By Bill Gorman – October 27, 2010
A CAPITAL IN CRISIS: SHOWTIME® DOCUMENTARY “THE OTHER CITY” EXPLORES THE HIV/AIDS EPIDEMIC IN WASHINGTON D.C.
To Premiere In Honor of World AIDS Day
Wednesday, December 1st at 7:30 PM ET/PT
LOS ANGELES, CA – (October 27, 2010) – Washington D.C. is a place where power and policy intersect, yet in the shadows of the U.S. Capitol lies the reality of a very different city – a city visitors rarely see. Last year, it was reported that 3% ofWashington D.C.’s residents are living with HIV or AIDS. How does the capital of the most powerful country in the world become the home of the highest HIV/AIDS rate in the nation – rivaling some African countries? On Wednesday, December 1stat 7:30 PM ET/PT, in honor of World AIDS Day, SHOWTIME will premiere THE OTHER CITY, a documentary that believes politics, ideology, corruption and bureaucracy have led the HIV/AIDS epidemic to grow out of control in Washington D.C., the city that is supposed to represent the best ideals of the United States of America.
THE OTHER CITY tells the stories of Washington D.C. citizens who have taken matters into their own hands and have not let the lack of government assistance stop them from pursuing effective treatment or from fighting the spread of HIV/AIDS every day. The individuals profiled include: J’Mia Edwards, a woman living with AIDS and fighting desperately to keep herself and her three young children from being thrown out of their home; Jose Ramirez, a young man who contracted the disease from a boyfriend – who didn’t disclose he was infected – but now, devotes his life to promoting HIV awareness among Hispanic teens; a one-time addict now living with AIDS, Ron Daniels saves lives by providing clean needles and helping drug users receive treatment; and finally, the staff of the AIDS hospice Joseph’s House struggles to provide solace to terminal patients’ last days, to deal with their own sense of loss, and their constantly declining funding.
The film is directed by Emmy®-and Peabody-winning filmmaker Susan Koch (“Kicking It”) and produced by entrepreneur and philanthropist Sheila C. Johnson. The co-producer is award-winning journalist Jose Antonio Vargas.
Source
October 27, 2010
Pharmasset to Webcast an Investor Event from the AASLD Meeting
PRINCETON, N.J., Oct. 27 /PRNewswire-FirstCall/ -- Pharmasset, Inc. (Nasdaq: VRUS) today announced that it will webcast an investor event from the American Association for the Study of Liver Diseases (AASLD) on Sunday, October 31, 2010 starting at 7:00pm ET. During this webcast, management will review Pharmasset's progress on the programs that are the subject of presentations at AASLD.
To access a simultaneous webcast of this event via the internet, log on to the "Events & Presentations" section of the Investor Center on Pharmasset's website at http://investor.pharmasset.com/events.cfm . Please connect to the website at least ten minutes prior to the start of the presentation to ensure adequate time for a reliable connection and any software download that may be necessary for the webcast.
The following abstracts are available on the AASLD website (AASLD.org).
RG7128
Abstract 81
"High rates of early viral response, promising safety profile and lack of resistance related breakthrough in HCV GT 1/4 patients treated with RG7128 plus PegIFN alfa-2a (40KD)/RBV: Planned Week 12 interim analysis from the PROPEL study" will be presented in the HCV Clinical Trials session on Sunday October 31st at 5:15pm ET. Authors of the study are Jensen, D. M. et al.
Abstract 799
"No evidence of drug resistance or baseline S282T resistance mutation among GT1 and GT4 HCV infected patients on nucleoside polymerase inhibitor RG7128 and Peg-IFN/RBV combination treatment for up to 12 weeks: Interim analysis from the PROPEL study" will be presented in a poster session on Sunday October 31st. Authors of the study are Le Pogam, S. et al.
PSI-7977
Abstract 806
"High Rapid Virologic Response (RVR) with PSI-7977 Daily Dosing plus PEG-IFN/RBV in a 28-day Phase 2a Trial" will be presented in a poster session on Sunday October 31st. Authors of the study are Lawitz, E. et al.
Abstract 1861
"Clinical synergy of an Anti-HCV Nucleotide Analog with SOC: Viral Kinetics of PSI-7977 with SOC" will be presented in a poster session on Tuesday November 2nd. Authors of the study are Lawitz E, et al.
Abstract 815
"IL28B SNP Geographical Distribution and Antiviral Responses in a 28-day Phase 2a Trial of PSI-7977 Daily Dosing plus PEG-IFN/RBV" will be presented in a poster session on Sunday October 31st. Authors of the study are McHutchison, J.G. et al.
PSI-938
Abstract 1890
"Pharmacokinetics, Safety, and Tolerability of PSI-938, a Novel Nucleotide Polymerase Inhibitor for HCV, Following Single Ascending Oral Doses in Healthy Subjects" will be presented in a poster session on Tuesday November 2nd. Authors of the study are Symonds, W. et al.
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 presently in a Phase 2b study, and PSI-938, an unpartnered guanosine nucleotide analog in a Phase 1 study. We also have in our pipeline an additional purine nucleotide analog, PSI-661, in advanced preclinical development. Racivir, for the treatment of HIV, has completed a Phase 2 clinical study.
Pegasys® and Copegus® are registered trademarks of Roche.
Contact
Richard E. T. Smith, Ph.D.
VP, Investor Relations and Corporate Communications
Office: +1 (609) 613-4181
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, 2009 and our Quarterly Reports on Form 10-Q for the periods ended December 31, 2009, March 31, 2010 and June 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.
SOURCE Pharmasset, Inc.
RELATED LINKS
http://www.pharmasset.com/
Source
To access a simultaneous webcast of this event via the internet, log on to the "Events & Presentations" section of the Investor Center on Pharmasset's website at http://investor.pharmasset.com/events.cfm . Please connect to the website at least ten minutes prior to the start of the presentation to ensure adequate time for a reliable connection and any software download that may be necessary for the webcast.
The following abstracts are available on the AASLD website (AASLD.org).
RG7128
Abstract 81
"High rates of early viral response, promising safety profile and lack of resistance related breakthrough in HCV GT 1/4 patients treated with RG7128 plus PegIFN alfa-2a (40KD)/RBV: Planned Week 12 interim analysis from the PROPEL study" will be presented in the HCV Clinical Trials session on Sunday October 31st at 5:15pm ET. Authors of the study are Jensen, D. M. et al.
Abstract 799
"No evidence of drug resistance or baseline S282T resistance mutation among GT1 and GT4 HCV infected patients on nucleoside polymerase inhibitor RG7128 and Peg-IFN/RBV combination treatment for up to 12 weeks: Interim analysis from the PROPEL study" will be presented in a poster session on Sunday October 31st. Authors of the study are Le Pogam, S. et al.
PSI-7977
Abstract 806
"High Rapid Virologic Response (RVR) with PSI-7977 Daily Dosing plus PEG-IFN/RBV in a 28-day Phase 2a Trial" will be presented in a poster session on Sunday October 31st. Authors of the study are Lawitz, E. et al.
Abstract 1861
"Clinical synergy of an Anti-HCV Nucleotide Analog with SOC: Viral Kinetics of PSI-7977 with SOC" will be presented in a poster session on Tuesday November 2nd. Authors of the study are Lawitz E, et al.
Abstract 815
"IL28B SNP Geographical Distribution and Antiviral Responses in a 28-day Phase 2a Trial of PSI-7977 Daily Dosing plus PEG-IFN/RBV" will be presented in a poster session on Sunday October 31st. Authors of the study are McHutchison, J.G. et al.
PSI-938
Abstract 1890
"Pharmacokinetics, Safety, and Tolerability of PSI-938, a Novel Nucleotide Polymerase Inhibitor for HCV, Following Single Ascending Oral Doses in Healthy Subjects" will be presented in a poster session on Tuesday November 2nd. Authors of the study are Symonds, W. et al.
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 presently in a Phase 2b study, and PSI-938, an unpartnered guanosine nucleotide analog in a Phase 1 study. We also have in our pipeline an additional purine nucleotide analog, PSI-661, in advanced preclinical development. Racivir, for the treatment of HIV, has completed a Phase 2 clinical study.
Pegasys® and Copegus® are registered trademarks of Roche.
Contact
Richard E. T. Smith, Ph.D.
VP, Investor Relations and Corporate Communications
Office: +1 (609) 613-4181
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, 2009 and our Quarterly Reports on Form 10-Q for the periods ended December 31, 2009, March 31, 2010 and June 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.
SOURCE Pharmasset, Inc.
RELATED LINKS
http://www.pharmasset.com/
Source
Heavy Alcohol Consumption May Increase HIV Disease Progression
By Mariana Plazas-Mayorca and Courtney McQueen
Published: Oct 27, 2010 9:00 am
A new review of several studies has found some evidence linking heavy alcohol use to accelerated HIV disease progression. In particular, alcohol use influences how reliably people take their medication, which can affect HIV progression. However, it is still unclear whether alcohol affects progression independently of antiretroviral adherence.
“There is strong evidence that alcohol consumption interferes with antiretroviral therapy adherence. The more a person drinks alcohol, the more medication he/she misses,” said Professors Judith Hahn and Jeffrey Samet, the authors of the review, in correspondence with The AIDS Beacon.
“Suboptimal adherence to these medications can cause HIV to become resistant and for the treatment regimen to fail,” they added.
However, whether alcohol affects disease progression independently of missed antiretroviral drug doses is more controversial.
Scientists have long speculated that alcohol and drug use affects the rate of HIV progression. Alcohol is known to have suppressive effects on the immune system, and illegal drug use (particularly stimulant use) has been linked to faster progression (see related AIDS Beacon news).
However, the role of alcohol in HIV progression has remained elusive.
“While many studies conducted in the early 1990s found no link between alcohol consumption and HIV disease progression, more recent studies have suggested that there is such a link,” said the authors.
To better understand the connection between alcohol and disease progression, the authors of the review examined a number of studies from before and after the advent of antiretroviral therapy, as well as animal studies where alcohol use was more controlled.
Results showed that prior to the advent of highly active antiretroviral therapy (HAART), studies found no relationship between heavy alcohol consumption and HIV disease progression.
However, more recent studies from the post-HAART era have been inconclusive. Three of the six studies from the post-HAART era included in the review demonstrated an association between heavy alcohol use and at least one measure of HIV disease progression, such as higher viral load (amount of HIV in the blood), lower CD4 (white blood cell) count, opportunistic infections, or death.
The other three studies found no association between alcohol consumption and HIV progression, aside from alcohol’s impact on treatment adherence.
Since studies of alcohol consumption in people can be complicated by other factors – heavy drinkers may be more likely to be depressed, for example, and depression can affect HIV progression – the review authors also examined studies of alcohol use in monkeys.
Monkeys can be infected with simian immunodeficiency virus (SIV), the monkey version of HIV. Since both their alcohol intake and antiretroviral adherence can be carefully controlled, these studies can potentially illuminate purely biological effects of alcohol consumption on disease progression, rather than effects of behavior, such as treatment adherence.
Results of these studies suggest that there might in fact be a biological basis for alcohol’s effects on HIV progression. For example, several studies found higher viral loads in monkeys that drank heavily, and one study found that monkeys with high alcohol consumption progressed faster than monkeys that did not drink alcohol.
The authors speculated on a variety of reasons why alcohol might affect HIV progression. Alcohol is known to have detrimental effects on the immune system, for example, and can also lead to vitamin and mineral deficiencies.
In addition, there is evidence that alcohol may interfere with the body’s metabolism of antiretroviral medications. As a result, chronic alcohol users might be at higher risk for ineffective therapy due to low concentrations of antiretrovirals in the blood.
Aside from these potential biological factors, heavy drinkers may be less likely to receive HIV care and more likely to take illegal drugs, which are known to increase disease progression. HIV-positive individuals who suffer from other conditions, such as hepatitis C, should be particularly cautious when consuming alcohol.
“Many persons living with HIV are also infected with hepatitis C virus (HCV), and for those patients, using alcohol can speed HCV disease progression,” said Professors Hahn and Samet.
The authors suggested that people with HIV be cautious about alcohol consumption.
“All persons who are living with HIV and who drink alcohol should discuss their alcohol consumption with their physicians,” said the authors. “There are several effective methods to reduce or quit alcohol consumption; counseling, medications, and mutual support groups (e.g., Alcoholics Anonymous) are options that can help.”
“Even if they do not stop drinking, their physicians should know so that they can monitor their liver function,” the authors added. “Physicians treating those with HIV should be aware of the potential effects of alcohol on HIV disease progression and routinely screen all of their patients for alcohol consumption.”
They concluded that the evidence linking alcohol abuse to HIV progression is suggestive but not conclusive, and that further study is needed to elucidate the link.
Brown University announced earlier this month that a new research institute, the Brown Alcohol Research Center on HIV, will be devoted to studying the health effects of drinking in people with HIV. The institute will conduct studies on the effects of alcohol and HIV on metabolism and brain function, and the interaction between alcohol, HIV, and HCV, among others.
For more information, please see the review article in Current HIV/AIDS Reports. For more information on the Brown Alcohol Research Center on HIV, please see the Brown University website.
Source
Also See: HIV, alcohol topic for Brown study
Published: Oct 27, 2010 9:00 am
A new review of several studies has found some evidence linking heavy alcohol use to accelerated HIV disease progression. In particular, alcohol use influences how reliably people take their medication, which can affect HIV progression. However, it is still unclear whether alcohol affects progression independently of antiretroviral adherence.
“There is strong evidence that alcohol consumption interferes with antiretroviral therapy adherence. The more a person drinks alcohol, the more medication he/she misses,” said Professors Judith Hahn and Jeffrey Samet, the authors of the review, in correspondence with The AIDS Beacon.
“Suboptimal adherence to these medications can cause HIV to become resistant and for the treatment regimen to fail,” they added.
However, whether alcohol affects disease progression independently of missed antiretroviral drug doses is more controversial.
Scientists have long speculated that alcohol and drug use affects the rate of HIV progression. Alcohol is known to have suppressive effects on the immune system, and illegal drug use (particularly stimulant use) has been linked to faster progression (see related AIDS Beacon news).
However, the role of alcohol in HIV progression has remained elusive.
“While many studies conducted in the early 1990s found no link between alcohol consumption and HIV disease progression, more recent studies have suggested that there is such a link,” said the authors.
To better understand the connection between alcohol and disease progression, the authors of the review examined a number of studies from before and after the advent of antiretroviral therapy, as well as animal studies where alcohol use was more controlled.
Results showed that prior to the advent of highly active antiretroviral therapy (HAART), studies found no relationship between heavy alcohol consumption and HIV disease progression.
However, more recent studies from the post-HAART era have been inconclusive. Three of the six studies from the post-HAART era included in the review demonstrated an association between heavy alcohol use and at least one measure of HIV disease progression, such as higher viral load (amount of HIV in the blood), lower CD4 (white blood cell) count, opportunistic infections, or death.
The other three studies found no association between alcohol consumption and HIV progression, aside from alcohol’s impact on treatment adherence.
Since studies of alcohol consumption in people can be complicated by other factors – heavy drinkers may be more likely to be depressed, for example, and depression can affect HIV progression – the review authors also examined studies of alcohol use in monkeys.
Monkeys can be infected with simian immunodeficiency virus (SIV), the monkey version of HIV. Since both their alcohol intake and antiretroviral adherence can be carefully controlled, these studies can potentially illuminate purely biological effects of alcohol consumption on disease progression, rather than effects of behavior, such as treatment adherence.
Results of these studies suggest that there might in fact be a biological basis for alcohol’s effects on HIV progression. For example, several studies found higher viral loads in monkeys that drank heavily, and one study found that monkeys with high alcohol consumption progressed faster than monkeys that did not drink alcohol.
The authors speculated on a variety of reasons why alcohol might affect HIV progression. Alcohol is known to have detrimental effects on the immune system, for example, and can also lead to vitamin and mineral deficiencies.
In addition, there is evidence that alcohol may interfere with the body’s metabolism of antiretroviral medications. As a result, chronic alcohol users might be at higher risk for ineffective therapy due to low concentrations of antiretrovirals in the blood.
Aside from these potential biological factors, heavy drinkers may be less likely to receive HIV care and more likely to take illegal drugs, which are known to increase disease progression. HIV-positive individuals who suffer from other conditions, such as hepatitis C, should be particularly cautious when consuming alcohol.
“Many persons living with HIV are also infected with hepatitis C virus (HCV), and for those patients, using alcohol can speed HCV disease progression,” said Professors Hahn and Samet.
The authors suggested that people with HIV be cautious about alcohol consumption.
“All persons who are living with HIV and who drink alcohol should discuss their alcohol consumption with their physicians,” said the authors. “There are several effective methods to reduce or quit alcohol consumption; counseling, medications, and mutual support groups (e.g., Alcoholics Anonymous) are options that can help.”
“Even if they do not stop drinking, their physicians should know so that they can monitor their liver function,” the authors added. “Physicians treating those with HIV should be aware of the potential effects of alcohol on HIV disease progression and routinely screen all of their patients for alcohol consumption.”
They concluded that the evidence linking alcohol abuse to HIV progression is suggestive but not conclusive, and that further study is needed to elucidate the link.
Brown University announced earlier this month that a new research institute, the Brown Alcohol Research Center on HIV, will be devoted to studying the health effects of drinking in people with HIV. The institute will conduct studies on the effects of alcohol and HIV on metabolism and brain function, and the interaction between alcohol, HIV, and HCV, among others.
For more information, please see the review article in Current HIV/AIDS Reports. For more information on the Brown Alcohol Research Center on HIV, please see the Brown University website.
Source
Also See: HIV, alcohol topic for Brown study
Few Veterans at US Government Care Facilities Receive Testing for HIV: Presented at IDSA
By Ed Susman
VANCOUVER -- October 26, 2010 -- The percentage of patients in the US government-run Veterans Affairs medical facilities who have been tested for HIV infection is less than 10%, despite government recommendations that patients receive routine HIV testing, researchers stated here at the 48th Annual Meeting of the Infectious Diseases Society of America (IDSA).
"We don't know why these testing levels are so low, but they are even low in areas where HIV has a large prevalence," said Meredith Welch, MD, Veterans Affairs Medical Center/George Washington University Medical Center, Washington, DC.
Dr. Welch noted that 5.7 million outpatients were seen in the Veterans Affairs system in 2009. In a detailed survey of that system, however, it appeared that, as of 2009, just 9.2% of these outpatients had been tested ever before for HIV, with 2.5% of these patients tested within that year.
In the District of Columbia, where HIV infection prevalence is just over 1,402/100,000 persons, about 21.6% of outpatients have ever been tested for HIV, Dr. Welch said here at her poster presentation on October 23.
In New York, where the prevalence of HIV is just over 777/100,000 persons, about 11.8% of people in the Veterans Affairs health system have ever been tested for HIV.
