April 4, 2011
Sustained Virologic Response to Antiviral Therapy for Chronic Hepatitis C Virus Infection: A Cure and So Much More
Clin Infect Dis. (2011) 52 (7): 889-900.
doi: 10.1093/cid/cir076
Brian L. Pearlman 1,3,4 and Nomi Traub 2,3
+ Author Affiliations
1 Center for Hepatitis C, Atlanta Medical Center, Atlanta, Georgia
2 Atlanta Medical Center, Department of Graduate Medical Education, Atlanta, Georgia
3 Medical College of Georgia, Department of Medicine, Augusta, Georgia
4 Emory School of Medicine, Department of Medicine, Atlanta, Georgia
Correspondence: Brian Pearlman, MD, FACP, Center for Hepatitis C, 285 Blvd NE Ste 140, Atlanta, GA 30312 (brianpearlman@hotmail.com).
Abstract
Sustained virologic response (SVR) is defined as aviremia 24 weeks after completion of antiviral therapy for chronic hepatitis C virus (HCV) infection. In analyses of SVR durability, the incidence of late relapse is extremely low (<1%). Histologic regression of both necroinflammation and fibrosis has been demonstrated in paired liver biopsy samples in SVR-achieving patients. More noteworthy is the sustained responder's favorable prognosis even with baseline cirrhosis; despite mostly retrospective analyses, relative to nonresponders or to those untreated, patients with SVR have significantly fewer liver-related complications, less hepatocellular carcinoma, and fewer liver-related deaths. Although HCV is associated with insulin resistance, successful eradication of HCV appears to reduce the risk of impaired fasting glucose and diabetes development. In summary, chronic HCV infection is curable with SVR attainment, and with cure comes improved liver histology and more favorable clinical outcomes, in comparison with patients who do not achieve the same therapeutic milestone.
Received September 10, 2010.
Accepted January 19, 2011
Source
EASL: Avalanche of hepatitis C products on the way
World News April 04, 2011
Ian Mason in Berlin
Having had no new drugs for hepatitis C since ribavirin’s approval more than a decade ago, doctors will shortly be spoilt for choice.
A wave of new products are emerging from R&D pipelines, with more than 30 companies developing scores of novel antivirals. At the European Association for the Study of the Liver (EASL) annual congress in Berlin, which ended yesterday (April 3), Mark Thursz of Imperial College, London and vice-secretary of EASL reviewed what to look out for.
The two front runners are both protease inhibitors (PIs) - Victrelis (boceprevir) from Merck & Co and telaprevir from Vertex, Tibotec and Mitsubishi Tanabe Pharma. Launches of both drugs are expected this year and snapping at their heels are second generation PIs such as Boehringer Ingelheim’s BI 201335 – an oral once-daily offering which has just moved into Phase III and been fast-tracked by the US Food and Drug Administration.
Boceprevir is given three times a day; telaprevir every eight hours. Asked how clinicians would choose between the two PIs, Prof Thursz said that although there was no head-to-head data, the products differed in their side effect profiles: “With boceprevir there is more anaemia and dysgeusia (foul taste in the mouth) and with telaprevir, the main side effect is a rash which some patients may not be able to tolerate.”
'Remarkable' results
Overall, he said that results with the new PIs were “remarkable”, offering unprecedented levels of sustained virological response, however the drugs still need to be given against a relatively toxic ‘back-bone’ of pegylated interferon-alfa plus ribavirin. For him, the "light at the end of the tunnel" would be an interferon-free regimen, such as combination therapy with a PI plus an NS5b-polymerase or NS5a inhibitor.
Boehringer’s HCV polymerase inhibitor BI 207127 has been FDA- fast-tracked in combination with the German firm’s aforementioned BI 201335. Bristol-Myers Squibb is trialling its PI, BMS 650032, in combination with the NS5A inhibitor BMS 790052 – albeit in a quadruple regimen with PEG-IFN/ribavirin.
Prof Thursz sounded a note of caution about potential resistance to PIs. “We are going to face a problem with resistant variants,” he said. “These new drugs will need to be handled by specialists who have some understanding of these patterns of resistance and their future implications.”
Patients not getting proper treatment
He concluded that despite ‘fantastic’ new drugs upcoming for hepatitis C, they would have little impact on the global burden of this potentially eradicable disease unless health policies change (up to 170 million people are estimated to be infected with the virus). France has the highest rates of treatment in the European Union, but even there only 16% of hepatitis C patients currently receive treatment. “In the UK, I am embarrassed to say, only 3% of our hepatitis C patients receive treatment. We cannot expect to have much of an impact if we do not screen and treat patients and get rid of the virus,” he said.
In other presentations, early data from Phase I trials of an HCV vaccine were unveiled. Two studies flagged by EASL reported high immunogenicity and good safety profile for a novel T-cell vaccine based on adenovirus vectors (abstracts 750 and 2104). The therapeutic vaccine is being developed by a team at the University of Oxford, UK.
Source
Ian Mason in Berlin
Having had no new drugs for hepatitis C since ribavirin’s approval more than a decade ago, doctors will shortly be spoilt for choice.
A wave of new products are emerging from R&D pipelines, with more than 30 companies developing scores of novel antivirals. At the European Association for the Study of the Liver (EASL) annual congress in Berlin, which ended yesterday (April 3), Mark Thursz of Imperial College, London and vice-secretary of EASL reviewed what to look out for.
The two front runners are both protease inhibitors (PIs) - Victrelis (boceprevir) from Merck & Co and telaprevir from Vertex, Tibotec and Mitsubishi Tanabe Pharma. Launches of both drugs are expected this year and snapping at their heels are second generation PIs such as Boehringer Ingelheim’s BI 201335 – an oral once-daily offering which has just moved into Phase III and been fast-tracked by the US Food and Drug Administration.
Boceprevir is given three times a day; telaprevir every eight hours. Asked how clinicians would choose between the two PIs, Prof Thursz said that although there was no head-to-head data, the products differed in their side effect profiles: “With boceprevir there is more anaemia and dysgeusia (foul taste in the mouth) and with telaprevir, the main side effect is a rash which some patients may not be able to tolerate.”
'Remarkable' results
Overall, he said that results with the new PIs were “remarkable”, offering unprecedented levels of sustained virological response, however the drugs still need to be given against a relatively toxic ‘back-bone’ of pegylated interferon-alfa plus ribavirin. For him, the "light at the end of the tunnel" would be an interferon-free regimen, such as combination therapy with a PI plus an NS5b-polymerase or NS5a inhibitor.
Boehringer’s HCV polymerase inhibitor BI 207127 has been FDA- fast-tracked in combination with the German firm’s aforementioned BI 201335. Bristol-Myers Squibb is trialling its PI, BMS 650032, in combination with the NS5A inhibitor BMS 790052 – albeit in a quadruple regimen with PEG-IFN/ribavirin.
Prof Thursz sounded a note of caution about potential resistance to PIs. “We are going to face a problem with resistant variants,” he said. “These new drugs will need to be handled by specialists who have some understanding of these patterns of resistance and their future implications.”
Patients not getting proper treatment
He concluded that despite ‘fantastic’ new drugs upcoming for hepatitis C, they would have little impact on the global burden of this potentially eradicable disease unless health policies change (up to 170 million people are estimated to be infected with the virus). France has the highest rates of treatment in the European Union, but even there only 16% of hepatitis C patients currently receive treatment. “In the UK, I am embarrassed to say, only 3% of our hepatitis C patients receive treatment. We cannot expect to have much of an impact if we do not screen and treat patients and get rid of the virus,” he said.
In other presentations, early data from Phase I trials of an HCV vaccine were unveiled. Two studies flagged by EASL reported high immunogenicity and good safety profile for a novel T-cell vaccine based on adenovirus vectors (abstracts 750 and 2104). The therapeutic vaccine is being developed by a team at the University of Oxford, UK.
Source
Boehringer Ingelheim’s lead hepatitis C compound moves into phase III – the first within the BI HCV portfolio
02 April 2011
FDA Fast Track designations granted for both: the protease inhibitor BI 201335 plus standard-of-care and the interferon-free combination of BI 201335 with polymerase inhibitor, BI 207127
Not for U.S. media
INGELHEIM, Germany, 2 April 2011 – Boehringer Ingelheim today announced the study outline for the pivotal Phase III clinical trials designed to evaluate BI 201335, its investigational once-daily oral protease inhibitor, in both treatment-naïve and -experienced patients with chronic genotype-1 hepatitis C virus (HCV), the most challenging genotype to treat.
In parallel, the U.S. Food and Drug Administration (FDA) has granted Fast Track designations for BI 201335 plus standard-of care (SOC), and as part of the interferon-free combination with the polymerase inhibitor, BI 207127, in chronic genotype-1 HCV patients.
"We are delighted to receive the FDA’s Fast Track designation for both, our BI 201335 plus SOC, and interferon-free combination treatment approaches. If successful, the combination therapy carries the potential for patients to live without the burden of interferon’s side effects," said Professor Klaus Dugi, Corporate Senior Vice President Medicine at Boehringer Ingelheim.
"We are committed to bringing BI 201335 forward, with the ambition of improving cure rates for the benefit of those living with hepatitis C."
BI 201335 Phase III Trials*
BI 201335 will be evaluated in multiple randomised, double-blind, placebo-controlled trials in combination with pegylated-interferon and ribavirin (PegIFN/RBV), the current HCV SOC. The Phase III trials include two studies in treatment- naïve and one study in treatment-experienced chronic genotype-1 HCV patients. The two studies in treatment-naïve patients will be conducted in the European Union and Japan, as well as the U.S., Canada, Taiwan and Korea. The study in treatment-experienced patients will be conducted globally. BI 201335 will be dosed once-daily at either 120mg or 240mg in combination with PegIFN/RBV and treatment durations will range from 24 to 48 weeks. The primary endpoint of each trial is sustained viral response (SVR), which is considered viral cure. These studies are part of a broader Phase III trial programme expected to commence in the second quarter of 2011.
PegIFN-Free Phase II Trials of BI 201335 + BI 207127
In parallel, Boehringer Ingelheim is developing BI 207127, an oral HCV polymerase inhibitor that has completed Phase I clinical trials in combination with BI 201335. Phase II trials evaluating BI 207127 plus BI 201335 in PegIFN-free regimens, both with and without ribavirin, are currently underway. The FDA has designated this investigation as a Fast Track development programme. Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious diseases and fill an unmet medical need. The purpose is to get important new drugs to patients earlier.
About Hepatitis C Virus (HCV)
HCV is an infectious disease of the liver and is a leading cause of chronic liver disease and liver transplant. The number of individuals chronically infected with HCV globally has been estimated at 170 million, with 3–4 million new infections occurring each year. Only about 20–45% of patients clear the virus in the acute phase. Of the remaining chronically infected patients, 20% will develop cirrhosis within a mean of 20 years. The mortality rate after cirrhosis has developed is 2-5% per year. End-stage liver disease due to HCV infection currently represents the major cause for liver transplantation in the Western world.
About Boehringer Ingelheim in Virology
Boehringer Ingelheim has more than 6,900 scientists working in cross disciplinary teams within our global R&D network in six large therapeutic areas, including virology. In addition to its ongoing research programme for HCV, Boehringer Ingelheim has a long-standing history in virology drug development, including compounds for the treatment of HIV (VIRAMUNE® (nevirapine) tablets/oral suspension, the first approved HIV non-nucleoside reverse transcriptase inhibitor (NNRTI) and Aptivus®, an HIV protease inhibitor). The company has a well established research centre in Laval, Canada, dedicated to virology research since the early 1990’s, and is committed to developing new therapies for virological diseases with a high unmet medical need.
Boehringer Ingelheim in Hepatitis C Virus (HCV)
BI 201335 is an investigational oral HCV NS3/4A protease inhibitor, discovered from Boehringer Ingelheim’s own research and development, which has completed clinical trials through Phase IIb (SILEN-C studies). This Phase II programme supports the investigation of BI 201335 in Phase III trials. Boehringer Ingelheim is also developing BI 207127, an NS5B RNA-dependent polymerase inhibitor that has completed Phase I clinical trials. Phase II trials evaluating BI 207127 with BI 201335 in interferon-sparing regimens, both with and without ribavirin, are currently underway.
Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
In 2009, Boehringer Ingelheim posted net sales of 12.7 billion euro (US $17.7 billion) while spending 21% of net sales in its largest business segment, Prescription Medicines, on research and development.
For more information, please visit http://www.boehringer-ingelheim.com/
www.twitter.com/boehringer
*Final results of the Phase II studies SILEN-C1 and SILEN-C2 for BI 201335 were presented yesterday at the International Liver Congress TM 2011, the 46 th Annual Meeting of the European Association for the study of the liver (EASL) in Berlin.
Source
FDA Fast Track designations granted for both: the protease inhibitor BI 201335 plus standard-of-care and the interferon-free combination of BI 201335 with polymerase inhibitor, BI 207127
Not for U.S. media
INGELHEIM, Germany, 2 April 2011 – Boehringer Ingelheim today announced the study outline for the pivotal Phase III clinical trials designed to evaluate BI 201335, its investigational once-daily oral protease inhibitor, in both treatment-naïve and -experienced patients with chronic genotype-1 hepatitis C virus (HCV), the most challenging genotype to treat.
In parallel, the U.S. Food and Drug Administration (FDA) has granted Fast Track designations for BI 201335 plus standard-of care (SOC), and as part of the interferon-free combination with the polymerase inhibitor, BI 207127, in chronic genotype-1 HCV patients.
"We are delighted to receive the FDA’s Fast Track designation for both, our BI 201335 plus SOC, and interferon-free combination treatment approaches. If successful, the combination therapy carries the potential for patients to live without the burden of interferon’s side effects," said Professor Klaus Dugi, Corporate Senior Vice President Medicine at Boehringer Ingelheim.
"We are committed to bringing BI 201335 forward, with the ambition of improving cure rates for the benefit of those living with hepatitis C."
BI 201335 Phase III Trials*
BI 201335 will be evaluated in multiple randomised, double-blind, placebo-controlled trials in combination with pegylated-interferon and ribavirin (PegIFN/RBV), the current HCV SOC. The Phase III trials include two studies in treatment- naïve and one study in treatment-experienced chronic genotype-1 HCV patients. The two studies in treatment-naïve patients will be conducted in the European Union and Japan, as well as the U.S., Canada, Taiwan and Korea. The study in treatment-experienced patients will be conducted globally. BI 201335 will be dosed once-daily at either 120mg or 240mg in combination with PegIFN/RBV and treatment durations will range from 24 to 48 weeks. The primary endpoint of each trial is sustained viral response (SVR), which is considered viral cure. These studies are part of a broader Phase III trial programme expected to commence in the second quarter of 2011.
PegIFN-Free Phase II Trials of BI 201335 + BI 207127
In parallel, Boehringer Ingelheim is developing BI 207127, an oral HCV polymerase inhibitor that has completed Phase I clinical trials in combination with BI 201335. Phase II trials evaluating BI 207127 plus BI 201335 in PegIFN-free regimens, both with and without ribavirin, are currently underway. The FDA has designated this investigation as a Fast Track development programme. Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious diseases and fill an unmet medical need. The purpose is to get important new drugs to patients earlier.
About Hepatitis C Virus (HCV)
HCV is an infectious disease of the liver and is a leading cause of chronic liver disease and liver transplant. The number of individuals chronically infected with HCV globally has been estimated at 170 million, with 3–4 million new infections occurring each year. Only about 20–45% of patients clear the virus in the acute phase. Of the remaining chronically infected patients, 20% will develop cirrhosis within a mean of 20 years. The mortality rate after cirrhosis has developed is 2-5% per year. End-stage liver disease due to HCV infection currently represents the major cause for liver transplantation in the Western world.
About Boehringer Ingelheim in Virology
Boehringer Ingelheim has more than 6,900 scientists working in cross disciplinary teams within our global R&D network in six large therapeutic areas, including virology. In addition to its ongoing research programme for HCV, Boehringer Ingelheim has a long-standing history in virology drug development, including compounds for the treatment of HIV (VIRAMUNE® (nevirapine) tablets/oral suspension, the first approved HIV non-nucleoside reverse transcriptase inhibitor (NNRTI) and Aptivus®, an HIV protease inhibitor). The company has a well established research centre in Laval, Canada, dedicated to virology research since the early 1990’s, and is committed to developing new therapies for virological diseases with a high unmet medical need.
Boehringer Ingelheim in Hepatitis C Virus (HCV)
BI 201335 is an investigational oral HCV NS3/4A protease inhibitor, discovered from Boehringer Ingelheim’s own research and development, which has completed clinical trials through Phase IIb (SILEN-C studies). This Phase II programme supports the investigation of BI 201335 in Phase III trials. Boehringer Ingelheim is also developing BI 207127, an NS5B RNA-dependent polymerase inhibitor that has completed Phase I clinical trials. Phase II trials evaluating BI 207127 with BI 201335 in interferon-sparing regimens, both with and without ribavirin, are currently underway.
Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
In 2009, Boehringer Ingelheim posted net sales of 12.7 billion euro (US $17.7 billion) while spending 21% of net sales in its largest business segment, Prescription Medicines, on research and development.
For more information, please visit http://www.boehringer-ingelheim.com/
www.twitter.com/boehringer
*Final results of the Phase II studies SILEN-C1 and SILEN-C2 for BI 201335 were presented yesterday at the International Liver Congress TM 2011, the 46 th Annual Meeting of the European Association for the study of the liver (EASL) in Berlin.
Source
EASL: Quadruple therapy shows 100 percent SVR for HCV patients previously unresponsive to treatment
April 02, 2011
Berlin, Germany, Saturday 02 April 2011: Exciting new data presented today at the International Liver CongressTM 2011 show that quadruple therapy in chronic hepatitis C (HCV) patients suppressed the emergence of resistant variants and resulted in a 100% rate of sustained virological response - undetectable HCV RNA - 12 weeks after treatment (SVR12).1
In the quadruple therapy study, HCV patients were given four drugs in combination; pegylated Interferon-alpha (PegIFN-alpha); ribavirin (RBV); and two different direct-acting antivirals (DAAs) BMS-650032 (an HCV NS3 protease inhibitor) and BMS-790052 (an HCV NS5A replication complex inhibitor).
The current standard of care (SoC) for HCV therapy is PegIFN-alpha plus RBV – a dual therapy. The addition of DAAs (currently in phase-III clinical trials) marks the next step in treatment evolution – a triple therapy. However, the new data presented today suggests that quadruple therapy could be the next generation of treatment for chronic HCV patients.
