepatitis C go on antiviral therapy, the likelihood of a response may be half of that seen in clinical trials, according to investigators who presented their findings here at the 70th annual meeting of the American College of Gastroenterology (ACG).
The research was presented on November 2nd by Ramsey C. Cheung, MD, Chief of Hepatology, Veterans Affairs Palo Alto Health Care System, and Associate Professor of Medicine, Stanford University Medical School, Stanford, California, United States.
"A lot of people with a diagnosis of hepatitis C are not being treated for multiple reasons," Dr. Cheung, MD, said in an email. "When we decide to treat a patient and when the patient decides to go on treatment, the probability of achieving a cure is important to both parties."
However, he added, his study showed that the response rate is much lower in clinical practice than has been seen in the registration trial. "It is important for the treating physician and the patient to know what the response rate is likely to be, not what has been reported in registration trial."
He noted that studies of patients with hepatitis C within the Veterans Affairs system showed that the sustained viral response rate was low. The investigative team conducted the current study to see if the same results would be seen in a community cohort.
The team reviewed several databases of selected sites within the Kaiser Permanente Northern California Health System, and identified 1470 patients with chronic hepatitis C who were seen within the system from 1999-2004. They obtained demographic information from administrative files on age, gender, and ethnicity and patients' laboratory records.
The system's pharmacy records held data on patients' treatment with interferon combined with ribavirin or pegylated interferon combined with ribavirin, along with information regarding the patients' use of erythropoetin (Procrit), filgrastim (Neupogen), antidepressants, and transfusions.
Results show that 246 (16.5%) underwent treatment; 65.3% of these patients were men. Data were completely evaluable for 242 patients; 119 of these were treated with interferon plus ribavirin, and 123 were treated with pegylated interferon plus ribavirin. Patients were an average of 47.1 years old (range 33.3-60.91).
The vast majority of treated patients (72.4%) had HCV genotype I, while 24% had HCV genotypes II and III, and 3.6% had HCCV genotypes IV-VI.
Patients were treated for an average of 29.2 weeks. A sustained virologic response occurred in 19.8% of treated patients, including 11.8% of those who received interferon plus ribavirin, and 27.6% of those treated with pegylated interferon plus ribavirin.
In clinical trials, sustained viral response rates have reached more than 70%, Dr. Cheung said.
Although the reasons for the gap are unclear, these findings may help physicians and patients have more realistic expectations of treatment, Dr. Cheung said.
[Presentation title: Practice Patterns and Treatment of Outcomes in the Management of Chronic Hepatitis C (CHC) Infection in a Large Managed Care Cohort. Abstract 785]
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