In places where prevalence of HIV is low, such as Utah with a prevalence of just over 105/100,000 persons, just 2.7% of outpatients in the Veterans Affairs facilities there have ever been tested for HIV.
"The Centers for Disease Control and Prevention has recommended HIV testing for all persons aged 13 to 64 or pregnant women since 2006," Dr. Welch said. "The federal law requiring written informed consent for HIV testing with pre- and post-test counselling within Veterans Affairs was repealed in 2008."
Despite removal of such barriers, there still appears to be a slow uptake of testing in the Veterans Affairs system. Dr. Welch suggested that her study could act as a baseline for future studies that will determine how well the Veterans Affairs health system is performing in testing for HIV.
"There may still be some stigma involved with HIV that prevents physicians from asking patients to undergo an HIV test," she speculated.
[Presentation title: Initial Assessment of HIV Testing Among Outpatient Veterans Compared With US Rates of HIV/AIDS. Abstract 1063]
Source
VANCOUVER -- October 26, 2010 -- The percentage of patients in the US government-run Veterans Affairs medical facilities who have been tested for HIV infection is less than 10%, despite government recommendations that patients receive routine HIV testing, researchers stated here at the 48th Annual Meeting of the Infectious Diseases Society of America (IDSA).
"We don't know why these testing levels are so low, but they are even low in areas where HIV has a large prevalence," said Meredith Welch, MD, Veterans Affairs Medical Center/George Washington University Medical Center, Washington, DC.
Dr. Welch noted that 5.7 million outpatients were seen in the Veterans Affairs system in 2009. In a detailed survey of that system, however, it appeared that, as of 2009, just 9.2% of these outpatients had been tested ever before for HIV, with 2.5% of these patients tested within that year.
In the District of Columbia, where HIV infection prevalence is just over 1,402/100,000 persons, about 21.6% of outpatients have ever been tested for HIV, Dr. Welch said here at her poster presentation on October 23.
In New York, where the prevalence of HIV is just over 777/100,000 persons, about 11.8% of people in the Veterans Affairs health system have ever been tested for HIV.
In places where prevalence of HIV is low, such as Utah with a prevalence of just over 105/100,000 persons, just 2.7% of outpatients in the Veterans Affairs facilities there have ever been tested for HIV.
"The Centers for Disease Control and Prevention has recommended HIV testing for all persons aged 13 to 64 or pregnant women since 2006," Dr. Welch said. "The federal law requiring written informed consent for HIV testing with pre- and post-test counselling within Veterans Affairs was repealed in 2008."
Despite removal of such barriers, there still appears to be a slow uptake of testing in the Veterans Affairs system. Dr. Welch suggested that her study could act as a baseline for future studies that will determine how well the Veterans Affairs health system is performing in testing for HIV.
"There may still be some stigma involved with HIV that prevents physicians from asking patients to undergo an HIV test," she speculated.
[Presentation title: Initial Assessment of HIV Testing Among Outpatient Veterans Compared With US Rates of HIV/AIDS. Abstract 1063]
Source
Presidio Pharmaceuticals, Inc. to Present First Clinical Data for PPI-461, a New HCV NS5A inhibitor, at the American Association for the Study of Liver Diseases (AASLD) Meeting, Supporting Initiation of a Trial in Hepatitis C Patients
October 27, 2010 03:00 AM Eastern Daylight Time
SAN FRANCISCO--(BUSINESS WIRE)--Presidio Pharmaceuticals, Inc. announced today that Nathaniel Brown, M.D., Chief Medical Officer, will present a late-breaker poster, “Safety and Pharmacokinetics of PPI-461, a Potent New Hepatitis C virus (HCV) NS5A Inhibitor with Pan-Genotype Activity” at the 61st AASLD meeting in Boston, MA, on November 1, 2010. The presentation provides the results of the first clinical trial of PPI-461, and will be available for review from 8:00A to 5:00P (EDT) in Exhibit Hall C at the Hynes Convention Center.
PPI-461
PPI-461 is a novel and promising NS5A inhibitor that interferes with HCV replication. Discovered at Presidio, PPI-461 exhibits highly potent and selective activity against all seven major HCV genotypes in laboratory assays. Inhibitors of the HCV NS5A protein represent a promising new class of HCV antivirals that are mechanistically distinct from HCV agents that target the viral protease or replicase (polymerase). Laboratory data suggest that NS5A inhibitors can potentially be used in combination with any of these other HCV agents, to achieve better efficacy in hepatitis C patients and combat the emergence of antiviral resistance.
About the Phase 1a Trial Results
The data to be reported at the AASLD meeting are the results of a Phase 1a dose-ranging trial of PPI-461 in healthy volunteers completed this year. This trial assessed the safety and pharmacokinetics of five different oral dosing regimens for PPI-461: four single doses (20, 50, 100, and 200 mg), and a multi-dose regimen (200 mg daily for five days). A total of 40 subjects participated in the study, with eight subjects in each of the five dosing groups.
As indicated in the LB-12 abstract, now viewable on the AASLD meeting website (AASLD.org), all PPI-461 dose regimens were well tolerated. All subjects completed the study, and there were no patterns of clinical adverse events or laboratory abnormalities associated with administration of PPI-461. The pharmacokinetic results indicated that all subjects rapidly achieved substantial blood levels of PPI-461, which far exceeded the concentrations of PPI-461 needed to inhibit HCV (genotypes 1-7) in the laboratory. For PPI-461 doses of 50 mg or more, all subjects achieved blood levels of PPI-461 that would be expected to inhibit HCV replication for 24 hours or longer. This profile suggests that PPI-461 may be effective when administered to hepatitis C patients at relatively low oral doses on a once-daily dosing schedule, which would facilitate its convenient use in future co-formulated combination therapies. Additional details of the Phase 1a results will be given with the November 1 presentation at AASLD.
First Study of PPI-461 in Hepatitis C Patients Underway
Based on the encouraging Phase 1a results, Presidio has initiated a Phase 1b proof-of-concept clinical trial of PPI-461 in hepatitis C patients. This dose-ranging trial will evaluate the safety, pharmacokinetics and antiviral efficacy of PPI-461 in previously-untreated patients with HCV genotype-1 infection.
“We are pleased to begin initial assessments of the tolerance and antiviral efficacy of PPI-461 in patients with chronic hepatitis C, following the encouraging results of the recent Phase 1a study,” said Nathaniel Brown, M.D., Chief Medical Officer. “HCV-related mortality and severe debilitation are projected to increase continually in the coming years, so there is an urgent need for improved therapies for hepatitis C.”
ABOUT PRESIDIO
Presidio Pharmaceuticals, Inc. is a San Francisco-based clinical stage specialty pharmaceutical company dedicated to the discovery and development of small-molecule antiviral therapeutics. For more information, please visit our website at: http://www.presidiopharma.com/.
Contacts
Presidio Pharmaceuticals, Inc.
Omar K. Haffar, PhD, 415-655-7561
omar@presidiopharma.com
Source
SAN FRANCISCO--(BUSINESS WIRE)--Presidio Pharmaceuticals, Inc. announced today that Nathaniel Brown, M.D., Chief Medical Officer, will present a late-breaker poster, “Safety and Pharmacokinetics of PPI-461, a Potent New Hepatitis C virus (HCV) NS5A Inhibitor with Pan-Genotype Activity” at the 61st AASLD meeting in Boston, MA, on November 1, 2010. The presentation provides the results of the first clinical trial of PPI-461, and will be available for review from 8:00A to 5:00P (EDT) in Exhibit Hall C at the Hynes Convention Center.
PPI-461
PPI-461 is a novel and promising NS5A inhibitor that interferes with HCV replication. Discovered at Presidio, PPI-461 exhibits highly potent and selective activity against all seven major HCV genotypes in laboratory assays. Inhibitors of the HCV NS5A protein represent a promising new class of HCV antivirals that are mechanistically distinct from HCV agents that target the viral protease or replicase (polymerase). Laboratory data suggest that NS5A inhibitors can potentially be used in combination with any of these other HCV agents, to achieve better efficacy in hepatitis C patients and combat the emergence of antiviral resistance.
About the Phase 1a Trial Results
The data to be reported at the AASLD meeting are the results of a Phase 1a dose-ranging trial of PPI-461 in healthy volunteers completed this year. This trial assessed the safety and pharmacokinetics of five different oral dosing regimens for PPI-461: four single doses (20, 50, 100, and 200 mg), and a multi-dose regimen (200 mg daily for five days). A total of 40 subjects participated in the study, with eight subjects in each of the five dosing groups.
As indicated in the LB-12 abstract, now viewable on the AASLD meeting website (AASLD.org), all PPI-461 dose regimens were well tolerated. All subjects completed the study, and there were no patterns of clinical adverse events or laboratory abnormalities associated with administration of PPI-461. The pharmacokinetic results indicated that all subjects rapidly achieved substantial blood levels of PPI-461, which far exceeded the concentrations of PPI-461 needed to inhibit HCV (genotypes 1-7) in the laboratory. For PPI-461 doses of 50 mg or more, all subjects achieved blood levels of PPI-461 that would be expected to inhibit HCV replication for 24 hours or longer. This profile suggests that PPI-461 may be effective when administered to hepatitis C patients at relatively low oral doses on a once-daily dosing schedule, which would facilitate its convenient use in future co-formulated combination therapies. Additional details of the Phase 1a results will be given with the November 1 presentation at AASLD.
First Study of PPI-461 in Hepatitis C Patients Underway
Based on the encouraging Phase 1a results, Presidio has initiated a Phase 1b proof-of-concept clinical trial of PPI-461 in hepatitis C patients. This dose-ranging trial will evaluate the safety, pharmacokinetics and antiviral efficacy of PPI-461 in previously-untreated patients with HCV genotype-1 infection.
“We are pleased to begin initial assessments of the tolerance and antiviral efficacy of PPI-461 in patients with chronic hepatitis C, following the encouraging results of the recent Phase 1a study,” said Nathaniel Brown, M.D., Chief Medical Officer. “HCV-related mortality and severe debilitation are projected to increase continually in the coming years, so there is an urgent need for improved therapies for hepatitis C.”
ABOUT PRESIDIO
Presidio Pharmaceuticals, Inc. is a San Francisco-based clinical stage specialty pharmaceutical company dedicated to the discovery and development of small-molecule antiviral therapeutics. For more information, please visit our website at: http://www.presidiopharma.com/.
Contacts
Presidio Pharmaceuticals, Inc.
Omar K. Haffar, PhD, 415-655-7561
omar@presidiopharma.com
Source
Hepatitis C increased risks for cerebrovascular-related death
Posted on October 27, 2010
Lee M. Stroke. 2010;doi:10.1161/STROKEAHA.110.598136.
Hepatitis C virus infection was an independent risk predictor of cerebrovascular deaths, indicating a biological gradient of cerebrovascular mortality with increasing serum hepatitis C virus RNA levels, researchers said.
The study included residents (n=23,665, aged 30 to 65 years) from a community-based prospective cohort who were enrolled from 1991 to 1992. Residents answered structured questionnaires and provided blood samples for various serological and biochemical tests at study entry. Researchers tested serum hepatitis C virus (HCV) RNA level and HCV genotype for participants seropositive for antibodies against HCV (anti-HCV).
During the 382,011 person-years of follow-up, researchers reported 255 cerebrovascular deaths, which translated into a cumulative risk for cerebrovascular deaths of 1% for seronegatives and 2.7% for seropositives of anti-HCV (P<.001). The corresponding multivariate-adjusted HR for cerebrovascular death was 2.18 (95% CI, 1.50-3.16) for anti-HCV seropositives.
In additional analysis, compared with patients seronegative for anti-HCV, the multivariate-adjusted HR for anti-HCV-seropositive participants with undetectable serum levels of HCV RNA was 1.40 (95% CI, 0.62-3.16), 2.36 (95% CI, 1.42-3.93) for low serum levels and 2.82 (95% CI, 1.25-6.37) for high serum levels (P<.001 for trend).
“HCV infection is associated with an increased risk of cerebrovascular mortality, particularly for those with elevated serum HCV RNA levels,” the researchers concluded. “If future additional studies confirm the role of HCV infection and the development of cerebrovascular disease, it may be possible to prevent cerebrovascular disease by using specific antiviral strategies.”
Source
Lee M. Stroke. 2010;doi:10.1161/STROKEAHA.110.598136.
Hepatitis C virus infection was an independent risk predictor of cerebrovascular deaths, indicating a biological gradient of cerebrovascular mortality with increasing serum hepatitis C virus RNA levels, researchers said.
The study included residents (n=23,665, aged 30 to 65 years) from a community-based prospective cohort who were enrolled from 1991 to 1992. Residents answered structured questionnaires and provided blood samples for various serological and biochemical tests at study entry. Researchers tested serum hepatitis C virus (HCV) RNA level and HCV genotype for participants seropositive for antibodies against HCV (anti-HCV).
During the 382,011 person-years of follow-up, researchers reported 255 cerebrovascular deaths, which translated into a cumulative risk for cerebrovascular deaths of 1% for seronegatives and 2.7% for seropositives of anti-HCV (P<.001). The corresponding multivariate-adjusted HR for cerebrovascular death was 2.18 (95% CI, 1.50-3.16) for anti-HCV seropositives.
In additional analysis, compared with patients seronegative for anti-HCV, the multivariate-adjusted HR for anti-HCV-seropositive participants with undetectable serum levels of HCV RNA was 1.40 (95% CI, 0.62-3.16), 2.36 (95% CI, 1.42-3.93) for low serum levels and 2.82 (95% CI, 1.25-6.37) for high serum levels (P<.001 for trend).
“HCV infection is associated with an increased risk of cerebrovascular mortality, particularly for those with elevated serum HCV RNA levels,” the researchers concluded. “If future additional studies confirm the role of HCV infection and the development of cerebrovascular disease, it may be possible to prevent cerebrovascular disease by using specific antiviral strategies.”
Source
Idenix Pharmaceuticals to Hold an Investor/Analyst Day Event on October 30, 2010
CAMBRIDGE, Mass., Oct. 27 /PRNewswire-FirstCall/ -- Idenix Pharmaceuticals, Inc. (Nasdaq: IDIX) announced today that the Company will hold an Analyst Day event during the upcoming 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) on Saturday, October 30, 2010 from 9:00 a.m. to 12:00 p.m. ET at the Mandarin Oriental, Boston.
The live and archived webcast of the presentation can be accessed under "Calendar of Events" in the Idenix Investor Center at www.idenix.com. Please log in approximately 5-10 minutes before the event to ensure a timely connection. The archived replays will be available on the Idenix website for two weeks following the event.
About Idenix
Idenix Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts, is a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases. Idenix's current focus is on the treatment of infections caused by the hepatitis C virus. For further information about Idenix, please refer to http://www.idenix.com/.
Idenix Pharmaceuticals' Contacts:
Jonae Barnes (617) 224-4485 (investors)
Kelly Barry (617) 995-9033 (media)
SOURCE Idenix Pharmaceuticals, Inc.
RELATED LINKS
http://www.idenix.com/
Source
The live and archived webcast of the presentation can be accessed under "Calendar of Events" in the Idenix Investor Center at www.idenix.com. Please log in approximately 5-10 minutes before the event to ensure a timely connection. The archived replays will be available on the Idenix website for two weeks following the event.
About Idenix
Idenix Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts, is a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases. Idenix's current focus is on the treatment of infections caused by the hepatitis C virus. For further information about Idenix, please refer to http://www.idenix.com/.
Idenix Pharmaceuticals' Contacts:
Jonae Barnes (617) 224-4485 (investors)
Kelly Barry (617) 995-9033 (media)
SOURCE Idenix Pharmaceuticals, Inc.
RELATED LINKS
http://www.idenix.com/
Source
October 26, 2010
Can Chronic Hepatitis C Patients with Genotypes 2 or 3 Benefit from Shorter Interferon Treatment?
SUMMARY: A shorter 12 to 16 week course of pegylated interferon plus ribavirin is not as effective overall for people with chronic hepatitis C virus (HCV) genotypes 2 or 3, according to a meta-analysis and 2 recent international trials. However, abbreviated treatment may be a viable option for selected patients with rapid virological response at 4 weeks, low HCV viral load, and inability to tolerate longer therapy.
By Liz Highleyman
HCV genotypes 2 and 3 are easier to treat than genotypes 1 or 4. The standard course of therapy for genotype 2 or 3 is pegylated interferon plus ribavirin for 24 weeks, increasing to 48 weeks for hard-to-treat genotype 1. Genotypes 2 and 3 also have a higher response rate of 70%-80% in most studies, compared with only about 50% for genotype 1.
Because chronic hepatitis C patients with genotypes 2 and 3 often respond rapidly to therapy -- and because interferon is expensive and can cause difficult side effects -- researchers have explored whether treatment for 12, 14, or 16 weeks might work as well as 24 weeks.
During hepatitis C treatment efficacy is assessed by measuring HCV viral load after 4 weeks (rapid virological response, or RVR), 12 weeks (early virological response, or EVR), 24 weeks (end-of-treatment response, or ETR), and 24 weeks after completion of therapy (sustained virological response, or SVR). Patients who experience RVR at week 4 are significantly more likely to go on to achieve SVR. People who still have undetectable viral load 24 weeks after finishing treatment are considered cured.
12-16 Weeks Meta-analysis
As reported in the September 2010 Journal of Clinical Gastroenterology, Ashwani Singal from the University of Texas Medical Branch in Galveston and colleagues performed a meta-analysis of prior studies of abbreviated treatment.
The study authors searched medical literature databases for studies that compared short-term (12 to 16 weeks) vs standard 24 week treatment using pegylated interferon plus 800 mg/day fixed-dose ribavirin for genotype 2 or 3 patients who had achieved RVR. They identified 6 relevant studies -- including a total of 2434 participants -- that reported data on ETR, SVR, and relapse rates.
After achieving RVR, patients treated for a total of 24 weeks were significantly more likely to achieve SVR than those treated for 16 weeks (79% vs 70%; P = 0.008). Conversely, 24 week patients had a significantly lower relapse rate (9% vs 23%, respectively; P < 0.00001). Results did not change when people with genotype 2 vs 3, or those with high vs low baseline viral load, were analyzed separately.
The pooled odds ratio for SVR using shorter treatment was 0.54, or about half as likely, while the pooled odds ratio for experiencing viral relapse was 3.12, or about 3 times more likely (P = 0.008 and < 0.00001, respectively).
However, people treated for 24 weeks were significantly more likely to discontinue therapy ahead of schedule than those receiving shorter-duration treatment (12% vs 5%; P < 0.0001). The researchers found that it would be cost-effective to reduce treatment duration to 12-16 weeks, and then re-treat patients who experience relapse with a second 24 week course of therapy.