Professor Heiner Wedemeyer, EASL'S Secretary General, said: "Quadruple therapy is possibly the future of HCV treatment; this study goes a way to confirming that. While it's expected that the first DAAs and triple therapy will be approved for use later this year, quadruple therapy appears to have a more profound effect on virological response, with less of a resistance problem."
The study may also provide new hope for a growing number of HCV patients who cannot be effectively treated for chronic hepatitis with current treatments.
The Phase-IIa trial looked at a cohort of 21 HCV genotype 1 null responders (patients who have failed to respond to previous treatment), of whom 19 had an unfavourable IL28B genotype, which predisposes HCV patients to treatment failure.
Only about 30% of null responders to PegIFN-alpha/RBV treatment achieve sustained virological response (SVR) when retreated with PegIFN-alpha/RBV plus telaprevir, demonstrating a high unmet medical need.1
More information: 1. Lok A et al. Quadruple therapy with BMS-790052, BMS-650032 and peg-IFNRBV for 24 weeks results in 100% SVR12 in HCV genotype 1 null responders. Abstract presented at The International Liver CongressTM 2011. http://www1.easl.eu/easl2011/program/Orals/418.htm
Provided by European Association for the Study of the Liver
Source
--------------------------------------------------------------------------
EASL 46th Annual Meeting
March 30th - April 3rd 2011
Berlin, Germany
Quadruple Therapy With BMS-790052, BMS-650032 and Peg-IFN/RBV for 24 Weeks Results in 100% SVR12 in HCV Genotype 1 Null Responders: "HCV infection can be cured without interferon & ribavirin: 2 orals BMS790052+BMS650032"
Reported by Jules Levin
EASL 2011 April 2 Berlin Germany
Presented by Anna Lok
from Jules of NATAP: this is the biggest story & news to come out of this meeting, needless to say, and the biggest advancement in medicine in 50 years. In this study 4/11 null-responders receiving BMS-790052 (NS5A inhibitor) + BMS-650032 (protease inhibitor) alone for 24 weeks achieved SVR12 & SVR24. The presentation says "HCV infection can be cured without interferon & ribavirin". BMS-790052 & BMS-650032 with peg/RBV for 24 weeks: 10/10 patients achieved SVR12 & 9/10 achieved SVR24: "QUAD therapy can result in a high rate of cure in this difficult to treat population" (1 patient < LLOQ at week 24 post treatment undetectable on retesting 35 days later). This is the proof of concept we have been waiting for that at least some patients can be cured without peg/rbv, now these are the hardest to treat patients null-responders.
Berlin, Germany, Saturday 02 April 2011: Exciting new data presented today at the International Liver CongressTM 2011 show that quadruple therapy in chronic hepatitis C (HCV) patients suppressed the emergence of resistant variants and resulted in a 100% rate of sustained virological response - undetectable HCV RNA - 12 weeks after treatment (SVR12).1
In the quadruple therapy study, HCV patients were given four drugs in combination; pegylated Interferon-alpha (PegIFN-alpha); ribavirin (RBV); and two different direct-acting antivirals (DAAs) BMS-650032 (an HCV NS3 protease inhibitor) and BMS-790052 (an HCV NS5A replication complex inhibitor).
The current standard of care (SoC) for HCV therapy is PegIFN-alpha plus RBV – a dual therapy. The addition of DAAs (currently in phase-III clinical trials) marks the next step in treatment evolution – a triple therapy. However, the new data presented today suggests that quadruple therapy could be the next generation of treatment for chronic HCV patients.
Professor Heiner Wedemeyer, EASL'S Secretary General, said: "Quadruple therapy is possibly the future of HCV treatment; this study goes a way to confirming that. While it's expected that the first DAAs and triple therapy will be approved for use later this year, quadruple therapy appears to have a more profound effect on virological response, with less of a resistance problem."
The study may also provide new hope for a growing number of HCV patients who cannot be effectively treated for chronic hepatitis with current treatments.
The Phase-IIa trial looked at a cohort of 21 HCV genotype 1 null responders (patients who have failed to respond to previous treatment), of whom 19 had an unfavourable IL28B genotype, which predisposes HCV patients to treatment failure.
Only about 30% of null responders to PegIFN-alpha/RBV treatment achieve sustained virological response (SVR) when retreated with PegIFN-alpha/RBV plus telaprevir, demonstrating a high unmet medical need.1
More information: 1. Lok A et al. Quadruple therapy with BMS-790052, BMS-650032 and peg-IFNRBV for 24 weeks results in 100% SVR12 in HCV genotype 1 null responders. Abstract presented at The International Liver CongressTM 2011. http://www1.easl.eu/easl2011/program/Orals/418.htm
Provided by European Association for the Study of the Liver
Source
--------------------------------------------------------------------------
EASL 46th Annual Meeting
March 30th - April 3rd 2011
Berlin, Germany
Quadruple Therapy With BMS-790052, BMS-650032 and Peg-IFN/RBV for 24 Weeks Results in 100% SVR12 in HCV Genotype 1 Null Responders: "HCV infection can be cured without interferon & ribavirin: 2 orals BMS790052+BMS650032"
Reported by Jules Levin
EASL 2011 April 2 Berlin Germany
Presented by Anna Lok
from Jules of NATAP: this is the biggest story & news to come out of this meeting, needless to say, and the biggest advancement in medicine in 50 years. In this study 4/11 null-responders receiving BMS-790052 (NS5A inhibitor) + BMS-650032 (protease inhibitor) alone for 24 weeks achieved SVR12 & SVR24. The presentation says "HCV infection can be cured without interferon & ribavirin". BMS-790052 & BMS-650032 with peg/RBV for 24 weeks: 10/10 patients achieved SVR12 & 9/10 achieved SVR24: "QUAD therapy can result in a high rate of cure in this difficult to treat population" (1 patient < LLOQ at week 24 post treatment undetectable on retesting 35 days later). This is the proof of concept we have been waiting for that at least some patients can be cured without peg/rbv, now these are the hardest to treat patients null-responders.
EASL: Entry inhibitors show promise as drugs with new MOA for treatment of HBV and HDV infection
Public release date: 2-Apr-2011
Contact: Travis Taylor
easlpressoffice@cohnwolfe.com
44-784-306-9451
European Association for the Study of the Liver
First new hepatitis B and D treatment for many years
Berlin, Germany, Saturday 02 April 2011: Promising new viral hepatitis data presented today at the International Liver CongressTM show that entry inhibitors --a new mechanism of action for drugs to treat viral hepatitis -- could provide the first new hepatitis B and hepatitis D treatments for many years.1,2
Most current approved therapies directly target viral replication (e.g. nucleotide/side analogues), and can lead to the development of viral resistance or viral rebound after the end of treatment. Entry inhibitors prevent the virus from entering the cell and forming a stable replication complex, limiting the issue of viral rebound and resistance development.
Professor Heiner Wedemeyer, EASL's Secretary General, commented: "The current treatments available for hepatitis B & D are limited. These novel drugs are the first promising treatments for many years. The shift in the mechanism of action of these drugs from inhibiting the virus's replication directly to inhibiting its entry into the cell, and thus its replication – means they are less likely to produce viral resistance; a huge problem faced by many of today's clinicians."
One study1 showed that treatment of ex-vivo liver cells with synthetic anti-lipopolysaccharide peptides (SALPs) during and prior to HBV infection was highly effective and dose dependent in inhibiting infection – reducing markers of HBV infection (e.g. HBV RNA, HBV antigens) in the concentration range of 4-5 µg/mL by 90% and 0.5-2 µg/mL by 50%.
The study also demonstrated that SALPs showed activity against other viral (e.g. HIV, herpes) and microbial (e.g. peritonitis, colitis and pneumonia) infections. Therefore, SALPs represent a very promising therapeutic strategy to treat viral hepatitis infection and concomitant bacterial infection – which often leads to life threatening systematic complications.
Other studies2,3 illustrated the enormous value of the chimaeric mouse model of chronic HBV and HDV infection for the preclinical evaluation of antiviral drugs. The study demonstrated that the HBV entry inhibitor Myrcludex-B was able to completely block the spread of HBV from cell to cell and to prevent de-novo HDV infection of human hepatocytes.
Professor Wedemeyer commented: "Although there are 35 million people around the world with HDV infection there is currently little to offer them therapeutically. I am therefore delighted to see these new drug developments."
###
Notes to Editors
About EASL
EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.
EASL's main focus on education and research is delivered through numerous events and initiatives, including:
• The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide
• Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year
• Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology
• Journal of Hepatology published monthly
• Participation in a number of policy initiatives at European level
About The International Liver CongressTM 2011
The International Liver Congress™ 2011, the 46th annual meeting of the European Association for the study of the Liver, is being held at the Internationales Congress Centrum, Berlin, Germany from March 30 – April 3, 2011. The congress annually attracts over 7,500 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field.
References
1. Lucifora J et al. Novel peptide-based microbiocides inhibiting hepatitis b virus entry by preventing virus interaction with the cell surface. Abstract presented at The International Liver CongressTM 2011. http://www1.easl.eu/easl2011/program/Orals/338.htm
2. Lutgehetmann M et al. Block of hepatitis delta infection by the entry inhibitor myrcludex b in upa mice: establishment of an efficient mouse model for human HBV/HDV infection. Abstract presented at The International Liver CongressTM 2011. http://www1.easl.eu/easl2011/program/Orals/390.htm
3. Ben M et al. Administration of the entry inhibitor Myrcludex-B after establishment of Hepatitis B Virus infection prevents viral spreading among human hepatocytes in uPA mice. Abstract presented at The International Liver CongressTM 2011. http://www1.easl.eu/easl2011/program/Orals/337.htm
Source
Contact: Travis Taylor
easlpressoffice@cohnwolfe.com
44-784-306-9451
European Association for the Study of the Liver
First new hepatitis B and D treatment for many years
Berlin, Germany, Saturday 02 April 2011: Promising new viral hepatitis data presented today at the International Liver CongressTM show that entry inhibitors --a new mechanism of action for drugs to treat viral hepatitis -- could provide the first new hepatitis B and hepatitis D treatments for many years.1,2
Most current approved therapies directly target viral replication (e.g. nucleotide/side analogues), and can lead to the development of viral resistance or viral rebound after the end of treatment. Entry inhibitors prevent the virus from entering the cell and forming a stable replication complex, limiting the issue of viral rebound and resistance development.
Professor Heiner Wedemeyer, EASL's Secretary General, commented: "The current treatments available for hepatitis B & D are limited. These novel drugs are the first promising treatments for many years. The shift in the mechanism of action of these drugs from inhibiting the virus's replication directly to inhibiting its entry into the cell, and thus its replication – means they are less likely to produce viral resistance; a huge problem faced by many of today's clinicians."
One study1 showed that treatment of ex-vivo liver cells with synthetic anti-lipopolysaccharide peptides (SALPs) during and prior to HBV infection was highly effective and dose dependent in inhibiting infection – reducing markers of HBV infection (e.g. HBV RNA, HBV antigens) in the concentration range of 4-5 µg/mL by 90% and 0.5-2 µg/mL by 50%.
The study also demonstrated that SALPs showed activity against other viral (e.g. HIV, herpes) and microbial (e.g. peritonitis, colitis and pneumonia) infections. Therefore, SALPs represent a very promising therapeutic strategy to treat viral hepatitis infection and concomitant bacterial infection – which often leads to life threatening systematic complications.
Other studies2,3 illustrated the enormous value of the chimaeric mouse model of chronic HBV and HDV infection for the preclinical evaluation of antiviral drugs. The study demonstrated that the HBV entry inhibitor Myrcludex-B was able to completely block the spread of HBV from cell to cell and to prevent de-novo HDV infection of human hepatocytes.
Professor Wedemeyer commented: "Although there are 35 million people around the world with HDV infection there is currently little to offer them therapeutically. I am therefore delighted to see these new drug developments."
###
Notes to Editors
About EASL
EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.
EASL's main focus on education and research is delivered through numerous events and initiatives, including:
• The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide
• Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year
• Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology
• Journal of Hepatology published monthly
• Participation in a number of policy initiatives at European level
About The International Liver CongressTM 2011
The International Liver Congress™ 2011, the 46th annual meeting of the European Association for the study of the Liver, is being held at the Internationales Congress Centrum, Berlin, Germany from March 30 – April 3, 2011. The congress annually attracts over 7,500 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field.
References
1. Lucifora J et al. Novel peptide-based microbiocides inhibiting hepatitis b virus entry by preventing virus interaction with the cell surface. Abstract presented at The International Liver CongressTM 2011. http://www1.easl.eu/easl2011/program/Orals/338.htm
2. Lutgehetmann M et al. Block of hepatitis delta infection by the entry inhibitor myrcludex b in upa mice: establishment of an efficient mouse model for human HBV/HDV infection. Abstract presented at The International Liver CongressTM 2011. http://www1.easl.eu/easl2011/program/Orals/390.htm
3. Ben M et al. Administration of the entry inhibitor Myrcludex-B after establishment of Hepatitis B Virus infection prevents viral spreading among human hepatocytes in uPA mice. Abstract presented at The International Liver CongressTM 2011. http://www1.easl.eu/easl2011/program/Orals/337.htm
Source
EASL: Idera Pharmaceuticals Presents Data from a Phase 1 Clinical Trial of IMO-2125 in Treatment-Naïve Genotype 1 HCV Patients at EASL 2011
April 02, 2011 03:30 AM Eastern Daylight Time
- Phase 2 clinical trial expected to begin in second quarter 2011-
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Idera Pharmaceuticals, Inc. (Nasdaq: IDRA) announced today the presentation of data from a four-week Phase 1 clinical trial of IMO-2125 in combination with ribavirin in treatment-naïve patients chronically infected with hepatitis C virus (HCV) genotype 1. During the four weeks of treatment, IMO-2125 in combination with ribavirin was well tolerated and produced clinically meaningful antiviral activity. IMO-2125 is a Toll-like Receptor 9 (TLR9) agonist that stimulates production of natural interferons and other antiviral cytokines. The presentation (Abstract #1209), entitled “IMO-2125 plus ribavirin gives substantial first-dose viral load reductions, cumulative antiviral effect, is well tolerated in naïve genotype 1 HCV patients: a Phase 1 trial”, was made at the 46th Annual Meeting of the European Association for the Study of the Liver (EASL) being held in Berlin, Germany from March 30 – April 3, 2011. The presentation provided additional detail from the trial for which interim data was announced in December 2010.
“This study provides several key results that support our IMO-2125 development program,” said Robert Arbeit, M.D., Vice President of Clinical Development at Idera. “First, IMO-2125 in combination with ribavirin had substantial antiviral activity in treatment-naïve patients. This antiviral activity was associated with decreases in serum liver enzyme levels over the four-week course of treatment. Second, IMO-2125 was well tolerated, and demonstrated important safety features in comparison to Pegasys® used in the control arm. These included shorter duration of flu-like symptoms and minimal hematologic toxicity, with no IMO-2125-treated patients developing neutropenia requiring intervention or platelet levels below lower limits of normal.”
Dr. Arbeit continued, “We are preparing to initiate a 12-week Phase 2 clinical trial of IMO-2125 plus ribavirin in treatment-naïve genotype 1 HCV patients in the second quarter of 2011. We expect to use data from that study to select dosages for subsequent clinical trials of IMO-2125 in combination with ribavirin and a direct acting antiviral agent.”
"We have now completed Phase 1 clinical evaluation of IMO-2125 in both treatment-naïve and null-responder HCV patients and have established that its immune stimulation mechanism of action provides clinically meaningful antiviral activity and is well tolerated,” said Tim Sullivan, Ph.D., Vice President of Development Programs and Alliance Management at Idera. "By the end of this year we expect to have completed chronic nonclinical safety studies to support further clinical development of IMO-2125 as an immune modulatory component of HCV therapy.”
"Our objective is to develop a novel immune modulator for the treatment of HCV as a potential alternative to pegylated interferons,” said Sudhir Agrawal, D.Phil., Chairman and Chief Executive Officer at Idera. “We have confirmed the intended mechanism of action of IMO-2125 and are very pleased with its safety profile and antiviral activity in both null-responder and treatment-naïve HCV patients. We look forward to initiating the Phase 2 clinical trial, which we expect will provide the additional data needed to advance the clinical development of IMO-2125 and support studies in combination with direct-acting antiviral agents.”
Phase 1 Clinical Trial in Treatment-naive HCV Patients
Study Design:
In this Phase 1 clinical trial, treatment-naïve genotype 1 HCV patients received IMO-2125 by subcutaneous injection over four weeks in combination with daily oral administration of standard, weight-based doses of ribavirin in one of four treatment regimens of 12 patients each. The four regimens of IMO-2125 were 0.08, 0.16, and 0.32 mg/kg once weekly and 0.16 mg/kg twice weekly. In addition, 12 patients received Pegasys® plus ribavirin. Study endpoints of safety and antiviral activity were measured through Day 29. Upon completion of the four weeks of protocol-specified treatment, all patients received follow-on treatment with Pegasys® plus ribavirin. Under the trial protocol, final safety and antiviral assessments were taken at Day 59, four weeks after the follow-on treatment with Pegasys® plus ribavirin was initiated.
Study Results:
Patient Population
All patients were Caucasian, except one Asian patient in the 0.16 mg/kg/week IMO-2125 group; all were infected with HCV genotype 1. Additional demographic and baseline data are summarized in the following table.
Safety
• IMO-2125 was well tolerated at all dose levels in combination with ribavirin over four weeks of treatment, with no treatment-related serious adverse events and no treatment discontinuations. The most common adverse events observed in the IMO-2125 regimens were mild to moderate flu-like symptoms and injection site reactions.
• Flu-like symptoms. Among patients who received IMO-2125, flu-like symptoms consisted primarily of fever and chills with onset within approximately eight hours of dosing and of brief duration, typically lasting less than one day. In contrast, the observations for the patients receiving Pegasys® who experienced flu-like symptoms were consistent with the extensively published experiences showing that flu-like symptoms generally include malaise and fatigue, have delayed onset at one or two days after dosing, and often last two days or more.
