Exploratory phase 2 trial in patients with HCV genotype 2 or 3 to receive PSI-7977 400mg QD and ribavirin, with 0-12 weeks of pegylated interferon
Interim data expected in first half of 2011
PRINCETON, N.J., Dec. 14, 2010 /PRNewswire/ -- Pharmasset, Inc. (Nasdaq: VRUS) announced today that dosing has begun in an exploratory study of PSI-7977, a nucleotide analog polymerase inhibitor, for the treatment of chronic hepatitis C (HCV). The trial will evaluate PSI-7977 400mg QD in combination with ribavirin (RBV), with 0, 4, 8, or 12 weeks of pegylated interferon alfa 2a (Peg-IFN) in treatment-naive patients infected with HCV genotype 2 or 3.
"Based on the encouraging efficacy, safety and resistance data from the Phase 2a trial with PSI-7977 in combination with pegylated interferon and ribavirin, we initiated a study to explore shorter durations of interferon, including an interferon-free regimen in treatment naïve patients with HCV genotype 2 or 3," stated Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "An important limitation to the current treatment of HCV patients is the use of interferon with its associated side effect profile. We believe that PSI-7977's high barrier to resistance and the lack of a significant effect of IL28B genotype in the Phase 2a trial provide us an opportunity with PSI-7977 to explore shorter durations of interferon, and potentially even removing it from the treatment regimen altogether."
About the Trial
The trial is anticipated to enroll approximately 40 patients infected with HCV genotype 2 or 3 who have not previously been treated. The primary endpoint of the trial will be the assessment of safety and tolerability of PSI-7977 400mg QD and RBV for 12 weeks, administered with or without pegylated interferon (Peg-IFN) in treatment naïve patients with HCV genotypes 2 or 3. The trial will be conducted in New Zealand. Patients will be randomized into one of 4 arms:
-- PSI-7977 400mg QD in combination with RBV for 12 weeks (no interferon);
-- PSI-7977 400mg QD in combination with RBV for 12 weeks, with only 4 weeks of Peg-IFN;
-- PSI-7977 400mg QD in combination with RBV for 12 weeks, with only 8 weeks of Peg-IFN;
-- PSI-7977 400mg QD in combination with Peg-IFN and RBV for 12 weeks.
Patients will be stratified by HCV genotype and IL28B status to ensure balance across cohorts.
Pharmasset anticipates reporting interim data from this trial in the first half of 2011.
About Pharmasset
Pharmasset is a clinical-stage pharmaceutical company committed to discovering, developing, and commercializing novel drugs to treat viral infections. Pharmasset's primary focus is on the development of oral therapeutics for the treatment of hepatitis C virus (HCV). Our research and development efforts focus on nucleoside/tide analogs, a class of compounds which act as alternative substrates for the viral polymerase, thus inhibiting viral replication. We currently have four clinical-stage product candidates. RG7128, a cytosine nucleoside analog for chronic HCV infection, is in two Phase 2b clinical studies in combination with Pegasys(R) plus Copegus(R) and is also in the INFORM studies, the first series of studies designed to assess the potential of combinations of small molecules without Pegasys(R) and Copegus(R) to treat chronic HCV. These clinical studies are being conducted through a strategic collaboration with Roche. Our other clinical stage HCV candidates include PSI-7977, an unpartnered uracil nucleotide analog that has recently initiated dosing in a Phase 2b study in patients with HCV genotypes 1, 2, or 3, and PSI-938, an unpartnered guanosine nucleotide analog which recently completed a 7-day monotherapy study. We also have in our pipeline an additional purine nucleotide analog, PSI-661, in advanced preclinical development.
Pegasys(R) and Copegus(R) are registered trademarks of Roche.
Forward-Looking Statements
Pharmasset "Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995: Statements in this press release that are not historical facts are "forward-looking statements," that involve risks, uncertainties, and other important factors, including, without limitation, the risk of cessation or delay of any of the ongoing or planned clinical trials and/or our development of our product candidates, the risk that the results of previously conducted studies involving our product candidates will not be repeated or observed in ongoing or future studies involving our product candidates, the risk that our collaboration with Roche will not continue or will not be successful, and the risk that any one or more of our product candidates will not be successfully developed and commercialized. For a discussion of risks, uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in our Annual Report on Form 10-K for the fiscal year ended September 30, 2010 filed with the Securities and Exchange Commission and discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission.
Contact
Richard E. T. Smith, Ph.D.
VP, Investor Relations and Corporate Communications
Office +1 (609) 613-4181
SOURCE Pharmasset, Inc.
RELATED LINKS
http://www.pharmasset.com/
Source
December 14, 2010
Steatosis, Obesity, Peg-IFN Dose Reduction & Menopause are Associated with Relapse in Chronic Hepatitis C Patients Treated with Pegylated Interferon Plus Ribavirin
Reported by Jules Levin, AASLD Nov 2 2010
C. Stern1; M. Martinot-Peignoux1; M. Ripault1; N. Boyer1; A. Cardoso1; A. El Ray1; T. Asselah1; D. Valla1; P. Marcellin1 1. Service d'Hepatologie, Hôpital Beaujon, Clichy, France.
BACKGROUND/AIMS: Relapse after treatment of chronic hepatitis C (CHC) patients with the combination of pegylated interferon (PEG-IFN)-α and ribavirin (RBV) is observed in 30% of patients with end of therapy (EOT) response. Factors associated with relapse are not well known. The aim of this study was to evaluate the factors related to relapse in CHC patients, particularly in female patients, treated with PEG-IFN in combination with RBV.
METHODS: A total of 249 consecutive naive CHC patients treated with PEG-IFN-α-2a or -2b plus RBV (800 to 1200 mg/day) and with EOT response were included. Among these, 84 (34%) patients were female. Duration of therapy was defined according to the current guidelines. Clinical, biological, virological and histological data were collected. Type of PEG-IFN, initial doses and modifications of therapy were analyzed. The efficacy of treatment was evaluated with a sensitive qualitative HCV RNA assay (<15 IU/mL). Factors associated with relapse were analyzed.
RESULTS: Relapse was observed in 34% of patients; 50% received PEG-IFN-α2a. Overall population presented the following characteristics: mean age 47±11, obesity (BMI ≥30) in 10%, genotype 1 in 33%, advanced fibrosis (≥F3) in 24% and marked steatosis (≥30%) in 27%.
In the logistic regression, factors related to relapse in overall population were: obesity (p=0.011), genotype 1 (p=0.001), marked steatosis (p=0.006) and PEG-IFN dose reduction (p<0.001). In female patients, menopause was observed in 59% (mean age 48±6). Therefore, to confirm a possible impact of menopause on relapse in CHC female patients, we compared patients under and older than 50 years according to gender. In males (n=165), relapse was present in 22% and 28% of patients under 50 years and older than 50 years (p=0.38), respectively. When relapse rates were analyzed in females (n=84), a statistically difference related to age was observed (14% vs 37%, p=0.023). Among female patients, factors associated with relapse were: menopause (p=0.006), obesity (p=0.031), high viral load (≥400,000 IU/mL) (p=0.014), genotype 1 (p=0.034) and necro-inflammatory activity ≥A2 (p=0.043). In the logistic regression, only menopause was independently associated with relapse in CHC female patients (p=0.007, 95% CI 1.66 - 24.47).
CONCLUSION: CHC patients infected with genotype 1 and presenting obesity and marked steatosis have higher rates of relapse. PEG-IFN reduction, but not ribavirin reduction, is associated with relapse. In female patients, menopause has a negative impact on SVR rates.
Source
C. Stern1; M. Martinot-Peignoux1; M. Ripault1; N. Boyer1; A. Cardoso1; A. El Ray1; T. Asselah1; D. Valla1; P. Marcellin1 1. Service d'Hepatologie, Hôpital Beaujon, Clichy, France.
BACKGROUND/AIMS: Relapse after treatment of chronic hepatitis C (CHC) patients with the combination of pegylated interferon (PEG-IFN)-α and ribavirin (RBV) is observed in 30% of patients with end of therapy (EOT) response. Factors associated with relapse are not well known. The aim of this study was to evaluate the factors related to relapse in CHC patients, particularly in female patients, treated with PEG-IFN in combination with RBV.
METHODS: A total of 249 consecutive naive CHC patients treated with PEG-IFN-α-2a or -2b plus RBV (800 to 1200 mg/day) and with EOT response were included. Among these, 84 (34%) patients were female. Duration of therapy was defined according to the current guidelines. Clinical, biological, virological and histological data were collected. Type of PEG-IFN, initial doses and modifications of therapy were analyzed. The efficacy of treatment was evaluated with a sensitive qualitative HCV RNA assay (<15 IU/mL). Factors associated with relapse were analyzed.
RESULTS: Relapse was observed in 34% of patients; 50% received PEG-IFN-α2a. Overall population presented the following characteristics: mean age 47±11, obesity (BMI ≥30) in 10%, genotype 1 in 33%, advanced fibrosis (≥F3) in 24% and marked steatosis (≥30%) in 27%.
In the logistic regression, factors related to relapse in overall population were: obesity (p=0.011), genotype 1 (p=0.001), marked steatosis (p=0.006) and PEG-IFN dose reduction (p<0.001). In female patients, menopause was observed in 59% (mean age 48±6). Therefore, to confirm a possible impact of menopause on relapse in CHC female patients, we compared patients under and older than 50 years according to gender. In males (n=165), relapse was present in 22% and 28% of patients under 50 years and older than 50 years (p=0.38), respectively. When relapse rates were analyzed in females (n=84), a statistically difference related to age was observed (14% vs 37%, p=0.023). Among female patients, factors associated with relapse were: menopause (p=0.006), obesity (p=0.031), high viral load (≥400,000 IU/mL) (p=0.014), genotype 1 (p=0.034) and necro-inflammatory activity ≥A2 (p=0.043). In the logistic regression, only menopause was independently associated with relapse in CHC female patients (p=0.007, 95% CI 1.66 - 24.47).
CONCLUSION: CHC patients infected with genotype 1 and presenting obesity and marked steatosis have higher rates of relapse. PEG-IFN reduction, but not ribavirin reduction, is associated with relapse. In female patients, menopause has a negative impact on SVR rates.
Source
IL-28B Genotype is a Major Determinant of the Induction of a Virological Response by High-Dose Peginterferon and Ribavirin in Null-responders to SOC Therapy: Pegasys double-dose significantly increased early virologic response
Reported by Jules Levin
AASLD Nov 2 2010 Boston
NATAP
Stephane Chevaliez1,2, Christophe Hezode1,3, Alexandre Soulier1,2, Bruno Costes2,4, Magali Bouvier-Alias1,2, Stephanie Rouanet5, Juliette Foucher6, Jean-Pierre Bronowicki7, Albert Tran8, Isabelle Rosa9, Philippe Mathurin10, Laurent Alric11, Vincent Leroy12, Victor De Ledinghen6, Ariane Mallat1,3, Mariem Charaf-Eddine5, Gerard Babany5, and Jean-Michel Pawlotsky1,2
1National Reference Center for Viral Hepatitis B, C and delta, Virology, Hôpital Henri Mondor, Creteil, France; 2INSERM U955, Creteil, France; 3Hepatology and Gastroenterology, Hôpital Henri Mondor, Creteil, France; 4 Biochemistry, Hôpital Henri Mondor, Creteil, France; 5Roche, Neuilly-Seine, France; 6Hepatology and Gastroenterology, Hôpital Haut-Levêque, Pessac, France; 7Hepatology and Gastroenterology, Hôpital de Brabois, Nancy, France; 8Hepatology and Gastroenterology, Hôpital de l'Archet, Nice, France; 9Hepatology and Gastroenterology, Centre Hospitalier Intercommunal, Creteil, France; 10Hepatology and Gastroenterology, Hôpital Claude Huriez, Lille, France; 11Internal Medicine, Hôpital Purpan, Toulouse, France; 12Hepatology and Gastroenterology, Hôpital de la Tronche, Grenoble, France
from Jules: we need to wait for the IL28B subanalyses from the telaprevir ADVANCE & boceprevir SPRINT2 studies in order to see how to use this information. Using double dose Pegasys in this study appeared to on average increase the virologic response quite a lot by weeks 4, 8 and 12 compared to prior use of the standard Pegasys dose for both TT and CT genotypes. CT genotype achieved better virologic response than TT genotype in this study, by week 24: 44% of TT and 70% of CT achieved >2 log viral load reduction. These data suggest that double-dose Pegasys 360 ug/week in combination with telaprevir or boceprevir may significantly increase virologic response and SVR. Conceivably, double-dose Pegasys during a lead-in and during therapy with telaprevir or boceprevir could increase SVR rates potentially quite a lot based on these data. There is a suggestion that an HCV protease resenesitizes the patient's internal interferon response so let's see how the TTs and CTs respond in the subanalyses from Advance & Sprint.
ABSTRACT:
Polymorphisms upstream of the region encoding IL28B have been shown to be associated with both natural and treatment-induced control of HCV infection. With new therapies using direct acting antiviral molecules, a null response to IFN is associated with treatment failure and selection of resistant viruses. Our goal was to assess, in null-responders to IFN-ribavirin therapy, whether the IL28B genotype has an influence and predictive value on the ability of high-dose pegylated IFN and ribavirin retreatment to induce a virological response.
METHODS:
83 genotype 1 null-responders received peg-IFN alpha-2a, 360 µg/week in one or two injections, plus ribavirin, 1000-1200 or 1200-1600 mg/d. Genotyping of the IL28B SNP rs12979860 was performed from host cell DNA by means of a real-time PCR method using minor groove binding probes. RESULTS: The IL28B genotype was determined in all 83 patients: 3 (3.6%) had a CC genotype and were removed to allow comparison between CT (n=55) and TT (n=25) patients. The difference between reductions in HCV RNA levels between TT and CT patients was significant at week 2 (<0.5 vs ≥0.5 Log, p=0.02), at week 4 (<1 vs ≥1 Log, p=0.008), and at weeks 12 and 24 (<2 vs ≥2 Log p=0.02). When comparing CT and TT patients, the odds ratio were 3.09 for a more than 0.5 Log drop at week 2; 3.86 for a more than 1 Log drop at week 4; 3.08 for a more than 2 Log drop at week 12; 3.10 for a more than 2 Log drop at week 24; and 3.57 for an undetectable HCV RNA at week 24.
CONCLUSIONS:
Most patients who fail to respond to pegylated IFN and ribavirin carry either TT or CT rs12979860 genotypes. CT patients are significantly more likely to respond to higher doses of IFN and the difference is significant at week 2. This indicates that the IL28B genotype is a marker of host cell responsiveness to IFN. These findings will have major implications in the treatment of HCV infection with higher peg-IFN doses in combination with ribavirin and direct acting antivirals.
Continue Reading ...
AASLD Nov 2 2010 Boston
NATAP
Stephane Chevaliez1,2, Christophe Hezode1,3, Alexandre Soulier1,2, Bruno Costes2,4, Magali Bouvier-Alias1,2, Stephanie Rouanet5, Juliette Foucher6, Jean-Pierre Bronowicki7, Albert Tran8, Isabelle Rosa9, Philippe Mathurin10, Laurent Alric11, Vincent Leroy12, Victor De Ledinghen6, Ariane Mallat1,3, Mariem Charaf-Eddine5, Gerard Babany5, and Jean-Michel Pawlotsky1,2
1National Reference Center for Viral Hepatitis B, C and delta, Virology, Hôpital Henri Mondor, Creteil, France; 2INSERM U955, Creteil, France; 3Hepatology and Gastroenterology, Hôpital Henri Mondor, Creteil, France; 4 Biochemistry, Hôpital Henri Mondor, Creteil, France; 5Roche, Neuilly-Seine, France; 6Hepatology and Gastroenterology, Hôpital Haut-Levêque, Pessac, France; 7Hepatology and Gastroenterology, Hôpital de Brabois, Nancy, France; 8Hepatology and Gastroenterology, Hôpital de l'Archet, Nice, France; 9Hepatology and Gastroenterology, Centre Hospitalier Intercommunal, Creteil, France; 10Hepatology and Gastroenterology, Hôpital Claude Huriez, Lille, France; 11Internal Medicine, Hôpital Purpan, Toulouse, France; 12Hepatology and Gastroenterology, Hôpital de la Tronche, Grenoble, France
from Jules: we need to wait for the IL28B subanalyses from the telaprevir ADVANCE & boceprevir SPRINT2 studies in order to see how to use this information. Using double dose Pegasys in this study appeared to on average increase the virologic response quite a lot by weeks 4, 8 and 12 compared to prior use of the standard Pegasys dose for both TT and CT genotypes. CT genotype achieved better virologic response than TT genotype in this study, by week 24: 44% of TT and 70% of CT achieved >2 log viral load reduction. These data suggest that double-dose Pegasys 360 ug/week in combination with telaprevir or boceprevir may significantly increase virologic response and SVR. Conceivably, double-dose Pegasys during a lead-in and during therapy with telaprevir or boceprevir could increase SVR rates potentially quite a lot based on these data. There is a suggestion that an HCV protease resenesitizes the patient's internal interferon response so let's see how the TTs and CTs respond in the subanalyses from Advance & Sprint.
ABSTRACT:
Polymorphisms upstream of the region encoding IL28B have been shown to be associated with both natural and treatment-induced control of HCV infection. With new therapies using direct acting antiviral molecules, a null response to IFN is associated with treatment failure and selection of resistant viruses. Our goal was to assess, in null-responders to IFN-ribavirin therapy, whether the IL28B genotype has an influence and predictive value on the ability of high-dose pegylated IFN and ribavirin retreatment to induce a virological response.
METHODS:
83 genotype 1 null-responders received peg-IFN alpha-2a, 360 µg/week in one or two injections, plus ribavirin, 1000-1200 or 1200-1600 mg/d. Genotyping of the IL28B SNP rs12979860 was performed from host cell DNA by means of a real-time PCR method using minor groove binding probes. RESULTS: The IL28B genotype was determined in all 83 patients: 3 (3.6%) had a CC genotype and were removed to allow comparison between CT (n=55) and TT (n=25) patients. The difference between reductions in HCV RNA levels between TT and CT patients was significant at week 2 (<0.5 vs ≥0.5 Log, p=0.02), at week 4 (<1 vs ≥1 Log, p=0.008), and at weeks 12 and 24 (<2 vs ≥2 Log p=0.02). When comparing CT and TT patients, the odds ratio were 3.09 for a more than 0.5 Log drop at week 2; 3.86 for a more than 1 Log drop at week 4; 3.08 for a more than 2 Log drop at week 12; 3.10 for a more than 2 Log drop at week 24; and 3.57 for an undetectable HCV RNA at week 24.
CONCLUSIONS:
Most patients who fail to respond to pegylated IFN and ribavirin carry either TT or CT rs12979860 genotypes. CT patients are significantly more likely to respond to higher doses of IFN and the difference is significant at week 2. This indicates that the IL28B genotype is a marker of host cell responsiveness to IFN. These findings will have major implications in the treatment of HCV infection with higher peg-IFN doses in combination with ribavirin and direct acting antivirals.