"Advantages of short-term treatment include better patient compliance, lower rate of adverse effects, and cost," the authors concluded. "Short-term treatment may be an option for patients unable to tolerate treatment."
Scandinavian Trials
In the second study, published in the May 2010 European Journal Gastroenterology and Hepatology, Olav Dalgard from Rikshospitalet in Oslo and colleagues compared 14 vs 24 week treatment in chronic genotype 2 or 3 patients with RVR, defined as HCV RNA < 50 IU/mL after 4 weeks of therapy.
The analysis included participants in 2 Scandinavian studies, one a non-randomized pilot trial with 122 patients, the other a randomized controlled trial with 428 patients. In both trials, treatment-naive participants were treated with 1.5 mcg/kg/week pegylated interferon alpha-2b (PegIntron) plus 800-1400 mg/day weight-adjusted ribavirin (genotype 2 or 3 patients typically receive a fixed dose of 800 mg regardless of weight).
In the pilot trial, all patients with RVR were treated for 14 weeks, while in the larger trial participants with RVR were randomized to receive therapy for either 14 or 24 weeks.
In an analysis of all RVR patients treated per protocol, 91% of those who received 14 weeks of therapy achieved SVR, compared with 95% of those treated for 24 weeks. The difference of 4% fell well within the pre-determined 10% margin needed to show inferiority, allowing the researchers to conclude that 14 week treatment was non-inferior to 24 weeks.
The relapse rate was highest among participants older than 40 years, those with genotype 3, and those with a high baseline viral load. However, prolonging treatment from 14 to 24 weeks did not reduce the relapse rate substantially for any of these groups.
International Study
Finally, in the third study, described in the June 2010 issue of Hepatology, Moises Diago from Hospital General de Valencia in Spain and an international team of colleagues compared SVR and relapse rates among patients with RVR (again < 50 IU/mL) who were randomly assigned to receive treatment for 16 or 24 weeks in the ACCELERATE trial.
This study included 863 genotype 2 or 3 participants with RVR (66% of the initial 1309 eligible patients in the study). All were treated with 180 mcg/week pegylated interferon alfa-2a (Pegasys) plus 800 mg/day ribavirin. The analysis included only those participants who took their assigned treatment for at least 80% of the planned duration.
The overall SVR rate was significantly higher among genotype 2 patients treated for 24 weeks rather than 16 weeks (91% vs 82%, respectively; P = 0.0006). The difference for participants with genotype 3, however, did not reach statistical significance (90% vs 84%, respectively; P = 0.1308). Among patients with low baseline viral load (HCV RNA <400.000 IU/mL), SVR rates with 24 or 16 weeks of treatment were also statistical equivalent (95% vs 91%, respectively; P = 0.2012).
Relapse rates were significantly lower among people randomized to 24 weeks of therapy vs 16 weeks, both overall (6% vs 15%; P < 0.0001) and when participants with genotype 2 (5% vs 17%; P = 0.0001) and those with genotype 3 (7% vs 14%; P = 0.0489) were analyzed separately.
Significant pre-treatment predictors of SVR included assigned treatment duration of 24 weeks (P = 0.0006), absence of advanced liver fibrosis or cirrhosis according to biopsy (P = 0.0032), lower HCV viral load (P = 0.0017), and lower body weight (P < 0.0001).
"The standard 24-week regimen of [Pegasys] plus ribavirin is significantly more effective than an abbreviated 16-week regimen in genotype 2/3 patients who achieve an RVR," the study authors concluded. "Abbreviated regimens may be considered in patients with a low baseline viral load who achieve an RVR."
Overview
In an editorial accompanying Singal's meta-analysis, Donald Jensen from the University of Chicago Medical Center attempted to make sense of the conflicting findings from studies to date of shorter treatment durations for genotype 2 or 3 patients. Even previous meta-analyses, which are intended to resolve such questions, have produced contradictory results.
Along with baseline viral load and genotype 2 vs 3, ribavirin dose may be an important factor, he suggested, since it reduces the chances of relapse after completion of treatment.
"In summary, finding convincing evidence to support RVR-guided duration shortening in all genotypes 2 and 3 subjects is still not available," Jensen wrote. "The difference in SVR rates, however, remains small (< 10%) and narrower still for those patients with low baseline viral load."
"As the authors point out, it may not be unreasonable in selected cases -- perhaps those with an RVR yet poorly tolerant of side effects -- to strongly consider shortening therapy and if relapse occurs, retreat for a longer duration," he concluded.
Investigator affiliations:
Singal study: Department of Gastroenterology and Hepatology, University of Texas Medical Branch, Galveston, TX; Department of Gastroenterology and Hepatology, Michael DeBakey VA Medical Center, Baylor College of Medicine, Houston, TX.
Dalgard study: Medical Department, Rikshospitalet, Oslo, Norway. Diago study: Hepatology Section, Hospital General de Valencia, Valencia, Spain; Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, VA; Department of Hepatology and Gastroenterology, INSERM U724, CHU de Nancy, Vandoeuvre-les-Nancy, France; J.W. Goethe University Hospital, Frankfurt, Germany; Fundacion de Investigacion de Diego, Santurce, Puerto Rico; St Luke's Center for Liver Disease, Houston, TX; Roche, Basel, Switzerland; University of Florida, Gainsville, FL.
10/26/10
References
AK Singal and BS Anand. Tailoring Treatment Duration to 12 to 16 Weeks in Hepatitis C Genotype 2 or 3 With Rapid Virologic Response: Systematic Review and Meta-analysis of Randomized Controlled Trials. Journal of Clinical Gastroenterology 44(8): 583-587 (Abstract). September 2010.
O Dalgard, K Bjoro, H Ring-Larsen, and H Verbaan. In patients with HCV genotype 2 or 3 infection and RVR 14 weeks treatment is noninferior to 24 weeks. Pooled analysis of two Scandinavian trials. European Journal Gastroenterology and Hepatology 22(5): 552-556 (Abstract). May 2010.
M Diago, ML Shiffman, JP Bronowicki, and others. Identifying hepatitis C virus genotype 2/3 patients who can receive a 16-week abbreviated course of peginterferon alfa-2a (40KD) plus ribavirin. Hepatology 51(6): 1897-1903 (Abstract). June 2010.
DM Jensen. Treatment duration for genotypes 2 and 3: still confusing after all these years (Editorial). Journal of Clinical Gastroenterology 44(8): 527-528 (Free full text). September 2010.
Source
By Liz Highleyman
HCV genotypes 2 and 3 are easier to treat than genotypes 1 or 4. The standard course of therapy for genotype 2 or 3 is pegylated interferon plus ribavirin for 24 weeks, increasing to 48 weeks for hard-to-treat genotype 1. Genotypes 2 and 3 also have a higher response rate of 70%-80% in most studies, compared with only about 50% for genotype 1.
Because chronic hepatitis C patients with genotypes 2 and 3 often respond rapidly to therapy -- and because interferon is expensive and can cause difficult side effects -- researchers have explored whether treatment for 12, 14, or 16 weeks might work as well as 24 weeks.
During hepatitis C treatment efficacy is assessed by measuring HCV viral load after 4 weeks (rapid virological response, or RVR), 12 weeks (early virological response, or EVR), 24 weeks (end-of-treatment response, or ETR), and 24 weeks after completion of therapy (sustained virological response, or SVR). Patients who experience RVR at week 4 are significantly more likely to go on to achieve SVR. People who still have undetectable viral load 24 weeks after finishing treatment are considered cured.
12-16 Weeks Meta-analysis
As reported in the September 2010 Journal of Clinical Gastroenterology, Ashwani Singal from the University of Texas Medical Branch in Galveston and colleagues performed a meta-analysis of prior studies of abbreviated treatment.
The study authors searched medical literature databases for studies that compared short-term (12 to 16 weeks) vs standard 24 week treatment using pegylated interferon plus 800 mg/day fixed-dose ribavirin for genotype 2 or 3 patients who had achieved RVR. They identified 6 relevant studies -- including a total of 2434 participants -- that reported data on ETR, SVR, and relapse rates.
After achieving RVR, patients treated for a total of 24 weeks were significantly more likely to achieve SVR than those treated for 16 weeks (79% vs 70%; P = 0.008). Conversely, 24 week patients had a significantly lower relapse rate (9% vs 23%, respectively; P < 0.00001). Results did not change when people with genotype 2 vs 3, or those with high vs low baseline viral load, were analyzed separately.
The pooled odds ratio for SVR using shorter treatment was 0.54, or about half as likely, while the pooled odds ratio for experiencing viral relapse was 3.12, or about 3 times more likely (P = 0.008 and < 0.00001, respectively).
However, people treated for 24 weeks were significantly more likely to discontinue therapy ahead of schedule than those receiving shorter-duration treatment (12% vs 5%; P < 0.0001). The researchers found that it would be cost-effective to reduce treatment duration to 12-16 weeks, and then re-treat patients who experience relapse with a second 24 week course of therapy.
"Advantages of short-term treatment include better patient compliance, lower rate of adverse effects, and cost," the authors concluded. "Short-term treatment may be an option for patients unable to tolerate treatment."
Scandinavian Trials
In the second study, published in the May 2010 European Journal Gastroenterology and Hepatology, Olav Dalgard from Rikshospitalet in Oslo and colleagues compared 14 vs 24 week treatment in chronic genotype 2 or 3 patients with RVR, defined as HCV RNA < 50 IU/mL after 4 weeks of therapy.
The analysis included participants in 2 Scandinavian studies, one a non-randomized pilot trial with 122 patients, the other a randomized controlled trial with 428 patients. In both trials, treatment-naive participants were treated with 1.5 mcg/kg/week pegylated interferon alpha-2b (PegIntron) plus 800-1400 mg/day weight-adjusted ribavirin (genotype 2 or 3 patients typically receive a fixed dose of 800 mg regardless of weight).
In the pilot trial, all patients with RVR were treated for 14 weeks, while in the larger trial participants with RVR were randomized to receive therapy for either 14 or 24 weeks.
In an analysis of all RVR patients treated per protocol, 91% of those who received 14 weeks of therapy achieved SVR, compared with 95% of those treated for 24 weeks. The difference of 4% fell well within the pre-determined 10% margin needed to show inferiority, allowing the researchers to conclude that 14 week treatment was non-inferior to 24 weeks.
The relapse rate was highest among participants older than 40 years, those with genotype 3, and those with a high baseline viral load. However, prolonging treatment from 14 to 24 weeks did not reduce the relapse rate substantially for any of these groups.
International Study
Finally, in the third study, described in the June 2010 issue of Hepatology, Moises Diago from Hospital General de Valencia in Spain and an international team of colleagues compared SVR and relapse rates among patients with RVR (again < 50 IU/mL) who were randomly assigned to receive treatment for 16 or 24 weeks in the ACCELERATE trial.
This study included 863 genotype 2 or 3 participants with RVR (66% of the initial 1309 eligible patients in the study). All were treated with 180 mcg/week pegylated interferon alfa-2a (Pegasys) plus 800 mg/day ribavirin. The analysis included only those participants who took their assigned treatment for at least 80% of the planned duration.
The overall SVR rate was significantly higher among genotype 2 patients treated for 24 weeks rather than 16 weeks (91% vs 82%, respectively; P = 0.0006). The difference for participants with genotype 3, however, did not reach statistical significance (90% vs 84%, respectively; P = 0.1308). Among patients with low baseline viral load (HCV RNA <400.000 IU/mL), SVR rates with 24 or 16 weeks of treatment were also statistical equivalent (95% vs 91%, respectively; P = 0.2012).
Relapse rates were significantly lower among people randomized to 24 weeks of therapy vs 16 weeks, both overall (6% vs 15%; P < 0.0001) and when participants with genotype 2 (5% vs 17%; P = 0.0001) and those with genotype 3 (7% vs 14%; P = 0.0489) were analyzed separately.
Significant pre-treatment predictors of SVR included assigned treatment duration of 24 weeks (P = 0.0006), absence of advanced liver fibrosis or cirrhosis according to biopsy (P = 0.0032), lower HCV viral load (P = 0.0017), and lower body weight (P < 0.0001).
"The standard 24-week regimen of [Pegasys] plus ribavirin is significantly more effective than an abbreviated 16-week regimen in genotype 2/3 patients who achieve an RVR," the study authors concluded. "Abbreviated regimens may be considered in patients with a low baseline viral load who achieve an RVR."
Overview
In an editorial accompanying Singal's meta-analysis, Donald Jensen from the University of Chicago Medical Center attempted to make sense of the conflicting findings from studies to date of shorter treatment durations for genotype 2 or 3 patients. Even previous meta-analyses, which are intended to resolve such questions, have produced contradictory results.
Along with baseline viral load and genotype 2 vs 3, ribavirin dose may be an important factor, he suggested, since it reduces the chances of relapse after completion of treatment.
"In summary, finding convincing evidence to support RVR-guided duration shortening in all genotypes 2 and 3 subjects is still not available," Jensen wrote. "The difference in SVR rates, however, remains small (< 10%) and narrower still for those patients with low baseline viral load."
"As the authors point out, it may not be unreasonable in selected cases -- perhaps those with an RVR yet poorly tolerant of side effects -- to strongly consider shortening therapy and if relapse occurs, retreat for a longer duration," he concluded.
Investigator affiliations:
Singal study: Department of Gastroenterology and Hepatology, University of Texas Medical Branch, Galveston, TX; Department of Gastroenterology and Hepatology, Michael DeBakey VA Medical Center, Baylor College of Medicine, Houston, TX.
Dalgard study: Medical Department, Rikshospitalet, Oslo, Norway. Diago study: Hepatology Section, Hospital General de Valencia, Valencia, Spain; Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, VA; Department of Hepatology and Gastroenterology, INSERM U724, CHU de Nancy, Vandoeuvre-les-Nancy, France; J.W. Goethe University Hospital, Frankfurt, Germany; Fundacion de Investigacion de Diego, Santurce, Puerto Rico; St Luke's Center for Liver Disease, Houston, TX; Roche, Basel, Switzerland; University of Florida, Gainsville, FL.
10/26/10
References
AK Singal and BS Anand. Tailoring Treatment Duration to 12 to 16 Weeks in Hepatitis C Genotype 2 or 3 With Rapid Virologic Response: Systematic Review and Meta-analysis of Randomized Controlled Trials. Journal of Clinical Gastroenterology 44(8): 583-587 (Abstract). September 2010.
O Dalgard, K Bjoro, H Ring-Larsen, and H Verbaan. In patients with HCV genotype 2 or 3 infection and RVR 14 weeks treatment is noninferior to 24 weeks. Pooled analysis of two Scandinavian trials. European Journal Gastroenterology and Hepatology 22(5): 552-556 (Abstract). May 2010.
M Diago, ML Shiffman, JP Bronowicki, and others. Identifying hepatitis C virus genotype 2/3 patients who can receive a 16-week abbreviated course of peginterferon alfa-2a (40KD) plus ribavirin. Hepatology 51(6): 1897-1903 (Abstract). June 2010.
DM Jensen. Treatment duration for genotypes 2 and 3: still confusing after all these years (Editorial). Journal of Clinical Gastroenterology 44(8): 527-528 (Free full text). September 2010.
Source
IL28B and the Control of Hepatitis C Virus Infection
Gastroenterology. 2010 Oct 12. [Epub ahead of print]
Balagopal A, Thomas DL, Thio CL.
Division of Infectious Diseases, Viral Hepatitis Center, Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland.
Abstract
Treatment-induced and spontaneous clearance of hepatitis C virus (HCV) infection are affected by various host factors. Polymorphisms in the region of the gene IL28B are associated with HCV clearance, implicating the gene product, interferon (IFN)-λ 3, in the immune response to HCV. Although it is not clear how the IL28B haplotype affects HCV clearance, IFNλ3 upregulates interferon-stimulated genes (ISGs), similar to interferon-α and β, but via a different receptor. There is also evidence that IFNλ3 affects the adaptive immune response. The IL28B genotype can be considered, along with other factors, in predicting patient responses to therapy with pegylated interferon-α and ribavirin. We review the genetic studies that uncovered the association between IL28B and HCV clearance, the biology of IFNλ3, the clinical implications of the genetic association, and areas of future research. All studies published in Gastroenterology are embargoed until 3PM ET of the day they are published as corrected proofs on-line. Studies cannot be publicized as accepted manuscripts or uncorrected proofs.
Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
PMID: 20950615 [PubMed - as supplied by publisher]
Source
Balagopal A, Thomas DL, Thio CL.
Division of Infectious Diseases, Viral Hepatitis Center, Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland.
Abstract
Treatment-induced and spontaneous clearance of hepatitis C virus (HCV) infection are affected by various host factors. Polymorphisms in the region of the gene IL28B are associated with HCV clearance, implicating the gene product, interferon (IFN)-λ 3, in the immune response to HCV. Although it is not clear how the IL28B haplotype affects HCV clearance, IFNλ3 upregulates interferon-stimulated genes (ISGs), similar to interferon-α and β, but via a different receptor. There is also evidence that IFNλ3 affects the adaptive immune response. The IL28B genotype can be considered, along with other factors, in predicting patient responses to therapy with pegylated interferon-α and ribavirin. We review the genetic studies that uncovered the association between IL28B and HCV clearance, the biology of IFNλ3, the clinical implications of the genetic association, and areas of future research. All studies published in Gastroenterology are embargoed until 3PM ET of the day they are published as corrected proofs on-line. Studies cannot be publicized as accepted manuscripts or uncorrected proofs.
Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
PMID: 20950615 [PubMed - as supplied by publisher]
Source
Vertex loss widens, drug application nears
Mon Oct 25, 2010 5:32pm EDT
* Loss widens as costs of telaprevir studies grow
* Expects to seek telaprevir approval in coming weeks
NEW YORK Oct 25 (Reuters) - Vertex Pharmaceuticals on Monday reported a wider third-quarter loss as it stepped up research on its promising experimental treatment for hepatitis C, and said it plans to seek U.S. approval for the medicine in coming weeks.
Vertex (VRTX.O) said it had a net loss $209 million, or $1.04 per share, in the third quarter, as it spent heavily on mid-stage and late-stage trials of its telaprevir treatment for the liver disease. That compared with a net loss of $149.6 million, or 84 cents per share, a year ago.
Analysts on average expected a loss of 93 cents per share in the most recent quarter, according to Thomson Reuters I/B/E/S.
Vertex reported third quarter revenue of $23.8 million. Wall Street was expecting revenue of $30.3 million.
The Cambridge, Massachusetts-based company, which is also developing treatments for inflammation, cystic fibrosis, and other diseases, said it continues to expect a net loss of $750 million for full-year 2010. Excluding special items, it expects a loss of $600 million.
Telaprevir is widely expected to become a game changer in the treatment of hepatitis C, which can severely damage the liver over a period of decades after infection with the virus. Some analysts believe the drug could eventually garner annual sales of more than $4 billion.