• Neutropenia. Neutropenia (absolute neutrophil count (ANC) <1000/mm3) with IMO-2125 plus ribavirin treatment was infrequent, occurring in five of 48 patients, or 10%, at some point during the four-week treatment period. Neutropenia in patients treated with IMO-2125 plus ribavirin was transient; no patients required intervention and at Day 29 no patients had ANC <1000/mm3. Neutropenia was more common with Pegasys® plus ribavirin treatment, occurring in seven of 12 patients, or 58%. Two of these patients, or 17%, required intervention for their neutropenia and at Day 29 two additional patients had ANC <1000/mm3.
At Day 29, all 48 patients who had received IMO-2125 initiated standard of care treatment with Pegasys® plus ribavirin. At Day 59, six of these patients, or 13%, had neutrophil counts less than 1000/mm3.
• Thrombocytopenia. On Day 29, all patients treated with IMO-2125 plus ribavirin had platelet counts of 145,000/mm3 or greater. Three of the 12 patients, or 25%, treated with Pegasys® plus ribavirin had platelet counts at or below 130,000/mm3 on Day 29.
At Day 29, all 48 patients who had received IMO-2125 initiated standard of care treatment with Pegasys® plus ribavirin. At Day 59, 13 of these patients, or 26%, had platelet counts at or below 130,000/mm3.
Liver Enzyme Normalization
• Serum liver enzyme levels, AST and ALT, are generally elevated in chronic hepatitis C patients. Treatment with all dose levels of IMO-2125 plus ribavirin led to progressive reductions in group means of AST and ALT to within normal limits by the end of the fourth week of treatment. Similar reductions in AST and ALT levels were observed in patients receiving treatment with Pegasys® plus ribavirin.
Effect on HCV RNA Viral Load
• Viral load reduction after first dose. IMO-2125 at all dose levels induced declines in viral levels at 48 hours after the first dose. The mean viral load reductions at 48 hours after the first dose with the 0.16 mg/kg once-weekly, 0.32 mg/kg once-weekly and 0.16 mg/kg twice-weekly IMO-2125 regimens were -2.5, -1.3, and -1.6 log10, respectively. The mean viral load reduction for patients treated with Pegasys® plus ribavirin at the same time point was -1.4 log10.
• Viral load reduction after four weeks. Antiviral response was variable within all treatment groups, including Pegasys® plus ribavirin. At Day 29, in each of the IMO-2125 treatment groups at 0.16 mg/kg/week or higher and in the Pegasys® plus ribavirin group, some patients achieved greater than 4 log10 reductions in viral load and some failed to achieve even a 1 log10 reduction.
Mean viral load reductions from baseline at the mid-week evaluation in the fourth week of treatment with the 0.16 mg/kg once-weekly, 0.32 mg/kg once-weekly and 0.16 mg/kg twice-weekly IMO-2125 regimens were -3.4, -2.0, and -3.3 log10, respectively. The mean viral load reduction for patients treated with Pegasys® plus ribavirin at the same timepoint was -3.8 log10.
Mean viral load reductions from baseline at Day 29 with the 0.16 mg/kg once-weekly, 0.32 mg/kg once-weekly and 0.16 mg/kg twice-weekly IMO-2125 regimens were -1.7, -0.6, and -2.4 log10, respectively. The mean viral load reduction for patients treated with Pegasys® plus ribavirin at Day 29 was -3.4 log10.
• Prognostic factors affecting antiviral activity. Uneven distribution of negative prognostic factors, such as IL28B CT or TT genotype, high baseline IP-10, and age, contributed to the variability in antiviral activity across the treatment groups. Additional data on IL28B genotype are being collected.
See Table 2
Authors of the presentation and study investigators include Dominique Guyader, M.D., of Universite de Rennes, France, Pavel Bogomolov, M.D., of the State Institution Moscow Region named after M.F. Vladymirsky, Moscow, Russia, Zhanna Kobalava, M.D., of GOUVPO Russian Peoples’ Friendship University (City Clinical Hospital #64), Moscow, Russia, Valentin Moiseev, M.D., of GOUVPO Russian Peoples’ Friendship University (City Clinical Hospital #3), Moscow, Russia, Janos Szlavik, M.D., of Szt László Hospital, Budapest, Hungary, Béatrice Astruc, M.D., of Biotrial, Rennes, France, Istan Varkonyi, M.D., of Kenezy Hospital, Debrecen, Hungary, Tim Sullivan, Ph.D., Kerry Horgan, Alice Bexon, MBChB, and Robert Arbeit, M.D., of Idera Pharmaceuticals.
About IMO-2125
IMO-2125, a Toll-like Receptor (TLR) 9 agonist, is a novel immune modulator being developed as a component of treatment for chronic hepatitis C virus (HCV) infection. IMO-2125 is designed to stimulate the immune system, causing the body to generate natural interferons and other antiviral cytokines. IMO-2125 has been evaluated in a Phase 1 clinical trial in null-responder HCV patients as monotherapy for 4 weeks and in a Phase 1 clinical trial in treatment-naïve HCV patients in combination with ribavirin for 4 weeks.
About Idera Pharmaceuticals, Inc.
Idera Pharmaceuticals develops drug candidates to treat chronic hepatitis C virus infection, autoimmune and inflammatory diseases, cancer, and respiratory diseases, and for use as vaccine adjuvants. The company's proprietary drug candidates are designed to modulate specific Toll-like Receptors, which are a family of immune system receptors. Idera's pioneering DNA and RNA chemistry expertise enables us to create drug candidates for internal development and generates opportunities for multiple collaborative alliances. For more information, visit http://www.iderapharma.com/.
Idera Forward Looking Statements
This press release contains forward-looking statements concerning Idera Pharmaceuticals, Inc. that involve a number of risks and uncertainties. For this purpose, any statements contained herein that are not statements of historical fact may be deemed to be forward-looking statements. Without limiting the foregoing, the words "believes," "anticipates," "plans," "expects," "estimates," "intends," "should," "could," "will," "may," and similar expressions are intended to identify forward-looking statements. There are a number of important factors that could cause Idera's actual results to differ materially from those indicated by such forward-looking statements, including whether results obtained in preclinical studies and early clinical trials such as the studies and trials referred to in this release will be indicative of results obtained in future clinical trials; whether products based on Idera's technology will advance into or through the clinical trial process on a timely basis or at all and receive approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies; whether, if the Company's products receive approval, they will be successfully distributed and marketed; whether the Company's collaborations will be successful; whether the patents and patent applications owned or licensed by the Company will protect the Company’s technology and prevent others from infringing it; whether Idera's cash resources will be sufficient to fund the Company's operations; and such other important factors as are set forth under the caption "Risk Factors" in Idera's Annual Report on Form 10-K for the year ended December 31, 2010 which important factors are incorporated herein by reference. Idera disclaims any intention or obligation to update any forward-looking statements.
Pegasys® is a registered trademark of F. Hoffmann-La Roche Company.
Contacts
Idera Pharmaceuticals, Inc.
Teri Dahlman, 617-679-5519
E-mail: tdahlman@iderapharma.com
or
MacDougall Biomedical Communications
Chris Erdman, 781-235-3060
E-mail: cerdman@macbiocom.com
Source
- Phase 2 clinical trial expected to begin in second quarter 2011-
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Idera Pharmaceuticals, Inc. (Nasdaq: IDRA) announced today the presentation of data from a four-week Phase 1 clinical trial of IMO-2125 in combination with ribavirin in treatment-naïve patients chronically infected with hepatitis C virus (HCV) genotype 1. During the four weeks of treatment, IMO-2125 in combination with ribavirin was well tolerated and produced clinically meaningful antiviral activity. IMO-2125 is a Toll-like Receptor 9 (TLR9) agonist that stimulates production of natural interferons and other antiviral cytokines. The presentation (Abstract #1209), entitled “IMO-2125 plus ribavirin gives substantial first-dose viral load reductions, cumulative antiviral effect, is well tolerated in naïve genotype 1 HCV patients: a Phase 1 trial”, was made at the 46th Annual Meeting of the European Association for the Study of the Liver (EASL) being held in Berlin, Germany from March 30 – April 3, 2011. The presentation provided additional detail from the trial for which interim data was announced in December 2010.
“This study provides several key results that support our IMO-2125 development program,” said Robert Arbeit, M.D., Vice President of Clinical Development at Idera. “First, IMO-2125 in combination with ribavirin had substantial antiviral activity in treatment-naïve patients. This antiviral activity was associated with decreases in serum liver enzyme levels over the four-week course of treatment. Second, IMO-2125 was well tolerated, and demonstrated important safety features in comparison to Pegasys® used in the control arm. These included shorter duration of flu-like symptoms and minimal hematologic toxicity, with no IMO-2125-treated patients developing neutropenia requiring intervention or platelet levels below lower limits of normal.”
Dr. Arbeit continued, “We are preparing to initiate a 12-week Phase 2 clinical trial of IMO-2125 plus ribavirin in treatment-naïve genotype 1 HCV patients in the second quarter of 2011. We expect to use data from that study to select dosages for subsequent clinical trials of IMO-2125 in combination with ribavirin and a direct acting antiviral agent.”
"We have now completed Phase 1 clinical evaluation of IMO-2125 in both treatment-naïve and null-responder HCV patients and have established that its immune stimulation mechanism of action provides clinically meaningful antiviral activity and is well tolerated,” said Tim Sullivan, Ph.D., Vice President of Development Programs and Alliance Management at Idera. "By the end of this year we expect to have completed chronic nonclinical safety studies to support further clinical development of IMO-2125 as an immune modulatory component of HCV therapy.”
"Our objective is to develop a novel immune modulator for the treatment of HCV as a potential alternative to pegylated interferons,” said Sudhir Agrawal, D.Phil., Chairman and Chief Executive Officer at Idera. “We have confirmed the intended mechanism of action of IMO-2125 and are very pleased with its safety profile and antiviral activity in both null-responder and treatment-naïve HCV patients. We look forward to initiating the Phase 2 clinical trial, which we expect will provide the additional data needed to advance the clinical development of IMO-2125 and support studies in combination with direct-acting antiviral agents.”
Phase 1 Clinical Trial in Treatment-naive HCV Patients
Study Design:
In this Phase 1 clinical trial, treatment-naïve genotype 1 HCV patients received IMO-2125 by subcutaneous injection over four weeks in combination with daily oral administration of standard, weight-based doses of ribavirin in one of four treatment regimens of 12 patients each. The four regimens of IMO-2125 were 0.08, 0.16, and 0.32 mg/kg once weekly and 0.16 mg/kg twice weekly. In addition, 12 patients received Pegasys® plus ribavirin. Study endpoints of safety and antiviral activity were measured through Day 29. Upon completion of the four weeks of protocol-specified treatment, all patients received follow-on treatment with Pegasys® plus ribavirin. Under the trial protocol, final safety and antiviral assessments were taken at Day 59, four weeks after the follow-on treatment with Pegasys® plus ribavirin was initiated.
Study Results:
Patient Population
All patients were Caucasian, except one Asian patient in the 0.16 mg/kg/week IMO-2125 group; all were infected with HCV genotype 1. Additional demographic and baseline data are summarized in the following table.
Safety
• IMO-2125 was well tolerated at all dose levels in combination with ribavirin over four weeks of treatment, with no treatment-related serious adverse events and no treatment discontinuations. The most common adverse events observed in the IMO-2125 regimens were mild to moderate flu-like symptoms and injection site reactions.
• Flu-like symptoms. Among patients who received IMO-2125, flu-like symptoms consisted primarily of fever and chills with onset within approximately eight hours of dosing and of brief duration, typically lasting less than one day. In contrast, the observations for the patients receiving Pegasys® who experienced flu-like symptoms were consistent with the extensively published experiences showing that flu-like symptoms generally include malaise and fatigue, have delayed onset at one or two days after dosing, and often last two days or more.
• Neutropenia. Neutropenia (absolute neutrophil count (ANC) <1000/mm3) with IMO-2125 plus ribavirin treatment was infrequent, occurring in five of 48 patients, or 10%, at some point during the four-week treatment period. Neutropenia in patients treated with IMO-2125 plus ribavirin was transient; no patients required intervention and at Day 29 no patients had ANC <1000/mm3. Neutropenia was more common with Pegasys® plus ribavirin treatment, occurring in seven of 12 patients, or 58%. Two of these patients, or 17%, required intervention for their neutropenia and at Day 29 two additional patients had ANC <1000/mm3.
At Day 29, all 48 patients who had received IMO-2125 initiated standard of care treatment with Pegasys® plus ribavirin. At Day 59, six of these patients, or 13%, had neutrophil counts less than 1000/mm3.
• Thrombocytopenia. On Day 29, all patients treated with IMO-2125 plus ribavirin had platelet counts of 145,000/mm3 or greater. Three of the 12 patients, or 25%, treated with Pegasys® plus ribavirin had platelet counts at or below 130,000/mm3 on Day 29.
At Day 29, all 48 patients who had received IMO-2125 initiated standard of care treatment with Pegasys® plus ribavirin. At Day 59, 13 of these patients, or 26%, had platelet counts at or below 130,000/mm3.
Liver Enzyme Normalization
• Serum liver enzyme levels, AST and ALT, are generally elevated in chronic hepatitis C patients. Treatment with all dose levels of IMO-2125 plus ribavirin led to progressive reductions in group means of AST and ALT to within normal limits by the end of the fourth week of treatment. Similar reductions in AST and ALT levels were observed in patients receiving treatment with Pegasys® plus ribavirin.
Effect on HCV RNA Viral Load
• Viral load reduction after first dose. IMO-2125 at all dose levels induced declines in viral levels at 48 hours after the first dose. The mean viral load reductions at 48 hours after the first dose with the 0.16 mg/kg once-weekly, 0.32 mg/kg once-weekly and 0.16 mg/kg twice-weekly IMO-2125 regimens were -2.5, -1.3, and -1.6 log10, respectively. The mean viral load reduction for patients treated with Pegasys® plus ribavirin at the same time point was -1.4 log10.
• Viral load reduction after four weeks. Antiviral response was variable within all treatment groups, including Pegasys® plus ribavirin. At Day 29, in each of the IMO-2125 treatment groups at 0.16 mg/kg/week or higher and in the Pegasys® plus ribavirin group, some patients achieved greater than 4 log10 reductions in viral load and some failed to achieve even a 1 log10 reduction.
Mean viral load reductions from baseline at the mid-week evaluation in the fourth week of treatment with the 0.16 mg/kg once-weekly, 0.32 mg/kg once-weekly and 0.16 mg/kg twice-weekly IMO-2125 regimens were -3.4, -2.0, and -3.3 log10, respectively. The mean viral load reduction for patients treated with Pegasys® plus ribavirin at the same timepoint was -3.8 log10.
Mean viral load reductions from baseline at Day 29 with the 0.16 mg/kg once-weekly, 0.32 mg/kg once-weekly and 0.16 mg/kg twice-weekly IMO-2125 regimens were -1.7, -0.6, and -2.4 log10, respectively. The mean viral load reduction for patients treated with Pegasys® plus ribavirin at Day 29 was -3.4 log10.
• Prognostic factors affecting antiviral activity. Uneven distribution of negative prognostic factors, such as IL28B CT or TT genotype, high baseline IP-10, and age, contributed to the variability in antiviral activity across the treatment groups. Additional data on IL28B genotype are being collected.
See Table 2
Authors of the presentation and study investigators include Dominique Guyader, M.D., of Universite de Rennes, France, Pavel Bogomolov, M.D., of the State Institution Moscow Region named after M.F. Vladymirsky, Moscow, Russia, Zhanna Kobalava, M.D., of GOUVPO Russian Peoples’ Friendship University (City Clinical Hospital #64), Moscow, Russia, Valentin Moiseev, M.D., of GOUVPO Russian Peoples’ Friendship University (City Clinical Hospital #3), Moscow, Russia, Janos Szlavik, M.D., of Szt László Hospital, Budapest, Hungary, Béatrice Astruc, M.D., of Biotrial, Rennes, France, Istan Varkonyi, M.D., of Kenezy Hospital, Debrecen, Hungary, Tim Sullivan, Ph.D., Kerry Horgan, Alice Bexon, MBChB, and Robert Arbeit, M.D., of Idera Pharmaceuticals.
About IMO-2125
IMO-2125, a Toll-like Receptor (TLR) 9 agonist, is a novel immune modulator being developed as a component of treatment for chronic hepatitis C virus (HCV) infection. IMO-2125 is designed to stimulate the immune system, causing the body to generate natural interferons and other antiviral cytokines. IMO-2125 has been evaluated in a Phase 1 clinical trial in null-responder HCV patients as monotherapy for 4 weeks and in a Phase 1 clinical trial in treatment-naïve HCV patients in combination with ribavirin for 4 weeks.
About Idera Pharmaceuticals, Inc.
Idera Pharmaceuticals develops drug candidates to treat chronic hepatitis C virus infection, autoimmune and inflammatory diseases, cancer, and respiratory diseases, and for use as vaccine adjuvants. The company's proprietary drug candidates are designed to modulate specific Toll-like Receptors, which are a family of immune system receptors. Idera's pioneering DNA and RNA chemistry expertise enables us to create drug candidates for internal development and generates opportunities for multiple collaborative alliances. For more information, visit http://www.iderapharma.com/.
Idera Forward Looking Statements
This press release contains forward-looking statements concerning Idera Pharmaceuticals, Inc. that involve a number of risks and uncertainties. For this purpose, any statements contained herein that are not statements of historical fact may be deemed to be forward-looking statements. Without limiting the foregoing, the words "believes," "anticipates," "plans," "expects," "estimates," "intends," "should," "could," "will," "may," and similar expressions are intended to identify forward-looking statements. There are a number of important factors that could cause Idera's actual results to differ materially from those indicated by such forward-looking statements, including whether results obtained in preclinical studies and early clinical trials such as the studies and trials referred to in this release will be indicative of results obtained in future clinical trials; whether products based on Idera's technology will advance into or through the clinical trial process on a timely basis or at all and receive approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies; whether, if the Company's products receive approval, they will be successfully distributed and marketed; whether the Company's collaborations will be successful; whether the patents and patent applications owned or licensed by the Company will protect the Company’s technology and prevent others from infringing it; whether Idera's cash resources will be sufficient to fund the Company's operations; and such other important factors as are set forth under the caption "Risk Factors" in Idera's Annual Report on Form 10-K for the year ended December 31, 2010 which important factors are incorporated herein by reference. Idera disclaims any intention or obligation to update any forward-looking statements.
Pegasys® is a registered trademark of F. Hoffmann-La Roche Company.
