- Complete results from pivotal Phase 3 REALIZE study of telaprevir in people who had not achieved a viral cure (SVR) with currently available medicines -
- First presentation of data from ongoing Phase 2 study evaluating response-guided, 12- and 24-week regimens of telaprevir and VX-222 combined with pegylated-interferon and ribavirin -
- Analyses of the relationship between IL28B genotype status on viral cure rates from two Phase 3 studies -
CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) announced today that 15 abstracts on the company's medicines in development for hepatitis C, including its protease inhibitor, telaprevir, and polymerase inhibitor, VX-222, were accepted for presentation at the 46th Annual Meeting of the European Association for the Study of the Liver (EASL) in Berlin, Germany, March 30 to April 3, 2011.
Highlights of data presentations include:
• Complete results from the pivotal Phase 3 REALIZE study will be presented for the first time. Topline results from this study, which evaluated telaprevir in combination with pegylated-interferon and ribavirin in people who had not achieved a viral cure (SVR) with currently available medicines, were announced in September 2010.
• The first data from an ongoing Phase 2 study evaluating 12- and 24-week response-guided regimens of telaprevir and VX-222 in combination with pegylated-interferon and ribavirin will be presented during a late-breaker session (Abstract #1363).
• Retrospective analyses of the relationship between IL28B genotype status and rates of viral cure with telaprevir-based combination therapy from the pivotal Phase 3 studies of REALIZE and ADVANCE will also be presented.
The titles of the abstracts related to Vertex's medicines in development for hepatitis C are included below and the complete abstracts are now available through the EASL website at http://www.easl.eu/.
"This is an exciting time for the treatment of hepatitis C and for Vertex," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer for Vertex. "At EASL, we will present, for the first time, complete results from the Phase 3 REALIZE study and early findings of a new study evaluating both of our oral medicines in development for hepatitis C, telaprevir and VX-222 in combination with available medicines."
The regulatory applications for the approval of telaprevir have been granted Priority Review by the U.S. Food and Drug Administration (FDA) and Health Canada and accelerated assessment by the European Medicines Agency for the treatment of people chronically infected with genotype 1 hepatitis C virus (HCV). The applications include data from three registrational studies, ADVANCE, ILLUMINATE and REALIZE, which evaluated telaprevir in people with hepatitis C who were new to treatment as well as those who did not achieve a viral cure after treatment with currently available medicines. For complete information on the telaprevir clinical trials or a fact sheet on the trial designs visit: www.vrtx.com/press.cfm.
Oral Presentations
• "REALIZE Trial Final Results: Telaprevir-based Regimen in Genotype 1 Hepatitis C Virus infection in Patients with Prior Null Response, Partial Response or Relapse to Peginterferon/Ribavirin"; March 31, 2011, 4:15 - 4:30 p.m. CET.
• "Subanalyses of the telaprevir lead-in arm in the REALIZE study: response at week 4 is not a substitute for prior null response categorization"; March 31, 2011, 5:00 - 5:15 p.m. CET.
• "Evolution of Treatment-Emergent Resistant Variants in Telaprevir Phase 3 Clinical Trials (ADVANCE, ILLUMINATE, REALIZE)"; March 31, 2011, 5:30 - 5:45 p.m. CET.
• "Similar SVR Rates in IL28B CC, CT or TT Prior Relapsers, Partial- or Null-Responders Patients Treated with Telaprevir/Peginterferon/ Ribavirin: Retrospective Analysis of the REALIZE Study"; March 31, 2011, 6:45 - 7:00 p.m. CET.
Poster Presentations
• Late Breaker #1363: "VX-222 with TVR Alone or in Combination with Peginterferon ALFA-2A and Ribavirin in Treatment-Naïve Patients With Chronic Hepatitis C: ZENITH Study Interim Results"; March 31 — April 2, 2011.
• Late Breaker #1369: "Telaprevir Substantially Improved SVR Rates Across All IL28B Genotypes in ADVANCE Trial"; March 31 — April 2, 2011.
• #451: "Telaprevir in Combination with Peginterferon Alfa-2a and Ribavirin: Analyses of Pre-Defined Subpopulations in the Phase 3 ADVANCE Trial"; March 31, 2011, 1:30 — 2:30 p.m. CET.
• #415: "Telaprevir in Combination with Peginterferon Alfa-2a and Ribavirin Increased Sustained Virologic Response Rates in Treatment-Naïve Patients Regardless of Race or Ethnicity"; March 31, 2011, 1:30 — 2:30 p.m. CET.