The lofty expectations are based on telaprevir's ability to cure a far higher percentage of patients than the tough to tolerate standard drugs, and its potential to cut the current 48-week treatment duration in half when used in combination with interferon and ribavirin.
In September, Vertex said telaprevir in a pivotal late-stage trial cured 65 percent of patients who had previously failed to be cured by standard drugs.
Telaprevir, from a new class of hepatitis C treatments, is an antiviral drug that is expected to compete with a similar medicine being developed by Merck & Co (MRK.N) called boceprevir. But analysts have been virtually unanimous in their belief that telaprevir is the superior medicine.
Merck has completed phase III trials. (Reporting by Ransdell Pierson; Editing by Carol Bishopric)
Source
Also See:
-- Vertex Quarter Blemished by Hep C Hiccup
-- Vertex Pharmaceuticals Reports Third Quarter 2010 Financial Results and Highlights Progress in Hepatitis C and Cystic Fibrosis Development Programs
* Loss widens as costs of telaprevir studies grow
* Expects to seek telaprevir approval in coming weeks
NEW YORK Oct 25 (Reuters) - Vertex Pharmaceuticals on Monday reported a wider third-quarter loss as it stepped up research on its promising experimental treatment for hepatitis C, and said it plans to seek U.S. approval for the medicine in coming weeks.
Vertex (VRTX.O) said it had a net loss $209 million, or $1.04 per share, in the third quarter, as it spent heavily on mid-stage and late-stage trials of its telaprevir treatment for the liver disease. That compared with a net loss of $149.6 million, or 84 cents per share, a year ago.
Analysts on average expected a loss of 93 cents per share in the most recent quarter, according to Thomson Reuters I/B/E/S.
Vertex reported third quarter revenue of $23.8 million. Wall Street was expecting revenue of $30.3 million.
The Cambridge, Massachusetts-based company, which is also developing treatments for inflammation, cystic fibrosis, and other diseases, said it continues to expect a net loss of $750 million for full-year 2010. Excluding special items, it expects a loss of $600 million.
Telaprevir is widely expected to become a game changer in the treatment of hepatitis C, which can severely damage the liver over a period of decades after infection with the virus. Some analysts believe the drug could eventually garner annual sales of more than $4 billion.
The lofty expectations are based on telaprevir's ability to cure a far higher percentage of patients than the tough to tolerate standard drugs, and its potential to cut the current 48-week treatment duration in half when used in combination with interferon and ribavirin.
In September, Vertex said telaprevir in a pivotal late-stage trial cured 65 percent of patients who had previously failed to be cured by standard drugs.
Telaprevir, from a new class of hepatitis C treatments, is an antiviral drug that is expected to compete with a similar medicine being developed by Merck & Co (MRK.N) called boceprevir. But analysts have been virtually unanimous in their belief that telaprevir is the superior medicine.
Merck has completed phase III trials. (Reporting by Ransdell Pierson; Editing by Carol Bishopric)
Source
Also See:
-- Vertex Quarter Blemished by Hep C Hiccup
-- Vertex Pharmaceuticals Reports Third Quarter 2010 Financial Results and Highlights Progress in Hepatitis C and Cystic Fibrosis Development Programs
HIV and HCV health beliefs in an inner-city community
J Viral Hepat. 2010 Oct 18. doi: 10.1111/j.1365-2893.2010.01383.x. [Epub ahead of print]
Krauskopf K, McGinn TG, Federman AD, Halm EA, Leventhal H, McGinn LK, Gardenier D, Oster A, Kronish IM.
Division of General Internal Medicine, Mount Sinai School of Medicine, New York, NY Division of General Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX Institute of Health, Health Care Policy and Aging Research, Rutgers, The State University of New Jersey, New Brunswick, NJ Ferkauf Graduate School of Psychology, Yeshiva University, Albert Einstein College of Medicine, New York, NY Charles B. Wang Community Health Center, New York, NY, USA.
Abstract
Summary. Chronic infection with the hepatitis C virus (HCV) is more prevalent than human immunodeficiency virus (HIV) infection, but more public health resources are allocated to HIV than to HCV. Given shared risk factors and epidemiology, we compared accuracy of health beliefs about HIV and HCV in an at-risk community. Between 2002 and 2003, we surveyed a random patient sample at a primary care clinic in New York. The survey was organized as domains of Common Sense Model of Self-Regulation: causes ('sharing needles'), timeline/consequences ('remains in body for life', 'causes cancer') and controllability ('I can avoid this illness', 'medications may cure this illness'). We compared differences in accuracy of beliefs about HIV and HCV and used multivariable linear regression to identify factors associated with relative accuracy of beliefs. One hundred and twenty-two subjects completed the survey (response rate 42%). Mean overall health belief accuracy was 12/15 questions (80%) for HIV vs 9/15 (60%) for HCV (P < 0.001). Belief accuracy was significantly different across all domains. Within the causes domain, 60% accurately believed sharing needles a risk factor for HCV compared to 92% for HIV (P < 0.001). Within the timeline/consequences domain, 42% accurately believed HCV results in lifelong infection compared to 89% for HIV (P < 0.001). Within the controllability domain, 25% accurately believed that there is a potential cure for HCV. Multivariable linear regression revealed female gender as significantly associated with greater health belief accuracy for HIV. Thus, study participants had significantly less accurate health beliefs about HCV than about HIV. Targeting inaccuracies might improve public health interventions to foster healthier behaviours and better hepatitis C outcomes.
© 2010 Blackwell Publishing Ltd.
Source
Krauskopf K, McGinn TG, Federman AD, Halm EA, Leventhal H, McGinn LK, Gardenier D, Oster A, Kronish IM.
Division of General Internal Medicine, Mount Sinai School of Medicine, New York, NY Division of General Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX Institute of Health, Health Care Policy and Aging Research, Rutgers, The State University of New Jersey, New Brunswick, NJ Ferkauf Graduate School of Psychology, Yeshiva University, Albert Einstein College of Medicine, New York, NY Charles B. Wang Community Health Center, New York, NY, USA.
Abstract
Summary. Chronic infection with the hepatitis C virus (HCV) is more prevalent than human immunodeficiency virus (HIV) infection, but more public health resources are allocated to HIV than to HCV. Given shared risk factors and epidemiology, we compared accuracy of health beliefs about HIV and HCV in an at-risk community. Between 2002 and 2003, we surveyed a random patient sample at a primary care clinic in New York. The survey was organized as domains of Common Sense Model of Self-Regulation: causes ('sharing needles'), timeline/consequences ('remains in body for life', 'causes cancer') and controllability ('I can avoid this illness', 'medications may cure this illness'). We compared differences in accuracy of beliefs about HIV and HCV and used multivariable linear regression to identify factors associated with relative accuracy of beliefs. One hundred and twenty-two subjects completed the survey (response rate 42%). Mean overall health belief accuracy was 12/15 questions (80%) for HIV vs 9/15 (60%) for HCV (P < 0.001). Belief accuracy was significantly different across all domains. Within the causes domain, 60% accurately believed sharing needles a risk factor for HCV compared to 92% for HIV (P < 0.001). Within the timeline/consequences domain, 42% accurately believed HCV results in lifelong infection compared to 89% for HIV (P < 0.001). Within the controllability domain, 25% accurately believed that there is a potential cure for HCV. Multivariable linear regression revealed female gender as significantly associated with greater health belief accuracy for HIV. Thus, study participants had significantly less accurate health beliefs about HCV than about HIV. Targeting inaccuracies might improve public health interventions to foster healthier behaviours and better hepatitis C outcomes.
© 2010 Blackwell Publishing Ltd.
Source
Management of Recurrent Hepatitis C Following Liver Transplantation: Fibrosing Cholestatic Hepatitis C
Posted by James
Although it occurs in less than 10% of transplant recipients with chronic HCV, a severe and rapidly progressive form of recurrent HCV infection characterized by cholestatic disease has a major impact on survival. In contrast to a chronic hepatitis observed in most patients with recurrent HCV, this syndrome is defined by a total serum bilirubin of more than 6 mg/dL, elevated alkaline phosphatase or gamma glutamyltransferase levels more than 5 times the upper limit of normal, high serum HCV RNA levels, and histologic features including central hepatocyte ballooning without necrosis, cholangiolar proliferation without loss of bile ducts, and intrahepatic cholestasis in the absence of significant inflammation, biliary obstructive disease, or vascular complications.15,18 Onset typically occurs within the first 6 months following liver transplantation, and rapid progression to allograft failure may occur within 1 year. In addition, patient survival following repeat liver transplantation for fibrosing cholestatic HCV is severely compromised; thus, retransplantation is not an acceptable management option in this case.
Risk Factors for Severe Liver Disease
Several recipient, donor, and viral factors, as well as the use of specific immunosuppressive agents, have been identified as risk factors for increased severity of disease progression, allograft loss, and decreased survival in patients with HCV who undergo liver transplantation (Table 1). The presence of a severe histologic grade of inflammation early in the post-transplant course, particularly within the first year, may be predictive of more rapid fibrosis progression and cirrhosis at 5 years. Elevated serum HCV RNA levels both prior to undergoing transplant and during the post-transplant period may also be associated with progressive disease. Donor age has been identified as a major risk factor, as increased age, particularly over 50 years, is associated with more rapid disease progression, development of cirrhosis, and HCV-associated graft failure. Additional factors that may potentially be associated with severe recurrent disease include infectionwith HCV genotype 1, presence of cryoglobulinemia, female gender, increased recipient age, non-white ethnicity of recipient, donor steatosis, and cold ischemia time. However, data that strongly support these factors, specifically in association with HCV disease progression, are limited or, in some cases, conflicting. viagra plus
Table 1. Established Risk Factors for Severe Recurrent Hepatitis C
Virus (HCV) Following Liver Transplantation:
• Fibrosing cholestatic HCV syndrome
• Increased serum HCV RNA levels (pre- or posttransplantation)
• Early recurrence or severe histologic inflammatory activity within 1 year
• Use of high-dose intravenous pulse corticosteroids or muromonab-CD3
• Increased donor age
• Cytomegalovirus infection
• HIV-HCV co-infection
Cytomegalovirus (CMV) infection is common in liver transplant recipients and is a major risk factor for severe recurrence of HCV-associated liver disease. HCV patients who develop CMV viremia following liver transplantation are at an increased risk of advanced histologic changes, including periportal and bridging necrosis, lobular inflammatory activity, and development of cirrhosis. The greatest risk of CMV disease occurs in the setting of donor CMV seropositivity and recipient sero- negativity. Prophylaxis or preemptive therapy have been described as a means of preventing CMV infection in at-risk individuals. Prophylaxis with valganciclovir for 3 months following liver transplantation has been reported as the most common strategy utilized in this population. Immunosuppression may have a significant impact on the risk of disease progression following transplant. Viral kinetics studies have described a rapid increase in serum HCV RNA levels in patients who receive high- dose intravenous corticosteroids intraoperatively or in the treatment of acute cellular rejection. Further studies have identified the use of pulse intravenous corticosteroid therapy or muromonab-CD3 (Orthoclone OKT3, Ortho Biotech; an anti-CD3 monoclonal antibody) as independent risk factors for development of cirrhosis and graft failure. Results of prospective studies evaluating outcomes in HIV-HCV co-infected individuals have revealed significantly reduced post- transplant survival in co-infected patients compared to other HIV-positive or non-HIV transplant recipients, with 3- and 5-year survival rates as low as 56% and 33%, respectively. In particular, HIV-HCV co-infected patients with CD4+ cell counts less than 200 cells/pL are at an increased risk, indicating the negative impact of an immunocompromised state in the setting of immunosuppressive therapy following transplantation. Additional factors associated with decreased survival in this population include elevated post-transplant HIV or HCV viral load, intolerance to antiretroviral therapy, and African American ethnicity. kamagra tablets
Post-Transplant Monitoring
The most accurate means of testing for the presence of HCV-associated disease resulting from recurrent HCV infection is a liver biopsy. Although elevations in serum aminotransferase and HCV RNA levels may occur in the setting of HCV recurrence, histopathologic assessment by an experienced pathologist provides the most definitive diagnostic information and is critical to distinguishing between recurrent HCV and other disease processes, including acute or chronic rejection, biliary disease, or other viral infections such as CMV. Annual liver biopsies are recommended in HCV liver transplant recipients in order to assess for progressive allograft fibrosis and potential candidacy for antiviral therapy, as combination peginterferon alfa (PegIFN) and ribavirin (RBV) should be considered in patients with histologic evidence of recurrent HCV and stage 2 fibrosis.
Source
Although it occurs in less than 10% of transplant recipients with chronic HCV, a severe and rapidly progressive form of recurrent HCV infection characterized by cholestatic disease has a major impact on survival. In contrast to a chronic hepatitis observed in most patients with recurrent HCV, this syndrome is defined by a total serum bilirubin of more than 6 mg/dL, elevated alkaline phosphatase or gamma glutamyltransferase levels more than 5 times the upper limit of normal, high serum HCV RNA levels, and histologic features including central hepatocyte ballooning without necrosis, cholangiolar proliferation without loss of bile ducts, and intrahepatic cholestasis in the absence of significant inflammation, biliary obstructive disease, or vascular complications.15,18 Onset typically occurs within the first 6 months following liver transplantation, and rapid progression to allograft failure may occur within 1 year. In addition, patient survival following repeat liver transplantation for fibrosing cholestatic HCV is severely compromised; thus, retransplantation is not an acceptable management option in this case.
Risk Factors for Severe Liver Disease
Several recipient, donor, and viral factors, as well as the use of specific immunosuppressive agents, have been identified as risk factors for increased severity of disease progression, allograft loss, and decreased survival in patients with HCV who undergo liver transplantation (Table 1). The presence of a severe histologic grade of inflammation early in the post-transplant course, particularly within the first year, may be predictive of more rapid fibrosis progression and cirrhosis at 5 years. Elevated serum HCV RNA levels both prior to undergoing transplant and during the post-transplant period may also be associated with progressive disease. Donor age has been identified as a major risk factor, as increased age, particularly over 50 years, is associated with more rapid disease progression, development of cirrhosis, and HCV-associated graft failure. Additional factors that may potentially be associated with severe recurrent disease include infectionwith HCV genotype 1, presence of cryoglobulinemia, female gender, increased recipient age, non-white ethnicity of recipient, donor steatosis, and cold ischemia time. However, data that strongly support these factors, specifically in association with HCV disease progression, are limited or, in some cases, conflicting. viagra plus
Table 1. Established Risk Factors for Severe Recurrent Hepatitis C
Virus (HCV) Following Liver Transplantation:
• Fibrosing cholestatic HCV syndrome
• Increased serum HCV RNA levels (pre- or posttransplantation)
• Early recurrence or severe histologic inflammatory activity within 1 year
• Use of high-dose intravenous pulse corticosteroids or muromonab-CD3
• Increased donor age
• Cytomegalovirus infection
• HIV-HCV co-infection
Cytomegalovirus (CMV) infection is common in liver transplant recipients and is a major risk factor for severe recurrence of HCV-associated liver disease. HCV patients who develop CMV viremia following liver transplantation are at an increased risk of advanced histologic changes, including periportal and bridging necrosis, lobular inflammatory activity, and development of cirrhosis. The greatest risk of CMV disease occurs in the setting of donor CMV seropositivity and recipient sero- negativity. Prophylaxis or preemptive therapy have been described as a means of preventing CMV infection in at-risk individuals. Prophylaxis with valganciclovir for 3 months following liver transplantation has been reported as the most common strategy utilized in this population. Immunosuppression may have a significant impact on the risk of disease progression following transplant. Viral kinetics studies have described a rapid increase in serum HCV RNA levels in patients who receive high- dose intravenous corticosteroids intraoperatively or in the treatment of acute cellular rejection. Further studies have identified the use of pulse intravenous corticosteroid therapy or muromonab-CD3 (Orthoclone OKT3, Ortho Biotech; an anti-CD3 monoclonal antibody) as independent risk factors for development of cirrhosis and graft failure. Results of prospective studies evaluating outcomes in HIV-HCV co-infected individuals have revealed significantly reduced post- transplant survival in co-infected patients compared to other HIV-positive or non-HIV transplant recipients, with 3- and 5-year survival rates as low as 56% and 33%, respectively. In particular, HIV-HCV co-infected patients with CD4+ cell counts less than 200 cells/pL are at an increased risk, indicating the negative impact of an immunocompromised state in the setting of immunosuppressive therapy following transplantation. Additional factors associated with decreased survival in this population include elevated post-transplant HIV or HCV viral load, intolerance to antiretroviral therapy, and African American ethnicity. kamagra tablets
Post-Transplant Monitoring
The most accurate means of testing for the presence of HCV-associated disease resulting from recurrent HCV infection is a liver biopsy. Although elevations in serum aminotransferase and HCV RNA levels may occur in the setting of HCV recurrence, histopathologic assessment by an experienced pathologist provides the most definitive diagnostic information and is critical to distinguishing between recurrent HCV and other disease processes, including acute or chronic rejection, biliary disease, or other viral infections such as CMV. Annual liver biopsies are recommended in HCV liver transplant recipients in order to assess for progressive allograft fibrosis and potential candidacy for antiviral therapy, as combination peginterferon alfa (PegIFN) and ribavirin (RBV) should be considered in patients with histologic evidence of recurrent HCV and stage 2 fibrosis.
Source
October 25, 2010
Early use of TIPS in patients with cirrhosis and variceal bleeding
N Engl J Med. 2010 Jun 24;362(25):2370-9.
GarcÃa-Pagán JC, Caca K, Bureau C, Laleman W, Appenrodt B, Luca A, Abraldes JG, Nevens F, Vinel JP, Mössner J, Bosch J; Early TIPS (Transjugular Intrahepatic Portosystemic Shunt) Cooperative Study Group.
Hepatic Hemodynamic Laboratory, Liver Unit, Institut de Malalties Digestives i Metaboliques, University of Barcelona, Barcelona, Spain. jcgarcia@clinic.ub.es
Comment in:
N Engl J Med. 2010 Sep 30;363(14):1375; author reply 1376.
N Engl J Med. 2010 Sep 30;363(14):1375; author reply 1376.
N Engl J Med. 2010 Sep 30;363(14):1375-6; author reply 1376.
N Engl J Med. 2010 Jun 24;362(25):2421-2.
Ann Intern Med. 2010 Oct 19;153(8):JC4-6.
Abstract
BACKGROUND: Patients with cirrhosis in Child-Pugh class C or those in class B who have persistent bleeding at endoscopy are at high risk for treatment failure and a poor prognosis, even if they have undergone rescue treatment with a transjugular intrahepatic portosystemic shunt (TIPS). This study evaluated the earlier use of TIPS in such patients.