Contacts
Idera Pharmaceuticals, Inc.
Teri Dahlman, 617-679-5519
E-mail: tdahlman@iderapharma.com
or
MacDougall Biomedical Communications
Chris Erdman, 781-235-3060
E-mail: cerdman@macbiocom.com
Source
EASL: New data show non-alcoholic fatty liver disease will reach epidemic status in the US
Public release date: 2-Apr-2011
Contact: Dimple Natali
easlpressoffice@cohnwolfe.com
44-797-160-8315
European Association for the Study of the Liver
Berlin, Germany, Saturday 02 April 2011: According to new data presented today at the International Liver CongressTM, the United States (U.S.) could soon be faced with an epidemic of Non-Alcoholic Fatty Liver Disease (NAFLD)1, one of the major contributing factors of chronic liver disease (CLD), considered as one of the major causes of morbidity and mortality worldwide. The study highlights that if the current rates of obesity and diabetes continue for another two decades, the prevalence of NAFLD in the US is expected to increase by 50% in 2030.
The study analysed pre-existing clinical survey data over a 10 year period (1988-1994, 1999-2004 and 2005-2008), which included 39,500 adults from three survey cycles. Over the three cycles the prevalence of NAFLD doubled from 5.51% to 11.0% respectively. Furthermore, during the first survey cycle (1988-1994) 46.8% of all CLD's was related to NAFLD but by 2005-2008 this had increased to 75.1%. In addition, the prevalence of obesity and diabetes, the two key risk factors for NAFLD also steadily increased.
Mark Thursz EASL's Vice Secretary commented: "Non-alcoholic fatty liver disease is fast becoming one of the top concerns for clinicians due to the obesity epidemic and it's potential to progress to advanced liver disease which significantly impacts on overall liver-related mortality. This data highlights a serious concern for the future, and the enormous increasing health burden of NAFLD. If the obesity epidemic is anything to go by, the U.S. NAFLD epidemic may have a ripple effect worldwide. It is imperative that health systems continue to drive effective educational programmes to reinforce awareness among the general public to alert them of the risks of obesity and promote the importance of diet and exercise".
NAFLD is the term used to describe fat build-up in liver cells in people who do not drink alcohol excessively and is the most common persistent liver disorder in Western countries with an estimated overall prevalence of 20-30%.2
NAFLD encompasses a spectrum of liver disease associated with insulin resistance, diabetes and obesity and as such people most at risk of NAFLD are those who are obese, have insulin resistance associated with diabetes, high blood pressure and cholesterol.3
###
Notes to Editors
About EASL
EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.
EASL's main focus on education and research is delivered through numerous events and initiatives, including:
• The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide
• Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year
• Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology
• Journal of Hepatology published monthly
• Participation in a number of policy initiatives at European level
About The International Liver CongressTM 2011
The International Liver Congress™ 2011, the 46th annual meeting of the European Association for the study of the Liver, is being held at the Internationales Congress Centrum, Berlin, Germany from March 30 – April 3, 2011. The congress annually attracts over 7,500 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field.
References
1. Younossi Z et al., The Changing Face of Chronic Liver Disease (CLD) in the United States: The Rising Epidemic of Non-Alcoholic Fatty Liver Disease (NAFLD). Presented at The International Liver CongressTM 2011. http://www1.easl.eu/easl2011/program/Orals/204.htm
2. Understanding and Preventing the Progression of Liver Disease in Non-Alcoholic Fatty Liver Disease (NAFLD). Fatty Liver Inhibition of Progression (FLIP) http://www.flip-fp7.eu/. Accessed March 2011.
3. Fatty Liver. Patient UK. Available at http://www.patient.co.uk/doctor/Steatohepatitis-and-Steatosis-(Fatty-Liver).htm. Accessed March 2011.
Source
Contact: Dimple Natali
easlpressoffice@cohnwolfe.com
44-797-160-8315
European Association for the Study of the Liver
Berlin, Germany, Saturday 02 April 2011: According to new data presented today at the International Liver CongressTM, the United States (U.S.) could soon be faced with an epidemic of Non-Alcoholic Fatty Liver Disease (NAFLD)1, one of the major contributing factors of chronic liver disease (CLD), considered as one of the major causes of morbidity and mortality worldwide. The study highlights that if the current rates of obesity and diabetes continue for another two decades, the prevalence of NAFLD in the US is expected to increase by 50% in 2030.
The study analysed pre-existing clinical survey data over a 10 year period (1988-1994, 1999-2004 and 2005-2008), which included 39,500 adults from three survey cycles. Over the three cycles the prevalence of NAFLD doubled from 5.51% to 11.0% respectively. Furthermore, during the first survey cycle (1988-1994) 46.8% of all CLD's was related to NAFLD but by 2005-2008 this had increased to 75.1%. In addition, the prevalence of obesity and diabetes, the two key risk factors for NAFLD also steadily increased.
Mark Thursz EASL's Vice Secretary commented: "Non-alcoholic fatty liver disease is fast becoming one of the top concerns for clinicians due to the obesity epidemic and it's potential to progress to advanced liver disease which significantly impacts on overall liver-related mortality. This data highlights a serious concern for the future, and the enormous increasing health burden of NAFLD. If the obesity epidemic is anything to go by, the U.S. NAFLD epidemic may have a ripple effect worldwide. It is imperative that health systems continue to drive effective educational programmes to reinforce awareness among the general public to alert them of the risks of obesity and promote the importance of diet and exercise".
NAFLD is the term used to describe fat build-up in liver cells in people who do not drink alcohol excessively and is the most common persistent liver disorder in Western countries with an estimated overall prevalence of 20-30%.2
NAFLD encompasses a spectrum of liver disease associated with insulin resistance, diabetes and obesity and as such people most at risk of NAFLD are those who are obese, have insulin resistance associated with diabetes, high blood pressure and cholesterol.3
###
Notes to Editors
About EASL
EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.
EASL's main focus on education and research is delivered through numerous events and initiatives, including:
• The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide
• Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year
• Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology
• Journal of Hepatology published monthly
• Participation in a number of policy initiatives at European level
About The International Liver CongressTM 2011
The International Liver Congress™ 2011, the 46th annual meeting of the European Association for the study of the Liver, is being held at the Internationales Congress Centrum, Berlin, Germany from March 30 – April 3, 2011. The congress annually attracts over 7,500 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field.
References
1. Younossi Z et al., The Changing Face of Chronic Liver Disease (CLD) in the United States: The Rising Epidemic of Non-Alcoholic Fatty Liver Disease (NAFLD). Presented at The International Liver CongressTM 2011. http://www1.easl.eu/easl2011/program/Orals/204.htm
2. Understanding and Preventing the Progression of Liver Disease in Non-Alcoholic Fatty Liver Disease (NAFLD). Fatty Liver Inhibition of Progression (FLIP) http://www.flip-fp7.eu/. Accessed March 2011.
3. Fatty Liver. Patient UK. Available at http://www.patient.co.uk/doctor/Steatohepatitis-and-Steatosis-(Fatty-Liver).htm. Accessed March 2011.
Source
EASL: First Vaccine for Viral Hepatitis C Could Become a Reality
ScienceDaily (Apr. 1, 2011) — Early data from phase I trials of an HCV vaccine presented April 1 at the International Liver Congress show encouraging results, with high immunogenicity and good safety profile.
In the first study, a therapeutic T-cell vaccine, based on novel adenoviral vectors was used on a small population of treatment naive patients with chronic genotype 1 HCV infection. Intra-muscular vaccination was administered 2 or 14 weeks into a 48-week course of treatment with Peg-IFNa2a/ribavirin. 50% of vaccinated patients had CD4+ and CD8+ HCV specific T-cell responses as detected by ELISpot at 2-8 weeks post boost, showing a strong immunogenicity for the vaccine. Local and systemic adverse events to vaccination were mild, with no evidence of liver immunopathology (measured by liver transaminase levels).
The second study looked at the potential for a prophylactic vaccine based on similar novel adenoviral vectors technology (replicative-defective human Ad6 and a novel simian AdCh3 vector that encode 1985 amino-acids derived from the NS3-5 region of a genotype-1b strain). 27 healthy volunteers were vaccinated following a double prime, heterologous boost strategy. The vaccine induced polyfunctional CD4+ and CD8+ T cells responses which were maintained up to 52 weeks post prime. Overall vaccination was very well tolerated with mild/moderate local and systemic reactions and no serious adverse advents.
Professor Heiner Wedemeyer, EASL's Secretary General commented: "Vaccines are an exciting area of research now with the potential to add to the range of treatments available for patients with chronic viral hepatitis. These are early data but results are very encouraging indeed and as experts, we look forward to more scientific evidence being made available to support this new technology as a future treatment option as well as potentially preventing infection."
Previous research and data presented at the International Liver Congress shows that vaccination with adenoviral vectors induced highly potent and durable T-cell responses in healthy human and that similar vectors may prevent chronic infection in animals.3 This is the first time the immunogenicity and safety of vaccination was tested on HCV patients and healthy subjects.
Source
In the first study, a therapeutic T-cell vaccine, based on novel adenoviral vectors was used on a small population of treatment naive patients with chronic genotype 1 HCV infection. Intra-muscular vaccination was administered 2 or 14 weeks into a 48-week course of treatment with Peg-IFNa2a/ribavirin. 50% of vaccinated patients had CD4+ and CD8+ HCV specific T-cell responses as detected by ELISpot at 2-8 weeks post boost, showing a strong immunogenicity for the vaccine. Local and systemic adverse events to vaccination were mild, with no evidence of liver immunopathology (measured by liver transaminase levels).
The second study looked at the potential for a prophylactic vaccine based on similar novel adenoviral vectors technology (replicative-defective human Ad6 and a novel simian AdCh3 vector that encode 1985 amino-acids derived from the NS3-5 region of a genotype-1b strain). 27 healthy volunteers were vaccinated following a double prime, heterologous boost strategy. The vaccine induced polyfunctional CD4+ and CD8+ T cells responses which were maintained up to 52 weeks post prime. Overall vaccination was very well tolerated with mild/moderate local and systemic reactions and no serious adverse advents.
Professor Heiner Wedemeyer, EASL's Secretary General commented: "Vaccines are an exciting area of research now with the potential to add to the range of treatments available for patients with chronic viral hepatitis. These are early data but results are very encouraging indeed and as experts, we look forward to more scientific evidence being made available to support this new technology as a future treatment option as well as potentially preventing infection."
Previous research and data presented at the International Liver Congress shows that vaccination with adenoviral vectors induced highly potent and durable T-cell responses in healthy human and that similar vectors may prevent chronic infection in animals.3 This is the first time the immunogenicity and safety of vaccination was tested on HCV patients and healthy subjects.
Source
EASL: Boceprevir Plays Well With Interferon Drugs
By Walter Alexander, Contributing Writer, MedPage Today Published: April 02, 2011
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
BERLIN -- Boceprevir, an investigational protease inhibitor for hepatitis C virus (HCV) infection, is effective against genotype 1 of the virus irrespective of the particular type of pegylated interferon alfa drug with which it is combined, a researcher said here.
In two studies just published in the New England Journal of Medicine, triple therapy including boceprevir (Victrelis) improved outcomes both in previously untreated patients and in those with inadequate responses to standard therapy, in comparison with standard two-drug therapy.
But both studies used peginterferon alfa-2b along with ribavirin as two-drug regimen, leaving open the question of whether boceprevir would be equally effective when used with peginterferon alfa-2a, the other major type of interferon drug for HCV.
In a late-breaking poster presentation here at the European Association for the Study of the Liver (EASL) annual meeting, a researcher from Northwestern University in Chicago reported response rates with "PEG2a" and boceprevir in prior nonresponders that were similar to those seen in the so-called RESPOND-2 trial reported in the NEJM with the 2b version.
"PEG2a is used throughout the world, too," the researcher, Steven Flamm, MD, told MedPage Today. "This is the first large-scale trial to look at boceprevir with PEG2a. It's important to establish that boceprevir also works with this other pegylated product."
The study he reported involved 201 patients with HCV genotype 1 who had relapsed or failed to maintain responses with previous interferon and ribavirin therapy.
They were randomized in a 2:1 ratio to two arms: 134 to receive a four-week lead-in of pegylated interferon alfa-2a and ribavirin with boceprevir then added for 44 weeks, and 67 to a control regimen with the same schedule but with placebo in place of boceprevir.
Patients with detectable HCV-RNA at week 12 were discontinued from treatment for futility. The study's primary endpoint was sustained viral response at 24-weeks post therapy.
Significantly more patients achieved a sustained response in the boceprevir group: 64% versus 21% in the control group (P<0.0001), nearly identical to the RESPOND-2 findings. The relapse rate was higher in the control group, at 33% versus 12% (P not reported).
Flamm also reported that viral response at eight weeks (defined as undetectable HCV RNA) strongly predicted a sustained response. In patients with early responses, sustained response rates were 89% with boceprevir versus 44% in the control group.
On the other hand, sustained response rates were poorer for patients failing to achieve undetectable viral load at eight weeks, with rates of 42% with boceprevir and 16% in the control group.
Compared with the control group, patients in the boceprevir arm were about twice as likely to suffer serious anemia or neutropenia, with higher rates of erythropoietin use as well.
Discontinuations and dose modifications because of adverse events were more common among patients taking boceprevir. But futility by week 12 was even more common in the control group.
As a result, the overall proportion of patients remaining on treatment at week 20 was substantially lower in the control arm -- 31% versus 72% -- and the median duration of treatment was 334 days in the boceprevir group compared with 105 days for controls.
Flamm underscored that HCV genotype 1 is the most common and least responsive form of HCV, and that in this population the standard-of-care treatment is usually a failure. "Many of these people are desperate, and there's nothing else we can do for them until we have a new treatment," he said.
He concluded, "Boceprevir is safe and effective with both peginterferon alfa-2a and 2b."
Mark Thursz, MD, a hepatologist at Imperial College in London and vice-secretary of EASL, told MedPage Today that the 2a form is the more commonly used peginterferon in Great Britain and Europe.
"It was necessary to show that boceprevir works with both interferons," he said.
The study was supported by Merck.
Flamm reported relationships with Amgen, Genzyme, and Schering-Plough (now Merck). Several co-authors were Merck employees.
Thursz declared he had no relevant financial relationships.
Primary source: European Association for the Study of the Liver
Source reference:
Flamm S, et al "High sustained virologic response (SVR) among genotype 1 previous non-responders and relapsers to peginterferon/ribavirin when re-treated with boceprevir (BOC) plus peginterferon alfa-2a/ribavirin" EASL 2011; Abstract 4.
Source
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
BERLIN -- Boceprevir, an investigational protease inhibitor for hepatitis C virus (HCV) infection, is effective against genotype 1 of the virus irrespective of the particular type of pegylated interferon alfa drug with which it is combined, a researcher said here.
In two studies just published in the New England Journal of Medicine, triple therapy including boceprevir (Victrelis) improved outcomes both in previously untreated patients and in those with inadequate responses to standard therapy, in comparison with standard two-drug therapy.
But both studies used peginterferon alfa-2b along with ribavirin as two-drug regimen, leaving open the question of whether boceprevir would be equally effective when used with peginterferon alfa-2a, the other major type of interferon drug for HCV.
In a late-breaking poster presentation here at the European Association for the Study of the Liver (EASL) annual meeting, a researcher from Northwestern University in Chicago reported response rates with "PEG2a" and boceprevir in prior nonresponders that were similar to those seen in the so-called RESPOND-2 trial reported in the NEJM with the 2b version.
"PEG2a is used throughout the world, too," the researcher, Steven Flamm, MD, told MedPage Today. "This is the first large-scale trial to look at boceprevir with PEG2a. It's important to establish that boceprevir also works with this other pegylated product."
The study he reported involved 201 patients with HCV genotype 1 who had relapsed or failed to maintain responses with previous interferon and ribavirin therapy.
They were randomized in a 2:1 ratio to two arms: 134 to receive a four-week lead-in of pegylated interferon alfa-2a and ribavirin with boceprevir then added for 44 weeks, and 67 to a control regimen with the same schedule but with placebo in place of boceprevir.
Patients with detectable HCV-RNA at week 12 were discontinued from treatment for futility. The study's primary endpoint was sustained viral response at 24-weeks post therapy.
Significantly more patients achieved a sustained response in the boceprevir group: 64% versus 21% in the control group (P<0.0001), nearly identical to the RESPOND-2 findings. The relapse rate was higher in the control group, at 33% versus 12% (P not reported).
Flamm also reported that viral response at eight weeks (defined as undetectable HCV RNA) strongly predicted a sustained response. In patients with early responses, sustained response rates were 89% with boceprevir versus 44% in the control group.
On the other hand, sustained response rates were poorer for patients failing to achieve undetectable viral load at eight weeks, with rates of 42% with boceprevir and 16% in the control group.
Compared with the control group, patients in the boceprevir arm were about twice as likely to suffer serious anemia or neutropenia, with higher rates of erythropoietin use as well.
Discontinuations and dose modifications because of adverse events were more common among patients taking boceprevir. But futility by week 12 was even more common in the control group.
As a result, the overall proportion of patients remaining on treatment at week 20 was substantially lower in the control arm -- 31% versus 72% -- and the median duration of treatment was 334 days in the boceprevir group compared with 105 days for controls.
Flamm underscored that HCV genotype 1 is the most common and least responsive form of HCV, and that in this population the standard-of-care treatment is usually a failure. "Many of these people are desperate, and there's nothing else we can do for them until we have a new treatment," he said.
He concluded, "Boceprevir is safe and effective with both peginterferon alfa-2a and 2b."
Mark Thursz, MD, a hepatologist at Imperial College in London and vice-secretary of EASL, told MedPage Today that the 2a form is the more commonly used peginterferon in Great Britain and Europe.
"It was necessary to show that boceprevir works with both interferons," he said.
The study was supported by Merck.
Flamm reported relationships with Amgen, Genzyme, and Schering-Plough (now Merck). Several co-authors were Merck employees.
Thursz declared he had no relevant financial relationships.
Primary source: European Association for the Study of the Liver
Source reference:
Flamm S, et al "High sustained virologic response (SVR) among genotype 1 previous non-responders and relapsers to peginterferon/ribavirin when re-treated with boceprevir (BOC) plus peginterferon alfa-2a/ribavirin" EASL 2011; Abstract 4.