Continue Reading ...
Doctors Claim HIV-Positive Man Cured by Stem Cell Transplant
Published December 14, 2010
FoxNews.com
There’s an estimated 33 million people worldwide living with HIV/AIDS, and now doctors believe one of them may have been cured of the virus after receiving a stem cell transplant in 2007, the medical journal Blood reported.
Timothy Ray Brown, an HIV-positive American living in Germany, had leukemia and was undergoing chemotherapy, when he received a transplant of stem cells from a donor carrying a rare, inherited gene mutation that seems to make carriers virtually immune to HIV infection.
The transplant appeared to wipe out both diseases, giving hope to doctors, but Dr. Anthony Fauci, director of the National Institutes of Allergy and Infectious Diseases, who has been studying HIV/AIDS for almost 30 years, said while this is an interesting proof of concept, it’s absurdly impractical.
“It’s hard enough to get a good compatible match for a transplant like this,” Fauci told FoxNews.com, “But you also have to find compatible donor that has this genetic defect, and this defect is only found in 1 percent of the Caucasian population and zero percent of the black population. This is very rare.”
Fauci said while this patient is “functionally cured” this is not something you can do with every HIV-infected individual.
“This is not prime time to me at all,” he said. “This is a very unusual situation that has little practical application for a simple reason. This donor not only had to be a good compatible match, but the donor had to have a genetic defect of cells that do not express the receptor that the HIV virus needs to enter the cell.”
Fauci also pointed to the fact that this transplant process is not only expensive, it’s incredibly painful and complicated, and requires the patient to start a whole new regimen of drugs.
“This patient is trading one poison for another. He may not have to be on antiretroviral drugs anymore, but he has to take immunosuppressant drugs now to prevent the rejection of his transplant cells. Again, what this is, is an interesting proof of concept, but it’s absolutely impractical.”
Dr. Thomas Quinn, director of Johns Hopkins Center for Global Health told FoxNews.com that he is very familiar with the “Berlin patient” case.
“This was a new report that looked much deeper into whether HIV could still be present or lurking in the body in some way, not cured, and since the transplant he remains viral free and his cells appear to be resistant to infection,” he said.
Quinn said he agrees with the researchers on this case that it would be qualified as the first HIV cure, opening the door to alternative means of curing HIV.
“He [Brown] has been without therapy for three years and appears to be free of the virus,” he said. “It gives hope to the millions of people infected with HIV that cure is a feasible option in the future.”
Even though Brown’s procedure proved to be successful, Quinn also warns that this was a rare case and a bone marrow transplant is not a cure-all for other HIV patients.
“It is a near fatal procedure that he had to have done because of the leukemia, but this procedure is very expensive and you have to be transplanted with a donor who is shown to be already resistant to HIV,” Quinn said. “You’re asking for a tall order to replicate this in the future.”
Brown’s case was published in a February 2009 issue of the New England Journal of Medicine.
Click here to read more from the journal Blood (subscription is required).
Source
FoxNews.com
There’s an estimated 33 million people worldwide living with HIV/AIDS, and now doctors believe one of them may have been cured of the virus after receiving a stem cell transplant in 2007, the medical journal Blood reported.
Timothy Ray Brown, an HIV-positive American living in Germany, had leukemia and was undergoing chemotherapy, when he received a transplant of stem cells from a donor carrying a rare, inherited gene mutation that seems to make carriers virtually immune to HIV infection.
The transplant appeared to wipe out both diseases, giving hope to doctors, but Dr. Anthony Fauci, director of the National Institutes of Allergy and Infectious Diseases, who has been studying HIV/AIDS for almost 30 years, said while this is an interesting proof of concept, it’s absurdly impractical.
“It’s hard enough to get a good compatible match for a transplant like this,” Fauci told FoxNews.com, “But you also have to find compatible donor that has this genetic defect, and this defect is only found in 1 percent of the Caucasian population and zero percent of the black population. This is very rare.”
Fauci said while this patient is “functionally cured” this is not something you can do with every HIV-infected individual.
“This is not prime time to me at all,” he said. “This is a very unusual situation that has little practical application for a simple reason. This donor not only had to be a good compatible match, but the donor had to have a genetic defect of cells that do not express the receptor that the HIV virus needs to enter the cell.”
Fauci also pointed to the fact that this transplant process is not only expensive, it’s incredibly painful and complicated, and requires the patient to start a whole new regimen of drugs.
“This patient is trading one poison for another. He may not have to be on antiretroviral drugs anymore, but he has to take immunosuppressant drugs now to prevent the rejection of his transplant cells. Again, what this is, is an interesting proof of concept, but it’s absolutely impractical.”
Dr. Thomas Quinn, director of Johns Hopkins Center for Global Health told FoxNews.com that he is very familiar with the “Berlin patient” case.
“This was a new report that looked much deeper into whether HIV could still be present or lurking in the body in some way, not cured, and since the transplant he remains viral free and his cells appear to be resistant to infection,” he said.
Quinn said he agrees with the researchers on this case that it would be qualified as the first HIV cure, opening the door to alternative means of curing HIV.
“He [Brown] has been without therapy for three years and appears to be free of the virus,” he said. “It gives hope to the millions of people infected with HIV that cure is a feasible option in the future.”
Even though Brown’s procedure proved to be successful, Quinn also warns that this was a rare case and a bone marrow transplant is not a cure-all for other HIV patients.
“It is a near fatal procedure that he had to have done because of the leukemia, but this procedure is very expensive and you have to be transplanted with a donor who is shown to be already resistant to HIV,” Quinn said. “You’re asking for a tall order to replicate this in the future.”
Brown’s case was published in a February 2009 issue of the New England Journal of Medicine.
Click here to read more from the journal Blood (subscription is required).
Source
Hepatitis Experts Create Roadmap for Accelerating the Development of Targeted Therapies for Hepatitis C Virus
WASHINGTON, Dec. 14, 2010 /PRNewswire-USNewswire/ -- To improve the care for individuals infected with the hepatitis C virus, a major health problem and a leading cause of chronic liver disease around the world, nearly 200 international hepatitis experts have taken an important step in escalating the introduction of a new class of targeted therapies for HCV – direct-acting antivirals (DAAs).
December 6 at a major scientific meeting – Advancing HCV Drug Development: A Collaborative Approach – convened by the Forum for Collaborative HIV Research, researchers, hepatitis advocates, members of industry and representatives from the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) created the roadmap for accelerating the development of DAAs, agreeing that this new class of drugs targeting specific hepatitis C virus proteins has the same potential to improve treatment outcomes for people with HCV as antiretroviral drugs changed the standard of care in HIV. Currently, two DAA compounds have advanced into phase 3 development in the United State and EU, and many more are in phase 2 trials and likely to advance to phase 3 research in the near future.
"If there was ever a time when we can change the course of HCV, it is now," said Veronica Miller, Ph.D., Director of the Forum. "We are now where we were with HIV more than a decade ago and can apply many of the lessons learned from HIV drug development to significantly accelerate the progress in bringing new and better HCV therapies to market."
DAAs directly attack the ability of the hepatitis C virus to replicate and can increase the cure rate in certain HCV patients to between 60 and 70 percent– a major advance over the 40 percent success rate associated with the currently recommended treatment for chronic HCV infection, the combination of pegylated interferon and ribavirin. Although the first DAAs still require concomitant use with current HCV medications, these new compounds will shorten the length of time on pegylated interferon and ribavirin therapy, which hepatitis specialists noted is often difficult to tolerate and has significant adverse event profiles that limit treatment in many patients. According to the latest data, between 15 and 30 percent of HCV patients started on current HCV therapy are unable to complete the year of treatment now required because they cannot tolerate the side effects.
Charting the future of HCV drug development, the meeting participants applied FDA's new guidance on conducting clinical trials on DAAs, which was issued in September 2010 in draft form and expected to be finalized in 2011. According to Jeffrey S. Murray, M.D., M.P.H., Deputy Director of the Division of Antiviral Drug Products in FDA's Center for Drug Evaluation and Research, the draft guidance follows the same approach FDA uses in developing HIV and oncology drugs. For early clinical testing, FDA recognizes that most if not all DAAs for HCV will be used in combination with other approved drug and therefore, recommends studies examining the relationship between the new DAA agent and both pegylated interferon and ribavirin as well as testing the combination antiviral activity. FDA's draft guidance also calls for using the results from proof-in-concept trials (meaning a study in HCV infected patients that demonstrates initial activity as measured by reductions in the HCV viral load) to guide dose selection for subsequent Phase 2 trials in which DAAs are studied for longer durations as part of a combination regimen. FDA is further encouraging drug sponsors to design development plans for combinations of two or more DAAs.
"The good news for the HCV community is that more drugs are coming," said Jur Strobos, MD, JD, FACEP, Deputy Director of the Forum. "The bad news is we don't know how to combine them and that is what we need to study."
With FDA's guidance as the framework, the hepatitis experts also identified the major factors researchers must take into account when designing clinical trials for DAAs and other new HCV therapies. Among the major issues cited are the emergence of resistant virus and its potential management, and including in future DAA clinical trials those special populations with significant unmet needs in HCV therapy. These patients include individuals co-infected with HIV, liver transplant recipients, patients with decompensated cirrhosis, opioid users and those on opiate substitution therapy, and children. According to the Centers for Disease Control and Prevention (CDC), between 5 and 6 percent of infants born to HCV infected women contract the infection from their mothers and the majority of those infants will develop a chronic infection.
Focusing on the special needs of pediatric patients, leaders from both FDA and EMA agreed that the time to start investigating DAAs in children is when sufficient safety data exist in adults. As explained by specialists in pediatric liver disease, children with HCV often tolerate drug therapy better than adults, which is why the ideal age to start children in pediatric trials for DAAs is when they are 3 years old. According to hepatitis experts, the beneficial impact of a 'cure' for children, preferably before they start school, cannot be overestimated.
Reducing Disparities in HCV Clinical Trials
Because identifying potential differences among groups treated with a therapeutic regimen is an important goal of human studies, the HCV community singled out the under-representation of women, older people and different ethnic subgroups in clinical trials as the problem requiring immediate attention and change at a systemic level. Although there is a higher prevalence of HCV in men than women, women metabolize HCV drugs differently and are more affected by autoimmune diseases, which share similar symptoms with HCV. Women also are twice as likely as men to suffer from depression, which is a common side effect of treatment with HCV medications.
Even more challenging for the HCV community is increasing the representation of older HCV-infected adults in HCV clinical trials, even though Baby Boomers constitute the majority of hepatitis C infections in the United States and are often less responsive than younger generations to antiviral treatment. Compounding the problem, older HCV patients are more difficult to treat, due to the increased prevalence of co-morbid conditions, such as diabetes, dyslipidemia, and other metabolic conditions that are correlated to chronic liver disease. Aging is also strongly associated with liver fibrosis progression, which means older HCV patients are likely to have advanced liver disease and a high risk for impending liver complications. But despite this reality, few studies have examined the age-specific factors of chronic HCV infection and the clinical management of the infection in this patient population.
More than an issue of fairness, HCV experts associate better designed clinical research studies with the increased ability of scientists to catalog and understand the influence of genetic and non-genetic factors on individual and group responses to new treatments. Findings from the large amount of genetic data generated to date show that more than 90 percent of the observed genetic variations occur within, rather than between groups. This underscores the fact that gender and ethnicity have biomedical consequences when evaluating patients with more resistant virus and with more severe disease.
Designing the Research Roadmap to Address a Growing Public Health Threat
Accelerating the development of DAAs to improve HCV treatment outcomes is especially warranted now that the hepatitis C virus has become the most common chronic blood borne infection in the U.S. According to new government estimates, approximately 4.1 million Americans are infected with HCV, of whom 60 to 70 percent will develop chronic liver disease. Currently, almost half of all liver transplants in the U.S. are performed for end-stage hepatitis C. Moreover, because liver disease is one of the leading causes of death in the U.S., the CDC predicts that deaths from chronic liver disease attributed to hepatitis C will double or triple over the next 15 to 20 years.
To change these statistics, hepatitis specialists focused on ways to advance HCV drug development so DAAs and other new classes of drugs for HCV can reach the market quickly. Here, the experts reached agreement on a number of issues:
• Exposure to new single agents – because HCV remains sensitive to ribavirin and pegylated interferon, longer initial studies may be recommended to evaluate single drugs and novel combinations of drugs
• Composition of patients in early studies (phase 1 and 2a) – early studies should be large enough so results with one type of virus or one group of patients can be easily discerned. Focusing on specific genetic sub-populations will also ensure that early studies do not produce confusing results
• Drug resistance in HCV patients – unlike HIV, drug resistance in HCV may not be as large a concern because HCV does not integrate into host DNA as HIV does. Thus, resistant strains are not archived and there is the potential that resistant patients can be retreated with different combinations regimens, as and when they become available
• Baseline parameters – there is the need to develop predictive algorithms based on baseline characteristics such as gender, body weight, HCV genotypes and subtypes
• Exclusion of former and current drug users in clinical trials – exclusion is unnecessary and does not serve the field well. Over 60 percent of patients with HCV are infected through drug use, indicating the need to have quality data to guide treatment decisions in this patient population
As a next step, the Forum for Collaborative HIV Research will publish the consensus of this scientific meeting to advance the research agenda. Once published, the report will be distributed widely to the Forum's many constituencies – government, industry, patient advocates, healthcare providers, foundations, health insurers and academia – with the goal of advancing research on HCV and driving public policy.
About the Forum for Collaborative HIV Research
Now part of the University of California (UC), Berkeley School of Public Health and based in Washington, DC, the Forum was founded in 1997 as the outgrowth of a White House initiative which called for an ongoing collaboration among stakeholders to address emerging issues in HIV/AIDS and set the research strategy. Representing government, industry, patient advocates, healthcare providers, foundations and academia, the Forum is a public/private partnership that is guided by an Executive Committee that sets the research agenda. The Forum organizes roundtables and issues reports on a range of global HIV/AIDS issues, including treatment-related toxicities, immune-based therapies, health services research, co-infections, prevention, and the transference of research results into care. Forum recommendations have changed how clinical trials are conducted, accelerated the delivery of new classes of drugs, heightened awareness of TB/HIV co-infection, and helped to spur national momentum toward universal testing for HIV. http://www.hivforum.org/
SOURCE Forum for Collaborative HIV Research
Source
December 6 at a major scientific meeting – Advancing HCV Drug Development: A Collaborative Approach – convened by the Forum for Collaborative HIV Research, researchers, hepatitis advocates, members of industry and representatives from the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) created the roadmap for accelerating the development of DAAs, agreeing that this new class of drugs targeting specific hepatitis C virus proteins has the same potential to improve treatment outcomes for people with HCV as antiretroviral drugs changed the standard of care in HIV. Currently, two DAA compounds have advanced into phase 3 development in the United State and EU, and many more are in phase 2 trials and likely to advance to phase 3 research in the near future.
"If there was ever a time when we can change the course of HCV, it is now," said Veronica Miller, Ph.D., Director of the Forum. "We are now where we were with HIV more than a decade ago and can apply many of the lessons learned from HIV drug development to significantly accelerate the progress in bringing new and better HCV therapies to market."
DAAs directly attack the ability of the hepatitis C virus to replicate and can increase the cure rate in certain HCV patients to between 60 and 70 percent– a major advance over the 40 percent success rate associated with the currently recommended treatment for chronic HCV infection, the combination of pegylated interferon and ribavirin. Although the first DAAs still require concomitant use with current HCV medications, these new compounds will shorten the length of time on pegylated interferon and ribavirin therapy, which hepatitis specialists noted is often difficult to tolerate and has significant adverse event profiles that limit treatment in many patients. According to the latest data, between 15 and 30 percent of HCV patients started on current HCV therapy are unable to complete the year of treatment now required because they cannot tolerate the side effects.
Charting the future of HCV drug development, the meeting participants applied FDA's new guidance on conducting clinical trials on DAAs, which was issued in September 2010 in draft form and expected to be finalized in 2011. According to Jeffrey S. Murray, M.D., M.P.H., Deputy Director of the Division of Antiviral Drug Products in FDA's Center for Drug Evaluation and Research, the draft guidance follows the same approach FDA uses in developing HIV and oncology drugs. For early clinical testing, FDA recognizes that most if not all DAAs for HCV will be used in combination with other approved drug and therefore, recommends studies examining the relationship between the new DAA agent and both pegylated interferon and ribavirin as well as testing the combination antiviral activity. FDA's draft guidance also calls for using the results from proof-in-concept trials (meaning a study in HCV infected patients that demonstrates initial activity as measured by reductions in the HCV viral load) to guide dose selection for subsequent Phase 2 trials in which DAAs are studied for longer durations as part of a combination regimen. FDA is further encouraging drug sponsors to design development plans for combinations of two or more DAAs.
"The good news for the HCV community is that more drugs are coming," said Jur Strobos, MD, JD, FACEP, Deputy Director of the Forum. "The bad news is we don't know how to combine them and that is what we need to study."
With FDA's guidance as the framework, the hepatitis experts also identified the major factors researchers must take into account when designing clinical trials for DAAs and other new HCV therapies. Among the major issues cited are the emergence of resistant virus and its potential management, and including in future DAA clinical trials those special populations with significant unmet needs in HCV therapy. These patients include individuals co-infected with HIV, liver transplant recipients, patients with decompensated cirrhosis, opioid users and those on opiate substitution therapy, and children. According to the Centers for Disease Control and Prevention (CDC), between 5 and 6 percent of infants born to HCV infected women contract the infection from their mothers and the majority of those infants will develop a chronic infection.
Focusing on the special needs of pediatric patients, leaders from both FDA and EMA agreed that the time to start investigating DAAs in children is when sufficient safety data exist in adults. As explained by specialists in pediatric liver disease, children with HCV often tolerate drug therapy better than adults, which is why the ideal age to start children in pediatric trials for DAAs is when they are 3 years old. According to hepatitis experts, the beneficial impact of a 'cure' for children, preferably before they start school, cannot be overestimated.
Reducing Disparities in HCV Clinical Trials
Because identifying potential differences among groups treated with a therapeutic regimen is an important goal of human studies, the HCV community singled out the under-representation of women, older people and different ethnic subgroups in clinical trials as the problem requiring immediate attention and change at a systemic level. Although there is a higher prevalence of HCV in men than women, women metabolize HCV drugs differently and are more affected by autoimmune diseases, which share similar symptoms with HCV. Women also are twice as likely as men to suffer from depression, which is a common side effect of treatment with HCV medications.