METHODS: We randomly assigned, within 24 hours after admission, a total of 63 patients with cirrhosis and acute variceal bleeding who had been treated with vasoactive drugs plus endoscopic therapy to treatment with a polytetrafluoroethylene-covered stent within 72 hours after randomization (early-TIPS group, 32 patients) or continuation of vasoactive-drug therapy, followed after 3 to 5 days by treatment with propranolol or nadolol and long-term endoscopic band ligation (EBL), with insertion of a TIPS if needed as rescue therapy (pharmacotherapy-EBL group, 31 patients).
RESULTS: During a median follow-up of 16 months, rebleeding or failure to control bleeding occurred in 14 patients in the pharmacotherapy-EBL group as compared with 1 patient in the early-TIPS group (P=0.001). The 1-year actuarial probability of remaining free of this composite end point was 50% in the pharmacotherapy-EBL group versus 97% in the early-TIPS group (P<0.001). Sixteen patients died (12 in the pharmacotherapy-EBL group and 4 in the early-TIPS group, P=0.01). The 1-year actuarial survival was 61% in the pharmacotherapy-EBL group versus 86% in the early-TIPS group (P<0.001). Seven patients in the pharmacotherapy-EBL group received TIPS as rescue therapy, but four died. The number of days in the intensive care unit and the percentage of time in the hospital during follow-up were significantly higher in the pharmacotherapy-EBL group than in the early-TIPS group. No significant differences were observed between the two treatment groups with respect to serious adverse events.
CONCLUSIONS: In these patients with cirrhosis who were hospitalized for acute variceal bleeding and at high risk for treatment failure, the early use of TIPS was associated with significant reductions in treatment failure and in mortality. (Current Controlled Trials number, ISRCTN58150114.)
2010 Massachusetts Medical Society
PMID: 20573925 [PubMed - indexed for MEDLINE]
Source
GarcÃa-Pagán JC, Caca K, Bureau C, Laleman W, Appenrodt B, Luca A, Abraldes JG, Nevens F, Vinel JP, Mössner J, Bosch J; Early TIPS (Transjugular Intrahepatic Portosystemic Shunt) Cooperative Study Group.
Hepatic Hemodynamic Laboratory, Liver Unit, Institut de Malalties Digestives i Metaboliques, University of Barcelona, Barcelona, Spain. jcgarcia@clinic.ub.es
Comment in:
N Engl J Med. 2010 Sep 30;363(14):1375; author reply 1376.
N Engl J Med. 2010 Sep 30;363(14):1375; author reply 1376.
N Engl J Med. 2010 Sep 30;363(14):1375-6; author reply 1376.
N Engl J Med. 2010 Jun 24;362(25):2421-2.
Ann Intern Med. 2010 Oct 19;153(8):JC4-6.
Abstract
BACKGROUND: Patients with cirrhosis in Child-Pugh class C or those in class B who have persistent bleeding at endoscopy are at high risk for treatment failure and a poor prognosis, even if they have undergone rescue treatment with a transjugular intrahepatic portosystemic shunt (TIPS). This study evaluated the earlier use of TIPS in such patients.
METHODS: We randomly assigned, within 24 hours after admission, a total of 63 patients with cirrhosis and acute variceal bleeding who had been treated with vasoactive drugs plus endoscopic therapy to treatment with a polytetrafluoroethylene-covered stent within 72 hours after randomization (early-TIPS group, 32 patients) or continuation of vasoactive-drug therapy, followed after 3 to 5 days by treatment with propranolol or nadolol and long-term endoscopic band ligation (EBL), with insertion of a TIPS if needed as rescue therapy (pharmacotherapy-EBL group, 31 patients).
RESULTS: During a median follow-up of 16 months, rebleeding or failure to control bleeding occurred in 14 patients in the pharmacotherapy-EBL group as compared with 1 patient in the early-TIPS group (P=0.001). The 1-year actuarial probability of remaining free of this composite end point was 50% in the pharmacotherapy-EBL group versus 97% in the early-TIPS group (P<0.001). Sixteen patients died (12 in the pharmacotherapy-EBL group and 4 in the early-TIPS group, P=0.01). The 1-year actuarial survival was 61% in the pharmacotherapy-EBL group versus 86% in the early-TIPS group (P<0.001). Seven patients in the pharmacotherapy-EBL group received TIPS as rescue therapy, but four died. The number of days in the intensive care unit and the percentage of time in the hospital during follow-up were significantly higher in the pharmacotherapy-EBL group than in the early-TIPS group. No significant differences were observed between the two treatment groups with respect to serious adverse events.
CONCLUSIONS: In these patients with cirrhosis who were hospitalized for acute variceal bleeding and at high risk for treatment failure, the early use of TIPS was associated with significant reductions in treatment failure and in mortality. (Current Controlled Trials number, ISRCTN58150114.)
2010 Massachusetts Medical Society
PMID: 20573925 [PubMed - indexed for MEDLINE]
Source
Hepatitis C Virus Treatment-Related Anemia Is Associated With Higher Sustained Virologic Response Rate
Gastroenterology. 2010 Aug 16. [Epub ahead of print]
Sulkowski MS, Shiffman ML, Afdhal NH, Reddy KR, McCone J, Lee WM, Herrine SK, Harrison SA, Poordad FF, Koury K, Deng W, Noviello S, Pedicone LD, Brass CA, Albrecht JK, McHutchison JG; IDEAL study team.
Johns Hopkins University School of Medicine, Baltimore, Maryland.
Abstract
BACKGROUND & AIMS: Hepatitis C virus (HCV) treatment is frequently complicated by anemia from ribavirin (RBV)-related hemolysis and peginterferon-alfa (PEG-IFN)-related bone marrow suppression. We investigated the relationships among treatment outcomes, anemia, and its management with RBV dose reduction and/or erythropoiesis-stimulating agents (ESAs).
METHODS: We analyzed data from a trial conducted at 118 United States academic and community centers in treatment-naïve patients with HCV genotype 1. Patients were treated for as many as 48 weeks with 1 of 3 PEG-IFN/RBV regimens. ESAs were given to anemic patients (hemoglobin [Hb] <10 g/dL) after RBV dose reduction. Sustained virologic responses (SVR) were assessed based on decreases in Hb, anemia, and ESA use.
RESULTS: While patients received treatment, 3023 had their Hb levels measured at least once. A SVR was associated with the magnitude of Hb decrease: >3 g/dL, 43.7%; ≤3 g/dL, 29.9% (P < .001). Anemia occurred in 865 patients (28.6%); 449 of these (51.9%) used ESAs. In patients with early-onset anemia (≤ 8 weeks of treatment), ESAs were associated with higher SVR rate (45.0% > 25.9%; P < .001) and reduced discontinuation of treatment because of adverse events (12.6% < 30.1%, P < .001). ESAs did not affect SVR or discontinuation rates among patients with late-stage anemia.
CONCLUSIONS: Among HCV genotype 1-infected patients treated with PEG-IFN/RBV, anemia was associated with higher rates of SVR. The effect of ESAs varied by time to anemia; patients with early-onset anemia had higher rates of SVR with ESA use, whereas no effect was observed in those with late-onset anemia. Prospective trials are needed to assess the role of ESAs in HCV treatment.
Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
PMID: 20723545 [PubMed - as supplied by publisher]
Source
Sulkowski MS, Shiffman ML, Afdhal NH, Reddy KR, McCone J, Lee WM, Herrine SK, Harrison SA, Poordad FF, Koury K, Deng W, Noviello S, Pedicone LD, Brass CA, Albrecht JK, McHutchison JG; IDEAL study team.
Johns Hopkins University School of Medicine, Baltimore, Maryland.
Abstract
BACKGROUND & AIMS: Hepatitis C virus (HCV) treatment is frequently complicated by anemia from ribavirin (RBV)-related hemolysis and peginterferon-alfa (PEG-IFN)-related bone marrow suppression. We investigated the relationships among treatment outcomes, anemia, and its management with RBV dose reduction and/or erythropoiesis-stimulating agents (ESAs).
METHODS: We analyzed data from a trial conducted at 118 United States academic and community centers in treatment-naïve patients with HCV genotype 1. Patients were treated for as many as 48 weeks with 1 of 3 PEG-IFN/RBV regimens. ESAs were given to anemic patients (hemoglobin [Hb] <10 g/dL) after RBV dose reduction. Sustained virologic responses (SVR) were assessed based on decreases in Hb, anemia, and ESA use.
RESULTS: While patients received treatment, 3023 had their Hb levels measured at least once. A SVR was associated with the magnitude of Hb decrease: >3 g/dL, 43.7%; ≤3 g/dL, 29.9% (P < .001). Anemia occurred in 865 patients (28.6%); 449 of these (51.9%) used ESAs. In patients with early-onset anemia (≤ 8 weeks of treatment), ESAs were associated with higher SVR rate (45.0% > 25.9%; P < .001) and reduced discontinuation of treatment because of adverse events (12.6% < 30.1%, P < .001). ESAs did not affect SVR or discontinuation rates among patients with late-stage anemia.
CONCLUSIONS: Among HCV genotype 1-infected patients treated with PEG-IFN/RBV, anemia was associated with higher rates of SVR. The effect of ESAs varied by time to anemia; patients with early-onset anemia had higher rates of SVR with ESA use, whereas no effect was observed in those with late-onset anemia. Prospective trials are needed to assess the role of ESAs in HCV treatment.
Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
PMID: 20723545 [PubMed - as supplied by publisher]
Source
Vertex Quarter Blemished by Hep C Hiccup
By Adam Feuerstein 10/25/10 - 07:44 PM EDT
CAMBRIDGE, Mass. (TheStreet) -- Two words investors don't want to see in a Vertex Pharmaceuticals'(VRTX_) press release: Viral breakthrough.
Yet that's what Vertex disclosed Monday in its otherwise unremarkable third-quarter earnings report. A phase IIb study combining two of the company's experimental hepatitis C drugs -- VX-222 and telaprevir -- had to be modified after viral loads in some patients rebounded during the first four weeks of treatment.
The adversely affected patients were being treated with a low-dose of VX-222 plus telaprevir. That dosing regimen is being discontinued due to the viral breakthrough, Vertex said. Other hepatitis C patients continue treatment in the ongoing study with a high dose of VX-222 plus telaprevir as well as four-drug regimens of VX-222, telaprevir, long-acting interferon and ribavirin.
The future of hepatitis C treatment is in the combination of new drugs that act powerfully and directly against the virus, eliminating the need for patients to rely on older, established drugs like long-acting interferons and ribavirin which work in less than half of patients and causes bothersome side effects.
Vertex's effort in this race is centered around the VX-222/telaprevir combination, so Monday's disclosure of a hiccup in the ongoing phase II study is likely to raise some investor concerns. Other companies developing their own direct-acting antiviral combinations include Roche, Bristol-Myers Squibb(BMY_), Gilead Sciences(GILD_)and Boehringer Ingelheim.
In its defense, Vertex said on a conference call that viral breakthrough in the low-dose VX-222/telaprevir arm of the study was not accompanied by any safety issues. Patients continue to be treated with a high-dose VX-222-telaprevir combination, also without safety issues. None of the patients in the remaining three arms of the 100-patient study have experienced viral breakthrough, the company said.
Vertex is gearing up to complete an approval filing for telaprevir in the coming weeks based on data from phase III studies which demonstrated the drug's ability to sharply increase the hepatitis C cure rate compared to the current standard of care. Vertex will seek telaprevir's approval for both hepatitis C patients starting treatment for the first time as well as patients who have failed to respond to previous treatment.
Data from these pivotal studies of telaprevir will be presented at the American Association for the Study of Liver Disease (AASLD) annual meeting, which runs Oct. 29 through Nov. 2. The AASLD meeting will also showcase for the first-ever presentation of phase III data from a Merck's(MRK_) competing hepatitis C drug boceprevir.
Vertex is hoping to launch telaprevir early next year. The drug will be dosed three times a day initially in combination with long-acting interferon and ribavirin, but Monday the company announced plans to start a new phase III trial testing a more convenient, twice-daily dose of telaprevir.
A completed phase II study of twice-daily telaprevir was presented at last year's AASLD meeting and showed promising results.
From the financial ledger, Vertex's third quarter loss widened to $209 million, or $1.04 a share from $149.6 million, or 84 cents a share, in the year-ago quarter.
Vertex ended the September quarter with $1.2 billion in cash, including $400 million raised last month in a new convertible debt offering. Vertex said it remains on track to lose $750 million this year, in line with previous guidance.
Vertex shares closed Friday at $37.32, ahead of the company's earnings announcement.
--Written by Adam Feuerstein in Boston.
Source
Also See:
Vertex Pharmaceuticals Reports Third Quarter 2010 Financial Results and Highlights Progress in Hepatitis C and Cystic Fibrosis Development Programs
CAMBRIDGE, Mass. (TheStreet) -- Two words investors don't want to see in a Vertex Pharmaceuticals'(VRTX_) press release: Viral breakthrough.
Yet that's what Vertex disclosed Monday in its otherwise unremarkable third-quarter earnings report. A phase IIb study combining two of the company's experimental hepatitis C drugs -- VX-222 and telaprevir -- had to be modified after viral loads in some patients rebounded during the first four weeks of treatment.
The adversely affected patients were being treated with a low-dose of VX-222 plus telaprevir. That dosing regimen is being discontinued due to the viral breakthrough, Vertex said. Other hepatitis C patients continue treatment in the ongoing study with a high dose of VX-222 plus telaprevir as well as four-drug regimens of VX-222, telaprevir, long-acting interferon and ribavirin.
The future of hepatitis C treatment is in the combination of new drugs that act powerfully and directly against the virus, eliminating the need for patients to rely on older, established drugs like long-acting interferons and ribavirin which work in less than half of patients and causes bothersome side effects.
Vertex's effort in this race is centered around the VX-222/telaprevir combination, so Monday's disclosure of a hiccup in the ongoing phase II study is likely to raise some investor concerns. Other companies developing their own direct-acting antiviral combinations include Roche, Bristol-Myers Squibb(BMY_), Gilead Sciences(GILD_)and Boehringer Ingelheim.
In its defense, Vertex said on a conference call that viral breakthrough in the low-dose VX-222/telaprevir arm of the study was not accompanied by any safety issues. Patients continue to be treated with a high-dose VX-222-telaprevir combination, also without safety issues. None of the patients in the remaining three arms of the 100-patient study have experienced viral breakthrough, the company said.
Vertex is gearing up to complete an approval filing for telaprevir in the coming weeks based on data from phase III studies which demonstrated the drug's ability to sharply increase the hepatitis C cure rate compared to the current standard of care. Vertex will seek telaprevir's approval for both hepatitis C patients starting treatment for the first time as well as patients who have failed to respond to previous treatment.
Data from these pivotal studies of telaprevir will be presented at the American Association for the Study of Liver Disease (AASLD) annual meeting, which runs Oct. 29 through Nov. 2. The AASLD meeting will also showcase for the first-ever presentation of phase III data from a Merck's(MRK_) competing hepatitis C drug boceprevir.
Vertex is hoping to launch telaprevir early next year. The drug will be dosed three times a day initially in combination with long-acting interferon and ribavirin, but Monday the company announced plans to start a new phase III trial testing a more convenient, twice-daily dose of telaprevir.
A completed phase II study of twice-daily telaprevir was presented at last year's AASLD meeting and showed promising results.
From the financial ledger, Vertex's third quarter loss widened to $209 million, or $1.04 a share from $149.6 million, or 84 cents a share, in the year-ago quarter.
Vertex ended the September quarter with $1.2 billion in cash, including $400 million raised last month in a new convertible debt offering. Vertex said it remains on track to lose $750 million this year, in line with previous guidance.
Vertex shares closed Friday at $37.32, ahead of the company's earnings announcement.
--Written by Adam Feuerstein in Boston.
Source
Also See:
Vertex Pharmaceuticals Reports Third Quarter 2010 Financial Results and Highlights Progress in Hepatitis C and Cystic Fibrosis Development Programs
Vertex Pharmaceuticals Announces Start of a Phase 3b Study of Twice-Daily Telaprevir in People Not Treated Previously for Hepatitis C
Oct. 25, 2010, 4:17 p.m. EDT
- First Phase 3 study to evaluate twice-daily (BID) dosing of a protease inhibitor for hepatitis C -
CAMBRIDGE, Mass., Oct 25, 2010 (BUSINESS WIRE) -- --- All patients will receive telaprevir-based combination therapy -
Vertex Pharmaceuticals Incorporated /quotes/comstock/15*!vrtx/quotes/nls/vrtx (VRTX 37.32, +0.89, +2.44%) today announced the initiation of a Phase 3b study called OPTIMIZE that will evaluate twice-daily (BID) dosing of a telaprevir-based combination regimen in people chronically infected with genotype 1 hepatitis C virus (HCV) who have not been treated previously. This is the first Phase 3 study to evaluate twice-daily dosing of a protease inhibitor for the treatment of hepatitis C. OPTIMIZE will not include a control arm of pegylated-interferon and ribavirin alone.
"The sustained viral response rates, or viral cures, seen across a broad range of people in the Phase 3 studies of telaprevir set a high bar in the development of treatments for hepatitis C, and we are committed to studying new ways to further improve treatment," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer for Vertex. "High viral cure rates were demonstrated in the Phase 2 study of twice-daily telaprevir and we're looking forward to conducting a larger study to confirm these findings."
The OPTIMIZE study will be conducted by Vertex's collaborator, Tibotec.
OPTIMIZE Study Design
In Vertex's recently completed Phase 3 registration program, patients who received telaprevir in combination with pegylated-interferon and ribavirin took telaprevir three times daily (750mg; every eight hours). OPTIMIZE is a randomized, open-label, Phase 3b study that will evaluate twice-daily dosing (BID) of telaprevir in people chronically infected with genotype 1 HCV who have not been treated previously. The study will be conducted globally at 135 clinical trial sites and enroll approximately 700 people. Patient screening for enrollment in the OPTIMIZE study is expected to start in November 2010.
For the first 12 weeks of the study, all patients will receive 2,250mg of telaprevir taken twice daily (1,125mg; BID) or three times daily (750mg; every eight hours) in combination with pegylated-interferon alpha-2a (PEGASYS(R)) and twice-daily ribavirin. Response guided therapy will be used to determine whether patients receive pegylated-interferon and ribavirin alone for an additional 12 weeks (24 weeks total) or 36 weeks (48 weeks total) based on their treatment response at week 4. The primary endpoint of the OPTIMIZE study is sustained viral response (SVR) 24 weeks after the end of all treatment. The primary objective is to demonstrate non-inferiority of BID telaprevir versus telaprevir dosed every eight hours as measured by SVR.
SVR data from the study are expected as early as 2012. If these data are positive, they may support the submission of a supplemental New Drug Application (sNDA) for twice-daily (BID) dosing of telaprevir.