Source
EASL: Telaprevir Helps in Prior HCV Tx Failures
By Walter Alexander, Contributing Writer, MedPage Today
Published: April 01, 2011
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
BERLIN -- Adding telaprevir, an investigational oral protease inhibitor, to peginterferon alfa-2a and ribavirin substantially increased sustained response rates in patients with genotype 1 hepatitis C virus (HCV) infection who had previously failed the standard therapy, a researcher said here.
Results from the phase III REALIZE trial indicated that, among prior relapsers, sustained response rates with two telaprevir-containing regimens were 83% and 88%, compared with 24% for peginterferon alfa-2a and ribavirin plus placebo (both P<0.001), reported Stefan Zeuzem, MD, of Johann Wolfgang Goethe University Medical Center in Frankfurt am Main, Germany.
Lower sustained viral response rates were seen in patients who previously showed partial or no response to the two standard drugs, but they were still significantly better than in the placebo group (41% in both telaprevir arms versus 9% in the control group, P<0.001).
Zeuzem presented the findings here at the European Association for the Study of the Liver (EASL) annual meeting.
"T plus P plus R was superior to P plus R alone in treatment-experienced populations including prior relapsers, partial responders, and null responders," he told attendees.
The findings confirm those of earlier studies, including one reported last year in the New England Journal of Medicine.
The current standard of care for HCV is the combination of peginterferon alfa-2a and ribavirin, Zeuzem explained, but it fails to achieved sustained viral responses in 60% of patients with HCV genotype 1.
REALIZE assigned 662 patients to three treatment arms in a 2:2:1 ratio:
• T12/PR48: Telaprevir, peginterferon, and ribavirin for 12 weeks followed by placebo plus peginterferon and ribavirin for four weeks and then the two standard drugs alone for 32 weeks
• LIT12/PR48: Placebo plus peginterferon and ribavirin for four weeks, followed by telaprevir and the standard drugs for 12 weeks, and then the standard drugs alone for 32 weeks
• Pbo/PR48: 48 weeks of peginterferon plus ribavirin, with placebo for the first 16 weeks
The REALIZE primary endpoint was the proportion of these patients achieving sustained viral responses, defined as undetectable plasma HCV RNA at 24 weeks after the last planned intake of study medication. Whether the four-week lead-in with standard therapy alone made a difference in responses was a secondary objective.
Telaprevir was given at 750 mg every eight hours. Standard doses of the other drugs were used (180 mcg/week for peginterferon, 1,000 to 1,200 mg/day for ribavirin).
Null responders, partial responders, and relapsers to previous peginterferon plus ribavirin constituted about 28%, 19%, and 54%, respectively, of the cohort. Nearly half of patients were in advanced stages of disease; 89% had a baseline HCV viral load of >800,000 IU/mL. Median age was about 51 and more than two-thirds were men.
Sustained viral responses were seen in 83% of the T12/PR48 group and 88% of the LIT12/PR48 patients versus 24% of the Pbo/PR48 group.
These results, Zeuzem pointed out, indicated that the four-week lead-in with standard therapy did not improve response rates compared with including telaprevir from the outset.
Responses rates of 41% were seen in the previous null or partial responders in both the T12/PR48 and LIT12/PR48 groups, compared with just 9% of the previously unresponsive Pbo/PR48 patients.
Zeuzem said that sustained response rates were higher for prior partial responders than for prior null responders.
Relapse rates were 10% each for the two telaprevir-containing arms and 23% for the Pbo/PR48 arm.
Among the most common adverse events during any treatment phase, fatigue occurred in 55% of the T12/PR48 patients, 50% of the LIT12/PR48 group, and 40% of the Pbo/PR48 group. Frequencies of pruritus were similar.
Anorectal symptoms (anal pruritus, anorectal discomfort, hemorrhoids) were reported in 28%, 22%, and 8% of the T12/PR48, LIT12/PR48, and Pbo/PR48 groups, respectively.
For each of these adverse events, and for anemia, rash, nausea and diarrhea, the incidence was more than 10% greater in the T12/PR48 arm than in the Pbo/PR48 arm.
Discontinuations of any study drug during telaprevir treatment occurred in 29% of patients. Rash and anemia were the most common adverse effects associated with drug stoppage.
"These are really exciting results for this particularly difficult-to-treat group of patients," commented Mark Thursz, MD, a hepatologist at Imperial College in London and vice-secretary of the EASL.
"Over 60% achieved an SVR. Compared with patients who previously relapsed after P-plus-R treatment, those who are partial responders did less well, and the null group was disappointing, but that was not entirely surprising."
A marketing application for telaprevir has been filed with the FDA, which is giving it priority review. The agency's deadline for a decision is May 23.
Zeuzem disclosed relationships with Abbott, Achillion, Anadys, BMS, Gilead, iTherX, Merck, Novartis, Pfizer, Pharmasset, Roche, Santaris, Tibotec, and Vertex.
Thursz declared he had no relevant industry relationships.
Primary source: European Association for the Study of the Liver
Source reference:
Zeuzem S, et al "REALIZE trial final results: telaprevir-based regimen for genotype 1 hepatitis C virus infection in patients with prior null response, partial response or relapse to peginterferon/ribavirin" EASL 2011; Abstract 192.
Source
Published: April 01, 2011
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
BERLIN -- Adding telaprevir, an investigational oral protease inhibitor, to peginterferon alfa-2a and ribavirin substantially increased sustained response rates in patients with genotype 1 hepatitis C virus (HCV) infection who had previously failed the standard therapy, a researcher said here.
Results from the phase III REALIZE trial indicated that, among prior relapsers, sustained response rates with two telaprevir-containing regimens were 83% and 88%, compared with 24% for peginterferon alfa-2a and ribavirin plus placebo (both P<0.001), reported Stefan Zeuzem, MD, of Johann Wolfgang Goethe University Medical Center in Frankfurt am Main, Germany.
Lower sustained viral response rates were seen in patients who previously showed partial or no response to the two standard drugs, but they were still significantly better than in the placebo group (41% in both telaprevir arms versus 9% in the control group, P<0.001).
Zeuzem presented the findings here at the European Association for the Study of the Liver (EASL) annual meeting.
"T plus P plus R was superior to P plus R alone in treatment-experienced populations including prior relapsers, partial responders, and null responders," he told attendees.
The findings confirm those of earlier studies, including one reported last year in the New England Journal of Medicine.
The current standard of care for HCV is the combination of peginterferon alfa-2a and ribavirin, Zeuzem explained, but it fails to achieved sustained viral responses in 60% of patients with HCV genotype 1.
REALIZE assigned 662 patients to three treatment arms in a 2:2:1 ratio:
• T12/PR48: Telaprevir, peginterferon, and ribavirin for 12 weeks followed by placebo plus peginterferon and ribavirin for four weeks and then the two standard drugs alone for 32 weeks
• LIT12/PR48: Placebo plus peginterferon and ribavirin for four weeks, followed by telaprevir and the standard drugs for 12 weeks, and then the standard drugs alone for 32 weeks
• Pbo/PR48: 48 weeks of peginterferon plus ribavirin, with placebo for the first 16 weeks
The REALIZE primary endpoint was the proportion of these patients achieving sustained viral responses, defined as undetectable plasma HCV RNA at 24 weeks after the last planned intake of study medication. Whether the four-week lead-in with standard therapy alone made a difference in responses was a secondary objective.
Telaprevir was given at 750 mg every eight hours. Standard doses of the other drugs were used (180 mcg/week for peginterferon, 1,000 to 1,200 mg/day for ribavirin).
Null responders, partial responders, and relapsers to previous peginterferon plus ribavirin constituted about 28%, 19%, and 54%, respectively, of the cohort. Nearly half of patients were in advanced stages of disease; 89% had a baseline HCV viral load of >800,000 IU/mL. Median age was about 51 and more than two-thirds were men.
Sustained viral responses were seen in 83% of the T12/PR48 group and 88% of the LIT12/PR48 patients versus 24% of the Pbo/PR48 group.
These results, Zeuzem pointed out, indicated that the four-week lead-in with standard therapy did not improve response rates compared with including telaprevir from the outset.
Responses rates of 41% were seen in the previous null or partial responders in both the T12/PR48 and LIT12/PR48 groups, compared with just 9% of the previously unresponsive Pbo/PR48 patients.
Zeuzem said that sustained response rates were higher for prior partial responders than for prior null responders.
Relapse rates were 10% each for the two telaprevir-containing arms and 23% for the Pbo/PR48 arm.
Among the most common adverse events during any treatment phase, fatigue occurred in 55% of the T12/PR48 patients, 50% of the LIT12/PR48 group, and 40% of the Pbo/PR48 group. Frequencies of pruritus were similar.
Anorectal symptoms (anal pruritus, anorectal discomfort, hemorrhoids) were reported in 28%, 22%, and 8% of the T12/PR48, LIT12/PR48, and Pbo/PR48 groups, respectively.
For each of these adverse events, and for anemia, rash, nausea and diarrhea, the incidence was more than 10% greater in the T12/PR48 arm than in the Pbo/PR48 arm.
Discontinuations of any study drug during telaprevir treatment occurred in 29% of patients. Rash and anemia were the most common adverse effects associated with drug stoppage.
"These are really exciting results for this particularly difficult-to-treat group of patients," commented Mark Thursz, MD, a hepatologist at Imperial College in London and vice-secretary of the EASL.
"Over 60% achieved an SVR. Compared with patients who previously relapsed after P-plus-R treatment, those who are partial responders did less well, and the null group was disappointing, but that was not entirely surprising."
A marketing application for telaprevir has been filed with the FDA, which is giving it priority review. The agency's deadline for a decision is May 23.
Zeuzem disclosed relationships with Abbott, Achillion, Anadys, BMS, Gilead, iTherX, Merck, Novartis, Pfizer, Pharmasset, Roche, Santaris, Tibotec, and Vertex.
Thursz declared he had no relevant industry relationships.
Primary source: European Association for the Study of the Liver
Source reference:
Zeuzem S, et al "REALIZE trial final results: telaprevir-based regimen for genotype 1 hepatitis C virus infection in patients with prior null response, partial response or relapse to peginterferon/ribavirin" EASL 2011; Abstract 192.
Source
EASL: Sustained viral response achieved in 83% of hepatitis C infected patients with new HCV protease inhibitor from Boehringer Ingelheim
April 01, 2011 10:07 AM Eastern Daylight Time
Final results from two clinical Phase IIb studies presented at EASL 2011 demonstrate up to 83% SVR in treatment naïve HCV patients and up to 41% in previously unsuccessfully treated patients, respectively
BERLIN & INGELHEIM, Germany--(BUSINESS WIRE)--New data presented today at the International Liver CongressTM 2011, the 46th Annual Meeting of the European Association for the Study of the Liver (EASL), in Berlin, highlighted the efficacy of Boehringer Ingelheim’s once-daily oral protease inhibitor BI 201335, in both treatment-naïve and -experienced patients with chronic genotype-1 hepatitis C virus (HCV) infection. Genotype-1 HCV is the most challenging genotype of HCV to treat.
Results from SILEN-C1 trial show high rates of sustained viral response (SVR, which is considered viral cure) in patients with no previous treatments, who received either 120mg or 240mg BI 201335 once-daily plus the current standard-of-care (SOC), i.e. pegylated interferon (PegIFN) and ribavirin (RBV). Up to 87% of patients were able to shorten overall treatment duration from 48 to 24 weeks.
In the SILEN-C2 trial, in non-responding patients, the 240mg dose of BI 201335 once daily also achieved impressive results in a population that has not responded to SOC, and achieved such without a lead in therapy.
“The final results from the SILEN-C1 and 2 trials have demonstrated the high potential for excellent efficacy of this once daily protease inhibitor in a broad range of HCV patients,” said Professor Klaus Dugi, Corporate Senior Vice President Medicine at Boehringer Ingelheim. “The current standard-of-care in HCV is not effective for many patients. The viral cure rates achieved by protease inhibitors such as BI 201335 highlight the possibility to improve treatment outcomes as well as the option to shorten the overall treatment duration for the majority of HCV patients.”
“Boehringer Ingelheim is continuing its long heritage in virology and is dedicated to developing new medicines to improve treatment for HCV patients,” continued Professor Klaus Dugi. “BI 201335 is part of our robust HCV portfolio that we are investigating with the goal of improving current treatment and ultimately paving a path for a simpler, more effective and better tolerated HCV therapy.”
Study Details:
(Oral Presentation at EASL, Parallel Session: HCV Drug Development, 16:00h-16:15h, Abstract 60) SILEN-C1: Sustained Virologic Response (SVR) and Safety of BI 201335 Combined with Peginterferon Alfa-2a and Ribavirin in Treatment-Naïve Patients with Chronic Genotype-1 HCV Infection
The Phase II SILEN-C1 study results show BI 201335 to have strong antiviral activity, with overall SVR rates reaching 83% in the 240mg once-daily group (plus current SOC). Of the patients achieving extended rapid viral response (eRVR, defined as plasma viral load less than 25 IU/ml at week 4 and undetectable at weeks 8-20), 93% achieved SVR with 24 weeks of SOC (PegIFN/RBV) treatment.
In addition to high efficacy at all dose levels, BI 201335 once daily with SOC also demonstrated good tolerability and safety:
The most frequent dose-dependent adverse events in BI 201335 treatment groups were mild gastrointestinal disorders, mild rash or photosensitivity and jaundice resulting from isolated unconjugated hyperbilirubinaemia. Average alanine aminotransferase (ALT) improved in all BI 201335 groups compared to placebo. Of note, there was no excess anaemia reported in the active groups compared to SOC. Phase III trials of BI 201335 are in preparation.
(Oral Presentation at EASL Parallel Session: HCV Drug Development, 17:30h-17:45h, Abstract 66) SILEN-C2: Sustained Virologic Response and Safety of BI 201335 Combined with Peginterferon Alfa-2a and Ribavirin in Chronic HCV Genotype-1 Patients with Non-Response to PegIFN/RBV
The Phase II SILEN-C2 study evaluated the virological response and safety of different doses of BI 201335 in treatment-experienced patients who did not respond to at least 12 weeks of prior treatment with PegIFN/RBV. The results demonstrate that treatment with BI 201335 once daily at 240mg, plus SOC provides high efficacy and good tolerability in this very difficult-to-treat patient population, with 41% achieving SVR. As is seen in SILEN-C1, a 3-day lead in with SOC was associated with decreased viral response. Phase III trials of BI 201335 are in preparation.
The most frequent dose-dependent adverse events in BI 201335 treatment groups were similar to those seen in SILEN-C1. Serious or severe adverse events were reported more frequently in the BI 201335 240mg BID with lead in (LI) group.
NOTES TO EDITORS
Additional BI 201335 Studies to be Presented at EASL
• SVR and pharmacokinetics of the HCV protease inhibitor BI 201335 with PegIFN/RBV in HCV genotype-1 patients with compensated liver cirrhosis and non-response to previous PegIFN/RBV (Poster 1231. S. Pol, et al.)
• Mechanisms of isolated unconjugated hyperbilirubinaemia induced by the HCV NS3/4A protease inhibitor BI 201335 (Poster 1236. R. Sane, et al.)
• BI 201335 pharmacokinetics and early effect on viral load in HCV genotype-1 patients (Poster 1249. C. Yong, et al.)
• Preclinical characterization of the hepatitis C virus NS5B polymerase non-nucleoside inhibitor BILB 1941 (Poster 1215. G. Kukolj et. al.)
Posters are presented on Saturday, 2 April, 2011, 09:00h - 18:00h.
About Hepatitis C Virus (HCV)
HCV is an infectious disease of the liver and is a leading cause of chronic liver disease and liver transplant. The number of individuals chronically infected with HCV globally has been estimated at 170 million, with 3–4 million new infections occurring each year. Only about 20–45% of patients clear the virus in the acute phase. Of the remaining chronically infected patients, 20% will develop cirrhosis within a mean of 20 years. The mortality rate after cirrhosis has developed is 2-5% per year. End-stage liver disease due to HCV infection currently represents the major cause for liver transplantation in the Western world.
About Boehringer Ingelheim in Virology
Boehringer Ingelheim has more than 6,900 scientists working in cross disciplinary teams within our global R&D network in six large therapeutic areas, including virology. In addition to its ongoing research program for HCV, Boehringer Ingelheim has a long-standing history in virology drug development, including compounds for the treatment of HIV (VIRAMUNE® (nevirapine) tablets/oral suspension, the first approved HIV non-nucleoside reverse transcriptase inhibitor (NNRTI) and Aptivus®, an HIV protease inhibitor). The company has a well established research centre in Laval, Canada, dedicated to virology research since the early 1990’s, and is committed to developing new therapies for virological diseases with a high unmet medical need.
Boehringer Ingelheim in Hepatitis C Virus (HCV)
BI 201335 is an investigational oral HCV NS3/4A protease inhibitor, discovered from Boehringer Ingelheim’s own research and development, which has completed clinical trials through Phase IIb (SILEN-C studies). This Phase II programme supports the investigation of BI 201335 in Phase III trials. Boehringer Ingelheim is also developing BI 207127, an NS5B RNA-dependent polymerase inhibitor that has completed Phase I clinical trials. Phase II trials evaluating BI 207127 with BI 201335 in interferon-sparing regimens, both with and without ribavirin, are currently underway.
Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
In 2009, Boehringer Ingelheim posted net sales of 12.7 billion euro (US $17.7 billion) while spending 21% of net sales in its largest business segment, Prescription Medicines, on research and development.
For more information, please visit http://www.boehringer-ingelheim.com/
www.twitter.com/boehringer
Contacts
Julia Meyer-Kleinmann
Director Corporate Communications
Boehringer Ingelheim GmbH
55216 Ingelheim/Germany
Phone: + 49 - 6132 – 77 8271
Fax: + 49 - 6132 – 77 70 77
E-mail: press@boehringer-ingelheim.com
Source
Final results from two clinical Phase IIb studies presented at EASL 2011 demonstrate up to 83% SVR in treatment naïve HCV patients and up to 41% in previously unsuccessfully treated patients, respectively
BERLIN & INGELHEIM, Germany--(BUSINESS WIRE)--New data presented today at the International Liver CongressTM 2011, the 46th Annual Meeting of the European Association for the Study of the Liver (EASL), in Berlin, highlighted the efficacy of Boehringer Ingelheim’s once-daily oral protease inhibitor BI 201335, in both treatment-naïve and -experienced patients with chronic genotype-1 hepatitis C virus (HCV) infection. Genotype-1 HCV is the most challenging genotype of HCV to treat.