Even more challenging for the HCV community is increasing the representation of older HCV-infected adults in HCV clinical trials, even though Baby Boomers constitute the majority of hepatitis C infections in the United States and are often less responsive than younger generations to antiviral treatment. Compounding the problem, older HCV patients are more difficult to treat, due to the increased prevalence of co-morbid conditions, such as diabetes, dyslipidemia, and other metabolic conditions that are correlated to chronic liver disease. Aging is also strongly associated with liver fibrosis progression, which means older HCV patients are likely to have advanced liver disease and a high risk for impending liver complications. But despite this reality, few studies have examined the age-specific factors of chronic HCV infection and the clinical management of the infection in this patient population.
More than an issue of fairness, HCV experts associate better designed clinical research studies with the increased ability of scientists to catalog and understand the influence of genetic and non-genetic factors on individual and group responses to new treatments. Findings from the large amount of genetic data generated to date show that more than 90 percent of the observed genetic variations occur within, rather than between groups. This underscores the fact that gender and ethnicity have biomedical consequences when evaluating patients with more resistant virus and with more severe disease.
Designing the Research Roadmap to Address a Growing Public Health Threat
Accelerating the development of DAAs to improve HCV treatment outcomes is especially warranted now that the hepatitis C virus has become the most common chronic blood borne infection in the U.S. According to new government estimates, approximately 4.1 million Americans are infected with HCV, of whom 60 to 70 percent will develop chronic liver disease. Currently, almost half of all liver transplants in the U.S. are performed for end-stage hepatitis C. Moreover, because liver disease is one of the leading causes of death in the U.S., the CDC predicts that deaths from chronic liver disease attributed to hepatitis C will double or triple over the next 15 to 20 years.
To change these statistics, hepatitis specialists focused on ways to advance HCV drug development so DAAs and other new classes of drugs for HCV can reach the market quickly. Here, the experts reached agreement on a number of issues:
• Exposure to new single agents – because HCV remains sensitive to ribavirin and pegylated interferon, longer initial studies may be recommended to evaluate single drugs and novel combinations of drugs
• Composition of patients in early studies (phase 1 and 2a) – early studies should be large enough so results with one type of virus or one group of patients can be easily discerned. Focusing on specific genetic sub-populations will also ensure that early studies do not produce confusing results
• Drug resistance in HCV patients – unlike HIV, drug resistance in HCV may not be as large a concern because HCV does not integrate into host DNA as HIV does. Thus, resistant strains are not archived and there is the potential that resistant patients can be retreated with different combinations regimens, as and when they become available
• Baseline parameters – there is the need to develop predictive algorithms based on baseline characteristics such as gender, body weight, HCV genotypes and subtypes
• Exclusion of former and current drug users in clinical trials – exclusion is unnecessary and does not serve the field well. Over 60 percent of patients with HCV are infected through drug use, indicating the need to have quality data to guide treatment decisions in this patient population
As a next step, the Forum for Collaborative HIV Research will publish the consensus of this scientific meeting to advance the research agenda. Once published, the report will be distributed widely to the Forum's many constituencies – government, industry, patient advocates, healthcare providers, foundations, health insurers and academia – with the goal of advancing research on HCV and driving public policy.
About the Forum for Collaborative HIV Research
Now part of the University of California (UC), Berkeley School of Public Health and based in Washington, DC, the Forum was founded in 1997 as the outgrowth of a White House initiative which called for an ongoing collaboration among stakeholders to address emerging issues in HIV/AIDS and set the research strategy. Representing government, industry, patient advocates, healthcare providers, foundations and academia, the Forum is a public/private partnership that is guided by an Executive Committee that sets the research agenda. The Forum organizes roundtables and issues reports on a range of global HIV/AIDS issues, including treatment-related toxicities, immune-based therapies, health services research, co-infections, prevention, and the transference of research results into care. Forum recommendations have changed how clinical trials are conducted, accelerated the delivery of new classes of drugs, heightened awareness of TB/HIV co-infection, and helped to spur national momentum toward universal testing for HIV. http://www.hivforum.org/
SOURCE Forum for Collaborative HIV Research
Source
Tips for the Media on How to Stop Screwing Up HIV/AIDS Coverage
Kellee Terrell
News Editor, TheBody.com
Posted: December 14, 2010 11:56 AM
This year, we saw a number of medical breakthroughs that made headlines: The discovery of two rare human antibodies that kill 90 percent of all HIV strains, which could provide the basis for a vaccine. The first-ever successful clinical trial of a microbicide, which could bring us one step closer to women being able to have more control over their sexual health. And the finding that pre-exposure prophylaxis can reduce HIV infections among gay men.
This year also brought major events that got heavy news coverage: The XVIII International AIDS Conference in Vienna. The first-ever national HIV/AIDS strategy for the U.S. The return of U.S. AIDS Drug Assistance Program (ADAP) waiting lists, which had been empty, but are now full again. A harsh reminder that you can be imprisoned and potentially executed for being gay in certain countries. And a confirmation that poverty is the top risk factor for HIV among heterosexuals living in inner cities.
On the pop culture end, HIV was also present. Part of the porn industry temporarily shut down when adult film actor Derrick Burts tested positive. Project Runway's Mondo Guerra disclosed his status on air. The Other City, a documentary about HIV/AIDS in Washington, D.C., debuted to rave reviews. And on World AIDS Day, celebrities "died" on social media, only to have some billionaire "resuscitate" them when it looked as if they might not be able to raise enough money to do so through smaller donations.
But even in the wake of all of this, the media still doesn't report enough about the global pandemic and, most importantly, there are not enough stories exploring the U.S. epidemic. (Newsflash: AIDS is still a huge problem here in the U.S.) And when the media does tackle AIDS in America, too many times it borrows from FOX News' playbook of sensationalism, fabrications and one-sided narratives.
Just how many down low and criminalization stories can a person take?
And this is where I come in. I looked over 2010's media coverage of HIV/AIDS and came up with some important lessons that journalists should keep in mind for next year:
Include More Voices of People Living With HIV: This is a "no duh" if we want to eliminate stigma. But minus the media frenzy around Project Runway's Mondo Guerra disclosing his HIV status on air, mainstream media almost never showcases the real voices of people living with HIV.
Wouldn't it be awesome if -- on a day other than World AIDS Day -- we could hear people living with HIV talk about love and marriage; stigma and discrimination; pregnancy and family; treatment and adhering to drugs; the trials and tribulations of being on an ADAP waiting list; disclosing to others; and all that other good stuff? Perhaps "reality" only works for the Kardashians.
Bigwigs Are Not the Only People You Should Pay Attention To: Did you know that, this summer at the XVIII International AIDS Conference in Vienna, sex workers from around the world had a major presence (including a huge rally)? Or that the same was true of drug users, who had an international declaration on their behalf signed by more than 18,000 people? Did you know that UNIFEM and the ATHENA Network released a comprehensive report that highlighted the lack of female leadership in HIV policymaking despite the fact that the global face of AIDS is more female than male?
Of course you did. But the rest of the world probably did not: All of those stories were overlooked, because journalists were more interested in writing about Bill Gates, Annie Lennox and other high-power players who were present at the conference. Please don't forget about the grassroots work that is being done to better the lives of people living with HIV. You might be missing out on a good story.
Teens and Seniors Have Sex Too: If it wasn't for the reality shows 16 and Pregnant and Sunset Daze, or the occasional sensationalized stories about "retirement homes gone wild" or "teen sex parties," one would think that these two groups never had sex. Oh, but they do -- and the media (along with most of society) needs to get over its hang-ups and begin exploring the alarming and rising rates of HIV and other sexually transmitted diseases among these demographics. This means fewer interviews with Bristol Palin and company, and more interviews with women such as Marvelyn Brown and Jane Fowler.
The Fight for LGBT Equality Is Connected to HIV Risk: While the media continues to improve its reporting on LGBT issues -- especially around bullying, homophobia, DADT (the U.S. military's "Don't Ask, Don't Tell" law), marriage equality and job discrimination -- more needs to be done to illustrate how these issues directly impact one's own HIV risk.
It may come as a surprise to some that there are still many cases (and many states) in which it is legal to fire someone based on their sexual orientation and gender identity and expression in the U.S. And if people can be fired from their job, that means they can lose their financial stability. They become less able to look after their health care, and in some cases may even become homeless. A slew of reasons begin to emerge that can make those individuals more vulnerable to HIV.
(Hint, hint: National LGBT organizations, perhaps now is the time to make HIV/AIDS a platform issue. If you do, the media might follow.)
Try Normalizing HIV; It's Not That Hard: HIV has always been the "cheese that stands alone" -- it's even classified separately from other sexually transmitted diseases. One way to help destigmatize the disease is to include a discussion about HIV into stories in which HIV is simply a fact to be noted, not the focus of the entire piece. For example, in a feature about people struggling to pay for their health care or the difficulties of adhering to daily medications, why not include a person living with HIV as one of the interviewees? Or in a story about Mother's Day, or Valentine's Day, or Veteran's Day, why not include the perspective of an HIV-positive person? HIV doesn't always have to exist outside the box.
Read the rest of the lessons here.
Want to learn more about the major HIV/AIDS developments, trends and advocates who rocked 2010? Take a look at TheBody.com's new series, HIV/AIDS Year in Review: Looking Back on 2010 (and Ahead to 2011).
Source
News Editor, TheBody.com
Posted: December 14, 2010 11:56 AM
This year, we saw a number of medical breakthroughs that made headlines: The discovery of two rare human antibodies that kill 90 percent of all HIV strains, which could provide the basis for a vaccine. The first-ever successful clinical trial of a microbicide, which could bring us one step closer to women being able to have more control over their sexual health. And the finding that pre-exposure prophylaxis can reduce HIV infections among gay men.
This year also brought major events that got heavy news coverage: The XVIII International AIDS Conference in Vienna. The first-ever national HIV/AIDS strategy for the U.S. The return of U.S. AIDS Drug Assistance Program (ADAP) waiting lists, which had been empty, but are now full again. A harsh reminder that you can be imprisoned and potentially executed for being gay in certain countries. And a confirmation that poverty is the top risk factor for HIV among heterosexuals living in inner cities.
On the pop culture end, HIV was also present. Part of the porn industry temporarily shut down when adult film actor Derrick Burts tested positive. Project Runway's Mondo Guerra disclosed his status on air. The Other City, a documentary about HIV/AIDS in Washington, D.C., debuted to rave reviews. And on World AIDS Day, celebrities "died" on social media, only to have some billionaire "resuscitate" them when it looked as if they might not be able to raise enough money to do so through smaller donations.
But even in the wake of all of this, the media still doesn't report enough about the global pandemic and, most importantly, there are not enough stories exploring the U.S. epidemic. (Newsflash: AIDS is still a huge problem here in the U.S.) And when the media does tackle AIDS in America, too many times it borrows from FOX News' playbook of sensationalism, fabrications and one-sided narratives.
Just how many down low and criminalization stories can a person take?
And this is where I come in. I looked over 2010's media coverage of HIV/AIDS and came up with some important lessons that journalists should keep in mind for next year:
Include More Voices of People Living With HIV: This is a "no duh" if we want to eliminate stigma. But minus the media frenzy around Project Runway's Mondo Guerra disclosing his HIV status on air, mainstream media almost never showcases the real voices of people living with HIV.
Wouldn't it be awesome if -- on a day other than World AIDS Day -- we could hear people living with HIV talk about love and marriage; stigma and discrimination; pregnancy and family; treatment and adhering to drugs; the trials and tribulations of being on an ADAP waiting list; disclosing to others; and all that other good stuff? Perhaps "reality" only works for the Kardashians.
Bigwigs Are Not the Only People You Should Pay Attention To: Did you know that, this summer at the XVIII International AIDS Conference in Vienna, sex workers from around the world had a major presence (including a huge rally)? Or that the same was true of drug users, who had an international declaration on their behalf signed by more than 18,000 people? Did you know that UNIFEM and the ATHENA Network released a comprehensive report that highlighted the lack of female leadership in HIV policymaking despite the fact that the global face of AIDS is more female than male?
Of course you did. But the rest of the world probably did not: All of those stories were overlooked, because journalists were more interested in writing about Bill Gates, Annie Lennox and other high-power players who were present at the conference. Please don't forget about the grassroots work that is being done to better the lives of people living with HIV. You might be missing out on a good story.
Teens and Seniors Have Sex Too: If it wasn't for the reality shows 16 and Pregnant and Sunset Daze, or the occasional sensationalized stories about "retirement homes gone wild" or "teen sex parties," one would think that these two groups never had sex. Oh, but they do -- and the media (along with most of society) needs to get over its hang-ups and begin exploring the alarming and rising rates of HIV and other sexually transmitted diseases among these demographics. This means fewer interviews with Bristol Palin and company, and more interviews with women such as Marvelyn Brown and Jane Fowler.
The Fight for LGBT Equality Is Connected to HIV Risk: While the media continues to improve its reporting on LGBT issues -- especially around bullying, homophobia, DADT (the U.S. military's "Don't Ask, Don't Tell" law), marriage equality and job discrimination -- more needs to be done to illustrate how these issues directly impact one's own HIV risk.
It may come as a surprise to some that there are still many cases (and many states) in which it is legal to fire someone based on their sexual orientation and gender identity and expression in the U.S. And if people can be fired from their job, that means they can lose their financial stability. They become less able to look after their health care, and in some cases may even become homeless. A slew of reasons begin to emerge that can make those individuals more vulnerable to HIV.
(Hint, hint: National LGBT organizations, perhaps now is the time to make HIV/AIDS a platform issue. If you do, the media might follow.)
Try Normalizing HIV; It's Not That Hard: HIV has always been the "cheese that stands alone" -- it's even classified separately from other sexually transmitted diseases. One way to help destigmatize the disease is to include a discussion about HIV into stories in which HIV is simply a fact to be noted, not the focus of the entire piece. For example, in a feature about people struggling to pay for their health care or the difficulties of adhering to daily medications, why not include a person living with HIV as one of the interviewees? Or in a story about Mother's Day, or Valentine's Day, or Veteran's Day, why not include the perspective of an HIV-positive person? HIV doesn't always have to exist outside the box.
Read the rest of the lessons here.
Want to learn more about the major HIV/AIDS developments, trends and advocates who rocked 2010? Take a look at TheBody.com's new series, HIV/AIDS Year in Review: Looking Back on 2010 (and Ahead to 2011).
Source
Amarillo Biosciences Announces Completion of Patient Enrollment in Phase 2 Hepatitis C Trial
Dec 14, 2010 11:08 ET\
AMARILLO, TX--(Marketwire - December 14, 2010) - Amarillo Biosciences, Inc. (ABI) (OTCBB: AMAR) today announced that enrollment in a Phase 2 clinical trial of 165 patients with chronic hepatitis C virus infection is now complete. The clinical trial is being conducted in Taiwan and funded by ABI's strategic partner, CytoPharm, Inc. The aim of the study is to reduce the virologic relapse rate for those patients who have successfully completed standard combination therapy for hepatitis C, which consists of injectable interferon alpha and Ribavirin.
Many patients with hepatitis C are found to be virus-free at the end of standard therapy, but up to half of those with certain viral genotypes relapse in the six months following treatment, once again becoming positive for hepatitis C virus. There are currently no FDA-approved medications shown to reduce the relapse rate for hepatitis C patients, so there is a clear medical need for effective new therapies.
All patients enrolled in this trial first completed standard therapy and were found to be negative for hepatitis C virus. The patients were then assigned to one of two different daily doses of ABI's human interferon alpha lozenges or placebo for 24 weeks, followed by untreated observation for 24 weeks to check for relapse. All patients are scheduled to complete the untreated observation phase by December 2011, and final results from this important study are expected to be available by the end of next year.
About Amarillo Biosciences
Amarillo Biosciences, Inc. is a U.S. biotechnology firm operating in global partnership with the Hayashibara Group, which also holds 5.4% of Amarillo Biosciences shares and has provided over $18 million in loans, grants and equity investments. The Company's primary focus is extensive and ongoing R&D into the use of low-dose, orally administered interferon as a treatment for a variety of conditions, including influenza, hepatitis C, chronic cough, and opportunistic infections in patients who are HIV positive. The Company has invested nearly $40 million to establish oral interferon as a therapeutic agent. The majority of those funds were invested in clinical trials in an effort to achieve FDA approval for interferon. Additional information is available on the web at http://www.amarbio.com/.
Except for the historical information contained herein, the matters discussed in this news release are forward-looking statements that involve risks and uncertainties, including uncertainties related to product development, uncertainties related to the need for regulatory and other government approvals, dependence on proprietary technology, uncertainty of market acceptance of oral interferon or the Company's other product candidates and other risks detailed from time to time in the Company's filings with the Securities and Exchange Commission. In particular, see "Item 1. Description of Business" and "Item 7A. Qualitative and Quantitative Disclosures About Market Risk" of the Company's Form 10-K for the fiscal year ended December 31, 2009.
Investor Relations:
Philippe Niemetz
PAN Consultants, Ltd.
e-mail: p.niemetz@panconsultants.com
Tel: 800-477-7570; 212-344-6464
Fax: 212-618-1276
Joseph M. Cummins, DVM, PhD
Amarillo Biosciences, Inc.
e-mail: jcummins@amarbio.com
Tel: 806-376-1741 x 13
Fax: 806-376-9301
Source
AMARILLO, TX--(Marketwire - December 14, 2010) - Amarillo Biosciences, Inc. (ABI) (OTCBB: AMAR) today announced that enrollment in a Phase 2 clinical trial of 165 patients with chronic hepatitis C virus infection is now complete. The clinical trial is being conducted in Taiwan and funded by ABI's strategic partner, CytoPharm, Inc. The aim of the study is to reduce the virologic relapse rate for those patients who have successfully completed standard combination therapy for hepatitis C, which consists of injectable interferon alpha and Ribavirin.
Many patients with hepatitis C are found to be virus-free at the end of standard therapy, but up to half of those with certain viral genotypes relapse in the six months following treatment, once again becoming positive for hepatitis C virus. There are currently no FDA-approved medications shown to reduce the relapse rate for hepatitis C patients, so there is a clear medical need for effective new therapies.
All patients enrolled in this trial first completed standard therapy and were found to be negative for hepatitis C virus. The patients were then assigned to one of two different daily doses of ABI's human interferon alpha lozenges or placebo for 24 weeks, followed by untreated observation for 24 weeks to check for relapse. All patients are scheduled to complete the untreated observation phase by December 2011, and final results from this important study are expected to be available by the end of next year.
About Amarillo Biosciences
Amarillo Biosciences, Inc. is a U.S. biotechnology firm operating in global partnership with the Hayashibara Group, which also holds 5.4% of Amarillo Biosciences shares and has provided over $18 million in loans, grants and equity investments. The Company's primary focus is extensive and ongoing R&D into the use of low-dose, orally administered interferon as a treatment for a variety of conditions, including influenza, hepatitis C, chronic cough, and opportunistic infections in patients who are HIV positive. The Company has invested nearly $40 million to establish oral interferon as a therapeutic agent. The majority of those funds were invested in clinical trials in an effort to achieve FDA approval for interferon. Additional information is available on the web at http://www.amarbio.com/.