Phase 2 C208 study
Study C208 was an exploratory, four-arm, randomized, open label, Phase 2 clinical trial that was conducted by Tibotec in Europe in 161 treatment-naive patients with genotype 1 HCV infection. The objective of Study C208 was to explore the safety, efficacy, tolerability and pharmacokinetics of telaprevir administered every 12 hours (1,125mg) or every eight hours (750mg). Each dosing regimen of telaprevir was studied in combination with either PEGASYS(R) or PEGINTRON(R) and ribavirin, the currently approved therapies for chronic HCV infection.
Across the four arms, SVR rates were 82% and 83% in patients treated with telaprevir-based regimens every 12 hours (PEGINTRON and PEGASYS, respectively) and 81% and 85% in patients treated with the every 8-hour regimen (PEGINTRON and PEGASYS, respectively). The primary endpoint was SVR, and data from this study were presented at the 2009 annual meeting of the American Association for the Study of Liver Diseases (AASLD). The Phase 2 C208 data supported the initiation of the Phase 3b OPTIMIZE study.
In the C208 study, the frequency and severity of adverse events (AEs) and the rate of treatment discontinuations were similar to those reported in prior telaprevir trials. The rates of viral breakthrough were similar to the every 8- and every 12-hour regimens. The most common adverse events reported in patients in Study C208 were pruritis, nausea, rash, anemia, flu-like illness, fatigue and headache, and were similar overall between the patient groups receiving every 8-hour dosing and those receiving every 12-hour dosing.
Updates on the status of clinical trials of telaprevir are available online at http://www.clinicaltrials.gov/.
About the Telaprevir Development Program
To date, more than 2,500 people with hepatitis C have received telaprevir-based therapy as part of Phase 2 studies and the Phase 3 ADVANCE, ILLUMINATE and REALIZE studies. Together, these studies enrolled people with genotype 1 hepatitis C who had not been treated for their disease previously (ADVANCE and ILLUMINATE) as well as people who had been treated before but did not achieve a viral cure (REALIZE). A fact sheet on the Phase 3 Telaprevir Development Program is available at http://www.vrtx.com/aasld2010.html.
Phase 3 ADVANCE Trial
The pivotal Phase 3 ADVANCE study evaluated telaprevir-based response-guided regimens in 1,095 treatment-naive patients. The primary endpoint of ADVANCE was SVR, defined as the proportion of people who had undetectable HCV RNA both at the end of treatment and 24 weeks after the end of treatment. The secondary endpoint was to evaluate the safety of telaprevir when dosed in combination with pegylated-interferon and ribavirin. As part of a response-guided design, people in the telaprevir-based treatment arms who had undetectable HCV RNA (<25IU/mL, and undetectable by Roche COBAS Taqman HCV test) at weeks 4 and 12 of treatment were eligible to receive a total of 24 weeks of therapy. Patients who did not meet the response-guided criterion but were undetectable at week 24, received 48 weeks of total therapy.
Phase 3 ILLUMINATE Trial
The ILLUMINATE trial was a supplemental, open-label, Phase 3 study designed to evaluate whether there was any benefit in extending therapy from 24 to 48 weeks in people whose hepatitis C was undetectable (<25IU/mL undetectable) at weeks 4 and 12 of therapy. The primary endpoint of the study was the proportion of people who achieved SVR in the randomized treatment groups, and evaluated by a non-inferiority analysis.
Phase 3 REALIZE Trial
REALIZE was the second Phase 3 pivotal trial designed to evaluate telaprevir-based regimens in people who had received pegylated-interferon based therapy but did not achieve a cure. REALIZE was the only Phase 3 clinical trial to date of an investigational direct-acting antiviral (DAA) to include all major subgroups of difficult-to-treat patients including null responders, defined as people who had a less than 2 log10 reduction in viral load by week 12 of a prior course of therapy.
Vertex retains commercial rights to telaprevir in North America. Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries.
About Hepatitis C
Hepatitis C is a liver disease caused by the hepatitis C virus, which is found in the blood of people with the disease.(2) According to a 2010 report from the Institute of Medicine, up to 3.9 million people in the United States have chronic hepatitis C and 75% of those infected are unaware of their infection.(3)Approximately 60 percent of genotype 1 patients who undergo an initial 48-week regimen with pegylated-interferon and ribavirin, the currently approved treatment regimen, do not achieve SVR, (4,5,6)or viral cure.(1)
Hepatitis C is spread through direct contact with the blood of infected people.(2) Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.(2) Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.(2) If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.(7,8,9,10,11) In the United States, hepatitis C is the leading cause of liver transplantations and is reported to contribute to 4,600 to 12,000 deaths annually.(8) The majority of people with hepatitis C were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.(11) By 2029, total annual medical costs in the U.S. for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.(11)
Additional resources for media, including a hepatitis C backgrounder and glossary of common terms, are available at: http://investors.vrtx.com/press.cfm
About Vertex
Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex's product pipeline is focused on viral diseases, cystic fibrosis, inflammation, autoimmune diseases, epilepsy, cancer and pain.
Vertex co-discovered the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.
Lexiva is a registered trademark of the GlaxoSmithKline group of companies.
PEGASYS(R) and COPEGASYS(R) are registered trademarks of Hoffman-La Roche.
References:
(1)Ghany, m.G., Strader, d.B., Thomas, d.L., Seeff, Leondard B. Diagnosis, Management and Treatment of Hepatitis C; An Update. 2009. Hepatology. 2009;49 (4):1-40. (2) Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf. Accessed May 25, 2010. (3) Institute of Medicine. Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C. Available at http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx. Accessed May 25, 2010. (4)Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965. (5) Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982. (6)McHutchison JG, Lawitz EJ, Shiffman ML, et al; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593. (7) Morgan T.R, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115). (8)Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW. Aging of hepatitis C virus (HCV)-infected persons in the United States: A multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010;138: 513-521 (9) Volk, Michael I., Tocco, Rachel, Saini, Sameer, Lok, Anna S.F. Public Health Impact of Antiviral Therapy for Hepatitis C in the United States. Hepatology.2009;50(6):1750-1755. (10) Veldt, B.J., Heathcote, J., Wedmeyer, H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684. (11) Pyenson, B., Fitch, K., Iwasaki, K. Consequences of Hepatitis C Virus (HCV): Costs of a Baby Boomer Epidemic of Liver Disease. Milliman, Inc. This report was commissioned by Vertex Pharmaceuticals, Inc. May, 2009.
Safe Harbor Statement
This press release contains forward-looking statements, including statements regarding (i) the viral cure rates in Phase 3 studies of telaprevir setting a high bar in the development of treatments for HCV and the Company's commitment to studying new ways to further improve treatment; (ii) the possibility that a larger study will confirm the findings from the Phase 2 study of twice-daily telaprevir; (iii) the design of the trial, including the objective of the trial and the primary endpoint, the expectation that patient screening will start in November 2010, the number of patients the Company expects to enroll, and the number and location of clinical trial sites, and that the trial will be conducted by Tibotec; (iv) the expectation that SVR data from the trial will be available as early as 2012 and (v) the expectation that if the data are positive they may support the submission of a supplemental New Drug Application for twice-daily dosing of telaprevir. While the company believes the forward-looking statements contained in this press release are accurate, those statements are subject to risks and uncertainties that could cause actual outcomes to vary materially from the outcomes referenced in the forward-looking statements. These risks and uncertainties include, among other things, the risk that efforts to develop telaprevir may not proceed due to technical, scientific, commercial, financial or other reasons, that clinical trials may not proceed as planned due to drug supply or patient enrollment issues, that additional clinical trials of telaprevir dosed twice-daily may not reflect the results obtained to date, that an adverse event profile for telaprevir could be revealed in further nonclinical or clinical studies that could put further development of telaprevir in jeopardy or adversely impact their therapeutic value and other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through the Company's website at http://www.vrtx.com/. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.
(VRTX-GEN)
SOURCE: Vertex Pharmaceuticals Incorporated
Vertex Pharmaceuticals Incorporated
Media:
Amy Pasqua, 617-444-6992
or
Dawn Kalmar, 617-444-6992
or
Zachry Barber, 617-444-6992
or
Investors:
Michael Partridge, 617-444-6108
or
Lora Pike, 617-444-6755
or
Matthew Osborne, 617-444-6057
Source
- First Phase 3 study to evaluate twice-daily (BID) dosing of a protease inhibitor for hepatitis C -
CAMBRIDGE, Mass., Oct 25, 2010 (BUSINESS WIRE) -- --- All patients will receive telaprevir-based combination therapy -
Vertex Pharmaceuticals Incorporated /quotes/comstock/15*!vrtx/quotes/nls/vrtx (VRTX 37.32, +0.89, +2.44%) today announced the initiation of a Phase 3b study called OPTIMIZE that will evaluate twice-daily (BID) dosing of a telaprevir-based combination regimen in people chronically infected with genotype 1 hepatitis C virus (HCV) who have not been treated previously. This is the first Phase 3 study to evaluate twice-daily dosing of a protease inhibitor for the treatment of hepatitis C. OPTIMIZE will not include a control arm of pegylated-interferon and ribavirin alone.
"The sustained viral response rates, or viral cures, seen across a broad range of people in the Phase 3 studies of telaprevir set a high bar in the development of treatments for hepatitis C, and we are committed to studying new ways to further improve treatment," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer for Vertex. "High viral cure rates were demonstrated in the Phase 2 study of twice-daily telaprevir and we're looking forward to conducting a larger study to confirm these findings."
The OPTIMIZE study will be conducted by Vertex's collaborator, Tibotec.
OPTIMIZE Study Design
In Vertex's recently completed Phase 3 registration program, patients who received telaprevir in combination with pegylated-interferon and ribavirin took telaprevir three times daily (750mg; every eight hours). OPTIMIZE is a randomized, open-label, Phase 3b study that will evaluate twice-daily dosing (BID) of telaprevir in people chronically infected with genotype 1 HCV who have not been treated previously. The study will be conducted globally at 135 clinical trial sites and enroll approximately 700 people. Patient screening for enrollment in the OPTIMIZE study is expected to start in November 2010.
For the first 12 weeks of the study, all patients will receive 2,250mg of telaprevir taken twice daily (1,125mg; BID) or three times daily (750mg; every eight hours) in combination with pegylated-interferon alpha-2a (PEGASYS(R)) and twice-daily ribavirin. Response guided therapy will be used to determine whether patients receive pegylated-interferon and ribavirin alone for an additional 12 weeks (24 weeks total) or 36 weeks (48 weeks total) based on their treatment response at week 4. The primary endpoint of the OPTIMIZE study is sustained viral response (SVR) 24 weeks after the end of all treatment. The primary objective is to demonstrate non-inferiority of BID telaprevir versus telaprevir dosed every eight hours as measured by SVR.
SVR data from the study are expected as early as 2012. If these data are positive, they may support the submission of a supplemental New Drug Application (sNDA) for twice-daily (BID) dosing of telaprevir.
Phase 2 C208 study
Study C208 was an exploratory, four-arm, randomized, open label, Phase 2 clinical trial that was conducted by Tibotec in Europe in 161 treatment-naive patients with genotype 1 HCV infection. The objective of Study C208 was to explore the safety, efficacy, tolerability and pharmacokinetics of telaprevir administered every 12 hours (1,125mg) or every eight hours (750mg). Each dosing regimen of telaprevir was studied in combination with either PEGASYS(R) or PEGINTRON(R) and ribavirin, the currently approved therapies for chronic HCV infection.
Across the four arms, SVR rates were 82% and 83% in patients treated with telaprevir-based regimens every 12 hours (PEGINTRON and PEGASYS, respectively) and 81% and 85% in patients treated with the every 8-hour regimen (PEGINTRON and PEGASYS, respectively). The primary endpoint was SVR, and data from this study were presented at the 2009 annual meeting of the American Association for the Study of Liver Diseases (AASLD). The Phase 2 C208 data supported the initiation of the Phase 3b OPTIMIZE study.
In the C208 study, the frequency and severity of adverse events (AEs) and the rate of treatment discontinuations were similar to those reported in prior telaprevir trials. The rates of viral breakthrough were similar to the every 8- and every 12-hour regimens. The most common adverse events reported in patients in Study C208 were pruritis, nausea, rash, anemia, flu-like illness, fatigue and headache, and were similar overall between the patient groups receiving every 8-hour dosing and those receiving every 12-hour dosing.
Updates on the status of clinical trials of telaprevir are available online at http://www.clinicaltrials.gov/.
About the Telaprevir Development Program
To date, more than 2,500 people with hepatitis C have received telaprevir-based therapy as part of Phase 2 studies and the Phase 3 ADVANCE, ILLUMINATE and REALIZE studies. Together, these studies enrolled people with genotype 1 hepatitis C who had not been treated for their disease previously (ADVANCE and ILLUMINATE) as well as people who had been treated before but did not achieve a viral cure (REALIZE). A fact sheet on the Phase 3 Telaprevir Development Program is available at http://www.vrtx.com/aasld2010.html.
Phase 3 ADVANCE Trial
The pivotal Phase 3 ADVANCE study evaluated telaprevir-based response-guided regimens in 1,095 treatment-naive patients. The primary endpoint of ADVANCE was SVR, defined as the proportion of people who had undetectable HCV RNA both at the end of treatment and 24 weeks after the end of treatment. The secondary endpoint was to evaluate the safety of telaprevir when dosed in combination with pegylated-interferon and ribavirin. As part of a response-guided design, people in the telaprevir-based treatment arms who had undetectable HCV RNA (<25IU/mL, and undetectable by Roche COBAS Taqman HCV test) at weeks 4 and 12 of treatment were eligible to receive a total of 24 weeks of therapy. Patients who did not meet the response-guided criterion but were undetectable at week 24, received 48 weeks of total therapy.
Phase 3 ILLUMINATE Trial
The ILLUMINATE trial was a supplemental, open-label, Phase 3 study designed to evaluate whether there was any benefit in extending therapy from 24 to 48 weeks in people whose hepatitis C was undetectable (<25IU/mL undetectable) at weeks 4 and 12 of therapy. The primary endpoint of the study was the proportion of people who achieved SVR in the randomized treatment groups, and evaluated by a non-inferiority analysis.
Phase 3 REALIZE Trial
REALIZE was the second Phase 3 pivotal trial designed to evaluate telaprevir-based regimens in people who had received pegylated-interferon based therapy but did not achieve a cure. REALIZE was the only Phase 3 clinical trial to date of an investigational direct-acting antiviral (DAA) to include all major subgroups of difficult-to-treat patients including null responders, defined as people who had a less than 2 log10 reduction in viral load by week 12 of a prior course of therapy.
Vertex retains commercial rights to telaprevir in North America. Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries.
About Hepatitis C
Hepatitis C is a liver disease caused by the hepatitis C virus, which is found in the blood of people with the disease.(2) According to a 2010 report from the Institute of Medicine, up to 3.9 million people in the United States have chronic hepatitis C and 75% of those infected are unaware of their infection.(3)Approximately 60 percent of genotype 1 patients who undergo an initial 48-week regimen with pegylated-interferon and ribavirin, the currently approved treatment regimen, do not achieve SVR, (4,5,6)or viral cure.(1)
Hepatitis C is spread through direct contact with the blood of infected people.(2) Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.(2) Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.(2) If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.(7,8,9,10,11) In the United States, hepatitis C is the leading cause of liver transplantations and is reported to contribute to 4,600 to 12,000 deaths annually.(8) The majority of people with hepatitis C were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.(11) By 2029, total annual medical costs in the U.S. for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.(11)
Additional resources for media, including a hepatitis C backgrounder and glossary of common terms, are available at: http://investors.vrtx.com/press.cfm
About Vertex
Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex's product pipeline is focused on viral diseases, cystic fibrosis, inflammation, autoimmune diseases, epilepsy, cancer and pain.
Vertex co-discovered the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.
Lexiva is a registered trademark of the GlaxoSmithKline group of companies.
PEGASYS(R) and COPEGASYS(R) are registered trademarks of Hoffman-La Roche.
References:
(1)Ghany, m.G., Strader, d.B., Thomas, d.L., Seeff, Leondard B. Diagnosis, Management and Treatment of Hepatitis C; An Update. 2009. Hepatology. 2009;49 (4):1-40. (2) Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf. Accessed May 25, 2010. (3) Institute of Medicine. Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C. Available at http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx. Accessed May 25, 2010. (4)Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965. (5) Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982. (6)McHutchison JG, Lawitz EJ, Shiffman ML, et al; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593. (7) Morgan T.R, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115). (8)Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW. Aging of hepatitis C virus (HCV)-infected persons in the United States: A multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010;138: 513-521 (9) Volk, Michael I., Tocco, Rachel, Saini, Sameer, Lok, Anna S.F. Public Health Impact of Antiviral Therapy for Hepatitis C in the United States. Hepatology.2009;50(6):1750-1755. (10) Veldt, B.J., Heathcote, J., Wedmeyer, H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684. (11) Pyenson, B., Fitch, K., Iwasaki, K. Consequences of Hepatitis C Virus (HCV): Costs of a Baby Boomer Epidemic of Liver Disease. Milliman, Inc. This report was commissioned by Vertex Pharmaceuticals, Inc. May, 2009.
Safe Harbor Statement
This press release contains forward-looking statements, including statements regarding (i) the viral cure rates in Phase 3 studies of telaprevir setting a high bar in the development of treatments for HCV and the Company's commitment to studying new ways to further improve treatment; (ii) the possibility that a larger study will confirm the findings from the Phase 2 study of twice-daily telaprevir; (iii) the design of the trial, including the objective of the trial and the primary endpoint, the expectation that patient screening will start in November 2010, the number of patients the Company expects to enroll, and the number and location of clinical trial sites, and that the trial will be conducted by Tibotec; (iv) the expectation that SVR data from the trial will be available as early as 2012 and (v) the expectation that if the data are positive they may support the submission of a supplemental New Drug Application for twice-daily dosing of telaprevir. While the company believes the forward-looking statements contained in this press release are accurate, those statements are subject to risks and uncertainties that could cause actual outcomes to vary materially from the outcomes referenced in the forward-looking statements. These risks and uncertainties include, among other things, the risk that efforts to develop telaprevir may not proceed due to technical, scientific, commercial, financial or other reasons, that clinical trials may not proceed as planned due to drug supply or patient enrollment issues, that additional clinical trials of telaprevir dosed twice-daily may not reflect the results obtained to date, that an adverse event profile for telaprevir could be revealed in further nonclinical or clinical studies that could put further development of telaprevir in jeopardy or adversely impact their therapeutic value and other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through the Company's website at http://www.vrtx.com/. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.