Results from SILEN-C1 trial show high rates of sustained viral response (SVR, which is considered viral cure) in patients with no previous treatments, who received either 120mg or 240mg BI 201335 once-daily plus the current standard-of-care (SOC), i.e. pegylated interferon (PegIFN) and ribavirin (RBV). Up to 87% of patients were able to shorten overall treatment duration from 48 to 24 weeks.
In the SILEN-C2 trial, in non-responding patients, the 240mg dose of BI 201335 once daily also achieved impressive results in a population that has not responded to SOC, and achieved such without a lead in therapy.
“The final results from the SILEN-C1 and 2 trials have demonstrated the high potential for excellent efficacy of this once daily protease inhibitor in a broad range of HCV patients,” said Professor Klaus Dugi, Corporate Senior Vice President Medicine at Boehringer Ingelheim. “The current standard-of-care in HCV is not effective for many patients. The viral cure rates achieved by protease inhibitors such as BI 201335 highlight the possibility to improve treatment outcomes as well as the option to shorten the overall treatment duration for the majority of HCV patients.”
“Boehringer Ingelheim is continuing its long heritage in virology and is dedicated to developing new medicines to improve treatment for HCV patients,” continued Professor Klaus Dugi. “BI 201335 is part of our robust HCV portfolio that we are investigating with the goal of improving current treatment and ultimately paving a path for a simpler, more effective and better tolerated HCV therapy.”
Study Details:
(Oral Presentation at EASL, Parallel Session: HCV Drug Development, 16:00h-16:15h, Abstract 60) SILEN-C1: Sustained Virologic Response (SVR) and Safety of BI 201335 Combined with Peginterferon Alfa-2a and Ribavirin in Treatment-Naïve Patients with Chronic Genotype-1 HCV Infection
The Phase II SILEN-C1 study results show BI 201335 to have strong antiviral activity, with overall SVR rates reaching 83% in the 240mg once-daily group (plus current SOC). Of the patients achieving extended rapid viral response (eRVR, defined as plasma viral load less than 25 IU/ml at week 4 and undetectable at weeks 8-20), 93% achieved SVR with 24 weeks of SOC (PegIFN/RBV) treatment.
In addition to high efficacy at all dose levels, BI 201335 once daily with SOC also demonstrated good tolerability and safety:
The most frequent dose-dependent adverse events in BI 201335 treatment groups were mild gastrointestinal disorders, mild rash or photosensitivity and jaundice resulting from isolated unconjugated hyperbilirubinaemia. Average alanine aminotransferase (ALT) improved in all BI 201335 groups compared to placebo. Of note, there was no excess anaemia reported in the active groups compared to SOC. Phase III trials of BI 201335 are in preparation.
(Oral Presentation at EASL Parallel Session: HCV Drug Development, 17:30h-17:45h, Abstract 66) SILEN-C2: Sustained Virologic Response and Safety of BI 201335 Combined with Peginterferon Alfa-2a and Ribavirin in Chronic HCV Genotype-1 Patients with Non-Response to PegIFN/RBV
The Phase II SILEN-C2 study evaluated the virological response and safety of different doses of BI 201335 in treatment-experienced patients who did not respond to at least 12 weeks of prior treatment with PegIFN/RBV. The results demonstrate that treatment with BI 201335 once daily at 240mg, plus SOC provides high efficacy and good tolerability in this very difficult-to-treat patient population, with 41% achieving SVR. As is seen in SILEN-C1, a 3-day lead in with SOC was associated with decreased viral response. Phase III trials of BI 201335 are in preparation.
The most frequent dose-dependent adverse events in BI 201335 treatment groups were similar to those seen in SILEN-C1. Serious or severe adverse events were reported more frequently in the BI 201335 240mg BID with lead in (LI) group.
NOTES TO EDITORS
Additional BI 201335 Studies to be Presented at EASL
• SVR and pharmacokinetics of the HCV protease inhibitor BI 201335 with PegIFN/RBV in HCV genotype-1 patients with compensated liver cirrhosis and non-response to previous PegIFN/RBV (Poster 1231. S. Pol, et al.)
• Mechanisms of isolated unconjugated hyperbilirubinaemia induced by the HCV NS3/4A protease inhibitor BI 201335 (Poster 1236. R. Sane, et al.)
• BI 201335 pharmacokinetics and early effect on viral load in HCV genotype-1 patients (Poster 1249. C. Yong, et al.)
• Preclinical characterization of the hepatitis C virus NS5B polymerase non-nucleoside inhibitor BILB 1941 (Poster 1215. G. Kukolj et. al.)
Posters are presented on Saturday, 2 April, 2011, 09:00h - 18:00h.
About Hepatitis C Virus (HCV)
HCV is an infectious disease of the liver and is a leading cause of chronic liver disease and liver transplant. The number of individuals chronically infected with HCV globally has been estimated at 170 million, with 3–4 million new infections occurring each year. Only about 20–45% of patients clear the virus in the acute phase. Of the remaining chronically infected patients, 20% will develop cirrhosis within a mean of 20 years. The mortality rate after cirrhosis has developed is 2-5% per year. End-stage liver disease due to HCV infection currently represents the major cause for liver transplantation in the Western world.
About Boehringer Ingelheim in Virology
Boehringer Ingelheim has more than 6,900 scientists working in cross disciplinary teams within our global R&D network in six large therapeutic areas, including virology. In addition to its ongoing research program for HCV, Boehringer Ingelheim has a long-standing history in virology drug development, including compounds for the treatment of HIV (VIRAMUNE® (nevirapine) tablets/oral suspension, the first approved HIV non-nucleoside reverse transcriptase inhibitor (NNRTI) and Aptivus®, an HIV protease inhibitor). The company has a well established research centre in Laval, Canada, dedicated to virology research since the early 1990’s, and is committed to developing new therapies for virological diseases with a high unmet medical need.
Boehringer Ingelheim in Hepatitis C Virus (HCV)
BI 201335 is an investigational oral HCV NS3/4A protease inhibitor, discovered from Boehringer Ingelheim’s own research and development, which has completed clinical trials through Phase IIb (SILEN-C studies). This Phase II programme supports the investigation of BI 201335 in Phase III trials. Boehringer Ingelheim is also developing BI 207127, an NS5B RNA-dependent polymerase inhibitor that has completed Phase I clinical trials. Phase II trials evaluating BI 207127 with BI 201335 in interferon-sparing regimens, both with and without ribavirin, are currently underway.
Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
In 2009, Boehringer Ingelheim posted net sales of 12.7 billion euro (US $17.7 billion) while spending 21% of net sales in its largest business segment, Prescription Medicines, on research and development.
For more information, please visit http://www.boehringer-ingelheim.com/
www.twitter.com/boehringer
Contacts
Julia Meyer-Kleinmann
Director Corporate Communications
Boehringer Ingelheim GmbH
55216 Ingelheim/Germany
Phone: + 49 - 6132 – 77 8271
Fax: + 49 - 6132 – 77 70 77
E-mail: press@boehringer-ingelheim.com
Source
EASL: Phase III Data Suggests IL28B Genotyping Helps Predict Response to Merck & Co.’s HCV Drug
GEN News Highlights: Apr 1, 2011
New analyses of Phase III trial data suggests that identifying HCV patients’ IL28B status and evaluating their initial response to peginterferon alfa-2b and ribavirin (PR) therapy can help predict those who will achieve a sustained virologic response (SVR) when Merck & Co.’s oral protease inhibitor candidate Victrelis® (boceprivir) is subsequently added to the treatment mix.
The new analyses, presented at the International Liver Congress/46th European Association for the Study of Liver (EASL) annual meeting, coincided with publication in The New England Journal of Medicine of data from the Phase III HCV Respond-2 and HCV Sprint-2 studies evaluating Vectrelis combined with PR in patients who had failed prior PR therapy and who were new to treatment, respectively. Both trials formed part of the regulatory submissions for Victrelis, which were accepted for accelerated review by both FDA and the EMA in January.
The new data presented at EASL emerged from additional analyses of both the Respond-2 and Sprint-2 studies. In the Sprint-2 treatment-naïve study, patients receiving Victrelis who had good response to PR therapy after the four-week lead-in period achieved SVR rates of 79% over the 48-week treatment period. The SVR rate for patients in the PR therapy control arm who initially responded well to PR therapy was 51%. Among patients with poor response after the four-week lead-in, the SVR rate was 38% for Vicrelis-treated patients in the 48-week treatment arm compared with an SVR rate of 4% in the PR control arm.
In the Respond-2 treatment-failure study, Victrelis-treated patients who responded well after the lead-in PR therapy period achieved SVR rates of 79%. The SVR for patients treated using only PR was 25%. Among patients with poor response after the four-week lead-in, the SVR rate was 34% for those receiving PR plus Victrelis, and 0% for those continuing on just PR therapy.
A prespecified analysis of the Phase III trials in addition showed that IL28B status was also a strong baseline predictor of viral response among Victrelis-treated patients. The data, also presented at EASL, showed that among patients carrying the CC gene allele, 89% of treatment-naive patients and 82% of previously treatment-failure patients had an early response defined as undetectable virus at treatment week eight and were eligible for shorter duration of therapy. Among patients carrying the ‘less favorable’ CT or TT alleles, the early response rates were 52% for the treatment-naive cohort and 48% for the treatment-failure patients.
Primary results from the NEJM-published Respond-2 and Sprint-2 studies showed that among patients who had previously failed treatment, the 48-week SVR rate was 66% for those treated using Victrelis plus PR compared with 21% for patients treated using PR and placebo. Among treatment naive patients the SVR rate was 66% for patients receiving Victrelis plus PR and 38% for the PR therapy cohort.
“Based on new analyses of these studies, identification of a patient’s IL28B status prior to treatment, used in conjunction with a patient’s response after the four-week lead-in period, provided information on the likelihood of achieving SVR when Victrelis was added to standard therapy,” concludes Fred Poordad, M.D., chief of hepatology and liver transplantation at Cedars-Sinai Medical Center in Los Angeles, and lead author of the HCV Sprint-2 study.
Source
New analyses of Phase III trial data suggests that identifying HCV patients’ IL28B status and evaluating their initial response to peginterferon alfa-2b and ribavirin (PR) therapy can help predict those who will achieve a sustained virologic response (SVR) when Merck & Co.’s oral protease inhibitor candidate Victrelis® (boceprivir) is subsequently added to the treatment mix.
The new analyses, presented at the International Liver Congress/46th European Association for the Study of Liver (EASL) annual meeting, coincided with publication in The New England Journal of Medicine of data from the Phase III HCV Respond-2 and HCV Sprint-2 studies evaluating Vectrelis combined with PR in patients who had failed prior PR therapy and who were new to treatment, respectively. Both trials formed part of the regulatory submissions for Victrelis, which were accepted for accelerated review by both FDA and the EMA in January.
The new data presented at EASL emerged from additional analyses of both the Respond-2 and Sprint-2 studies. In the Sprint-2 treatment-naïve study, patients receiving Victrelis who had good response to PR therapy after the four-week lead-in period achieved SVR rates of 79% over the 48-week treatment period. The SVR rate for patients in the PR therapy control arm who initially responded well to PR therapy was 51%. Among patients with poor response after the four-week lead-in, the SVR rate was 38% for Vicrelis-treated patients in the 48-week treatment arm compared with an SVR rate of 4% in the PR control arm.
In the Respond-2 treatment-failure study, Victrelis-treated patients who responded well after the lead-in PR therapy period achieved SVR rates of 79%. The SVR for patients treated using only PR was 25%. Among patients with poor response after the four-week lead-in, the SVR rate was 34% for those receiving PR plus Victrelis, and 0% for those continuing on just PR therapy.
A prespecified analysis of the Phase III trials in addition showed that IL28B status was also a strong baseline predictor of viral response among Victrelis-treated patients. The data, also presented at EASL, showed that among patients carrying the CC gene allele, 89% of treatment-naive patients and 82% of previously treatment-failure patients had an early response defined as undetectable virus at treatment week eight and were eligible for shorter duration of therapy. Among patients carrying the ‘less favorable’ CT or TT alleles, the early response rates were 52% for the treatment-naive cohort and 48% for the treatment-failure patients.
Primary results from the NEJM-published Respond-2 and Sprint-2 studies showed that among patients who had previously failed treatment, the 48-week SVR rate was 66% for those treated using Victrelis plus PR compared with 21% for patients treated using PR and placebo. Among treatment naive patients the SVR rate was 66% for patients receiving Victrelis plus PR and 38% for the PR therapy cohort.
“Based on new analyses of these studies, identification of a patient’s IL28B status prior to treatment, used in conjunction with a patient’s response after the four-week lead-in period, provided information on the likelihood of achieving SVR when Victrelis was added to standard therapy,” concludes Fred Poordad, M.D., chief of hepatology and liver transplantation at Cedars-Sinai Medical Center in Los Angeles, and lead author of the HCV Sprint-2 study.
Source
Boceprevir Effective for Hepatitis C Virus Infection
Laurie Barclay, MD
March 31, 2011 — Boceprevir is effective in the treatment of previously treated and untreated patients with hepatitis C virus (HCV) infection, according to the results of 2 randomized trials reported in the March 30 issue of the New England Journal of Medicine.
RESPOND-2 Trial
"In patients with chronic infection with [HCV] genotype 1 who do not have a sustained response to therapy with peginterferon–ribavirin, outcomes after retreatment are suboptimal," write Bruce R. Bacon, MD, from Saint Louis University School of Medicine in Missouri, and colleagues from the HCV Retreatment with HCV Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol 2 (RESPOND-2) investigators. "Boceprevir, a protease inhibitor that binds to the HCV nonstructural 3...active site, has been suggested as an additional treatment."
The study goal was to examine the effect of boceprevir added to peginterferon–ribavirin for retreatment of patients with chronic HCV genotype 1 infection. During the lead-in period, the 403 participants all received peginterferon alfa-2b and ribavirin for 4 weeks. Using a 1:2:2 ratio, participants were randomly assigned to group 1 (control group) receiving placebo plus peginterferon–ribavirin for 44 weeks, group 2, or group 3. Participants in group 2 received boceprevir plus peginterferon–ribavirin for 32 weeks, and patients in whom the HCV RNA level was detectable at week 8 received placebo plus peginterferon–ribavirin for 12 more weeks. In group 3, participants received boceprevir plus peginterferon–ribavirin for 44 weeks.
Compared with the control group, the 2 boceprevir groups had a significantly higher rate of sustained virologic response (group 2, 59%; group 3, 66%; control group, 21%; P < .001). Among participants with an undetectable HCV RNA level at week 8, sustained virologic response rate was 86% after 32 weeks of triple therapy and 88% after 44 weeks of triple therapy. Among the 102 patients in whom HCV RNA level decreased by less than 1 log10 IU/mL at treatment week 4, rates of sustained virologic response were 0%, 33%, and 34% in groups 1, 2, and 3, respectively.
The boceprevir groups had higher frequencies of anemia than the control group, resulting in administration of erythropoietin in 41% to 46% of boceprevir-treated patients compared with 21% of the control patients.
"The addition of boceprevir to peginterferon–ribavirin resulted in significantly higher rates of sustained virologic response in previously treated patients with chronic HCV genotype 1 infection, as compared with peginterferon–ribavirin alone," the study authors write.
SPRINT-2 Trial
The second study, a double-blind trial by Fred Poordad, MD, from Cedars-Sinai Medical Center in Los Angeles, California, and colleagues from the Serine Protease Inhibitor Therapy 2 (SPRINT-2) investigators, had a study design similar to that of the RESPOND-2 study except that participants were previously untreated adults with HCV genotype 1 infection. Nonblack patients (n = 938) and black patients (n = 159) were enrolled and analyzed separately.
Sustained virologic response in the nonblack cohort occurred in 40% (125/311) of the patients in group 1, 67% (211/316) of the patients in group 2 (P < .001), and 68% (213/311) of the patients in group 3 (P < .001). For the black cohort, the corresponding rates were 23% (12/52 patients), 42% (22/52 patients; P = .04), and 53% (29/55 patients; P = .004), respectively.
Forty-four percent of patients in group 2 received peginterferon–ribavirin for 28 weeks. Dose reductions caused by anemia occurred in 13% of control patients and 21% of patients receiving boceprevir, and discontinuations caused by anemia in occurred in 1% and 2% of control patients and patients receiving boceprevir, respectively.
"The addition of boceprevir to standard therapy with peginterferon–ribavirin, as compared with standard therapy alone, significantly increased the rates of sustained virologic response in previously untreated adults with chronic HCV genotype 1 infection," the study authors write. "The rates were similar with 24 weeks and 44 weeks of boceprevir."
Limitations of this study include relatively small numbers of patients with cirrhosis and relatively small numbers of black patients in whom the HCV RNA level was detectable between weeks 8 and 24, warranting further study to define optimal therapy in these populations.
New Era of HCV Therapy
In an accompanying editorial, Donald M. Jensen, MD, from the Center for Liver Diseases, University of Chicago Medical Center in Illinois, discusses the beginning of a new era of HCV therapy. He noted that adverse effects associated with boceprevir treatment included anemia, rash, dry skin, and dysgeusia. However, only 8% to 12% of patients discontinued boceprevir because of these adverse events.
"HCV protease inhibitors represent a major advance in our ability to treat chronic HCV infection," Dr. Jensen writes. "Future therapy will be more complex, not easier, but the improvement in the rate of sustained virologic response with boceprevir, to nearly 70% in the SPRINT-2 trial and to more than twice the rate in previously treated patients in HCV RESPOND-2, have been eagerly awaited. We will soon embark on a new era of successful HCV therapy."
Schering-Plough (now Merck) supported both studies. Disclosure forms provided by the study authors and editorialists are available with the full text of these articles at NEJM.org.
N Engl J Med. 2011;364:1207-1217, 1195-1206, 1272-1274.
Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.
Source
March 31, 2011 — Boceprevir is effective in the treatment of previously treated and untreated patients with hepatitis C virus (HCV) infection, according to the results of 2 randomized trials reported in the March 30 issue of the New England Journal of Medicine.