Except for the historical information contained herein, the matters discussed in this news release are forward-looking statements that involve risks and uncertainties, including uncertainties related to product development, uncertainties related to the need for regulatory and other government approvals, dependence on proprietary technology, uncertainty of market acceptance of oral interferon or the Company's other product candidates and other risks detailed from time to time in the Company's filings with the Securities and Exchange Commission. In particular, see "Item 1. Description of Business" and "Item 7A. Qualitative and Quantitative Disclosures About Market Risk" of the Company's Form 10-K for the fiscal year ended December 31, 2009.
Investor Relations:
Philippe Niemetz
PAN Consultants, Ltd.
e-mail: p.niemetz@panconsultants.com
Tel: 800-477-7570; 212-344-6464
Fax: 212-618-1276
Joseph M. Cummins, DVM, PhD
Amarillo Biosciences, Inc.
e-mail: jcummins@amarbio.com
Tel: 806-376-1741 x 13
Fax: 806-376-9301
Source
December 13, 2010
Coffee Slows Progression of Hep C Liver Disease
December 13, 2010
People living with chronic hepatitis C virus (HCV) infection and advanced liver disease who drink three or more cups of coffee per day have a 53 percent lower risk of liver disease progression than non-coffee drinkers, according to a new study published in the November issue of Hepatology. According to the paper, authored by Neal Freedman, PhD, MPH, of the National Cancer Institute and his colleagues, patients with hepatitis C–related bridging fibrosis or cirrhosis who did not respond to standard treatment benefited from increased coffee intake.
This study included 766 participants enrolled in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial who had hepatitis C–related bridging fibrosis or cirrhosis and failed to respond to standard treatment with pegylated interferon and ribavirin. Upon entering the study, HALT-C volunteers were asked to report their typical frequency of coffee intake and portion size over the past year. A similar question was asked for black and green tea intake.
Participants were seen every three months during the 3.8–year study period to assess clinical outcomes that included: ascites (abnormal accumulation of fluid in the abdomen), prognosis of chronic liver disease, death related to liver disease, hepatic encephalopathy (brain and nervous system damage), hepatocellular carcinoma (liver cancer), spontaneous bacterial peritonitis, variceal hemorrhage and/or increase in fibrosis. Liver biopsies were also taken at 1.5 and 3.5 years to determine the progression of liver disease.
Results showed that participants who drank three or more cups of coffee per day had a relative risk (RR) of 0.47 for reaching one of the clinical outcomes. An RR above 1.00 suggests an increase in the risk of disease progression, whereas an RR below 1.00 suggests a decrease in the risk of disease progression.
Researchers did not observe any association between tea intake and liver disease progression, though tea consumption was low in the study.
“Given the large number of people affected by HCV, it is important to identify modifiable risk factors associated with the progression of liver disease,” Freedman said. “Although we cannot rule out a possible role for other factors that go along with drinking coffee, results from our study suggest that patients with high coffee intake had a lower risk of disease progression.”
Results from this study should not be generalized to healthier populations, the authors cautioned.
Source
Also See:
AASLD: Coffee is associated with virologic response in chronic Hepatitis C: Findings from the Hepatitis C Long - Term Treatment against Cirrhosis Trial (HALT - C)
People living with chronic hepatitis C virus (HCV) infection and advanced liver disease who drink three or more cups of coffee per day have a 53 percent lower risk of liver disease progression than non-coffee drinkers, according to a new study published in the November issue of Hepatology. According to the paper, authored by Neal Freedman, PhD, MPH, of the National Cancer Institute and his colleagues, patients with hepatitis C–related bridging fibrosis or cirrhosis who did not respond to standard treatment benefited from increased coffee intake.
This study included 766 participants enrolled in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial who had hepatitis C–related bridging fibrosis or cirrhosis and failed to respond to standard treatment with pegylated interferon and ribavirin. Upon entering the study, HALT-C volunteers were asked to report their typical frequency of coffee intake and portion size over the past year. A similar question was asked for black and green tea intake.
Participants were seen every three months during the 3.8–year study period to assess clinical outcomes that included: ascites (abnormal accumulation of fluid in the abdomen), prognosis of chronic liver disease, death related to liver disease, hepatic encephalopathy (brain and nervous system damage), hepatocellular carcinoma (liver cancer), spontaneous bacterial peritonitis, variceal hemorrhage and/or increase in fibrosis. Liver biopsies were also taken at 1.5 and 3.5 years to determine the progression of liver disease.
Results showed that participants who drank three or more cups of coffee per day had a relative risk (RR) of 0.47 for reaching one of the clinical outcomes. An RR above 1.00 suggests an increase in the risk of disease progression, whereas an RR below 1.00 suggests a decrease in the risk of disease progression.
Researchers did not observe any association between tea intake and liver disease progression, though tea consumption was low in the study.
“Given the large number of people affected by HCV, it is important to identify modifiable risk factors associated with the progression of liver disease,” Freedman said. “Although we cannot rule out a possible role for other factors that go along with drinking coffee, results from our study suggest that patients with high coffee intake had a lower risk of disease progression.”
Results from this study should not be generalized to healthier populations, the authors cautioned.
Source
Also See:
AASLD: Coffee is associated with virologic response in chronic Hepatitis C: Findings from the Hepatitis C Long - Term Treatment against Cirrhosis Trial (HALT - C)
WATCH: Jewish boy saves Christmas for kids impacted by HIV/AIDS in Fort Worth
Posted on 13 Dec 2010 at 4:16pm
This story must be the antithesis to First Baptist Church of Dallas’ “Grinch alert” website .
Carter Haber, a 12-year-old Jewish boy from Aledo, saved Christmas for more than 50 children whose families are clients of Samaritan House, which provides housing for low-income people with HIV/AIDS in Tarrant County.
Carter raised $5,000 for the gifts as a service project for his bar mitzvah after the Samaritan House lost a corporate sponsor, according to CBS 11:
And the fact a Jewish rite of passage provides Christmas to children? “I don’t think it matters,” Haber said. “A good deed is a good deed any day, any time, anywhere.”
Now Carter wants to continue raising money to help Samaritan House clients pay their rent. To contribute, e-mail carter@fdtrainingssystems.com.
Source
This story must be the antithesis to First Baptist Church of Dallas’ “Grinch alert” website .
Carter Haber, a 12-year-old Jewish boy from Aledo, saved Christmas for more than 50 children whose families are clients of Samaritan House, which provides housing for low-income people with HIV/AIDS in Tarrant County.
Carter raised $5,000 for the gifts as a service project for his bar mitzvah after the Samaritan House lost a corporate sponsor, according to CBS 11:
And the fact a Jewish rite of passage provides Christmas to children? “I don’t think it matters,” Haber said. “A good deed is a good deed any day, any time, anywhere.”
Now Carter wants to continue raising money to help Samaritan House clients pay their rent. To contribute, e-mail carter@fdtrainingssystems.com.
Source
Development and Progression of Portal Hypertensive Gastropathy in Patients With Chronic Hepatitis C
Am J Gastroenterol. 2010 Dec 7. [Epub ahead of print]
Fontana RJ, Sanyal AJ, Ghany MG, Bonkovsky HL, Morgan TR, Litman HJ, Reid AE, Lee WM, Naishadham D.
Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Abstract
OBJECTIVES: The objective of this study was to determine the incidence and risk factors associated with new-onset and worsening portal hypertensive gastropathy (PHG) in patients with chronic hepatitis C (CHC).
METHODS: A total of 831 CHC patients with bridging fibrosis or cirrhosis at the time of entry were prospectively monitored for clinical and histological liver disease progression while receiving either low-dose peginterferon α2a or no antiviral therapy in the HALT-C (Hepatitis C Antiviral Long-term Treatment against Cirrhosis) trial. Upper endoscopy with grading of PHG was performed at baseline and at year 4 of the study. The presence and severity of PHG were determined using the NIEC (New Italian Endoscopy Conference) criteria, and worsening PHG was defined as a score increase of ≥1 point.
RESULTS: During a median follow-up of 3.85 years, 50% of 514 subjects without PHG developed new-onset PHG, whereas 26% of 317 patients with baseline PHG had worsening PHG. Independent predictors of new-onset PHG included higher alkaline phosphatase and being diabetic, whereas predictors of worsening PHG were Caucasian race, lower albumin, as well as higher serum aspartate transaminase/alanine transaminase ratio and homeostatic model assessment levels. New-onset and worsening PHG were significantly associated with clinical and histological progression. They were also associated with new-onset and worsening gastroesophageal varices.
CONCLUSIONS: New-onset and worsening PHG develop at a rate of 12.9% per year and 6.7% per year, respectively, in non-responder CHC patients with advanced fibrosis. If confirmed in other studies, endoscopic surveillance for PHG may need to be tailored to individual patient risk factors.Am J Gastroenterol advance online publication, 7 December 2010; doi:10.1038/ajg.2010.456.
PMID: 21139575 [PubMed - as supplied by publisher
Source
Fontana RJ, Sanyal AJ, Ghany MG, Bonkovsky HL, Morgan TR, Litman HJ, Reid AE, Lee WM, Naishadham D.
Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Abstract
OBJECTIVES: The objective of this study was to determine the incidence and risk factors associated with new-onset and worsening portal hypertensive gastropathy (PHG) in patients with chronic hepatitis C (CHC).
METHODS: A total of 831 CHC patients with bridging fibrosis or cirrhosis at the time of entry were prospectively monitored for clinical and histological liver disease progression while receiving either low-dose peginterferon α2a or no antiviral therapy in the HALT-C (Hepatitis C Antiviral Long-term Treatment against Cirrhosis) trial. Upper endoscopy with grading of PHG was performed at baseline and at year 4 of the study. The presence and severity of PHG were determined using the NIEC (New Italian Endoscopy Conference) criteria, and worsening PHG was defined as a score increase of ≥1 point.
RESULTS: During a median follow-up of 3.85 years, 50% of 514 subjects without PHG developed new-onset PHG, whereas 26% of 317 patients with baseline PHG had worsening PHG. Independent predictors of new-onset PHG included higher alkaline phosphatase and being diabetic, whereas predictors of worsening PHG were Caucasian race, lower albumin, as well as higher serum aspartate transaminase/alanine transaminase ratio and homeostatic model assessment levels. New-onset and worsening PHG were significantly associated with clinical and histological progression. They were also associated with new-onset and worsening gastroesophageal varices.
CONCLUSIONS: New-onset and worsening PHG develop at a rate of 12.9% per year and 6.7% per year, respectively, in non-responder CHC patients with advanced fibrosis. If confirmed in other studies, endoscopic surveillance for PHG may need to be tailored to individual patient risk factors.Am J Gastroenterol advance online publication, 7 December 2010; doi:10.1038/ajg.2010.456.
PMID: 21139575 [PubMed - as supplied by publisher
Source
Hepatitis C virus treatment rates and outcomes in HIV/hepatitis C virus co-infected individuals at an urban HIV clinic
Eur J Gastroenterol Hepatol. 2011 Jan;23(1):45-50.
Murray MC, Barrios R, Zhang W, Hull M, Montessori V, Hogg RS, Montaner JS.
aDivision of Infectious Disease bDivision of AIDS, Department of Medicine, University of British Columbia cBritish Columbia Centre for Excellence in HIV/AIDS, Providence Health Care dFaculty of Health Sciences, Simon Fraser University, Vancouver, Canada.
Abstract
OBJECTIVES: The factors associated with hepatitis C virus (HCV) treatment uptake and responses were assessed among HCV/HIV co-infected individuals referred for HCV therapy at an urban HIV clinic.
METHODS: Retrospective review of HIV/HCV patients enrolled in the HCV treatment program at the John Ruedy Immunodeficiency Clinic in Vancouver. The factors associated with treatment uptake were assessed using multivariate analysis.
RESULTS: A total of 134 HCV/HIV co-infected individuals were recalled for assessment for HCV therapy. Overall 64 (48%) initiated treatment, and of those treated 49 (76.6%) attained end treatment response, whereas 35 (57.8%) achieved sustained virological response (SVR). When evaluated by genotype, 53% (17/32) of those with genotype 1, and 65% (20/31) of those with genotype 2 or 3 infections attained SVR. In treated individuals, alanine aminotransferase dropped significantly after treatment (P<0.001). During treatment, CD4 counts dropped significantly (P<0.001) in all patients. The counts recovered to baseline in patients who achieved SVR, but remained lower in patients who failed the therapy (P=0.015). On multivariate analysis, history of injection drug use (odds ratio: 3.48; 95% confidence interval: 1.37-8.79; P=0.009) and low hemoglobin levels (odds ratio: 4.23; 95% confidence interval: 1.36-13.10; P=0.013) were associated with those who did not enter the treatment.
CONCLUSION: Only half of treatment-eligible co-infected patients referred for the therapy initiated treatment. Of those referred for the therapy, history of injection drug use was associated with lower rates of treatment uptake. Treated HIV/HCV co-infected individuals benefitted from both decreased alanine aminotransferase (independent of SVR), and rates of SVR similar to those described in HCV monoinfected patients.
PMID: 21139470 [PubMed - in process]
Source
Murray MC, Barrios R, Zhang W, Hull M, Montessori V, Hogg RS, Montaner JS.
aDivision of Infectious Disease bDivision of AIDS, Department of Medicine, University of British Columbia cBritish Columbia Centre for Excellence in HIV/AIDS, Providence Health Care dFaculty of Health Sciences, Simon Fraser University, Vancouver, Canada.
Abstract
OBJECTIVES: The factors associated with hepatitis C virus (HCV) treatment uptake and responses were assessed among HCV/HIV co-infected individuals referred for HCV therapy at an urban HIV clinic.
METHODS: Retrospective review of HIV/HCV patients enrolled in the HCV treatment program at the John Ruedy Immunodeficiency Clinic in Vancouver. The factors associated with treatment uptake were assessed using multivariate analysis.
RESULTS: A total of 134 HCV/HIV co-infected individuals were recalled for assessment for HCV therapy. Overall 64 (48%) initiated treatment, and of those treated 49 (76.6%) attained end treatment response, whereas 35 (57.8%) achieved sustained virological response (SVR). When evaluated by genotype, 53% (17/32) of those with genotype 1, and 65% (20/31) of those with genotype 2 or 3 infections attained SVR. In treated individuals, alanine aminotransferase dropped significantly after treatment (P<0.001). During treatment, CD4 counts dropped significantly (P<0.001) in all patients. The counts recovered to baseline in patients who achieved SVR, but remained lower in patients who failed the therapy (P=0.015). On multivariate analysis, history of injection drug use (odds ratio: 3.48; 95% confidence interval: 1.37-8.79; P=0.009) and low hemoglobin levels (odds ratio: 4.23; 95% confidence interval: 1.36-13.10; P=0.013) were associated with those who did not enter the treatment.
CONCLUSION: Only half of treatment-eligible co-infected patients referred for the therapy initiated treatment. Of those referred for the therapy, history of injection drug use was associated with lower rates of treatment uptake. Treated HIV/HCV co-infected individuals benefitted from both decreased alanine aminotransferase (independent of SVR), and rates of SVR similar to those described in HCV monoinfected patients.
PMID: 21139470 [PubMed - in process]
Source
Incidence and risk factors for steatosis progression in adults coinfected with HIV and hepatitis C virus
Gastroenterology. 2010 Dec 3. [Epub ahead of print]
Woreta TA, Sutcliffe CG, Mehta SH, Brown TT, Higgins Y, Thomas DL, Torbenson MS, Moore RD, Sulkowski MS.
Johns Hopkins Hospital/University School of Medicine.
Abstract
BACKGROUND AND AIMS: Hepatic steatosis is a common histological finding in patients that are co-infected with HIV and hepatitis C virus (HCV), although little is known about its natural history. We prospectively examined the natural history of steatosis in patients co-infected with HIV and HCV that attended an urban HIV clinic.
METHODS: The study cohort consisted of 222 co-infected patients (87% African American, 94% with HCV genotype 1 infection) who had at least 2 liver biopsies performed between 1993 and 2008. Biopsies were scored by a single pathologist; samples were classified as having trivial (< 5% of hepatocytes affected) or significant (>5%) levels of fat (steatosis). We characterized progression to significant levels of fat among patients whose first biopsy samples had no or trivial levels of fat, and regression among those with significant fat, using logistic regression.
RESULTS: Initial biopsies from most patients (88%) had no or trivial amounts of fat. Among second biopsy samples, 74% had no or trivial fat and 13% had significant amounts of fat. The strongest risk factors for steatosis progression were alcohol abuse and overweight/obesity; cumulative exposure to anti-retroviral therapy between biopsies and high counts of CD4+ T cells were associated with reduced progression of steatosis. Among the 28 patients whose initial biopsy had significant fat levels, most (75%) regressed.
CONCLUSIONS: Antiretroviral therapy and high counts of CD4+ T cells are associated with reduced progression of steatosis in patients co-infected with HIV and HCV. Efforts to diagnose and prevent steatosis should focus on persons with high body mass index and excessive alcohol intake.
Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
PMID: 21134375 [PubMed - as supplied by publisher]
Source
Woreta TA, Sutcliffe CG, Mehta SH, Brown TT, Higgins Y, Thomas DL, Torbenson MS, Moore RD, Sulkowski MS.
Johns Hopkins Hospital/University School of Medicine.
Abstract
BACKGROUND AND AIMS: Hepatic steatosis is a common histological finding in patients that are co-infected with HIV and hepatitis C virus (HCV), although little is known about its natural history. We prospectively examined the natural history of steatosis in patients co-infected with HIV and HCV that attended an urban HIV clinic.
METHODS: The study cohort consisted of 222 co-infected patients (87% African American, 94% with HCV genotype 1 infection) who had at least 2 liver biopsies performed between 1993 and 2008. Biopsies were scored by a single pathologist; samples were classified as having trivial (< 5% of hepatocytes affected) or significant (>5%) levels of fat (steatosis). We characterized progression to significant levels of fat among patients whose first biopsy samples had no or trivial levels of fat, and regression among those with significant fat, using logistic regression.
RESULTS: Initial biopsies from most patients (88%) had no or trivial amounts of fat. Among second biopsy samples, 74% had no or trivial fat and 13% had significant amounts of fat. The strongest risk factors for steatosis progression were alcohol abuse and overweight/obesity; cumulative exposure to anti-retroviral therapy between biopsies and high counts of CD4+ T cells were associated with reduced progression of steatosis. Among the 28 patients whose initial biopsy had significant fat levels, most (75%) regressed.
CONCLUSIONS: Antiretroviral therapy and high counts of CD4+ T cells are associated with reduced progression of steatosis in patients co-infected with HIV and HCV. Efforts to diagnose and prevent steatosis should focus on persons with high body mass index and excessive alcohol intake.
Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
PMID: 21134375 [PubMed - as supplied by publisher]
Source
Maintenance Peginterferon Therapy and Other Factors Associated with Hepatocellular Carcinoma in Patients with Advanced Hepatitis C
Gastroenterology. 2010 Nov 30. [Epub ahead of print]
Lok AS, Everhart JE, Wright EC, Di Bisceglie AM, Kim HY, Sterling RK, Everson GT, Lindsay KL, Lee WM, Bonkovsky HL, Dienstag JL, Ghany MG, Morishima C, Morgan TR; HALT-C Trial Group.
Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, MI.
Abstract
BACKGROUND & AIMS: Interferon reportedly decreases the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. The Hepatitis C anti-viral long-term treatment against cirrhosis (HALT-C) trial showed that 4 years of maintenance therapy with peginterferon does not reduce liver disease progression. We investigated whether peginterferon decreases the incidence of HCC in the HALT-C cohort over a longer post-treatment follow-up period.
METHODS: The study included 1,048 patients with chronic Hepatitis C (Ishak fibrosis scores ≥3) who did not have a sustained virological response (SVR) to therapy. They were randomly assigned to groups given a half-dose of peginterferon or no treatment (controls) for 3.5 years and followed for a median 6.1 (maximum 8.7) years.
RESULTS: Eighty-eight patients developed HCC (68 definite, 20 presumed): 37/515 that were given peginterferon (7.2%) and 51/533 controls (9.6%; P=0.24). There was a significantly lower incidence of HCC among patients given peginterferon therapy who had cirrhosis, but not fibrosis, based on analysis of baseline biopsy samples. After 7 years, the cumulative incidences of HCC in treated and control patients with cirrhosis were 7.8% and 24.2%, respectively (hazard ratio [HR]=0.45; 95% confidence interval [CI]: 0.24-0.83); in treated and control patients with fibrosis they were 8.3% and 6.8%, respectively (HR=1.44; 95% CI: 0.77-2.69). Treated patients with a ≥2-point decrease in the histologic activity index, based on a follow-up biopsy, had a lower incidence of HCC than those with unchanged or increased scores (2.9% vs. 9.4%; P=0.03).
CONCLUSIONS: Extended analysis of the HALT-C cohort showed that long-term peginterferon therapy does not reduce the incidence of HCC among patients with advanced hepatitis C who did not achieve SVRs. Patients with cirrhosis who received peginterferon treatment had a lower risk for HCC than controls.
Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
PMID: 21129375 [PubMed - as supplied by publisher]
Source
Lok AS, Everhart JE, Wright EC, Di Bisceglie AM, Kim HY, Sterling RK, Everson GT, Lindsay KL, Lee WM, Bonkovsky HL, Dienstag JL, Ghany MG, Morishima C, Morgan TR; HALT-C Trial Group.
Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, MI.
Abstract
BACKGROUND & AIMS: Interferon reportedly decreases the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. The Hepatitis C anti-viral long-term treatment against cirrhosis (HALT-C) trial showed that 4 years of maintenance therapy with peginterferon does not reduce liver disease progression. We investigated whether peginterferon decreases the incidence of HCC in the HALT-C cohort over a longer post-treatment follow-up period.
METHODS: The study included 1,048 patients with chronic Hepatitis C (Ishak fibrosis scores ≥3) who did not have a sustained virological response (SVR) to therapy. They were randomly assigned to groups given a half-dose of peginterferon or no treatment (controls) for 3.5 years and followed for a median 6.1 (maximum 8.7) years.
RESULTS: Eighty-eight patients developed HCC (68 definite, 20 presumed): 37/515 that were given peginterferon (7.2%) and 51/533 controls (9.6%; P=0.24). There was a significantly lower incidence of HCC among patients given peginterferon therapy who had cirrhosis, but not fibrosis, based on analysis of baseline biopsy samples. After 7 years, the cumulative incidences of HCC in treated and control patients with cirrhosis were 7.8% and 24.2%, respectively (hazard ratio [HR]=0.45; 95% confidence interval [CI]: 0.24-0.83); in treated and control patients with fibrosis they were 8.3% and 6.8%, respectively (HR=1.44; 95% CI: 0.77-2.69). Treated patients with a ≥2-point decrease in the histologic activity index, based on a follow-up biopsy, had a lower incidence of HCC than those with unchanged or increased scores (2.9% vs. 9.4%; P=0.03).
CONCLUSIONS: Extended analysis of the HALT-C cohort showed that long-term peginterferon therapy does not reduce the incidence of HCC among patients with advanced hepatitis C who did not achieve SVRs. Patients with cirrhosis who received peginterferon treatment had a lower risk for HCC than controls.
Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
PMID: 21129375 [PubMed - as supplied by publisher]
Source
Predictive value of tumor markers for hepatocarcinogenesis in patients with hepatitis C virus
J Gastroenterol. 2010 Dec 7. [Epub ahead of print]
Kumada T, Toyoda H, Kiriyama S, Tanikawa M, Hisanaga Y, Kanamori A, Tada T, Tanaka J, Yoshizawa H.
Department of Gastroenterology, Ogaki Municipal Hospital, 4-86, Minaminokawa-cho, Ogaki, Gifu, 503-8052, Japan, hosp3@omh.ogaki.gifu.jp.
Abstract
BACKGROUND: Increases in tumor markers are sometimes seen in patients with chronic liver disease without hepatocellular carcinoma (HCC). The aim of this study was to determine the relationship between the levels of three tumor markers [alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3%), and des-γ-carboxy prothrombin (DCP)] and hepatic carcinogenesis to identify hepatitis C virus (HCV) carriers at high risk for cancer development.
METHODS: A total of 623 consecutive HCV carriers with follow-up periods of >3 years were included. The average integration values were calculated from biochemical tests, and tumor markers, including AFP, AFP-L3%, and DCP, and factors associated with the cumulative incidence of HCC were analyzed.
RESULTS: HCC developed in 120 (19.3%) of the 623 patients. Age >65 years [adjusted relative risk, 2.303 (95% confidence interval, 1.551-3.418), P < 0.001], low platelet count [3.086 (1.997-4.768), P < 0.001], high aspartate aminotransferase value [3.001 (1.373-6.562), P < 0.001], high AFP level [≥10, <20 ng/mL: 2.814 (1.686-4.697), P < 0.001; ≥20 ng/mL: 3.405 (2.087-5.557), P < 0.001] compared to <10 ng/mL, and high AFP-L3% level [≥5, <10%: 2.494 (1.291-4.816), P = 0.007; ≥10%: 3.555 (1.609-7.858), P < 0.001] compared to <5% were significantly associated with an increased incidence of HCC on multivariate analysis.
CONCLUSIONS: Increased AFP or AFP-L3% levels were significantly associated with an increased incidence of HCC. Among HCV carriers, patients with ≥10 ng/mL AFP or patients with ≥5% AFP-L3% are at very high risk for the development of HCC even if AFP is less than 20 ng/mL or AFP-L3% is less than 10%, which are the most commonly reported cutoff values.
PMID: 21132575 [PubMed - as supplied by publisher]
Source
Kumada T, Toyoda H, Kiriyama S, Tanikawa M, Hisanaga Y, Kanamori A, Tada T, Tanaka J, Yoshizawa H.
Department of Gastroenterology, Ogaki Municipal Hospital, 4-86, Minaminokawa-cho, Ogaki, Gifu, 503-8052, Japan, hosp3@omh.ogaki.gifu.jp.
Abstract
BACKGROUND: Increases in tumor markers are sometimes seen in patients with chronic liver disease without hepatocellular carcinoma (HCC). The aim of this study was to determine the relationship between the levels of three tumor markers [alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3%), and des-γ-carboxy prothrombin (DCP)] and hepatic carcinogenesis to identify hepatitis C virus (HCV) carriers at high risk for cancer development.
METHODS: A total of 623 consecutive HCV carriers with follow-up periods of >3 years were included. The average integration values were calculated from biochemical tests, and tumor markers, including AFP, AFP-L3%, and DCP, and factors associated with the cumulative incidence of HCC were analyzed.
RESULTS: HCC developed in 120 (19.3%) of the 623 patients. Age >65 years [adjusted relative risk, 2.303 (95% confidence interval, 1.551-3.418), P < 0.001], low platelet count [3.086 (1.997-4.768), P < 0.001], high aspartate aminotransferase value [3.001 (1.373-6.562), P < 0.001], high AFP level [≥10, <20 ng/mL: 2.814 (1.686-4.697), P < 0.001; ≥20 ng/mL: 3.405 (2.087-5.557), P < 0.001] compared to <10 ng/mL, and high AFP-L3% level [≥5, <10%: 2.494 (1.291-4.816), P = 0.007; ≥10%: 3.555 (1.609-7.858), P < 0.001] compared to <5% were significantly associated with an increased incidence of HCC on multivariate analysis.
CONCLUSIONS: Increased AFP or AFP-L3% levels were significantly associated with an increased incidence of HCC. Among HCV carriers, patients with ≥10 ng/mL AFP or patients with ≥5% AFP-L3% are at very high risk for the development of HCC even if AFP is less than 20 ng/mL or AFP-L3% is less than 10%, which are the most commonly reported cutoff values.
PMID: 21132575 [PubMed - as supplied by publisher]
Source
Pre-treatment prediction of response to pegylated-interferon plus ribavirin for chronic hepatitis C using genetic polymorphism in IL28B and viral factors
J Hepatol. 2010 Sep 19. [Epub ahead of print]
Kurosaki M, Tanaka Y, Nishida N, Sakamoto N, Enomoto N, Honda M, Sugiyama M, Matsuura K, Sugauchi F, Asahina Y, Nakagawa M, Watanabe M, Sakamoto M, Maekawa S, Sakai A, Kaneko S, Ito K, Masaki N, Tokunaga K, Izumi N, Mizokami M.
Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
Abstract
BACKGROUND & AIMS: Pegylated interferon and ribavirin (PEG-IFN/RBV) therapy for chronic hepatitis C virus (HCV) genotype 1 infection is effective in 50% of patients. Recent studies revealed an association between the IL28B genotype and treatment response. We aimed to develop a model for the pre-treatment prediction of response using host and viral factors.
METHODS: Data were collected from 496 patients with HCV genotype 1 treated with PEG-IFN/RBV at five hospitals and universities in Japan. IL28B genotype and mutations in the core and IFN sensitivity determining region (ISDR) of HCV were analyzed to predict response to therapy. The decision model was generated by data mining analysis.
RESULTS: The IL28B polymorphism correlated with early virological response and predicted null virological response (NVR) (odds ratio=20.83, p<0.0001) and sustained virological response (SVR) (odds ratio=7.41, p<0.0001) independent of other covariates. Mutations in the ISDR predicted relapse and SVR independent of IL28B. The decision model revealed that patients with the minor IL28B allele and low platelet counts had the highest NVR (84%) and lowest SVR (7%), whereas those with the major IL28B allele and mutations in the ISDR or high platelet counts had the lowest NVR (0-17%) and highest SVR (61-90%). The model had high reproducibility and predicted SVR with 78% specificity and 70% sensitivity.
CONCLUSIONS: The IL28B polymorphism and mutations in the ISDR of HCV were significant pre-treatment predictors of response to PEG-IFN/RBV. The decision model, including these host and viral factors may support selection of optimum treatment strategy for individual patients.
Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
PMID: 21129805 [PubMed - as supplied by publisher]
Source
Kurosaki M, Tanaka Y, Nishida N, Sakamoto N, Enomoto N, Honda M, Sugiyama M, Matsuura K, Sugauchi F, Asahina Y, Nakagawa M, Watanabe M, Sakamoto M, Maekawa S, Sakai A, Kaneko S, Ito K, Masaki N, Tokunaga K, Izumi N, Mizokami M.
Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
Abstract
BACKGROUND & AIMS: Pegylated interferon and ribavirin (PEG-IFN/RBV) therapy for chronic hepatitis C virus (HCV) genotype 1 infection is effective in 50% of patients. Recent studies revealed an association between the IL28B genotype and treatment response. We aimed to develop a model for the pre-treatment prediction of response using host and viral factors.
METHODS: Data were collected from 496 patients with HCV genotype 1 treated with PEG-IFN/RBV at five hospitals and universities in Japan. IL28B genotype and mutations in the core and IFN sensitivity determining region (ISDR) of HCV were analyzed to predict response to therapy. The decision model was generated by data mining analysis.
RESULTS: The IL28B polymorphism correlated with early virological response and predicted null virological response (NVR) (odds ratio=20.83, p<0.0001) and sustained virological response (SVR) (odds ratio=7.41, p<0.0001) independent of other covariates. Mutations in the ISDR predicted relapse and SVR independent of IL28B. The decision model revealed that patients with the minor IL28B allele and low platelet counts had the highest NVR (84%) and lowest SVR (7%), whereas those with the major IL28B allele and mutations in the ISDR or high platelet counts had the lowest NVR (0-17%) and highest SVR (61-90%). The model had high reproducibility and predicted SVR with 78% specificity and 70% sensitivity.
CONCLUSIONS: The IL28B polymorphism and mutations in the ISDR of HCV were significant pre-treatment predictors of response to PEG-IFN/RBV. The decision model, including these host and viral factors may support selection of optimum treatment strategy for individual patients.
Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
PMID: 21129805 [PubMed - as supplied by publisher]
Source
A comparison of the natural history and outcome of treatment for Asian and non-Asian hepatitis C-infected patients
J Viral Hepat. 2010 Dec 7. doi: 10.1111/j.1365-2893.2010.01406.x. [Epub ahead of print]
Lawson A; on behalf of the Trent Hepatitis C Study Group.
Department of Hepatology, Royal Derby Hospital, Derby, UK.
Abstract
Summary. Ethnicity is an important host variable, but its impact on disease progression and response to therapy in Hepatitis C infection is unclear. Here we compare the natural history and outcome of therapy in White and Asian (Indian subcontinent) Hepatitis C infected patients. A total of 2123 White and 120 Asian HCV infected patients were identified within the Trent HCV study. Response to therapy was assessed in 224 White and 46 Asian patients with genotype 3 infection who received Pegylated Interferon and Ribavirin. Asian patients were more likely to be older, female, infected with genotype 3 and to consume no alcohol. At time of first biopsy, fibrosis stage was significantly higher in Asian patients than in Whites (3.0 ± 2.3 vs 1.8 ± 2.0, P < 0.001), as were necro-inflammation and steatosis scores. However, in those patients where duration of infection could be estimated, fibrosis progression was similar for both groups (0.25 ± 0.31 vs 0.16 ± 0.54 Ishak points/year, P = 0.068). 78.3% of Asian and 67.9% of White genotype 3 patients had a sustained virological response following Pegylated Interferon and Ribavirin. Cirrhosis and increased levels of GGT, but not ethnicity were associated with a reduction in the likelihood of a sustained virological response on multivariate analysis. Asian patients with Hepatitis C are more likely to be female, less likely to give a history of risk factors, present to medical services at an older age, and have more severe liver disease at diagnosis, but disease progression and response to treatment are similar to White patients.
© 2010 Blackwell Publishing Ltd.
PMID: 21138506 [PubMed - as supplied by publisher]
Source
Lawson A; on behalf of the Trent Hepatitis C Study Group.
Department of Hepatology, Royal Derby Hospital, Derby, UK.
Abstract
Summary. Ethnicity is an important host variable, but its impact on disease progression and response to therapy in Hepatitis C infection is unclear. Here we compare the natural history and outcome of therapy in White and Asian (Indian subcontinent) Hepatitis C infected patients. A total of 2123 White and 120 Asian HCV infected patients were identified within the Trent HCV study. Response to therapy was assessed in 224 White and 46 Asian patients with genotype 3 infection who received Pegylated Interferon and Ribavirin. Asian patients were more likely to be older, female, infected with genotype 3 and to consume no alcohol. At time of first biopsy, fibrosis stage was significantly higher in Asian patients than in Whites (3.0 ± 2.3 vs 1.8 ± 2.0, P < 0.001), as were necro-inflammation and steatosis scores. However, in those patients where duration of infection could be estimated, fibrosis progression was similar for both groups (0.25 ± 0.31 vs 0.16 ± 0.54 Ishak points/year, P = 0.068). 78.3% of Asian and 67.9% of White genotype 3 patients had a sustained virological response following Pegylated Interferon and Ribavirin. Cirrhosis and increased levels of GGT, but not ethnicity were associated with a reduction in the likelihood of a sustained virological response on multivariate analysis. Asian patients with Hepatitis C are more likely to be female, less likely to give a history of risk factors, present to medical services at an older age, and have more severe liver disease at diagnosis, but disease progression and response to treatment are similar to White patients.
© 2010 Blackwell Publishing Ltd.
PMID: 21138506 [PubMed - as supplied by publisher]
Source
Integrated internist - addiction medicine - hepatology model for hepatitis C management for individuals on methadone maintenance
J Viral Hepat. 2010 Dec 3. doi: 10.1111/j.1365-2893.2010.01411.x. [Epub ahead of print]
Martinez AD, Dimova R, Marks KM, Beeder AB, Zeremski M, Kreek MJ, Talal AH.
Division of General Internal Medicine and Hepatology, Department of Medicine, University of California San Diego, San Diego, CA Division of Gastroenterology and Hepatology, Center for the Study of Hepatitis C Division of Infectious Diseases, Department of Medicine Department of Public Health, Weill Cornell Medical College The Laboratory of the Biology of Addictive Diseases, Rockefeller University, New York, NY, USA.
Abstract
Summary. Despite a high prevalence of hepatitis C virus (HCV) among drug users, HCV evaluation and treatment acceptance are extremely low among these patients when referred from drug treatment facilities for HCV management. We sought to increase HCV treatment effectiveness among patients from a methadone maintenance treatment program (MMTP) by maintaining continuity of care. We developed, instituted and retrospectively assessed the effectiveness of an integrated, co-localized care model in which an internist-addiction medicine specialist from MMTP was embedded in the hepatitis clinic. Methadone maintenance treatment program patients were referred, evaluated by the internist and hepatologist in hepatitis clinic and provided HCV treatment with integration between both sites. Of 401 evaluated patients, anti-HCV antibody was detected in 257, 86% of whom were older than 40 years. Hepatitis C virus RNA levels were measured in 222 patients, 65 of whom were aviremic. Of 157 patients with detectable HCV RNA, 125 were eligible for referral to the hepatitis clinic, 76 (61%) of whom accepted and adhered with the referral. Men engaged in MMTP <36 months were significantly less likely to be seen in hepatitis clinic than men in MMTP more than 36 months (odds ratio = 7.7; 95% confidence interval 2.6-22.9) or women. We evaluated liver histology in 63 patients, and 83% had moderate to advanced liver disease. Twenty-four patients initiated treatment with 19 completing and 13 (54%) achieving sustained response. In conclusion, integrated care between the MMTP and the hepatitis clinic improves adherence with HCV evaluation and treatment compared to standard referral practices.
© 2010 Blackwell Publishing Ltd.
PMID: 21129131 [PubMed - as supplied by publisher]
Source
Martinez AD, Dimova R, Marks KM, Beeder AB, Zeremski M, Kreek MJ, Talal AH.