(VRTX-GEN)
SOURCE: Vertex Pharmaceuticals Incorporated
Vertex Pharmaceuticals Incorporated
Media:
Amy Pasqua, 617-444-6992
or
Dawn Kalmar, 617-444-6992
or
Zachry Barber, 617-444-6992
or
Investors:
Michael Partridge, 617-444-6108
or
Lora Pike, 617-444-6755
or
Matthew Osborne, 617-444-6057
Source
Vertex Pharmaceuticals Reports Third Quarter 2010 Financial Results and Highlights Progress in Hepatitis C and Cystic Fibrosis Development Programs
October 25, 2010 04:17 PM Eastern Daylight Time
- Hepatitis C: New Drug Application submission for telaprevir on track for fourth quarter 2010-
- Cystic Fibrosis: Phase 3 registration program ongoing for VX-770-
- Pipeline: Ongoing proof-of-concept clinical trials in hepatitis C, cystic fibrosis, epilepsy and rheumatoid arthritis-
- Financial: Company ends third quarter with a cash position of $1.2 billion-
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today reviewed recent business and clinical progress and reported consolidated financial results for the quarter ended September 30, 2010.
“With the recent completion of our Phase 3 registration program for telaprevir, we remain on track to submit our New Drug Application in the coming weeks, marking what we believe will be an important milestone in our effort to bring telaprevir to people with hepatitis C,” said Matthew Emmens, Chairman, President and Chief Executive Officer of Vertex Pharmaceuticals.
Mr. Emmens continued, “Later this week, clinical investigators will present Phase 3 data for telaprevir at the annual AASLD meeting in Boston. We continue to have high confidence in the potential for telaprevir to help the majority of people with hepatitis C – regardless of their treatment history – and we look forward to sharing additional telaprevir data with the medical community.
“Importantly, with a cash position of $1.2 billion at the end of the third quarter, we will enter 2011 with the financial strength needed to support the planned launch of telaprevir as well as the continued discovery and development of other new breakthrough medicines,” concluded Mr. Emmens.
Hepatitis C
Telaprevir Phase 3 Program Complete; Rolling NDA Submission On Track
• In the third quarter, Vertex completed its Phase 3 registration program for telaprevir. The company remains on track to complete the submission of its rolling New Drug Application (NDA) for telaprevir in combination with pegylated-interferon and ribavirin in the fourth quarter of 2010 with clinical data from its three Phase 3 trials in people who had not been previously treated for hepatitis C and in people who received prior treatment but were not cured.
Phase 3 ADVANCE and ILLUMINATE Trials to be Presented at AASLD This Week
• Vertex expects that final sustained viral response (SVR or viral cure) and safety data from the Phase 3 ADVANCE and ILLUMINATE trials will be presented as part of oral presentation sessions at the upcoming annual meeting for the American Association for the Study of Liver Diseases (AASLD or The Liver Meeting), being held October 29 to November 2 in Boston. In total, eight Vertex abstracts were accepted for presentation at the AASLD meeting.
Initiation of Phase 3b Clinical Trial to Evaluate Twice-Daily (BID) Dosing of Telaprevir
• Vertex today announced the initiation of a Phase 3b clinical trial to evaluate twice-daily dosing of telaprevir (1,125 mg; BID) compared to three-times-daily dosing of telaprevir (750 mg; q8h) in combination with pegylated-interferon and ribavirin for people with genotype 1 hepatitis C. Patient screening for enrollment in the study is expected to start in November 2010. Additional details on this trial were provided today in a separate press release.
Ongoing Phase 2 Trial Evaluating Combination Regimens of VX-222 and Telaprevir
• Vertex announced today that it has modified its clinical trial evaluating telaprevir dosed in combination with Vertex's lead HCV polymerase inhibitor, VX-222. The company will discontinue Arm A of this study as a result of patients meeting a pre-defined stopping rule related to viral breakthrough during the first four weeks of dosing. Arm A was designed to evaluate a two-drug regimen of VX-222 (low dose; 100 mg) and telaprevir (1,125 mg) both dosed twice daily without pegylated-interferon and ribavirin. The additional three arms of the study are continuing without modification, and no viral breakthrough has been reported in these arms.
• This Phase 2 proof-of-concept trial began dosing patients in August 2010 and is designed to evaluate safety and SVR rates using 12-week response-guided regimens of telaprevir/VX-222-based combination therapy in people with genotype 1 hepatitis C. The trial is continuing to evaluate treatment regimens that include four-drug regimens of telaprevir, VX-222, pegylated-interferon and ribavirin, as well as a two-drug regimen of only telaprevir (1,125 mg) and a higher dose of VX-222 (400 mg), both dosed twice daily.
• Trial sites have now completed patient recruitment, which Vertex expects will enable it to reach the initial target enrollment of 100 patients for the study. Vertex expects to obtain on-treatment clinical data from this trial in the first half of 2011 and SVR data in the second half of 2011.
Enrollment Complete in Phase 2 Trial Evaluating Telaprevir in People Co-Infected with Hepatitis C Virus and Human Immunodeficiency Virus
• Vertex today announced that it has completed enrollment of 60 patients in a Phase 2 clinical trial of telaprevir-based regimens in people who are infected with genotype 1 hepatitis C virus and the human immunodeficiency virus (HIV), also know as HCV-HIV co-infection. The primary endpoint of the trial is to evaluate the safety and tolerability of telaprevir-based therapy in people co-infected with HCV and HIV. A secondary endpoint is to evaluate SVR, or viral cure, rates.
• The trial enrolled 13 people who had not previously received treatment for hepatitis C and who were not currently being treated for HIV infection. The trial also enrolled 47 people who had not previously received treatment for hepatitis C and who were currently being treated for HIV infection with highly active antiretroviral therapy (HAART). Of the 47 patients on HAART, 23 were receiving a Reyataz-based regimen and 24 were receiving Atripla.
Cystic Fibrosis
Phase 3 Registration Program for VX-770
• Three trials of the novel cystic fibrosis transmembrane conductance regulator protein (CFTR) potentiator VX-770 are fully enrolled and ongoing as part of a global Phase 3 registration program focused on patients with the G551D mutation.
• Data from the Phase 3 registration program of VX-770 are expected in the first half of 2011. Pending results from the Phase 3 registration program, Vertex expects to submit a New Drug Application for VX-770 in the second half of 2011.
Initiation of Combination Trial of VX-770 and VX-809
• Vertex recently initiated a Phase 2a clinical trial that is evaluating combination regimens of VX-809 and VX-770 in people with cystic fibrosis who have two copies of the F508del mutation. Additional details on this trial can be found in a press release issued on October 18.
Pipeline
Proof-of-Concept Trials of VX-765 in Epilepsy and VX-509 in Rheumatoid Arthritis
• Vertex expects to complete a Phase 2 proof-of-concept trial of the novel caspase-1 inhibitor VX-765 in epilepsy in 2010. Top-line data, including safety and seizure frequency data, are expected later this year.
• Enrollment is ongoing in a Phase 2 proof-of-concept clinical trial of the novel Janus kinase 3 (JAK3) inhibitor VX-509 in rheumatoid arthritis (RA). Interim data from the trial are expected in 2011.
Third Quarter Results
For the quarter ended September 30, 2010, the company’s GAAP net loss was $209.0 million, or $1.04 per share, including certain charges totaling $34.4 million, compared to a GAAP net loss for the quarter ended September 30, 2009 of $149.6 million, or $0.84 per share, including certain charges totaling $22.6 million.
The non-GAAP loss, before certain charges, for the quarter ended September 30, 2010 was $174.6 million, or $0.87 per share, compared to $126.9 million, or $0.71 per share, for the quarter ended September 30, 2009. The increase in the company's 2010 non-GAAP loss was attributable to increased costs to support advancement of telaprevir toward potential launch.
Total revenues for the quarter ended September 30, 2010 were $23.8 million, compared to $25.0 million for the third quarter of 2009.
Research and development (R&D) expenses for the quarter ended September 30, 2010 were $170.4 million, compared to $132.1 million for the third quarter of 2009. The increase reflects greater commercial supply investment for telaprevir and increases in other development activities.
Sales, general and administrative (SG&A) expenses for the quarter ended September 30, 2010 were $48.9 million, compared to $36.6 million for the third quarter of 2009. This increase reflects building of capabilities, including an increase in the number of employees and our commercial investments, to support advancement of telaprevir toward potential launch.
At September 30, 2010, Vertex had $1.2 billion in cash, cash equivalents and marketable securities. In September 2010, Vertex issued $400.0 million of 3.35% convertible senior subordinated notes due 2015, with a conversion price of approximately $48.83 per share.
Full Year 2010 Financial Guidance
This section contains forward-looking guidance about the financial outlook for Vertex Pharmaceuticals.
The company is today reiterating its guidance for 2010 non-GAAP loss of approximately $600 million, as provided on February 4, 2010, and for its 2010 GAAP net loss of approximately $750 million, as provided on July 28, 2010.
Non-GAAP Financial Measures
In this press release, Vertex's financial results are provided both in accordance with accounting principles generally accepted in the United States (GAAP) and using certain non-GAAP financial measures. In particular, Vertex provides its third quarter 2010 and 2009 loss, and guidance for its projected 2010 loss, excluding stock-based compensation and executive transition expenses, restructuring expense, acquisition-related expenses, loss on exchange of convertible subordinated notes, and revenue and expenses related to certain September 2009 financial transactions. These results are provided as a complement to results provided in accordance with GAAP because management believes these non-GAAP financial measures help indicate underlying trends in the company's business, are important in comparing current results with prior period results and provide additional information regarding its financial position. Management also uses these non-GAAP financial measures to establish budgets and operational goals that are communicated internally and externally, and to manage the company's business and to evaluate its performance. A reconciliation of the other non-GAAP financial results to GAAP financial results is included in the attached financial statements.
About Vertex
Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company’s strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex’s product pipeline is focused on viral diseases, cystic fibrosis, inflammation, autoimmune diseases, cancer and pain. Vertex co-discovered the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.
Lexiva is a registered trademark of the GlaxoSmithKline group of companies.
Reyataz is a registered trademark of Bristol-Myers Squibb.
Atripla is a registered trademark of Bristol-Myers Squibb and Gilead Sciences, LLC.
Special Note Regarding Forward-looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including statements regarding (i) Vertex remaining on track to submit its New Drug Application for telaprevir in the fourth quarter of 2010; (ii) clinical investigators presenting Phase 3 data for telaprevir at AASLD; (iii) the potential for telaprevir to help the majority of people with hepatitis C regardless of their treatment history; (iv) the company entering 2011 with the financial strength needed to support the planned launch of telaprevir as well as the continued discovery and development of other new breakthrough medicines; (v) the expectation that patient screening for the Phase 3b clinical trial of telaprevir will start in November 2010; (vi) the telaprevir/VX-222 Phase 2 clinical trial being designed to evaluate safety and SVR rates using telaprevir/VX-222 based combination therapy and continuing to evaluate treatment regimens that include four-drug regimens and a two-drug regimen of only telaprevir and VX-222; (vii) Vertex expecting to reach its initial target enrollment of 100 patients, and to obtain on-treatment clinical data from the Phase 2 clinical trial of telaprevir and VX-222 in the first half of 2011 and SVR data in the second half of 2011; (viii) the expectation that data from the Phase 3 registration program for VX-770 will be available in the first half of 2011 and the possibility that the company will submit a New Drug Application for VX-770 in the second half of 2011; (ix) the expectation that the company will complete and receive top-line data from a clinical trial of VX-765 in 2010; (x) the expectation that interim data from a Phase 2 clinical trial of VX-509 will be received in 2011; and (xi) the company’s expectations regarding its 2010 non-GAAP and GAAP net loss. While the company believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that the outcomes for each of its planned clinical trials and studies may not be favorable, that regulatory authorities may require supplemental clinical trials in order to support registration of telaprevir and/or VX-770, that planned or potential clinical trials may be delayed or may not be conducted, that the company may not be able to successfully develop telaprevir, VX-770, VX-509, VX-765 or combination therapies involving telaprevir and VX-222 or VX-770 and VX-809, that the company's expectations regarding its 2010 GAAP and non-GAAP net loss may be incorrect, and other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through the company's website at www.vrtx.com. The company disclaims any obligation to update the information contained in this press release as new information becomes available.
Source
- Hepatitis C: New Drug Application submission for telaprevir on track for fourth quarter 2010-
- Cystic Fibrosis: Phase 3 registration program ongoing for VX-770-
- Pipeline: Ongoing proof-of-concept clinical trials in hepatitis C, cystic fibrosis, epilepsy and rheumatoid arthritis-
- Financial: Company ends third quarter with a cash position of $1.2 billion-
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today reviewed recent business and clinical progress and reported consolidated financial results for the quarter ended September 30, 2010.
“With the recent completion of our Phase 3 registration program for telaprevir, we remain on track to submit our New Drug Application in the coming weeks, marking what we believe will be an important milestone in our effort to bring telaprevir to people with hepatitis C,” said Matthew Emmens, Chairman, President and Chief Executive Officer of Vertex Pharmaceuticals.
Mr. Emmens continued, “Later this week, clinical investigators will present Phase 3 data for telaprevir at the annual AASLD meeting in Boston. We continue to have high confidence in the potential for telaprevir to help the majority of people with hepatitis C – regardless of their treatment history – and we look forward to sharing additional telaprevir data with the medical community.
“Importantly, with a cash position of $1.2 billion at the end of the third quarter, we will enter 2011 with the financial strength needed to support the planned launch of telaprevir as well as the continued discovery and development of other new breakthrough medicines,” concluded Mr. Emmens.
Hepatitis C
Telaprevir Phase 3 Program Complete; Rolling NDA Submission On Track
• In the third quarter, Vertex completed its Phase 3 registration program for telaprevir. The company remains on track to complete the submission of its rolling New Drug Application (NDA) for telaprevir in combination with pegylated-interferon and ribavirin in the fourth quarter of 2010 with clinical data from its three Phase 3 trials in people who had not been previously treated for hepatitis C and in people who received prior treatment but were not cured.
Phase 3 ADVANCE and ILLUMINATE Trials to be Presented at AASLD This Week
• Vertex expects that final sustained viral response (SVR or viral cure) and safety data from the Phase 3 ADVANCE and ILLUMINATE trials will be presented as part of oral presentation sessions at the upcoming annual meeting for the American Association for the Study of Liver Diseases (AASLD or The Liver Meeting), being held October 29 to November 2 in Boston. In total, eight Vertex abstracts were accepted for presentation at the AASLD meeting.
Initiation of Phase 3b Clinical Trial to Evaluate Twice-Daily (BID) Dosing of Telaprevir
• Vertex today announced the initiation of a Phase 3b clinical trial to evaluate twice-daily dosing of telaprevir (1,125 mg; BID) compared to three-times-daily dosing of telaprevir (750 mg; q8h) in combination with pegylated-interferon and ribavirin for people with genotype 1 hepatitis C. Patient screening for enrollment in the study is expected to start in November 2010. Additional details on this trial were provided today in a separate press release.
Ongoing Phase 2 Trial Evaluating Combination Regimens of VX-222 and Telaprevir
• Vertex announced today that it has modified its clinical trial evaluating telaprevir dosed in combination with Vertex's lead HCV polymerase inhibitor, VX-222. The company will discontinue Arm A of this study as a result of patients meeting a pre-defined stopping rule related to viral breakthrough during the first four weeks of dosing. Arm A was designed to evaluate a two-drug regimen of VX-222 (low dose; 100 mg) and telaprevir (1,125 mg) both dosed twice daily without pegylated-interferon and ribavirin. The additional three arms of the study are continuing without modification, and no viral breakthrough has been reported in these arms.
• This Phase 2 proof-of-concept trial began dosing patients in August 2010 and is designed to evaluate safety and SVR rates using 12-week response-guided regimens of telaprevir/VX-222-based combination therapy in people with genotype 1 hepatitis C. The trial is continuing to evaluate treatment regimens that include four-drug regimens of telaprevir, VX-222, pegylated-interferon and ribavirin, as well as a two-drug regimen of only telaprevir (1,125 mg) and a higher dose of VX-222 (400 mg), both dosed twice daily.
• Trial sites have now completed patient recruitment, which Vertex expects will enable it to reach the initial target enrollment of 100 patients for the study. Vertex expects to obtain on-treatment clinical data from this trial in the first half of 2011 and SVR data in the second half of 2011.
Enrollment Complete in Phase 2 Trial Evaluating Telaprevir in People Co-Infected with Hepatitis C Virus and Human Immunodeficiency Virus
• Vertex today announced that it has completed enrollment of 60 patients in a Phase 2 clinical trial of telaprevir-based regimens in people who are infected with genotype 1 hepatitis C virus and the human immunodeficiency virus (HIV), also know as HCV-HIV co-infection. The primary endpoint of the trial is to evaluate the safety and tolerability of telaprevir-based therapy in people co-infected with HCV and HIV. A secondary endpoint is to evaluate SVR, or viral cure, rates.
• The trial enrolled 13 people who had not previously received treatment for hepatitis C and who were not currently being treated for HIV infection. The trial also enrolled 47 people who had not previously received treatment for hepatitis C and who were currently being treated for HIV infection with highly active antiretroviral therapy (HAART). Of the 47 patients on HAART, 23 were receiving a Reyataz-based regimen and 24 were receiving Atripla.
Cystic Fibrosis
Phase 3 Registration Program for VX-770
• Three trials of the novel cystic fibrosis transmembrane conductance regulator protein (CFTR) potentiator VX-770 are fully enrolled and ongoing as part of a global Phase 3 registration program focused on patients with the G551D mutation.
• Data from the Phase 3 registration program of VX-770 are expected in the first half of 2011. Pending results from the Phase 3 registration program, Vertex expects to submit a New Drug Application for VX-770 in the second half of 2011.
Initiation of Combination Trial of VX-770 and VX-809
• Vertex recently initiated a Phase 2a clinical trial that is evaluating combination regimens of VX-809 and VX-770 in people with cystic fibrosis who have two copies of the F508del mutation. Additional details on this trial can be found in a press release issued on October 18.
Pipeline
Proof-of-Concept Trials of VX-765 in Epilepsy and VX-509 in Rheumatoid Arthritis
• Vertex expects to complete a Phase 2 proof-of-concept trial of the novel caspase-1 inhibitor VX-765 in epilepsy in 2010. Top-line data, including safety and seizure frequency data, are expected later this year.
• Enrollment is ongoing in a Phase 2 proof-of-concept clinical trial of the novel Janus kinase 3 (JAK3) inhibitor VX-509 in rheumatoid arthritis (RA). Interim data from the trial are expected in 2011.
Third Quarter Results
For the quarter ended September 30, 2010, the company’s GAAP net loss was $209.0 million, or $1.04 per share, including certain charges totaling $34.4 million, compared to a GAAP net loss for the quarter ended September 30, 2009 of $149.6 million, or $0.84 per share, including certain charges totaling $22.6 million.