RESPOND-2 Trial
"In patients with chronic infection with [HCV] genotype 1 who do not have a sustained response to therapy with peginterferon–ribavirin, outcomes after retreatment are suboptimal," write Bruce R. Bacon, MD, from Saint Louis University School of Medicine in Missouri, and colleagues from the HCV Retreatment with HCV Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol 2 (RESPOND-2) investigators. "Boceprevir, a protease inhibitor that binds to the HCV nonstructural 3...active site, has been suggested as an additional treatment."
The study goal was to examine the effect of boceprevir added to peginterferon–ribavirin for retreatment of patients with chronic HCV genotype 1 infection. During the lead-in period, the 403 participants all received peginterferon alfa-2b and ribavirin for 4 weeks. Using a 1:2:2 ratio, participants were randomly assigned to group 1 (control group) receiving placebo plus peginterferon–ribavirin for 44 weeks, group 2, or group 3. Participants in group 2 received boceprevir plus peginterferon–ribavirin for 32 weeks, and patients in whom the HCV RNA level was detectable at week 8 received placebo plus peginterferon–ribavirin for 12 more weeks. In group 3, participants received boceprevir plus peginterferon–ribavirin for 44 weeks.
Compared with the control group, the 2 boceprevir groups had a significantly higher rate of sustained virologic response (group 2, 59%; group 3, 66%; control group, 21%; P < .001). Among participants with an undetectable HCV RNA level at week 8, sustained virologic response rate was 86% after 32 weeks of triple therapy and 88% after 44 weeks of triple therapy. Among the 102 patients in whom HCV RNA level decreased by less than 1 log10 IU/mL at treatment week 4, rates of sustained virologic response were 0%, 33%, and 34% in groups 1, 2, and 3, respectively.
The boceprevir groups had higher frequencies of anemia than the control group, resulting in administration of erythropoietin in 41% to 46% of boceprevir-treated patients compared with 21% of the control patients.
"The addition of boceprevir to peginterferon–ribavirin resulted in significantly higher rates of sustained virologic response in previously treated patients with chronic HCV genotype 1 infection, as compared with peginterferon–ribavirin alone," the study authors write.
SPRINT-2 Trial
The second study, a double-blind trial by Fred Poordad, MD, from Cedars-Sinai Medical Center in Los Angeles, California, and colleagues from the Serine Protease Inhibitor Therapy 2 (SPRINT-2) investigators, had a study design similar to that of the RESPOND-2 study except that participants were previously untreated adults with HCV genotype 1 infection. Nonblack patients (n = 938) and black patients (n = 159) were enrolled and analyzed separately.
Sustained virologic response in the nonblack cohort occurred in 40% (125/311) of the patients in group 1, 67% (211/316) of the patients in group 2 (P < .001), and 68% (213/311) of the patients in group 3 (P < .001). For the black cohort, the corresponding rates were 23% (12/52 patients), 42% (22/52 patients; P = .04), and 53% (29/55 patients; P = .004), respectively.
Forty-four percent of patients in group 2 received peginterferon–ribavirin for 28 weeks. Dose reductions caused by anemia occurred in 13% of control patients and 21% of patients receiving boceprevir, and discontinuations caused by anemia in occurred in 1% and 2% of control patients and patients receiving boceprevir, respectively.
"The addition of boceprevir to standard therapy with peginterferon–ribavirin, as compared with standard therapy alone, significantly increased the rates of sustained virologic response in previously untreated adults with chronic HCV genotype 1 infection," the study authors write. "The rates were similar with 24 weeks and 44 weeks of boceprevir."
Limitations of this study include relatively small numbers of patients with cirrhosis and relatively small numbers of black patients in whom the HCV RNA level was detectable between weeks 8 and 24, warranting further study to define optimal therapy in these populations.
New Era of HCV Therapy
In an accompanying editorial, Donald M. Jensen, MD, from the Center for Liver Diseases, University of Chicago Medical Center in Illinois, discusses the beginning of a new era of HCV therapy. He noted that adverse effects associated with boceprevir treatment included anemia, rash, dry skin, and dysgeusia. However, only 8% to 12% of patients discontinued boceprevir because of these adverse events.
"HCV protease inhibitors represent a major advance in our ability to treat chronic HCV infection," Dr. Jensen writes. "Future therapy will be more complex, not easier, but the improvement in the rate of sustained virologic response with boceprevir, to nearly 70% in the SPRINT-2 trial and to more than twice the rate in previously treated patients in HCV RESPOND-2, have been eagerly awaited. We will soon embark on a new era of successful HCV therapy."
Schering-Plough (now Merck) supported both studies. Disclosure forms provided by the study authors and editorialists are available with the full text of these articles at NEJM.org.
N Engl J Med. 2011;364:1207-1217, 1195-1206, 1272-1274.
Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.
Source
Inhibition of HCV 3a core gene through Silymarin and its Fractions
Published on: 2011-04-01
Hepatitis C is a major health problem affecting 270 million individuals in world including Pakistan. Current treatment regimen, interferon alpha and ribavirin only cure half of patients due to side effects and high cost.
Results: In the present study Silybum marianum (Milk thistle) seeds were collected, extracted and analyzed against HCV 3a core gene by transiently transfecting the liver cells with HCV core plasmid.
Our results demonstrated that Silymarin (SM) dose dependently inhibit the expression or function of HCV core gene at a non toxic concentration while the GAPDH remained constant. To identify the active ingredient, SM was fractioned by thin layer chromatography (TLC), column chromatography and HPLC.
Purified fractions were tested for HCV core gene and western blotting results showed that two factions of SM (S1 and S2) inhibit HCV 3a core expression or function in liver cells.
Conclusion: Our results suggest SM and its fractions (S1 and S2) inhibit HCV core gene of 3a genotype and combination of SM and its fractions with interferon will be a better option to treat HCV infection.
Author: Usman AshfaqTariq JavedSidra RehmanZafar NawazSheikh Riazuddin
Credits/Source: Virology Journal 2011, 8:153
Source
Hepatitis C is a major health problem affecting 270 million individuals in world including Pakistan. Current treatment regimen, interferon alpha and ribavirin only cure half of patients due to side effects and high cost.
Results: In the present study Silybum marianum (Milk thistle) seeds were collected, extracted and analyzed against HCV 3a core gene by transiently transfecting the liver cells with HCV core plasmid.
Our results demonstrated that Silymarin (SM) dose dependently inhibit the expression or function of HCV core gene at a non toxic concentration while the GAPDH remained constant. To identify the active ingredient, SM was fractioned by thin layer chromatography (TLC), column chromatography and HPLC.
Purified fractions were tested for HCV core gene and western blotting results showed that two factions of SM (S1 and S2) inhibit HCV 3a core expression or function in liver cells.
Conclusion: Our results suggest SM and its fractions (S1 and S2) inhibit HCV core gene of 3a genotype and combination of SM and its fractions with interferon will be a better option to treat HCV infection.
Author: Usman AshfaqTariq JavedSidra RehmanZafar NawazSheikh Riazuddin
Credits/Source: Virology Journal 2011, 8:153
Source
Cirrhosis and HCC Have Risen Dramatically in Hepatitis C Patients
By: MARY ANN MOON, Internal Medicine News Digital Network
04/01/11
The burden of cirrhosis, hepatic decompensation, and hepatocellular carcinoma has risen dramatically during the past decade among patients with chronic hepatitis C virus infection, Dr. Fasiha Kanwal and her colleagues reported in the April issue of Gastroenterology.
In a large retrospective cohort study of more than 300,000 patients at Department of Veterans Affairs medical centers across the country, the prevalence of cirrhosis and hepatic decompensation doubled – and that of hepatocellular carcinoma increased 19-fold – between 1996 and 2006.
"Thus, 1 of 5 patients with HCV had cirrhosis and 1 of 100 patients with HCV had hepatocellular carcinoma in the 2006 calendar year," said Dr. Kanwal of the John Cochran division of the St. Louis VA Medical Center, and her associates.
This increase was significantly greater than that predicted by several mathematical models, they noted.
The investigators examined the burden of HCV illness directly, quantifying changes in the prevalence of cirrhosis and assessing trends in its related complications, because indirect data had suggested that it was increasing. "Our data are the first to provide direct and contemporary estimates of the time trends in the burden of cirrhosis from the largest assembled group of HCV patients anywhere in the world," the researchers said.
"Measuring the burden in HCV is important ... to understand changes in the pattern of care delivery, provide a critical insight into the magnitude of the problem, and guide both clinicians and the health care system to develop strategies [for] providing timely and effective care to this highly vulnerable group of patients," they said.
They analyzed data from the VA’s HCV database, which included HCV patients who sought treatment at any of 128 VA medical centers in 1996-2006. There were 17,261 patients in the database in 1996, a total that increased to 106,242 in 2006.
Overall, the number of patients with HCV who had cirrhosis rose from 2,061 to 23,294 during the study period, the number with hepatic decompensation rose from 1,012 to 13,724, and the number with hepatocellular carcinoma rose from 17 to 1,619.
The prevalence of cirrhosis doubled from 9% to 18.5% during that time, and still continues to rise. The prevalence of hepatic decompensation rose in parallel, with a twofold increase (from 5% to 11%).
The prevalence of hepatocellular carcinoma also rose, but the upward slope became particularly steep from 2003 onward. Prevalence grew 19-fold (from 0.07% to 1.3%) during the study period overall. This pattern suggests that "there might be a greater epidemic of hepatocellular carcinoma [coming] than we were expecting,’ Dr. Kanwal and her colleagues said.
Mortality of cirrhosis patients also increased over time, with a greater proportion of patients dying in recent years than in the 1990s.
The aging of the cohort explains part of these increases, but all of them persisted even after the data were adjusted to account for aging. It is not yet known what other factors play a role in these trends.
"The morbidity and mortality associated with cirrhosis and hepatocellular carcinoma may be greatly reduced if potentially life-saving interventions – such as liver transplantation and, for HCC, local ablation and surgical resection – are applied in a timely manner," they noted.
However, recent data from other studies demonstrate that patients with cirrhosis rarely receive high-quality health care, and their own previous research found that "the quality of health care given to patients with HCV infection falls far short of that recommended by practice guidelines."
In this study, only 16% of the cohort had ever received a prescription for interferon.
"Given the significant increase in the number of patients with cirrhosis, and given the data suggesting marked gaps in the quality of care, the health care system may need to rechannel its efforts in patients with HCV to provide timely and effective care to the patients with cirrhosis," the investigators said.
The research was supported in part by grants from the Department of Veterans Affairs. The authors had nothing to disclose.
Source
04/01/11
The burden of cirrhosis, hepatic decompensation, and hepatocellular carcinoma has risen dramatically during the past decade among patients with chronic hepatitis C virus infection, Dr. Fasiha Kanwal and her colleagues reported in the April issue of Gastroenterology.
In a large retrospective cohort study of more than 300,000 patients at Department of Veterans Affairs medical centers across the country, the prevalence of cirrhosis and hepatic decompensation doubled – and that of hepatocellular carcinoma increased 19-fold – between 1996 and 2006.
"Thus, 1 of 5 patients with HCV had cirrhosis and 1 of 100 patients with HCV had hepatocellular carcinoma in the 2006 calendar year," said Dr. Kanwal of the John Cochran division of the St. Louis VA Medical Center, and her associates.
This increase was significantly greater than that predicted by several mathematical models, they noted.
The investigators examined the burden of HCV illness directly, quantifying changes in the prevalence of cirrhosis and assessing trends in its related complications, because indirect data had suggested that it was increasing. "Our data are the first to provide direct and contemporary estimates of the time trends in the burden of cirrhosis from the largest assembled group of HCV patients anywhere in the world," the researchers said.
"Measuring the burden in HCV is important ... to understand changes in the pattern of care delivery, provide a critical insight into the magnitude of the problem, and guide both clinicians and the health care system to develop strategies [for] providing timely and effective care to this highly vulnerable group of patients," they said.
They analyzed data from the VA’s HCV database, which included HCV patients who sought treatment at any of 128 VA medical centers in 1996-2006. There were 17,261 patients in the database in 1996, a total that increased to 106,242 in 2006.
Overall, the number of patients with HCV who had cirrhosis rose from 2,061 to 23,294 during the study period, the number with hepatic decompensation rose from 1,012 to 13,724, and the number with hepatocellular carcinoma rose from 17 to 1,619.
The prevalence of cirrhosis doubled from 9% to 18.5% during that time, and still continues to rise. The prevalence of hepatic decompensation rose in parallel, with a twofold increase (from 5% to 11%).
The prevalence of hepatocellular carcinoma also rose, but the upward slope became particularly steep from 2003 onward. Prevalence grew 19-fold (from 0.07% to 1.3%) during the study period overall. This pattern suggests that "there might be a greater epidemic of hepatocellular carcinoma [coming] than we were expecting,’ Dr. Kanwal and her colleagues said.
Mortality of cirrhosis patients also increased over time, with a greater proportion of patients dying in recent years than in the 1990s.
The aging of the cohort explains part of these increases, but all of them persisted even after the data were adjusted to account for aging. It is not yet known what other factors play a role in these trends.
"The morbidity and mortality associated with cirrhosis and hepatocellular carcinoma may be greatly reduced if potentially life-saving interventions – such as liver transplantation and, for HCC, local ablation and surgical resection – are applied in a timely manner," they noted.
However, recent data from other studies demonstrate that patients with cirrhosis rarely receive high-quality health care, and their own previous research found that "the quality of health care given to patients with HCV infection falls far short of that recommended by practice guidelines."
In this study, only 16% of the cohort had ever received a prescription for interferon.
"Given the significant increase in the number of patients with cirrhosis, and given the data suggesting marked gaps in the quality of care, the health care system may need to rechannel its efforts in patients with HCV to provide timely and effective care to the patients with cirrhosis," the investigators said.
The research was supported in part by grants from the Department of Veterans Affairs. The authors had nothing to disclose.
Source
EASL: Medivir: Week 24 Interim Results from TMC435 Hepatitis C Phase 2b ASPIRE Study presented at EASL
Results show potent antiviral efficacy of once daily 150 mg TMC435 in hepatitis C patients who have failed earlier treatment, especially in prior null responders, and excellent safety and tolerability
01-Apr-11 Huddinge, Sweden - Medivir AB (OMX: MVIR), the emerging research-based specialty pharmaceutical company focused on infectious diseases, announces that their partner, Tibotec has presented the results of a planned Week 24 interim analysis of the phase 2b ASPIRE study for TMC435 in treatment experienced hepatitis C patients in a late-breaker session at the 46th Annual meeting of the European Association for the Study of the Liver (EASL), Berlin, Germany.
Treatment experienced patients are known to be the most difficult to treat hepatitis C patient group.
TMC435 is a potent, once-daily, oral hepatitis C virus protease inhibitor which recently entered clinical phase 3 studies. The study enrolled patients chronically infected with genotype-1 hepatitis C virus (HCV) that had previously failed treatment with standard of care therapy (peginterferon and ribavarin). TMC435 is being jointly developed by Medivir and its partner Tibotec.
In this Week 24 interim analysis, treatment-experienced patients who failed peginterferon and ribavarin treatment achieved significantly greater virologic response rates following treatment with TMC435-containing regimen at all doses, compared with placebo. Results demonstrated that the TMC435 150 mg dose group showed the highest response, particularly in prior null responders. In this 150 mg dose group, HCV RNA levels were undetectable at week 24 for between 82% and 91% of the patients. Results also showed that there was no statistically relevant difference in safety and tolerability between the TMC435 and placebo treated groups.
Ron Long, CEO of Medivir, commented: “We are delighted that these strong results are to be presented at such a prestigious scientific conference as EASL. TMC435 continues to demonstrate why Medivir are so confident that hepatitis C treatment can be significantly changed by a more convenient, once daily protease inhibitor especially for treatment experienced patients. These data and the recent start of phase 3 clinical studies for TMC435, represent an exciting stage in Medivir’s development as a significant player in the infectious disease market.”
On-treatment response rates are shown below.
TMC12/PR48 TMC24/PR48 TMC48/PR48 TMC12/PR48 TMC24/PR48 TMC48/PR48 Pbo48/PR48
100mg 100mg 100mg 150mg 150mg 150mg
(N=66) (N=65) (N=66) (N=66) (N=68) (N=65) (N=66)
HCV RNA <25 IU/mL undetectable, % (u/N)
Overall population 67,7 (44/65) 59,4 (38/64) 53,8 (35/65) 63,1 (41/65) 70,8 (46/65) 66,2 (43/65) 1,5 (1/65)
Week 4 (RVR) *** *** *** *** *** ***
Prior null responders 33,3 (5/15) 50,0 (8/16) 25,0 (4/16) 35,3 (6/17) 41,2 (7/17) 41,2 (7/17) 0,0 (0/16)
Prior partial responders 65,2 (15/23) 40,9 (9/22) 60,9 (14/23) 65,2 (15/23) 69,6 (16/23) 68,2 (15/22) 0,0 (0/23)
Prior relapser 88,9 (24/27) 80,8 (21/26) 65,4 (17/26) 80,0 (20/25) 92,0 (23/25) 80,8 (21/26) 3,8 (1/26)
Overall population 87,1 (54/62) 84,5 (49/58) 85,2 (52/61) 85,7 (54/63) 90,8 (59/65) 90,3 (56/62) 51,9 (28/54)
Week 24 *** *** *** *** *** ***
Prior null responders 71,4 (10/14) 83,3 (10/12) 68,8 (11/16) 70,6 (12/17) 81,3 (13/16) 93,3 (14/15) 44,4 (4/9)
Prior partial responders 86,6 (19/22) 80,0 (16/20) 85,7 (18/21) 86,4 (19/22) 90,9 (20/22) 86,4 (19/22) 19,0 (4/21)
Prior relapser 96,2 (25/26) 88,5 (23/26) 95,8 (23/24) 95,8 (23/24) 96,3 (26/27) 92,0 (23/25) 83,3 (20/24)
*** Statistically significant difference versus placebo, p<0,0
The ASPIRE study evaluates the effect of TMC435 in combination with standard of care (SoC) in 462 patients infected with the difficult to treat genotype-1 hepatitis C virus who had undergone and failed prior treatment with (SoC). The study includes patients that have relapsed, achieved partial response, or achieved no response (null responders) to treatment with standard of care. TMC435 was administered once daily at a dose of either 100 mg or 150mg given for either 12, 24, or 48 weeks in combination with standard of care. Standard of care treatment was continued until the study completion at week 48.