Division of General Internal Medicine and Hepatology, Department of Medicine, University of California San Diego, San Diego, CA Division of Gastroenterology and Hepatology, Center for the Study of Hepatitis C Division of Infectious Diseases, Department of Medicine Department of Public Health, Weill Cornell Medical College The Laboratory of the Biology of Addictive Diseases, Rockefeller University, New York, NY, USA.
Abstract
Summary. Despite a high prevalence of hepatitis C virus (HCV) among drug users, HCV evaluation and treatment acceptance are extremely low among these patients when referred from drug treatment facilities for HCV management. We sought to increase HCV treatment effectiveness among patients from a methadone maintenance treatment program (MMTP) by maintaining continuity of care. We developed, instituted and retrospectively assessed the effectiveness of an integrated, co-localized care model in which an internist-addiction medicine specialist from MMTP was embedded in the hepatitis clinic. Methadone maintenance treatment program patients were referred, evaluated by the internist and hepatologist in hepatitis clinic and provided HCV treatment with integration between both sites. Of 401 evaluated patients, anti-HCV antibody was detected in 257, 86% of whom were older than 40 years. Hepatitis C virus RNA levels were measured in 222 patients, 65 of whom were aviremic. Of 157 patients with detectable HCV RNA, 125 were eligible for referral to the hepatitis clinic, 76 (61%) of whom accepted and adhered with the referral. Men engaged in MMTP <36 months were significantly less likely to be seen in hepatitis clinic than men in MMTP more than 36 months (odds ratio = 7.7; 95% confidence interval 2.6-22.9) or women. We evaluated liver histology in 63 patients, and 83% had moderate to advanced liver disease. Twenty-four patients initiated treatment with 19 completing and 13 (54%) achieving sustained response. In conclusion, integrated care between the MMTP and the hepatitis clinic improves adherence with HCV evaluation and treatment compared to standard referral practices.
© 2010 Blackwell Publishing Ltd.
PMID: 21129131 [PubMed - as supplied by publisher]
Source
Quantification of hepatitis C virus in patients treated with peginterferon-alfa 2a plus ribavirin treatment by COBAS TaqMan HCV test
J Viral Hepat. 2010 Dec 3. doi: 10.1111/j.1365-2893.2010.01409.x. [Epub ahead of print]
Kanda T, Imazeki F, Yonemitsu Y, Mikami S, Takada N, Nishino T, Takashi M, Tsubota A, Kato K, Sugiura N, Tawada A, Wu S, Tanaka T, Nakamoto S, Mikata R, Tada M, Chiba T, Kurihara T, Arai M, Fujiwara K, Kanai F, Yokosuka O.
Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan Kikkoman Hospital, Noda, Japan Toho University Sakura Medical Center, Sakura, Japan Tokyo Women's Medical University Yachiyo Medical Center, Yachiyo, Japan Saiseikai Narashino Hospital, Narashino, Japan Institute of Clinical Medicine and Research, Jikei University School of Medicine, Kashiwa, Japan Narita Red Cross Hospital, Narita, Japan National Hospital Organization Chiba Medical Center, Chiba, Japan.
Abstract
Summary. Extremely low levels of serum hepatitis C virus (HCV) RNA can be detected by COBAS TaqMan HCV test. To investigate whether the COBAS TaqMan HCV test is useful for measuring rapid virological response (RVR) and early virological response (EVR) to predict sustained virological response (SVR), we compared the virological response to PEG-IFN-alfa 2a plus RBV in 76 patients infected with HCV genotype 1 when undetectable HCV RNA by the COBAS TaqMan HCV test was used, with those when below 1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test was used, which corresponded to the use of traditional methods. Among the 76 patients, 28 (36.8%) had SVR, 13 (17.1%) relapsed, 19 (25.0%) did not respond, and 16 (21.0%) discontinued the treatment due to side effects. The positive predictive values for SVR based on undetectable HCV RNA by COBAS TaqMan HCV test at 24 weeks after the end of treatment [10/10 (100%) at week 4, 21/23 (91.3%) at week 8 and 26/33 (78.7%) at week 12] were superior to those based on <1.7 log IU/mL HCV RNA [17/19 (89.4%) at week 4, 27/38 (71.0%) at week 8, and 27/43 (62.7%) at week 12]. The negative predictive values for SVR based on <1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test [46/57 (80.7%) at week 4, 37/38 (97.3%) at week 8, and 32/33 (96.9%) at week 12] were superior to those based on undetectable HCV RNA [48/66 (72.7%) at week 4, 46/53 (86.7%) at week 8, and 41/43 (95.3%) at week 12]. The utilization of both undetectable RNA and <1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test is useful and could predict SVR and non-SVR patients with greater accuracy.
© 2010 Blackwell Publishing Ltd.
PMID: 21129130 [PubMed - as supplied by publisher]
Source
Kanda T, Imazeki F, Yonemitsu Y, Mikami S, Takada N, Nishino T, Takashi M, Tsubota A, Kato K, Sugiura N, Tawada A, Wu S, Tanaka T, Nakamoto S, Mikata R, Tada M, Chiba T, Kurihara T, Arai M, Fujiwara K, Kanai F, Yokosuka O.
Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan Kikkoman Hospital, Noda, Japan Toho University Sakura Medical Center, Sakura, Japan Tokyo Women's Medical University Yachiyo Medical Center, Yachiyo, Japan Saiseikai Narashino Hospital, Narashino, Japan Institute of Clinical Medicine and Research, Jikei University School of Medicine, Kashiwa, Japan Narita Red Cross Hospital, Narita, Japan National Hospital Organization Chiba Medical Center, Chiba, Japan.
Abstract
Summary. Extremely low levels of serum hepatitis C virus (HCV) RNA can be detected by COBAS TaqMan HCV test. To investigate whether the COBAS TaqMan HCV test is useful for measuring rapid virological response (RVR) and early virological response (EVR) to predict sustained virological response (SVR), we compared the virological response to PEG-IFN-alfa 2a plus RBV in 76 patients infected with HCV genotype 1 when undetectable HCV RNA by the COBAS TaqMan HCV test was used, with those when below 1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test was used, which corresponded to the use of traditional methods. Among the 76 patients, 28 (36.8%) had SVR, 13 (17.1%) relapsed, 19 (25.0%) did not respond, and 16 (21.0%) discontinued the treatment due to side effects. The positive predictive values for SVR based on undetectable HCV RNA by COBAS TaqMan HCV test at 24 weeks after the end of treatment [10/10 (100%) at week 4, 21/23 (91.3%) at week 8 and 26/33 (78.7%) at week 12] were superior to those based on <1.7 log IU/mL HCV RNA [17/19 (89.4%) at week 4, 27/38 (71.0%) at week 8, and 27/43 (62.7%) at week 12]. The negative predictive values for SVR based on <1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test [46/57 (80.7%) at week 4, 37/38 (97.3%) at week 8, and 32/33 (96.9%) at week 12] were superior to those based on undetectable HCV RNA [48/66 (72.7%) at week 4, 46/53 (86.7%) at week 8, and 41/43 (95.3%) at week 12]. The utilization of both undetectable RNA and <1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test is useful and could predict SVR and non-SVR patients with greater accuracy.
© 2010 Blackwell Publishing Ltd.
PMID: 21129130 [PubMed - as supplied by publisher]
Source
Impact of liver steatosis on the correlation between liver stiffness and fibrosis measured by transient elastography in patients coinfected with human immunodeficiency virus and hepatitis C virus
J Viral Hepat. 2010 Dec 3. doi: 10.1111/j.1365-2893.2010.01407.x. [Epub ahead of print]
Sánchez-Conde M, Montes Ramírez ML, Bellón Cano JM, Caminoa A, Rodríguez FA, Garcia JG, Martín PM, Bernardino de la Serna I, Bernardo de Quirós JC, Arribas López JR, Ochaíta JC, Pascual Pareja JF, Alvarez E, Berenguer JB.
Infectious Diseases and HIV Unit, Hospital Universitario Gregorio Marañón, Madrid, Spain Department of Internal Medicine 2, Hospital Universitario La Paz, Madrid, Spain Biomedical Research Foundation, Hospital Universitario Gregorio Marañón, Madrid, Spain Department of Pathology, Hospital Universitario La Paz, Madrid, Spain Department of Pathology, Hospital Universitario Gregorio Marañón, Madrid, Spain.
Abstract
Summary. We assessed the effect of different hepatic conditions such as fibrosis, steatosis and necroinflammatory activity on liver stiffness as measured by transient elastography in HIV/HCV-coinfected patients. We studied all consecutive HIV/HCV-coinfected patients who underwent liver biopsy and elastography between January 2007 and December 2008. Liver fibrosis was staged following METAVIR Cooperative Study Group criteria. Steatosis was categorized according to the percentage of affected hepatocytes as low (≤10%), moderate (<25%) and severe (≥25%). A total of 110 patients were included. Fibrosis was distributed by stage as follows: F0, n = 13; F1, n = 47; F2, n = 29; F3, n = 18; and F4, n = 3. Liver biopsy revealed the presence of hepatic steatosis in 68 patients (low to moderate, n = 53; and severe n = 15). By univariate regression analysis, fibrosis, necroinflammatory activity, and the degree of steatosis were correlated with liver stiffness. However, in a multiple regression analysis, steatosis and fibrosis were the only independent variables significantly associated with liver stiffness. With a cut-off of 9.5 kPa to distinguish patients with F ≤ 2 from F ≥ 3, elastography led to a significantly higher number of misclassification errors (25%vs 5%; P = 0.014), most of which were false positives for F ≥ 3. Our study suggests that the correlation between liver stiffness and fibrosis as estimated by transient elastography may be affected by the presence of hepatic steatosis in HIV/HCV-coinfected patients.
© 2010 Blackwell Publishing Ltd.
PMID: 21129129 [PubMed - as supplied by publisher]
Source
Sánchez-Conde M, Montes Ramírez ML, Bellón Cano JM, Caminoa A, Rodríguez FA, Garcia JG, Martín PM, Bernardino de la Serna I, Bernardo de Quirós JC, Arribas López JR, Ochaíta JC, Pascual Pareja JF, Alvarez E, Berenguer JB.
Infectious Diseases and HIV Unit, Hospital Universitario Gregorio Marañón, Madrid, Spain Department of Internal Medicine 2, Hospital Universitario La Paz, Madrid, Spain Biomedical Research Foundation, Hospital Universitario Gregorio Marañón, Madrid, Spain Department of Pathology, Hospital Universitario La Paz, Madrid, Spain Department of Pathology, Hospital Universitario Gregorio Marañón, Madrid, Spain.
Abstract
Summary. We assessed the effect of different hepatic conditions such as fibrosis, steatosis and necroinflammatory activity on liver stiffness as measured by transient elastography in HIV/HCV-coinfected patients. We studied all consecutive HIV/HCV-coinfected patients who underwent liver biopsy and elastography between January 2007 and December 2008. Liver fibrosis was staged following METAVIR Cooperative Study Group criteria. Steatosis was categorized according to the percentage of affected hepatocytes as low (≤10%), moderate (<25%) and severe (≥25%). A total of 110 patients were included. Fibrosis was distributed by stage as follows: F0, n = 13; F1, n = 47; F2, n = 29; F3, n = 18; and F4, n = 3. Liver biopsy revealed the presence of hepatic steatosis in 68 patients (low to moderate, n = 53; and severe n = 15). By univariate regression analysis, fibrosis, necroinflammatory activity, and the degree of steatosis were correlated with liver stiffness. However, in a multiple regression analysis, steatosis and fibrosis were the only independent variables significantly associated with liver stiffness. With a cut-off of 9.5 kPa to distinguish patients with F ≤ 2 from F ≥ 3, elastography led to a significantly higher number of misclassification errors (25%vs 5%; P = 0.014), most of which were false positives for F ≥ 3. Our study suggests that the correlation between liver stiffness and fibrosis as estimated by transient elastography may be affected by the presence of hepatic steatosis in HIV/HCV-coinfected patients.
© 2010 Blackwell Publishing Ltd.
PMID: 21129129 [PubMed - as supplied by publisher]
Source
Effect of maintenance therapy with low-dose peginterferon for recurrent hepatitis C after living donor liver transplantation
J Viral Hepat. 2010 Dec 3. doi: 10.1111/j.1365-2893.2010.01398.x. [Epub ahead of print]
Ueda Y, Marusawa H, Kaido T, Ogura Y, Oike F, Mori A, Ogawa K, Yoshizawa A, Hatano E, Miyagawa-Hayashino A, Haga H, Egawa H, Takada Y, Uemoto S, Chiba T.
Department of Gastroenterology and Hepatology Department of Surgery Department of Diagnostic Pathology, Graduate School of Medicine, Kyoto University, Shogoin, Sakyo-ku, Kyoto, Japan.
Abstract
Summary. Approximately 30% of patients who have recurrent hepatitis C after liver transplantation achieve sustained virological response (SVR) by taking a combination therapy of pegylated interferon and ribavirin. For the remaining non-SVR patients, an effective management treatment has not yet been established. In this study, efficacy of long-term peginterferon maintenance therapy for non-SVR patients was evaluated. Forty patients who had previously received the combination therapy for hepatitis C after living donor liver transplantation were classified into one of the following three groups: the SVR group (n = 11); the non-SVR-IFN group (n = 17), which received low-dose peginterferon maintenance therapy for non-SVR patients; and the non-SVR-Withdrawal group (n = 12), which discontinued the interferon treatment. We then compared histological changes among these three groups after 2 or more years follow-up. Activity grade of liver histology improved or remained stable in patients in the SVR and non-SVR-IFN groups, but deteriorated in half of the patients in the non-SVR-Withdrawal group. Fibrosis improved or remained stable in 10 of 11 SVR patients and in 13 of 17 non-SVR-IFN patients, but deteriorated in all non-SVR-Withdrawal patients. Mean changes in fibrosis stage between pretreatment and final liver biopsy were -0.18, +0.06 and +2.2 in the SVR, non-SVR-IFN and non-SVR-Withdrawal groups, respectively. Fibrosis stage deteriorated to F3 or F4 significantly more rapidly in the non-SVR-Withdrawal group than in the other two groups. In conclusion, continuing long-term maintenance therapy with peginterferon prevented histological progression of hepatitis C in patients who had undergone living donor liver transplantation.
© 2010 Blackwell Publishing Ltd.
PMID: 21129128 [PubMed - as supplied by publisher]
Source
Ueda Y, Marusawa H, Kaido T, Ogura Y, Oike F, Mori A, Ogawa K, Yoshizawa A, Hatano E, Miyagawa-Hayashino A, Haga H, Egawa H, Takada Y, Uemoto S, Chiba T.
Department of Gastroenterology and Hepatology Department of Surgery Department of Diagnostic Pathology, Graduate School of Medicine, Kyoto University, Shogoin, Sakyo-ku, Kyoto, Japan.
Abstract
Summary. Approximately 30% of patients who have recurrent hepatitis C after liver transplantation achieve sustained virological response (SVR) by taking a combination therapy of pegylated interferon and ribavirin. For the remaining non-SVR patients, an effective management treatment has not yet been established. In this study, efficacy of long-term peginterferon maintenance therapy for non-SVR patients was evaluated. Forty patients who had previously received the combination therapy for hepatitis C after living donor liver transplantation were classified into one of the following three groups: the SVR group (n = 11); the non-SVR-IFN group (n = 17), which received low-dose peginterferon maintenance therapy for non-SVR patients; and the non-SVR-Withdrawal group (n = 12), which discontinued the interferon treatment. We then compared histological changes among these three groups after 2 or more years follow-up. Activity grade of liver histology improved or remained stable in patients in the SVR and non-SVR-IFN groups, but deteriorated in half of the patients in the non-SVR-Withdrawal group. Fibrosis improved or remained stable in 10 of 11 SVR patients and in 13 of 17 non-SVR-IFN patients, but deteriorated in all non-SVR-Withdrawal patients. Mean changes in fibrosis stage between pretreatment and final liver biopsy were -0.18, +0.06 and +2.2 in the SVR, non-SVR-IFN and non-SVR-Withdrawal groups, respectively. Fibrosis stage deteriorated to F3 or F4 significantly more rapidly in the non-SVR-Withdrawal group than in the other two groups. In conclusion, continuing long-term maintenance therapy with peginterferon prevented histological progression of hepatitis C in patients who had undergone living donor liver transplantation.
© 2010 Blackwell Publishing Ltd.
PMID: 21129128 [PubMed - as supplied by publisher]
Source
December 12, 2010
Benitec Limited (ASX:BLT) Granted Another RNA Interference Patent In Europe Providing Further Support For The Hepatitis C Program
Press Releases
Distributed: Dec 13, 2010
Melbourne, Dec 13, 2010 (ABN Newswire) - Benitec Limited (ASX:BLT) (PINK:BNIKF) is pleased to announce that the European Patent Office (EPO) has issued a Communication of Intent to Grant on application 2005 727 680 "Multiple promoter expression cassettes for simultaneous delivery of RNAi agents". The claims cover the use of an RNA interference construct (with multiple promoters) to inhibit the level of Hepatitis C virus in cells, tissues and organs. Additional related applications remain pending to extend the scope of protection, including constructs having single promoters.
Benitec has licensed the rights to use this patent for Hepatitis C exclusively to Tacere Therapeutics, Inc., who are working with Pfizer to further develop and commercialise Tacere's Hepatitis C Virus (HCV) compounds.
Tacere Therapeutics' Chief Executive Officer Sara Hall Renison stated "We are very pleased with the news from the EPO. Benitec has been a strong ally in developing this and other patent families, and Tacere and Pfizer look forward to continuing clinical development of this first-in-class drug".
Benitec's Chief Executive Officer Dr Peter French said, "The intention of the EPO to grant this patent is an important addition to our already broad and robust patent portfolio in RNAi, and complements the patents already granted for this work in the United States, Australia and New Zealand."
About Benitec Limited
Benitec Limited (ASX:BLT) (PINK:BNIKF) is an Australian biotechnology company focused on licensing its extensive intellectual property portfolio and developing therapeutics to treat serious diseases using its proprietary ddRNAi technology. For additional information, please visit http://www.benitec.com/.
Contact
Peter French
Chief Executive Officer
Benitec Limited
Tel: +61-412-457-595
http://www.benitec.com/
Source
Distributed: Dec 13, 2010
Melbourne, Dec 13, 2010 (ABN Newswire) - Benitec Limited (ASX:BLT) (PINK:BNIKF) is pleased to announce that the European Patent Office (EPO) has issued a Communication of Intent to Grant on application 2005 727 680 "Multiple promoter expression cassettes for simultaneous delivery of RNAi agents". The claims cover the use of an RNA interference construct (with multiple promoters) to inhibit the level of Hepatitis C virus in cells, tissues and organs. Additional related applications remain pending to extend the scope of protection, including constructs having single promoters.
Benitec has licensed the rights to use this patent for Hepatitis C exclusively to Tacere Therapeutics, Inc., who are working with Pfizer to further develop and commercialise Tacere's Hepatitis C Virus (HCV) compounds.