The non-GAAP loss, before certain charges, for the quarter ended September 30, 2010 was $174.6 million, or $0.87 per share, compared to $126.9 million, or $0.71 per share, for the quarter ended September 30, 2009. The increase in the company's 2010 non-GAAP loss was attributable to increased costs to support advancement of telaprevir toward potential launch.
Total revenues for the quarter ended September 30, 2010 were $23.8 million, compared to $25.0 million for the third quarter of 2009.
Research and development (R&D) expenses for the quarter ended September 30, 2010 were $170.4 million, compared to $132.1 million for the third quarter of 2009. The increase reflects greater commercial supply investment for telaprevir and increases in other development activities.
Sales, general and administrative (SG&A) expenses for the quarter ended September 30, 2010 were $48.9 million, compared to $36.6 million for the third quarter of 2009. This increase reflects building of capabilities, including an increase in the number of employees and our commercial investments, to support advancement of telaprevir toward potential launch.
At September 30, 2010, Vertex had $1.2 billion in cash, cash equivalents and marketable securities. In September 2010, Vertex issued $400.0 million of 3.35% convertible senior subordinated notes due 2015, with a conversion price of approximately $48.83 per share.
Full Year 2010 Financial Guidance
This section contains forward-looking guidance about the financial outlook for Vertex Pharmaceuticals.
The company is today reiterating its guidance for 2010 non-GAAP loss of approximately $600 million, as provided on February 4, 2010, and for its 2010 GAAP net loss of approximately $750 million, as provided on July 28, 2010.
Non-GAAP Financial Measures
In this press release, Vertex's financial results are provided both in accordance with accounting principles generally accepted in the United States (GAAP) and using certain non-GAAP financial measures. In particular, Vertex provides its third quarter 2010 and 2009 loss, and guidance for its projected 2010 loss, excluding stock-based compensation and executive transition expenses, restructuring expense, acquisition-related expenses, loss on exchange of convertible subordinated notes, and revenue and expenses related to certain September 2009 financial transactions. These results are provided as a complement to results provided in accordance with GAAP because management believes these non-GAAP financial measures help indicate underlying trends in the company's business, are important in comparing current results with prior period results and provide additional information regarding its financial position. Management also uses these non-GAAP financial measures to establish budgets and operational goals that are communicated internally and externally, and to manage the company's business and to evaluate its performance. A reconciliation of the other non-GAAP financial results to GAAP financial results is included in the attached financial statements.
About Vertex
Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company’s strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex’s product pipeline is focused on viral diseases, cystic fibrosis, inflammation, autoimmune diseases, cancer and pain. Vertex co-discovered the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.
Lexiva is a registered trademark of the GlaxoSmithKline group of companies.
Reyataz is a registered trademark of Bristol-Myers Squibb.
Atripla is a registered trademark of Bristol-Myers Squibb and Gilead Sciences, LLC.
Special Note Regarding Forward-looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including statements regarding (i) Vertex remaining on track to submit its New Drug Application for telaprevir in the fourth quarter of 2010; (ii) clinical investigators presenting Phase 3 data for telaprevir at AASLD; (iii) the potential for telaprevir to help the majority of people with hepatitis C regardless of their treatment history; (iv) the company entering 2011 with the financial strength needed to support the planned launch of telaprevir as well as the continued discovery and development of other new breakthrough medicines; (v) the expectation that patient screening for the Phase 3b clinical trial of telaprevir will start in November 2010; (vi) the telaprevir/VX-222 Phase 2 clinical trial being designed to evaluate safety and SVR rates using telaprevir/VX-222 based combination therapy and continuing to evaluate treatment regimens that include four-drug regimens and a two-drug regimen of only telaprevir and VX-222; (vii) Vertex expecting to reach its initial target enrollment of 100 patients, and to obtain on-treatment clinical data from the Phase 2 clinical trial of telaprevir and VX-222 in the first half of 2011 and SVR data in the second half of 2011; (viii) the expectation that data from the Phase 3 registration program for VX-770 will be available in the first half of 2011 and the possibility that the company will submit a New Drug Application for VX-770 in the second half of 2011; (ix) the expectation that the company will complete and receive top-line data from a clinical trial of VX-765 in 2010; (x) the expectation that interim data from a Phase 2 clinical trial of VX-509 will be received in 2011; and (xi) the company’s expectations regarding its 2010 non-GAAP and GAAP net loss. While the company believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that the outcomes for each of its planned clinical trials and studies may not be favorable, that regulatory authorities may require supplemental clinical trials in order to support registration of telaprevir and/or VX-770, that planned or potential clinical trials may be delayed or may not be conducted, that the company may not be able to successfully develop telaprevir, VX-770, VX-509, VX-765 or combination therapies involving telaprevir and VX-222 or VX-770 and VX-809, that the company's expectations regarding its 2010 GAAP and non-GAAP net loss may be incorrect, and other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through the company's website at www.vrtx.com. The company disclaims any obligation to update the information contained in this press release as new information becomes available.
Source
Prevalence and Challenges of Liver Diseases in Patients With Chronic Hepatitis C Virus Infection
Clinical Gastroenterology and Hepatology
Volume 8, Issue 11 , Pages 924-933, November 2010
Ira M. Jacobson, Gary L. Davis, Hashem El–Serag, Francesco Negro, Christian Trépo
published online 16 August 2010
Abstract
Hepatitis C virus (HCV) infections pose a growing challenge to health care systems. Although chronic HCV infection begins as an asymptomatic condition with few short-term effects, it can progress to cirrhosis, hepatic decompensation, hepatocellular carcinoma (HCC), and death. The rate of new HCV infections is decreasing, yet the number of infected people with complications of the disease is increasing. In the United States, people born between 1945 and 1964 (baby boomers) are developing more complications of infection. Men and African Americans have a higher prevalence of HCV infection. Progression of fibrosis can be accelerated by factors such as older age, duration of HCV infection, sex, and alcohol intake. Furthermore, insulin resistance can cause hepatic steatosis and is associated with fibrosis progression and inflammation. If more effective therapies are not adopted for HCV, more than 1 million patients could develop HCV-related cirrhosis, hepatic decompensation, or HCC by 2020, which will impact the US health care system. It is important to recognize the impact of HCV on liver disease progression and apply new therapeutic strategies.
Keywords: Hepatitis C Virus, Burden of Disease, Hepatic Comorbidities, Prevalence
Abbreviations used in this paper: AASLD, American Association for the Study of Liver Diseases, CHC, chronic hepatitis C, ECC, extrahepatic cholangiocarcinoma, HCC, hepatocellular carcinoma, HIV, human immunodeficiency virus, ICC, intrahepatic cholangiocarcinoma, IDU, injection drug use, IOM, Institute of Medicine, MeSH, Medical Subject Headings, NHANES, National Health and Nutrition Examination Survey, SVR, sustained virologic response
This article has an accompanying continuing medical education activity on page e117. Learning Objectives—At the end of this activity, the learner should be able to appreciate the prevalence of HCV virus infection in the United States as well as worldwide, understand the natural history of HCV infection, including the long-term risk of cirrhosis and hepatocellular cancer, and recognize that a sustained viral response represents a virologic cure.
Conflicts of Interest The authors disclose the following: Ira M Jacobson is a consultant for Abbott, Anadys, Boehringer Ingelheim, Bristol-Meyers Sqibb, Genetech, Gilead Sciences, GlobeImmune, Human Genome Sciences, Merck, Novartis, Pfizer, Pharmasset, Tibotec, Zymogenetics, and Vertex Pharmaceuticals (including advisory board for manuscript); an investigator for Abbott, Anadys, Boehringer Ingelheim, Genetech, Gilead Sciences, GlobeImmune, Human Genome Sciences, Idenix, Merck, Novartis, Pfizer, Pharmasset, Tibotec, Vertex Pharmaceuticals, and Zymogenetics; and a speaker for Bristol-Myers Squibb, Genetech, Gilead Sciences, Merck, and Novartis. Gary L. Davis is an investigator and consultant (including advisory board for manuscript) for Vertex Pharmaceuticals and receives research funding from Human Genome Science, Merck, Roche, Schering-Plough, and Vertex Pharmaceuticals. Hashem El-Serag is a consultant for Vertex Pharmaceuticals (including advisory board for manuscript). Francesco Negro is a consultant for Vertex Pharmaceuticals (including advisory board for manuscript) and receives educational grant support from Roche. Christian Trépo is an investigator and consultant for Vertex Pharmaceuticals (including advisory board for manuscript).
Funding This report is based on material identified by the authors during an advisory board meeting conducted by Vertex Pharmaceuticals Incorporated.
PII: S1542-3565(10)00780-9
doi:10.1016/j.cgh.2010.06.032
© 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
Source
Volume 8, Issue 11 , Pages 924-933, November 2010
Ira M. Jacobson, Gary L. Davis, Hashem El–Serag, Francesco Negro, Christian Trépo
published online 16 August 2010
Abstract
Hepatitis C virus (HCV) infections pose a growing challenge to health care systems. Although chronic HCV infection begins as an asymptomatic condition with few short-term effects, it can progress to cirrhosis, hepatic decompensation, hepatocellular carcinoma (HCC), and death. The rate of new HCV infections is decreasing, yet the number of infected people with complications of the disease is increasing. In the United States, people born between 1945 and 1964 (baby boomers) are developing more complications of infection. Men and African Americans have a higher prevalence of HCV infection. Progression of fibrosis can be accelerated by factors such as older age, duration of HCV infection, sex, and alcohol intake. Furthermore, insulin resistance can cause hepatic steatosis and is associated with fibrosis progression and inflammation. If more effective therapies are not adopted for HCV, more than 1 million patients could develop HCV-related cirrhosis, hepatic decompensation, or HCC by 2020, which will impact the US health care system. It is important to recognize the impact of HCV on liver disease progression and apply new therapeutic strategies.
Keywords: Hepatitis C Virus, Burden of Disease, Hepatic Comorbidities, Prevalence
Abbreviations used in this paper: AASLD, American Association for the Study of Liver Diseases, CHC, chronic hepatitis C, ECC, extrahepatic cholangiocarcinoma, HCC, hepatocellular carcinoma, HIV, human immunodeficiency virus, ICC, intrahepatic cholangiocarcinoma, IDU, injection drug use, IOM, Institute of Medicine, MeSH, Medical Subject Headings, NHANES, National Health and Nutrition Examination Survey, SVR, sustained virologic response
This article has an accompanying continuing medical education activity on page e117. Learning Objectives—At the end of this activity, the learner should be able to appreciate the prevalence of HCV virus infection in the United States as well as worldwide, understand the natural history of HCV infection, including the long-term risk of cirrhosis and hepatocellular cancer, and recognize that a sustained viral response represents a virologic cure.
Conflicts of Interest The authors disclose the following: Ira M Jacobson is a consultant for Abbott, Anadys, Boehringer Ingelheim, Bristol-Meyers Sqibb, Genetech, Gilead Sciences, GlobeImmune, Human Genome Sciences, Merck, Novartis, Pfizer, Pharmasset, Tibotec, Zymogenetics, and Vertex Pharmaceuticals (including advisory board for manuscript); an investigator for Abbott, Anadys, Boehringer Ingelheim, Genetech, Gilead Sciences, GlobeImmune, Human Genome Sciences, Idenix, Merck, Novartis, Pfizer, Pharmasset, Tibotec, Vertex Pharmaceuticals, and Zymogenetics; and a speaker for Bristol-Myers Squibb, Genetech, Gilead Sciences, Merck, and Novartis. Gary L. Davis is an investigator and consultant (including advisory board for manuscript) for Vertex Pharmaceuticals and receives research funding from Human Genome Science, Merck, Roche, Schering-Plough, and Vertex Pharmaceuticals. Hashem El-Serag is a consultant for Vertex Pharmaceuticals (including advisory board for manuscript). Francesco Negro is a consultant for Vertex Pharmaceuticals (including advisory board for manuscript) and receives educational grant support from Roche. Christian Trépo is an investigator and consultant for Vertex Pharmaceuticals (including advisory board for manuscript).
Funding This report is based on material identified by the authors during an advisory board meeting conducted by Vertex Pharmaceuticals Incorporated.
PII: S1542-3565(10)00780-9
doi:10.1016/j.cgh.2010.06.032
© 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
Source
Roche Receives FDA Approval for a Second-Generation Hepatitis C Viral Load Test
Another Roche FDA approval in the COBAS® TaqMan® viral load portfolio
PLEASANTON, Calif., Oct. 25 /PRNewswire/ -- Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the U.S. Food & Drug Administration (FDA) has approved the real-time PCR COBAS® TaqMan® HCV Test, v2.0. Clinical research organizations have depended on COBAS® TaqMan® technology to support hepatitis C pharmaceutical trials and development. This new test will help clinicians to more confidently and effectively monitor their patients, and to improve treatment outcomes.
"This HCV quantitative test is key to measuring the effectiveness of many antivirals that are currently in clinical development for the treatment of hepatitis C," said Teresa Wright, M.D., Chief Medical Officer of Roche Molecular Diagnostics. "Roche is committed to providing complete diagnostic and treatment solutions for this important global disease."
About COBAS® TaqMan® HCV Test, v2.0 For Use With High Pure System
Designed for use with the High Pure System Viral Nucleic Acid Kit, the COBAS® TaqMan® HCV Test, v2.0 is intended to quantify the amount of hepatitis C viral RNA in human plasma or serum of HCV infected individuals. The test incorporates a manual specimen preparation and the COBAS® TaqMan® 48 Analyzer for automated amplification and detection. Roche now offers HCV viral load test for both automated and manual specimen preparation methods; further demonstrating Roche's commitment in providing workflow options and flexibilities for the diverse needs of laboratories. The test system benefits from the proven contamination controls designed into all COBAS® TaqMan® assays, including built-in Roche-proprietary AmpErase enzyme.
About Hepatitis C
According to the Centers for Disease Control, Hepatitis C virus (HCV) infection is the most common chronic blood borne infection in the United States; approximately 3.2 million persons are chronically infected.
Each year in the U.S. approximately 8,000 – 10,000 people die from hepatitis C-related liver disease. An estimated 3.2 million persons in the United States have chronic hepatitis C virus infection. Most people do not know they are infected because they don't look or feel sick. However, approximately 75 – 85% of people who become infected with hepatitis C virus develop infection.(1)
Hepatitis C infections can range in severity from a mile of "acute" illness lasting a few weeks to a serious, lifelong or "chronic" illness. For most people, acute infection leads to chronic infection. Chronic hepatitis C infection is a serious disease that can result in long-term health problems, including liver damage, liver failure, liver cancer, or even death. Hepatitis C is the leading cause of cirrhosis and liver cancer and the most common reason for liver transplantation in the United States.
Hepatitis C virus is passed when infected blood enters the body of someone who is not infected. People can be infected by sharing contaminated needles, high risk sex with an infected partner, and from an infected mother to her infant during pregnancy and childbirth.
About Roche
Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world's largest biotech company with truly differentiated medicines in oncology, virology, inflammation, metabolism and CNS. Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche's personalised healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2009, Roche had over 80,000 employees worldwide and invested almost 10 billion Swiss francs in R&D. The Group posted sales of 49.1 billion Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority stake in Chugai Pharmaceutical, Japan. For more information: http://www.roche.com/.
(1) U.S. Centers for Disease Control. http://www.cdc.gov/
All trademarks used or mentioned in this release are legally protected by law.
For further information please contact:
Jacqueline Wallach
Molecular Diagnostics Communication
925.730.8114
SOURCE Roche
RELATED LINKS
http://www.roche.com/
Source
PLEASANTON, Calif., Oct. 25 /PRNewswire/ -- Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the U.S. Food & Drug Administration (FDA) has approved the real-time PCR COBAS® TaqMan® HCV Test, v2.0. Clinical research organizations have depended on COBAS® TaqMan® technology to support hepatitis C pharmaceutical trials and development. This new test will help clinicians to more confidently and effectively monitor their patients, and to improve treatment outcomes.
"This HCV quantitative test is key to measuring the effectiveness of many antivirals that are currently in clinical development for the treatment of hepatitis C," said Teresa Wright, M.D., Chief Medical Officer of Roche Molecular Diagnostics. "Roche is committed to providing complete diagnostic and treatment solutions for this important global disease."
About COBAS® TaqMan® HCV Test, v2.0 For Use With High Pure System
Designed for use with the High Pure System Viral Nucleic Acid Kit, the COBAS® TaqMan® HCV Test, v2.0 is intended to quantify the amount of hepatitis C viral RNA in human plasma or serum of HCV infected individuals. The test incorporates a manual specimen preparation and the COBAS® TaqMan® 48 Analyzer for automated amplification and detection. Roche now offers HCV viral load test for both automated and manual specimen preparation methods; further demonstrating Roche's commitment in providing workflow options and flexibilities for the diverse needs of laboratories. The test system benefits from the proven contamination controls designed into all COBAS® TaqMan® assays, including built-in Roche-proprietary AmpErase enzyme.
About Hepatitis C
According to the Centers for Disease Control, Hepatitis C virus (HCV) infection is the most common chronic blood borne infection in the United States; approximately 3.2 million persons are chronically infected.
Each year in the U.S. approximately 8,000 – 10,000 people die from hepatitis C-related liver disease. An estimated 3.2 million persons in the United States have chronic hepatitis C virus infection. Most people do not know they are infected because they don't look or feel sick. However, approximately 75 – 85% of people who become infected with hepatitis C virus develop infection.(1)
Hepatitis C infections can range in severity from a mile of "acute" illness lasting a few weeks to a serious, lifelong or "chronic" illness. For most people, acute infection leads to chronic infection. Chronic hepatitis C infection is a serious disease that can result in long-term health problems, including liver damage, liver failure, liver cancer, or even death. Hepatitis C is the leading cause of cirrhosis and liver cancer and the most common reason for liver transplantation in the United States.
Hepatitis C virus is passed when infected blood enters the body of someone who is not infected. People can be infected by sharing contaminated needles, high risk sex with an infected partner, and from an infected mother to her infant during pregnancy and childbirth.
About Roche
Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world's largest biotech company with truly differentiated medicines in oncology, virology, inflammation, metabolism and CNS. Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche's personalised healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2009, Roche had over 80,000 employees worldwide and invested almost 10 billion Swiss francs in R&D. The Group posted sales of 49.1 billion Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority stake in Chugai Pharmaceutical, Japan. For more information: http://www.roche.com/.
(1) U.S. Centers for Disease Control. http://www.cdc.gov/
All trademarks used or mentioned in this release are legally protected by law.
For further information please contact:
Jacqueline Wallach
Molecular Diagnostics Communication
925.730.8114
SOURCE Roche
RELATED LINKS
http://www.roche.com/
Source
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