As well as the late-breaker ASPIRE data presented, a further three presentations will be made at EASL on TMC435. These include:
Oral presentation: Impact of IL28b genotype and pretreatment serum IP-10 in treatment-naïve genotype-1 HCV patients treated with TMC435 in combination with peginterferonα-2a and ribavirin in PILLAR study, J. Aerssens, which found that during 24 weeks of treatment, IL28B genotype and serum IP-10 were predictive of response in patients receiving standard of care (peginterferon and ribavirin) but had limited predictive value in patients treated with both TMC435 and peginterferon and ribavirin, therefore suggesting that TMC435, a potent, once daily oral protease inhibitor, may overcome the negative consequences of unfavourable host genotype encountered with pegIFN/RBV.
Poster presentation No.472: Pharmacokinetics of TMC435 in subjects with moderate hepatic impairment, V. Sekar, which found that no TMC435 dose adjustment was necessary for patients with moderate liver impairment.
Poster presentation No.1221: Treatment outcome and resistance analysis in HCV genotype 1 patients previously exposed to TMC435 monotherapy and re-treated with TMC435 in combination with pegifnα‑2a/ribavirin, O. Lenz, which found that viral variants in patients who had received TMC435 as a monotherapy were no longer detected over time and successful treatment after prior exposure to TMC435 with emergence of resistance variants was possible in 3/5 patients who had failed interferon-based therapy.
About TMC435 in other clinical studies
TMC435 is a once-daily (q.d.) protease inhibitor drug jointly developed by Medivir and Tibotec Pharmaceuticals, to treat chronic hepatitis C virus infections.
Three clinical phase 3 response guided studies were recently initiated:
· TMC435-C208 or QUEST-1 includes approximately 375 treatment-naïve patients
· TMC435-C216 or QUEST-2 includes approximately 375 treatment-naïve patients
· TMC435-C3007 or PROMISE includes approximately 375 who have relapsed after prior interferon-based treatment
In parallel to the recent start of the global phase 3-studies, TMC435 is currently in a follow up phase in three phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215) in G1 treatment-naïve and in G1 patients that failed previous IFN-based treatment. More safety and efficacy data from the phase 2b trials will be presented at scientific meetings later in 2011.
A phase 3 program for TMC435 has also recently been launched in Japan.
For additional information for these studies, please see http://www.clinicaltrials.gov/
For more information about Medivir, please contact:
Medivir (http://www.medivir.com/ (http://www.medivir.com/)):
Rein Piir, CFO & VP Investor Relations Mobile: +46 708 537 292
Bertil Samuelsson, CFO Mobile: +46 (70) 576 13 50
M:Communications: Mary-Jane Elliott / Amber Bielecka / Katja Toon Medivir@mcomgroup.com (Medivir@mcomgroup.com) +44(0)20 7920 2330
USA: Roland Tomforde +1 212-232-2356
About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The CDC has reported that almost three million people in the United States are chronically infected with HCV.
About Medivir
Medivir is an emerging research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company’s key pipeline asset is TMC435, a protease inhibitor which has recently entered phase 3 clinical development for hepatitis C and is partnered with Tibotec Pharmaceuticals.
Medivir is also marketing its first product, the unique cold sore product Xerese™/Xerclear® which has recently been launched on the US market. Xerese™/Xerclear®, which is also approved in Europe, is partnered with GlaxoSmithKline to be sold OTC in Europe, Japan and Russia and with Meda AB in North America, Canada and Mexico. Medivir has retained the Rx rights for Xerclear® in Sweden and Finland.
For more information about Medivir, please visit the Company’s website: www.medivir.com (http://www.medivir.com/).
Source
01-Apr-11 Huddinge, Sweden - Medivir AB (OMX: MVIR), the emerging research-based specialty pharmaceutical company focused on infectious diseases, announces that their partner, Tibotec has presented the results of a planned Week 24 interim analysis of the phase 2b ASPIRE study for TMC435 in treatment experienced hepatitis C patients in a late-breaker session at the 46th Annual meeting of the European Association for the Study of the Liver (EASL), Berlin, Germany.
Treatment experienced patients are known to be the most difficult to treat hepatitis C patient group.
TMC435 is a potent, once-daily, oral hepatitis C virus protease inhibitor which recently entered clinical phase 3 studies. The study enrolled patients chronically infected with genotype-1 hepatitis C virus (HCV) that had previously failed treatment with standard of care therapy (peginterferon and ribavarin). TMC435 is being jointly developed by Medivir and its partner Tibotec.
In this Week 24 interim analysis, treatment-experienced patients who failed peginterferon and ribavarin treatment achieved significantly greater virologic response rates following treatment with TMC435-containing regimen at all doses, compared with placebo. Results demonstrated that the TMC435 150 mg dose group showed the highest response, particularly in prior null responders. In this 150 mg dose group, HCV RNA levels were undetectable at week 24 for between 82% and 91% of the patients. Results also showed that there was no statistically relevant difference in safety and tolerability between the TMC435 and placebo treated groups.
Ron Long, CEO of Medivir, commented: “We are delighted that these strong results are to be presented at such a prestigious scientific conference as EASL. TMC435 continues to demonstrate why Medivir are so confident that hepatitis C treatment can be significantly changed by a more convenient, once daily protease inhibitor especially for treatment experienced patients. These data and the recent start of phase 3 clinical studies for TMC435, represent an exciting stage in Medivir’s development as a significant player in the infectious disease market.”
On-treatment response rates are shown below.
TMC12/PR48 TMC24/PR48 TMC48/PR48 TMC12/PR48 TMC24/PR48 TMC48/PR48 Pbo48/PR48
100mg 100mg 100mg 150mg 150mg 150mg
(N=66) (N=65) (N=66) (N=66) (N=68) (N=65) (N=66)
HCV RNA <25 IU/mL undetectable, % (u/N)
Overall population 67,7 (44/65) 59,4 (38/64) 53,8 (35/65) 63,1 (41/65) 70,8 (46/65) 66,2 (43/65) 1,5 (1/65)
Week 4 (RVR) *** *** *** *** *** ***
Prior null responders 33,3 (5/15) 50,0 (8/16) 25,0 (4/16) 35,3 (6/17) 41,2 (7/17) 41,2 (7/17) 0,0 (0/16)
Prior partial responders 65,2 (15/23) 40,9 (9/22) 60,9 (14/23) 65,2 (15/23) 69,6 (16/23) 68,2 (15/22) 0,0 (0/23)
Prior relapser 88,9 (24/27) 80,8 (21/26) 65,4 (17/26) 80,0 (20/25) 92,0 (23/25) 80,8 (21/26) 3,8 (1/26)
Overall population 87,1 (54/62) 84,5 (49/58) 85,2 (52/61) 85,7 (54/63) 90,8 (59/65) 90,3 (56/62) 51,9 (28/54)
Week 24 *** *** *** *** *** ***
Prior null responders 71,4 (10/14) 83,3 (10/12) 68,8 (11/16) 70,6 (12/17) 81,3 (13/16) 93,3 (14/15) 44,4 (4/9)
Prior partial responders 86,6 (19/22) 80,0 (16/20) 85,7 (18/21) 86,4 (19/22) 90,9 (20/22) 86,4 (19/22) 19,0 (4/21)
Prior relapser 96,2 (25/26) 88,5 (23/26) 95,8 (23/24) 95,8 (23/24) 96,3 (26/27) 92,0 (23/25) 83,3 (20/24)
*** Statistically significant difference versus placebo, p<0,0
The ASPIRE study evaluates the effect of TMC435 in combination with standard of care (SoC) in 462 patients infected with the difficult to treat genotype-1 hepatitis C virus who had undergone and failed prior treatment with (SoC). The study includes patients that have relapsed, achieved partial response, or achieved no response (null responders) to treatment with standard of care. TMC435 was administered once daily at a dose of either 100 mg or 150mg given for either 12, 24, or 48 weeks in combination with standard of care. Standard of care treatment was continued until the study completion at week 48.
As well as the late-breaker ASPIRE data presented, a further three presentations will be made at EASL on TMC435. These include:
Oral presentation: Impact of IL28b genotype and pretreatment serum IP-10 in treatment-naïve genotype-1 HCV patients treated with TMC435 in combination with peginterferonα-2a and ribavirin in PILLAR study, J. Aerssens, which found that during 24 weeks of treatment, IL28B genotype and serum IP-10 were predictive of response in patients receiving standard of care (peginterferon and ribavirin) but had limited predictive value in patients treated with both TMC435 and peginterferon and ribavirin, therefore suggesting that TMC435, a potent, once daily oral protease inhibitor, may overcome the negative consequences of unfavourable host genotype encountered with pegIFN/RBV.
Poster presentation No.472: Pharmacokinetics of TMC435 in subjects with moderate hepatic impairment, V. Sekar, which found that no TMC435 dose adjustment was necessary for patients with moderate liver impairment.
Poster presentation No.1221: Treatment outcome and resistance analysis in HCV genotype 1 patients previously exposed to TMC435 monotherapy and re-treated with TMC435 in combination with pegifnα‑2a/ribavirin, O. Lenz, which found that viral variants in patients who had received TMC435 as a monotherapy were no longer detected over time and successful treatment after prior exposure to TMC435 with emergence of resistance variants was possible in 3/5 patients who had failed interferon-based therapy.
About TMC435 in other clinical studies
TMC435 is a once-daily (q.d.) protease inhibitor drug jointly developed by Medivir and Tibotec Pharmaceuticals, to treat chronic hepatitis C virus infections.
Three clinical phase 3 response guided studies were recently initiated:
· TMC435-C208 or QUEST-1 includes approximately 375 treatment-naïve patients
· TMC435-C216 or QUEST-2 includes approximately 375 treatment-naïve patients
· TMC435-C3007 or PROMISE includes approximately 375 who have relapsed after prior interferon-based treatment
In parallel to the recent start of the global phase 3-studies, TMC435 is currently in a follow up phase in three phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215) in G1 treatment-naïve and in G1 patients that failed previous IFN-based treatment. More safety and efficacy data from the phase 2b trials will be presented at scientific meetings later in 2011.
A phase 3 program for TMC435 has also recently been launched in Japan.
For additional information for these studies, please see http://www.clinicaltrials.gov/
For more information about Medivir, please contact:
Medivir (http://www.medivir.com/ (http://www.medivir.com/)):
Rein Piir, CFO & VP Investor Relations Mobile: +46 708 537 292
Bertil Samuelsson, CFO Mobile: +46 (70) 576 13 50
M:Communications: Mary-Jane Elliott / Amber Bielecka / Katja Toon Medivir@mcomgroup.com (Medivir@mcomgroup.com) +44(0)20 7920 2330
USA: Roland Tomforde +1 212-232-2356
About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The CDC has reported that almost three million people in the United States are chronically infected with HCV.
About Medivir
Medivir is an emerging research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company’s key pipeline asset is TMC435, a protease inhibitor which has recently entered phase 3 clinical development for hepatitis C and is partnered with Tibotec Pharmaceuticals.
Medivir is also marketing its first product, the unique cold sore product Xerese™/Xerclear® which has recently been launched on the US market. Xerese™/Xerclear®, which is also approved in Europe, is partnered with GlaxoSmithKline to be sold OTC in Europe, Japan and Russia and with Meda AB in North America, Canada and Mexico. Medivir has retained the Rx rights for Xerclear® in Sweden and Finland.
For more information about Medivir, please visit the Company’s website: www.medivir.com (http://www.medivir.com/).
Source
EASL: Importance of policy action to help reduce HCV-related deaths across Europe by 2025
Public release date: 31-Mar-2011
Contact: Isabelle Scali
easlpressoffice@cohnwolfe.com
44-771-743-5103
European Association for the Study of the Liver
Current health inequalities could limit results
New findings from two modeling studies presented at the International Liver Congress support the call to action from medical experts and patients in relation to the challenge health inequalities represent in the diagnosis and access to HCV treatment.
The first modelling study looks at current treatment practices and available epidemiological data across a number of EU countries (including Belgium, France, Germany, Italy, Spain and the UK), and shows that based on current practice HCV-related morbidity and mortality (linked to liver cancer deaths) will be reduced by 10% over nine years (2012 – 2021). In addition, the incidence of cirrhosis will also be reduced by 16%. Both results take into consideration variations across countries in screening, diagnosis and treatment standards.
The study also considered HCV progression if 70% of treatment naive patients and all non-responders and relapsers were treated with a protease inhibitor from 2012 onwards (increasing average SVR to 70% and 60.5% in non-responders and treatment-naive genotype 1 patients respectively). Based on this scenario, findings show that the overall HCV-related mortality would decrease by a further 12% over the same period, corresponding to a relative impact of 117% compared to current practice.
Based on these forecasts, experts conclude that the development and implementation of ambitious policy strategies to ensure effective access to diagnosis and treatment alongside the availability of new therapies (such as proteases inhibitors) could have a major impact in further reducing HCV-related mortality in the future.
A second modelling study looked at French health resource allocation and how this may change with the introduction of triple therapy for non-responders in the near future. In France, the data show the number of patients eligible for treatment (treatment-naive and previous non-responders) will increase two to three folds, which equates to an additional 9,900 to 14,300 patients by 2012.
This demonstrates the need to adjust allocation of health resources at national level to meet this demand.
Mark Thursz, EASL's Vice-Secretary commented: "These types of modelling studies are useful in providing us with data to support our policy efforts with political audiences. We have been saying, alongside patients, that the current challenges to managing viral hepatitis effectively are linked to a wide discrepancy in diagnosis and treatment standards across the different Member States. Now we can build a stronger case when discussing the development of effective health strategies within the EU and at Member State level. The good news is that antiviral treatments are being proven to be effective in substantially reducing HCV-related mortality in Europe. We must strengthen our efforts towards a better identification of carriers needing management and treatment."
HCV is a major cause of acute hepatitis and chronic liver disease. Globally, an estimated 130� million people are chronically infected with HCV and 3 million are newly infected each year.
###
Notes to Editors
About EASL
EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.
EASL's main focus on education and research is delivered through numerous events and initiatives, including:
• The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide
• Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year
• Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology
• Journal of Hepatology published monthly
• Participation in a number of policy initiatives at European level
About The International Liver CongressTM 2011
The International Liver Congress™ 2011, the 46th annual meeting of the European Association for the study of the Liver, is being held at the Internationales Congress Centrum, Berlin, Germany from March 30 – April 3, 2011. The congress annually attracts over 7,500 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field.
References
1. Deuffic-Burban S et al. HCV burden in Europe: Impact of national treatment practices on future HCV-related morbidity and mortality through a modelling approach. Abstract presented at the International Liver CongressTM 2011
2. Deuffic-Burban S et al. The availability of direct acting antivirals in 2012: A French model-based analysis of the increased number of patients treated for chronic HCV infection. Abstract presented at the International Liver CongressTM 2011
3. WHO Europe. Hepatitis C facts and figures. http://www.euro.who.int/en/what-we-do/health-topics/diseases-and-conditions/hepatitis/facts-and-figures/hepatitis-c. Accessed 08 March 2011
Source
Contact: Isabelle Scali
easlpressoffice@cohnwolfe.com
44-771-743-5103
European Association for the Study of the Liver
Current health inequalities could limit results
New findings from two modeling studies presented at the International Liver Congress support the call to action from medical experts and patients in relation to the challenge health inequalities represent in the diagnosis and access to HCV treatment.
The first modelling study looks at current treatment practices and available epidemiological data across a number of EU countries (including Belgium, France, Germany, Italy, Spain and the UK), and shows that based on current practice HCV-related morbidity and mortality (linked to liver cancer deaths) will be reduced by 10% over nine years (2012 – 2021). In addition, the incidence of cirrhosis will also be reduced by 16%. Both results take into consideration variations across countries in screening, diagnosis and treatment standards.
The study also considered HCV progression if 70% of treatment naive patients and all non-responders and relapsers were treated with a protease inhibitor from 2012 onwards (increasing average SVR to 70% and 60.5% in non-responders and treatment-naive genotype 1 patients respectively). Based on this scenario, findings show that the overall HCV-related mortality would decrease by a further 12% over the same period, corresponding to a relative impact of 117% compared to current practice.
Based on these forecasts, experts conclude that the development and implementation of ambitious policy strategies to ensure effective access to diagnosis and treatment alongside the availability of new therapies (such as proteases inhibitors) could have a major impact in further reducing HCV-related mortality in the future.
A second modelling study looked at French health resource allocation and how this may change with the introduction of triple therapy for non-responders in the near future. In France, the data show the number of patients eligible for treatment (treatment-naive and previous non-responders) will increase two to three folds, which equates to an additional 9,900 to 14,300 patients by 2012.
This demonstrates the need to adjust allocation of health resources at national level to meet this demand.
Mark Thursz, EASL's Vice-Secretary commented: "These types of modelling studies are useful in providing us with data to support our policy efforts with political audiences. We have been saying, alongside patients, that the current challenges to managing viral hepatitis effectively are linked to a wide discrepancy in diagnosis and treatment standards across the different Member States. Now we can build a stronger case when discussing the development of effective health strategies within the EU and at Member State level. The good news is that antiviral treatments are being proven to be effective in substantially reducing HCV-related mortality in Europe. We must strengthen our efforts towards a better identification of carriers needing management and treatment."
HCV is a major cause of acute hepatitis and chronic liver disease. Globally, an estimated 130� million people are chronically infected with HCV and 3 million are newly infected each year.
###
Notes to Editors
About EASL
EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.
EASL's main focus on education and research is delivered through numerous events and initiatives, including:
• The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide
• Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year
• Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology
• Journal of Hepatology published monthly
• Participation in a number of policy initiatives at European level
About The International Liver CongressTM 2011
The International Liver Congress™ 2011, the 46th annual meeting of the European Association for the study of the Liver, is being held at the Internationales Congress Centrum, Berlin, Germany from March 30 – April 3, 2011. The congress annually attracts over 7,500 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field.
References
1. Deuffic-Burban S et al. HCV burden in Europe: Impact of national treatment practices on future HCV-related morbidity and mortality through a modelling approach. Abstract presented at the International Liver CongressTM 2011
2. Deuffic-Burban S et al. The availability of direct acting antivirals in 2012: A French model-based analysis of the increased number of patients treated for chronic HCV infection. Abstract presented at the International Liver CongressTM 2011
3. WHO Europe. Hepatitis C facts and figures. http://www.euro.who.int/en/what-we-do/health-topics/diseases-and-conditions/hepatitis/facts-and-figures/hepatitis-c. Accessed 08 March 2011
Source
Subscribe to:
Posts (Atom)