Tacere Therapeutics' Chief Executive Officer Sara Hall Renison stated "We are very pleased with the news from the EPO. Benitec has been a strong ally in developing this and other patent families, and Tacere and Pfizer look forward to continuing clinical development of this first-in-class drug".
Benitec's Chief Executive Officer Dr Peter French said, "The intention of the EPO to grant this patent is an important addition to our already broad and robust patent portfolio in RNAi, and complements the patents already granted for this work in the United States, Australia and New Zealand."
About Benitec Limited
Benitec Limited (ASX:BLT) (PINK:BNIKF) is an Australian biotechnology company focused on licensing its extensive intellectual property portfolio and developing therapeutics to treat serious diseases using its proprietary ddRNAi technology. For additional information, please visit http://www.benitec.com/.
Contact
Peter French
Chief Executive Officer
Benitec Limited
Tel: +61-412-457-595
http://www.benitec.com/
Source
Pfizer Withdraws Thelin; Blood Pressure Drug Linked to Fatal Liver Damage
By AP Dec 10th 2010 10:33AM
Categories: News
Pfizer Inc. said Friday it is pulling its blood pressure drug Thelin off the market and stopping all clinical trials because the drug can cause fatal liver damage.
Thelin is sold in the European Union, Canada, and Australia as an oral treatment for severe pulmonary arterial hypertension, or high blood pressure in the pulmonary artery. Pfizer said two patients who were taking Thelin died during a clinical trial, and a review of data from clinical studies and post-marketing reports showed a new link to liver injury.
Liver damage was a known side effect of Thelin and similar drugs, the company said, but the review uncovered a link to liver damage that was not tied to identifiable risk factors. It said the problem was unlikely to be detected by routine monitoring, and in some cases, the problems did not go away after patients stopped taking Thelin.
Pfizer said the withdrawal was voluntary and added that it has withdrawn its filing for marketing approval in the U.S.
Since there are other treatment options, Pfizer said the benefits of Thelin don't outweigh the risks. It is stopping all studies of the drug, which Pfizer acquired in 2008 when it bought Encysive Pharmaceuticals Inc. Encysive had been trying to win marketing approval for Thelin since 2005, but the Food and Drug Administration said it was not effective enough. Other agencies only approved the drug for hypertension that was so debilitating that patients' physical activity was severely limited.
The New York company said worldwide sales of Thelin, or sitaxsentan, totaled $44.4 million in the first nine months of 2010.
Source
Categories: News
Pfizer Inc. said Friday it is pulling its blood pressure drug Thelin off the market and stopping all clinical trials because the drug can cause fatal liver damage.
Thelin is sold in the European Union, Canada, and Australia as an oral treatment for severe pulmonary arterial hypertension, or high blood pressure in the pulmonary artery. Pfizer said two patients who were taking Thelin died during a clinical trial, and a review of data from clinical studies and post-marketing reports showed a new link to liver injury.
Liver damage was a known side effect of Thelin and similar drugs, the company said, but the review uncovered a link to liver damage that was not tied to identifiable risk factors. It said the problem was unlikely to be detected by routine monitoring, and in some cases, the problems did not go away after patients stopped taking Thelin.
Pfizer said the withdrawal was voluntary and added that it has withdrawn its filing for marketing approval in the U.S.
Since there are other treatment options, Pfizer said the benefits of Thelin don't outweigh the risks. It is stopping all studies of the drug, which Pfizer acquired in 2008 when it bought Encysive Pharmaceuticals Inc. Encysive had been trying to win marketing approval for Thelin since 2005, but the Food and Drug Administration said it was not effective enough. Other agencies only approved the drug for hypertension that was so debilitating that patients' physical activity was severely limited.
The New York company said worldwide sales of Thelin, or sitaxsentan, totaled $44.4 million in the first nine months of 2010.
Source
December 11, 2010
A Targeted Approach to Hepatitis C Treatment
Peter Mueller PhD, CSO and EVP of Global R&D; Vertex Pharmaceuticals, Cambridge, Mass.
Drug Discovery & Development - December 01, 2010
Hepatitis C is a serious liver disease caused by the hepatitis C virus (HCV) that affects approximately 170 million people worldwide.1 Up to 3.9 million Americans may be infected with HCV and 75 percent are unaware of their infection.2,3 Hepatitis C can be cured with drug therapy. However, for people infected with the most common form of HCV in the United States (genotype 1), less than half achieve a sustained viral response (SVR), or viral cure, with current therapies.4-6
Without effective treatment, chronic hepatitis C can cause liver failure, liver cancer, and death.1 The need for more effective therapy for people with genotype 1 hepatitis C has led to research into direct-acting antivirals (DAAs) that target viral replication proteins such as the HCV protease and HCV polymerase.
Vertex Pharmaceuticals used a structure-based drug design approach to identify telaprevir, a novel small molecule DAA.7 Telaprevir inhibits a protease essential for viral replication, HCV NS3-4A. The complex formed between telaprevir and HCV NS3-4A is covalent yet reversible, with a slow-on, slow-off process.7 This potent, selective inhibitor significantly reduced HCV RNA levels (an indicator of reduced viral replication) in both cell culture systems and early-phase clinical trials.7,8
To date, more than 2,500 people with genotype 1 hepatitis C have received telaprevir-based therapy as part of Phase 2 and Phase 3 clinical trials. Telaprevir was given in combination with pegylated-interferon and ribavirin for the first 12 weeks of treatment followed by pegylated-interferon and ribavirin alone for either 12 or 36 weeks of additional therapy. Telaprevir has been studied in three Phase 3 trials: ADVANCE, ILLUMINATE, and REALIZE. ADVANCE and ILLUMINATE included patients who had never received treatment for hepatitis C (treatment-naïve), whereas REALIZE included patients who had not achieved SVR, or viral cure, after a prior course of interferon-based treatment (treatment-experienced).9-11 REALIZE was the only Phase 3 study of an investigational DAA designed to evaluate all major subgroups of people whose prior treatment was unsuccessful, including those who had a null response (less than a 2-log10 drop in HCV RNA by week 12 of a prior course of treatment) as defined by the U.S. Food and Drug Administration (FDA).6,11,12
The telaprevir Phase 2 study results were published in the New England Journal of Medicine, and Phase 3 results from ADVANCE and ILLUMINATE were presented at the annual meeting of the American Association for the Study of Liver Diseases in October 2010.9,10,13-15
Vertex submitted a new drug application to the FDA in November of 2010 and plans to request priority (6-month) review of the application.
References
1. World Health Organization. Hepatitis C. http://www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index.html. Updated 2002. Accessed August 18, 2010.
2. Institute of Medicine of the National Academies. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Colvin HM and Mitchell AE, ed. http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx. Updated January 11, 2010. Accessed August 18, 2010.
3. Pyenson B, Fitch K, Iwasaki K. Consequences of hepatitis C virus (HCV): costs of a baby boomer epidemic of liver disease. http://www.natap.org/2009/HCV/051809_01.htm. Updated May 2009. Accessed August 18, 2010. This report was commissioned by Vertex Pharmaceuticals.
4. Blatt LM, Mutchnick MG, Tong MJ, et al. Assessment of hepatitis C virus RNA and genotype from 6807 patients with chronic hepatitis in the United States. J Viral Hepat. 2000;7:196-202.
5. Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. New Eng J Med. 2002;347(13):975-982.
6. Ghany MG, Strader DB, Thomas DL, Seeff LB. Diagnosis, management and treatment of hepatitis C: An update. Hepatology. 2009;49(4): 1335-1374.
7. Perni RB, Almquist SJ, Byrn RA, et al. Preclinical profile of VX-950, a potent, selective, and orally bioavailable inhibitor of hepatitis C virus NS3-4A serine protease. Antimicrob Agents Chemother. 2006;50(3):899-909.
8. Reesink HW, Zeuzem S, Weegink CJ, et al. Rapid decline of viral RNA in hepatitis C patients treated with VX-950: a phase Ib, placebo-controlled, randomized study. Gastroenterology. 2006;131(4):997–1002.
9. Jacobson IM, McHutchison JG, Dusheiko GM et al. Telaprevir in combination with Peginterferon and ribavirin in genotype 1 HCV treatment-naïve patients: Final results of phase 3 ADVANCE study. Hepatology. 2010;52(Suppl 4): 427A. Abstract 211.
10. Vertex Pharmaceuticals Press Release: Vertex Pharmaceuticals to Start Phase 3 'REALIZE' Trial with Telaprevir in Treatment-Failure HCV Patients, August 19, 2008. Available at: http://investors.vrtx.com/releasedetail.cfm?ReleaseID=328603. Accessed on August 25, 2010.
11. Sherman KE, Flamm SL, Afdhal NH, et al. Telaprevir in combination with peginterferon alfa3a and ribavirin for 34 or 48 weeks in treatment-naïve genotype 1 HCV patients who achieved an extended rapid viral response: Final results of the Phase 3 ILLUMINATE study. Hepatology. 2010;52(Suppl 4):401A. Abstract LB-2.
12 United States Food and Drug Administration. Chronic hepatitis C virus infection: developing direct-acting antiviral agents for treatment. http://www.federalregister.gov/articles/2010/09/14/2010-22806/draft-guidance-for-industry-on-chronic-hepatitis-c-virus-infection-developing-directacting-antiviral. Updated September 14, 2010. Accessed September 14, 2010.
13. McHutchison JG, Everson GT, Gordon SC, et al. and the PROVE1 Study Team. Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. New Eng J Med. 2009;360(18):1827-1838.
14. Hezode C, Forestier N, Dusheiko G, et al. and the PROVE2 Study Team. Telaprevir and peginterferon with or without ribavirin for chronic HCV infection. New Eng J Med. 2009;360(18):1839-1850.
15. McHutchison JG, Manns MP, Muir AJ, et al. and the PROVE3 Study Team. Telaprevir for previously treated chronic HCV infection. New Eng J Med. 2010;362(14):1292-1303.
Source
Drug Discovery & Development - December 01, 2010
Hepatitis C is a serious liver disease caused by the hepatitis C virus (HCV) that affects approximately 170 million people worldwide.1 Up to 3.9 million Americans may be infected with HCV and 75 percent are unaware of their infection.2,3 Hepatitis C can be cured with drug therapy. However, for people infected with the most common form of HCV in the United States (genotype 1), less than half achieve a sustained viral response (SVR), or viral cure, with current therapies.4-6
Without effective treatment, chronic hepatitis C can cause liver failure, liver cancer, and death.1 The need for more effective therapy for people with genotype 1 hepatitis C has led to research into direct-acting antivirals (DAAs) that target viral replication proteins such as the HCV protease and HCV polymerase.
Vertex Pharmaceuticals used a structure-based drug design approach to identify telaprevir, a novel small molecule DAA.7 Telaprevir inhibits a protease essential for viral replication, HCV NS3-4A. The complex formed between telaprevir and HCV NS3-4A is covalent yet reversible, with a slow-on, slow-off process.7 This potent, selective inhibitor significantly reduced HCV RNA levels (an indicator of reduced viral replication) in both cell culture systems and early-phase clinical trials.7,8
To date, more than 2,500 people with genotype 1 hepatitis C have received telaprevir-based therapy as part of Phase 2 and Phase 3 clinical trials. Telaprevir was given in combination with pegylated-interferon and ribavirin for the first 12 weeks of treatment followed by pegylated-interferon and ribavirin alone for either 12 or 36 weeks of additional therapy. Telaprevir has been studied in three Phase 3 trials: ADVANCE, ILLUMINATE, and REALIZE. ADVANCE and ILLUMINATE included patients who had never received treatment for hepatitis C (treatment-naïve), whereas REALIZE included patients who had not achieved SVR, or viral cure, after a prior course of interferon-based treatment (treatment-experienced).9-11 REALIZE was the only Phase 3 study of an investigational DAA designed to evaluate all major subgroups of people whose prior treatment was unsuccessful, including those who had a null response (less than a 2-log10 drop in HCV RNA by week 12 of a prior course of treatment) as defined by the U.S. Food and Drug Administration (FDA).6,11,12
The telaprevir Phase 2 study results were published in the New England Journal of Medicine, and Phase 3 results from ADVANCE and ILLUMINATE were presented at the annual meeting of the American Association for the Study of Liver Diseases in October 2010.9,10,13-15
Vertex submitted a new drug application to the FDA in November of 2010 and plans to request priority (6-month) review of the application.
References
1. World Health Organization. Hepatitis C. http://www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index.html. Updated 2002. Accessed August 18, 2010.
2. Institute of Medicine of the National Academies. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Colvin HM and Mitchell AE, ed. http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx. Updated January 11, 2010. Accessed August 18, 2010.
3. Pyenson B, Fitch K, Iwasaki K. Consequences of hepatitis C virus (HCV): costs of a baby boomer epidemic of liver disease. http://www.natap.org/2009/HCV/051809_01.htm. Updated May 2009. Accessed August 18, 2010. This report was commissioned by Vertex Pharmaceuticals.
4. Blatt LM, Mutchnick MG, Tong MJ, et al. Assessment of hepatitis C virus RNA and genotype from 6807 patients with chronic hepatitis in the United States. J Viral Hepat. 2000;7:196-202.
5. Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. New Eng J Med. 2002;347(13):975-982.
6. Ghany MG, Strader DB, Thomas DL, Seeff LB. Diagnosis, management and treatment of hepatitis C: An update. Hepatology. 2009;49(4): 1335-1374.
7. Perni RB, Almquist SJ, Byrn RA, et al. Preclinical profile of VX-950, a potent, selective, and orally bioavailable inhibitor of hepatitis C virus NS3-4A serine protease. Antimicrob Agents Chemother. 2006;50(3):899-909.
8. Reesink HW, Zeuzem S, Weegink CJ, et al. Rapid decline of viral RNA in hepatitis C patients treated with VX-950: a phase Ib, placebo-controlled, randomized study. Gastroenterology. 2006;131(4):997–1002.
9. Jacobson IM, McHutchison JG, Dusheiko GM et al. Telaprevir in combination with Peginterferon and ribavirin in genotype 1 HCV treatment-naïve patients: Final results of phase 3 ADVANCE study. Hepatology. 2010;52(Suppl 4): 427A. Abstract 211.
10. Vertex Pharmaceuticals Press Release: Vertex Pharmaceuticals to Start Phase 3 'REALIZE' Trial with Telaprevir in Treatment-Failure HCV Patients, August 19, 2008. Available at: http://investors.vrtx.com/releasedetail.cfm?ReleaseID=328603. Accessed on August 25, 2010.
11. Sherman KE, Flamm SL, Afdhal NH, et al. Telaprevir in combination with peginterferon alfa3a and ribavirin for 34 or 48 weeks in treatment-naïve genotype 1 HCV patients who achieved an extended rapid viral response: Final results of the Phase 3 ILLUMINATE study. Hepatology. 2010;52(Suppl 4):401A. Abstract LB-2.
12 United States Food and Drug Administration. Chronic hepatitis C virus infection: developing direct-acting antiviral agents for treatment. http://www.federalregister.gov/articles/2010/09/14/2010-22806/draft-guidance-for-industry-on-chronic-hepatitis-c-virus-infection-developing-directacting-antiviral. Updated September 14, 2010. Accessed September 14, 2010.
13. McHutchison JG, Everson GT, Gordon SC, et al. and the PROVE1 Study Team. Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. New Eng J Med. 2009;360(18):1827-1838.
14. Hezode C, Forestier N, Dusheiko G, et al. and the PROVE2 Study Team. Telaprevir and peginterferon with or without ribavirin for chronic HCV infection. New Eng J Med. 2009;360(18):1839-1850.
15. McHutchison JG, Manns MP, Muir AJ, et al. and the PROVE3 Study Team. Telaprevir for previously treated chronic HCV infection. New Eng J Med. 2010;362(14):1292-1303.
Source
SeraCare Introduces New HCV Seroconversion Panels
SeraCare Life Sciences, a leading expert in human biologicals and the manufacturer of ACCURUN® controls, introduces two new, highly characterized HCV seroconversion panels designed to help diagnostic manufacturers and clinical laboratories effectively evaluate their HCV test systems.
Milford, MA (PRWEB) December 11, 2010
The safety of the blood supply and the accurate diagnosis of Hepatitis C infection depend on the sensitivity and overall quality of tests for markers of HCV. Test developers, regulators and clinical laboratories require highly characterized panels and control materials to challenge sensitivity accuracy and reproducibility of their assays.
SeraCare Life Sciences, a leading expert in human biologicals and the manufacturer of ACCURUN® controls, introduces two new, highly characterized HCV seroconversion panels designed to help diagnostic manufacturers and clinical laboratories effectively evaluate their HCV test systems. The specimens in each panel are collected from a single individual during the evolution of the immune response to HCV. Accurate detection of early HCV infection is especially important for tests used to screen the blood supply, as HCV is not initially symptomatic upon infection.
The two new seroconversion panels, designated PHV922 and PHV923, each consist of a set of undiluted plasma samples collected from a single individual during seroconversion, the period of time during development of infection and early immune response. PHV922 and PHV923 were collected from deferred plasma donors in different regions of the U.S. over 17 and 23 days respectively, in 2008. PHV922 is HCV genotype 3a; PHV923 is HCV genotype 1a. Both series demonstrate the early evolution of the human immune response to HCV, and contain naturally occurring samples to challenge the sensitivity of tests for HCV antibody.
Data for the SeraCare HCV Seroconversion Panels are available at http://www.seracarepanels.com/. The enhanced online data sheets graphically portray the evolution of the HCV markers, and display test results from multiple test methods for each marker. For additional information call +1 508-244-6400 or visit the webpage at http://www.seracarecatalog.com/, or email info(at)seracare(dot)com.
About SeraCare Life Sciences, Inc.:
SeraCare serves the global life sciences industry by providing vital products and services to facilitate the discovery, development and production of human diagnostics and therapeutics. The Company’s innovative portfolio includes diagnostic controls, plasma-derived reagents and molecular biomarkers, biobanking and contract research services. SeraCare’s quality systems, scientific expertise and state-of-the-art facilities support its customers in meeting the stringent requirements of the highly regulated life sciences industry.
Source
Milford, MA (PRWEB) December 11, 2010
The safety of the blood supply and the accurate diagnosis of Hepatitis C infection depend on the sensitivity and overall quality of tests for markers of HCV. Test developers, regulators and clinical laboratories require highly characterized panels and control materials to challenge sensitivity accuracy and reproducibility of their assays.
SeraCare Life Sciences, a leading expert in human biologicals and the manufacturer of ACCURUN® controls, introduces two new, highly characterized HCV seroconversion panels designed to help diagnostic manufacturers and clinical laboratories effectively evaluate their HCV test systems. The specimens in each panel are collected from a single individual during the evolution of the immune response to HCV. Accurate detection of early HCV infection is especially important for tests used to screen the blood supply, as HCV is not initially symptomatic upon infection.
The two new seroconversion panels, designated PHV922 and PHV923, each consist of a set of undiluted plasma samples collected from a single individual during seroconversion, the period of time during development of infection and early immune response. PHV922 and PHV923 were collected from deferred plasma donors in different regions of the U.S. over 17 and 23 days respectively, in 2008. PHV922 is HCV genotype 3a; PHV923 is HCV genotype 1a. Both series demonstrate the early evolution of the human immune response to HCV, and contain naturally occurring samples to challenge the sensitivity of tests for HCV antibody.
Data for the SeraCare HCV Seroconversion Panels are available at http://www.seracarepanels.com/. The enhanced online data sheets graphically portray the evolution of the HCV markers, and display test results from multiple test methods for each marker. For additional information call +1 508-244-6400 or visit the webpage at http://www.seracarecatalog.com/, or email info(at)seracare(dot)com.
About SeraCare Life Sciences, Inc.:
SeraCare serves the global life sciences industry by providing vital products and services to facilitate the discovery, development and production of human diagnostics and therapeutics. The Company’s innovative portfolio includes diagnostic controls, plasma-derived reagents and molecular biomarkers, biobanking and contract research services. SeraCare’s quality systems, scientific expertise and state-of-the-art facilities support its customers in meeting the stringent requirements of the highly regulated life sciences industry.
Source
Hepatitis C: Disease Treatment Insight
Writer Toni Brown
MedPredict Market Research, a global provider of pharmaceutical competitive intelligence and market research, has published a new report entitled “Thought Leader Insight & Analysis: Hepatitis C Virus (HCV),” designed to provide critical strategic insight for pharma and biotech companies with a stake in the market for treatments in this disease area.
“This report summarizes the perspectives of renowned thought leaders who specialize in the treatment of hepatitis C,” according to Elizabeth Mathews, MedPredict’s CEO. “We conducted in-depth interviews with these experts immediately following AASLD to understand the effect that the upcoming approvals of telaprevir and boceprevir will have on the treatment of HCV, as well as to gain insight into how combination therapy will address the unmet needs still remaining after the approval of these protease inhibitors.”
Some of the topics discussed by in this report include:
- Goals of therapy,
- Who should treat HCV,
- Unmet needs and favorite future cocktails; interferon-sparing regimens,
- Warehousing patients in the age of protease inhibitors,
- Potential for resistance development,
- Dosing/compliance,
- IL-28b / CC, CT and TT patients; US, EU and Asian populations,
- Fibrosis score,
- Possible reimbursement/bundling strategies,
- Cost of therapy and duration of treatment, and
- Side effects: rash vs. anemia.
The full report may be purchased by contacting MedPredict.
About MedPredict
MedPredict maintains a proprietary database of over 1,000 global physician thought leaders. Based on primary interviews with these thought leaders, MedPredict publishes periodic therapeutic area reports to keep clients up-to-date on emerging trends and competitive activity. The reports include thought leader reactions to recent publications and presentations, as well as clinical, regulatory and marketing activity.
For more information contact:
Elizabeth Mathews
MedPredict
513.271.1924
Source
`Natural killers' unleashed to search and destroy cancer
Doctors at the University of Miami are treating liver cancer patients by giving immune-system cells more muscle in the lab to recognize and attack their cancer cells.
BY FRED TASKER
ftasker@MiamiHerald.com
They're called ``natural killer cells'' but they're a part of the human immune system that helps save lives. Now doctors from Miami and Japan have developed new ways to pump up the cells to attack cancer even more aggressively.
Encarnacion Miranda, a 58-year-old car salesman from Key Largo, is counting on the cells -- which exist in healthy livers -- to save his life. He's the first patient in a clinical trial at the University of Miami of 25 liver patients seeking Food and Drug Administration approval of the new treatment.
``It's scary,'' Miranda said Thursday, during an announcement of the medical trial. ``But I feel really good.''
Miranda's liver had been dogging him since 1979, when he contracted hepatitis C from a blood transfusion. By October 2009, chronic exhaustion forced him to give up his favorite sport, fishing for yellowtail snapper in the Florida Keys. That's when he learned his hepatitis had become liver cancer.
Doctors gave Miranda a liver transplant. But, knowing that liver cancer recurs in up to 20 percent of cases due to tumor cells left hiding in the body, they went further. Before the transplant, they took blood from the donated liver, extracted the natural killer immune cells from it, then cultured and expanded them in laboratory flasks for four days to increase their power against any remaining cancer cells. They fed them intravenously back into Miranda's new liver.
Doctors say the killer cells, which recognize cancer cells as alien and try to destroy them, also will help fight any remaining hepatitis C. They aren't sure yet whether their findings on natural killer cell expansion might be broadened to work in other organs and combat other cancers.
The procedure was studied for four years at the University of Hiroshima. Dr. Masahiro Ohira performed the procedure on 24 patients; 22 survived cancer-free for more than three years. It cut in half the recurrence of cancer.
``The killer cells act like smart bombs in going after the cancer,'' Ohira said.
Miranda is grateful to the team at the University of Miami Medical School that worked with him at Jackson Memorial Medical Center.
``I was up and walking three days after my [Oct. 19] transplant,'' he said. ``Yesterday I walked six miles.''
Treating Miranda was actually far more complicated than his recovery would indicate. When his three liver tumors were found, they were too big to permit a transplant. So the team from UM used several courses of chemotherapy and radio-frequency ablation -- the use of radio-frequency waves to destroy tumor tissue -- to attack them, finally reducing them enough to make possible the transplant.
When a donor liver became available, the doctors flushed out some of its natural killer cells before transplanting it into Miranda. Ohira put the cells into a laboratory flask and applied an agent known to increase the cells' potency, even though it doesn't increase their number.
``It increases their activity against cancer and hepatitis C by four times,'' he said.
The team included Dr. Andreas Tzakis, director of the Liver Transplant Program, Ohira, now a research associate in the UM Department of Surgery and Drs. Seigo Nishida and David Levi, professors of clinical surgery at UM.
``They're my heroes,'' Miranda said. ``They never gave up.''
Miranda's prognosis?
``We think it's good,'' Tzakis said. ``Of course there are no guarantees.''
Miranda says he has far more energy now.
``Last year I was so exhausted I felt like I was passing away. Today I feel like a new person.''
Miranda's doctors say by next year he and his companion of 14 years, Linda Cozby, can return to catching yellowtail snapper.
Miranda grinned.
``Next year is only three weeks away.''
Source
BY FRED TASKER
ftasker@MiamiHerald.com
They're called ``natural killer cells'' but they're a part of the human immune system that helps save lives. Now doctors from Miami and Japan have developed new ways to pump up the cells to attack cancer even more aggressively.
Encarnacion Miranda, a 58-year-old car salesman from Key Largo, is counting on the cells -- which exist in healthy livers -- to save his life. He's the first patient in a clinical trial at the University of Miami of 25 liver patients seeking Food and Drug Administration approval of the new treatment.
``It's scary,'' Miranda said Thursday, during an announcement of the medical trial. ``But I feel really good.''
Miranda's liver had been dogging him since 1979, when he contracted hepatitis C from a blood transfusion. By October 2009, chronic exhaustion forced him to give up his favorite sport, fishing for yellowtail snapper in the Florida Keys. That's when he learned his hepatitis had become liver cancer.
Doctors gave Miranda a liver transplant. But, knowing that liver cancer recurs in up to 20 percent of cases due to tumor cells left hiding in the body, they went further. Before the transplant, they took blood from the donated liver, extracted the natural killer immune cells from it, then cultured and expanded them in laboratory flasks for four days to increase their power against any remaining cancer cells. They fed them intravenously back into Miranda's new liver.
Doctors say the killer cells, which recognize cancer cells as alien and try to destroy them, also will help fight any remaining hepatitis C. They aren't sure yet whether their findings on natural killer cell expansion might be broadened to work in other organs and combat other cancers.
The procedure was studied for four years at the University of Hiroshima. Dr. Masahiro Ohira performed the procedure on 24 patients; 22 survived cancer-free for more than three years. It cut in half the recurrence of cancer.
``The killer cells act like smart bombs in going after the cancer,'' Ohira said.
Miranda is grateful to the team at the University of Miami Medical School that worked with him at Jackson Memorial Medical Center.
``I was up and walking three days after my [Oct. 19] transplant,'' he said. ``Yesterday I walked six miles.''
Treating Miranda was actually far more complicated than his recovery would indicate. When his three liver tumors were found, they were too big to permit a transplant. So the team from UM used several courses of chemotherapy and radio-frequency ablation -- the use of radio-frequency waves to destroy tumor tissue -- to attack them, finally reducing them enough to make possible the transplant.
When a donor liver became available, the doctors flushed out some of its natural killer cells before transplanting it into Miranda. Ohira put the cells into a laboratory flask and applied an agent known to increase the cells' potency, even though it doesn't increase their number.
``It increases their activity against cancer and hepatitis C by four times,'' he said.
The team included Dr. Andreas Tzakis, director of the Liver Transplant Program, Ohira, now a research associate in the UM Department of Surgery and Drs. Seigo Nishida and David Levi, professors of clinical surgery at UM.
``They're my heroes,'' Miranda said. ``They never gave up.''
Miranda's prognosis?
``We think it's good,'' Tzakis said. ``Of course there are no guarantees.''
Miranda says he has far more energy now.
``Last year I was so exhausted I felt like I was passing away. Today I feel like a new person.''
Miranda's doctors say by next year he and his companion of 14 years, Linda Cozby, can return to catching yellowtail snapper.
Miranda grinned.
``Next year is only three weeks away.''
Source
Fat Index Associated With Liver Damage in Hep C Patients
Last Updated: December 09, 2010
The visceral adiposity index, a score that combines body mass index, waist circumference, triglycerides, and high-density lipoprotein levels, is associated with liver damage and viral load in patients with genotype 1 chronic hepatitis C, according to a study in the November issue of Hepatology.
THURSDAY, Dec. 9 (HealthDay News) -- The visceral adiposity index (VAI), a score that combines body mass index, waist circumference, triglycerides, and high-density lipoprotein levels, is associated with liver damage and viral load in patients with genotype 1 chronic hepatitis C (G1 CHC), according to a study in the November issue of Hepatology.
Salvatore Petta, M.D., of the University of Palermo in Italy, and colleagues performed liver biopsies on 236 patients with G1 CHC and conducted examinations to assess for steatosis, evidence of liver damage (such as necroinflammatory activity and fibrosis), and viral loads. The researchers also conducted metabolic and anthropometric tests and computed each subject's VAI.
The researchers found that VAI scores were independently associated with homeostasis model assessment score, hepatitis C virus (HCV) RNA levels, necroinflammatory activity, and steatosis. Also, in regression analyses, insulin resistance, higher VAI score, and fibrosis all were associated with moderate to severe steatosis, while older age, higher VAI score, and fibrosis were independently associated with steatosis of at least 30 percent, and older age, higher VAI score, and fibrosis were independently related to moderate to severe necroinflammatory activity.
"In conclusion, VAI, a new index of both fat function and distribution, appears to be independently associated with steatosis and necroinflammatory activity in G1 CHC patients and has a direct correlation with HCV viral load. These data suggest a direct role of adipose tissue in liver damage and a possible interference of HCV with adipocyte function. Experimental studies are needed to determine the mechanisms responsible for these associations," the authors write.
Abstract
Full Text (subscription or payment may be required)
Source
The visceral adiposity index, a score that combines body mass index, waist circumference, triglycerides, and high-density lipoprotein levels, is associated with liver damage and viral load in patients with genotype 1 chronic hepatitis C, according to a study in the November issue of Hepatology.
THURSDAY, Dec. 9 (HealthDay News) -- The visceral adiposity index (VAI), a score that combines body mass index, waist circumference, triglycerides, and high-density lipoprotein levels, is associated with liver damage and viral load in patients with genotype 1 chronic hepatitis C (G1 CHC), according to a study in the November issue of Hepatology.
Salvatore Petta, M.D., of the University of Palermo in Italy, and colleagues performed liver biopsies on 236 patients with G1 CHC and conducted examinations to assess for steatosis, evidence of liver damage (such as necroinflammatory activity and fibrosis), and viral loads. The researchers also conducted metabolic and anthropometric tests and computed each subject's VAI.
The researchers found that VAI scores were independently associated with homeostasis model assessment score, hepatitis C virus (HCV) RNA levels, necroinflammatory activity, and steatosis. Also, in regression analyses, insulin resistance, higher VAI score, and fibrosis all were associated with moderate to severe steatosis, while older age, higher VAI score, and fibrosis were independently associated with steatosis of at least 30 percent, and older age, higher VAI score, and fibrosis were independently related to moderate to severe necroinflammatory activity.
"In conclusion, VAI, a new index of both fat function and distribution, appears to be independently associated with steatosis and necroinflammatory activity in G1 CHC patients and has a direct correlation with HCV viral load. These data suggest a direct role of adipose tissue in liver damage and a possible interference of HCV with adipocyte function. Experimental studies are needed to determine the mechanisms responsible for these associations," the authors write.
Abstract
Full Text (subscription or payment may be required)
Source
Lab21 secures new patents in Hepatitis C drug resistance andfluorescent carbon-based nanoparticle technology
Cambridge, UK, December 8th - Lab21 Limited, the Cambridge, UK-based specialist in personalised medicine has secured new patents in Europe and the USA relating to Hepatitis C and its SelahDOTS™ fluorescent nanoparticles, as it continues to expand its intellectual property portfolio.
The hepatitis C patent extends an existing patent, and refers to technology allowing the genotypic identification of drug resistant mutations in the 4 major global genotypes of HCV. With the imminent launch of a series of new small molecule therapies in HCV, this technology will allow accurate monitoring of when drug resistance appears in individual patients, improving patient care.
The SelahDOTS™ nanoparticles technology covers a generic approach to the development of new diagnostic and imaging reagents using carbon-based non-toxic nanoparticles. This platform technology has multiple applications in clinical diagnostics and was originally developed through a licence from Clemson University. The grant of the patent now allows Lab21 to develop a series of new product and service applications in areas such as in vivo imaging, immunodiagnostics and point-of-care biomarker analysis,
The securing of these patents builds on Lab21’s growing intellectual property portfolio as it expands its competitive proprietary position in pharmacogenetic markers, disease markers and its assay technology.
Dr Berwyn Clarke, CSO at Lab21 commented: ‘The HCV patent further strengthens our portfolio in the important HCV diagnostic area while the nanoparticle platform technology has potential to transform the ways in which particulate diagnostics are used, particularly in vivo, where particle-related toxicity has been a significant problem. Additionally we are seeing early development progress in incorporating the SelahDOTS™ technology in our own new molecular and protein based assays.’
Graham Mullis, Lab21 CEO added: ‘The development of an extensive intellectual property portfolio will be an important part of Lab21’s strategy as we continue to grow. Patents such as these will ensure we are able to remain uniquely competitive and ensure we are able to provide our customers with the most advanced products and services in the markets we choose to serve.’
For further information: Lab21 Graham Mullis, CEO Dr Berwyn Clarke, CSDO t: +44 (0)1223 395461 e: graham.mullis@lab-21.com
For media and investor enquiries: College Hill Tony Stephenson/Gemma Howe/Nicole Yost t: +44 (0)20 7866 7864 m: +44 (0)7989 855113 e: lab21@collegehill.com
About Lab21 Lab21 is a global provider of state-of-the-art diagnostic products and services, supporting blood bank screening, medical diagnostics and drug discovery. Its customers include international healthcare providers, pharmaceutical and biotechnology companies. The product division of the Company manufactures immunodiagnostic kits and reagents that are distributed into 110 international countries and is focused on infectious diseases for the blood-banking market. The service division has a growing test portfolio providing companion diagnostics and high technology molecular assays for the growing integration of personalised medicine into healthcare. These services are currently in infectious diseases, oncology and pharmacogenetics areas with emerging interests in cardiovascular and metabolic disease. Lab21's clinical reference laboratory and corporate office is based in Cambridge and has additional UK sites in Newmarket, Bridport, Liverpool and Ipswich. It also has operations in South Carolina, USA. The Company's investors include Merlin Biosciences, Nexus Medical Partners, Medicis Capital, Rowan Dartington and Kreos Capital. Website: http://www.lab21.com/
Source
The hepatitis C patent extends an existing patent, and refers to technology allowing the genotypic identification of drug resistant mutations in the 4 major global genotypes of HCV. With the imminent launch of a series of new small molecule therapies in HCV, this technology will allow accurate monitoring of when drug resistance appears in individual patients, improving patient care.
The SelahDOTS™ nanoparticles technology covers a generic approach to the development of new diagnostic and imaging reagents using carbon-based non-toxic nanoparticles. This platform technology has multiple applications in clinical diagnostics and was originally developed through a licence from Clemson University. The grant of the patent now allows Lab21 to develop a series of new product and service applications in areas such as in vivo imaging, immunodiagnostics and point-of-care biomarker analysis,
The securing of these patents builds on Lab21’s growing intellectual property portfolio as it expands its competitive proprietary position in pharmacogenetic markers, disease markers and its assay technology.
Dr Berwyn Clarke, CSO at Lab21 commented: ‘The HCV patent further strengthens our portfolio in the important HCV diagnostic area while the nanoparticle platform technology has potential to transform the ways in which particulate diagnostics are used, particularly in vivo, where particle-related toxicity has been a significant problem. Additionally we are seeing early development progress in incorporating the SelahDOTS™ technology in our own new molecular and protein based assays.’
Graham Mullis, Lab21 CEO added: ‘The development of an extensive intellectual property portfolio will be an important part of Lab21’s strategy as we continue to grow. Patents such as these will ensure we are able to remain uniquely competitive and ensure we are able to provide our customers with the most advanced products and services in the markets we choose to serve.’
For further information: Lab21 Graham Mullis, CEO Dr Berwyn Clarke, CSDO t: +44 (0)1223 395461 e: graham.mullis@lab-21.com
For media and investor enquiries: College Hill Tony Stephenson/Gemma Howe/Nicole Yost t: +44 (0)20 7866 7864 m: +44 (0)7989 855113 e: lab21@collegehill.com
About Lab21 Lab21 is a global provider of state-of-the-art diagnostic products and services, supporting blood bank screening, medical diagnostics and drug discovery. Its customers include international healthcare providers, pharmaceutical and biotechnology companies. The product division of the Company manufactures immunodiagnostic kits and reagents that are distributed into 110 international countries and is focused on infectious diseases for the blood-banking market. The service division has a growing test portfolio providing companion diagnostics and high technology molecular assays for the growing integration of personalised medicine into healthcare. These services are currently in infectious diseases, oncology and pharmacogenetics areas with emerging interests in cardiovascular and metabolic disease. Lab21's clinical reference laboratory and corporate office is based in Cambridge and has additional UK sites in Newmarket, Bridport, Liverpool and Ipswich. It also has operations in South Carolina, USA. The Company's investors include Merlin Biosciences, Nexus Medical Partners, Medicis Capital, Rowan Dartington and Kreos Capital. Website: http://www.lab21.com/
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