• #477: "Anemia Had no Effect on Efficacy Outcomes in Treatment-Naïve Patients who Received Telaprevir-Based Regimen in the ADVANCE and ILLUMINATE Phase 3 Studies"; March 31, 2011, 1:30 — 2:30 p.m. CET.
• #400: "Modeling, Clinical and Virology Data From Phase 2 and 3 Studies Support 12-week Telaprevir Duration In Combination with 24- or 48-week Peginterferon/Ribavirin Duration"; March 31, 2011, 1:30 — 2:30 p.m. CET.
• #1202: "Characterization of HCV Variants in Non-SVR Patients in the REALIZE Study Suggests that Telaprevir Exhibits a Consistent resistance profile Irrespective of a Lead-in", April 2, 2011, 12:30 — 1:30 p.m. CET.
• #1244: "The Pharmacokinetic Interaction between Methadone and the Investigational HCV Protease Inhibitor Telaprevir"; April 2, 2011, 12:30 — 1:30 p.m. CET.
• #1245: "The Effect of Severe Renal Impairment on the Pharmacokinetics of the Investigational HCV Protease Inhibitor Telaprevir"; April 2, 2011, 12:30 — 1:30 p.m. CET.
• #1208: "Impact of Telaprevir-based Treatment Regimens on Fatigue in Genotype 1 HCV Treatment-naïve Patients: Results from ADVANCE and ILLUMINATE Studies"; April 2, 2011, 12:30 — 1:30 p.m. CET.
• #1242: "Long-term Follow-up of Chronic Hepatitis C Infected Patients Treated with Telaprevir: Evaluation of Persistence of Resistant Variants by Ultra-deep Sequencing"; April 2, 2011, 12:30 — 1:30 p.m. CET.
About Telaprevir and VX-222
Vertex has two oral medicines in late-stage development for the treatment of hepatitis C: telaprevir and VX-222. Telaprevir is an investigational, oral inhibitor that acts directly on the HCV protease, an enzyme essential for viral replication. To date, more than 2,500 people with genotype 1 hepatitis C have received telaprevir in Phase 2 and Phase 3 studies. Vertex has received priority review for its applications for the approval of telaprevir by the U.S. FDA and Health Canada.
Vertex is developing telaprevir in collaboration with Tibotec BVBA and Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America. Through its affiliate, Janssen, Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries.
VX-222 is an investigational, oral, non-nucleoside inhibitor of HCV NS5B polymerase. VX-222 is currently being evaluated in combination with telaprevir, pegylated-interferon and ribavirin in a Phase 2 study. Vertex has worldwide commercial rights for VX-222.
About Hepatitis C
Hepatitis C is a serious liver disease caused by the hepatitis C virus, which is spread through direct contact with the blood of infected people and ultimately affects the liver.1 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.1 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.1 Approximately 60 percent of genotype 1 hepatitis C patients who undergo treatment with an initial 48-week regimen with pegylated-interferon and ribavirin, the currently approved medicines, do not achieve SVR,2,3,4 or viral cure.5 If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.6,7,8.9,10
More than 170 million people worldwide are chronically infected with hepatitis C. In the United States, up to 3.9 million people have chronic hepatitis C and of those, 75 percent are unaware of their infection.11 The majority of people with hepatitis C in the United States were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.10 Hepatitis C is the leading cause of liver transplantations in the United States and is reported to contribute to 4,600 to 12,000 deaths annually.7 By 2029, total annual medical costs in the United States for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.10
PEGASYS® and COPEGUS® are registered trademarks of Hoffman-LA Roche.
Special Note Regarding Forward-looking Statements
This press release contains forward-looking statements regarding the data from clinical trials involving telaprevir and/or VX-222 that Vertex expects to feature in poster and oral presentations at EASL, March 30 to April 3, 2011. While Vertex believes these data will be presented at EASL, it is possible that future developments could adversely affect the content, timing or form of those presentations.
About Vertex
Vertex creates new possibilities in medicine. Our team aims to discover, develop and commercialize innovative therapies so people with serious diseases can lead better lives.
Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, epilepsy and other life-threatening diseases.
Founded more than 20 years ago in Cambridge, MA, we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada.
For more information and to view Vertex's press releases, please visit http://www.vrtx.com/.
(VRTX - GEN)
References:
1 Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf. Accessed May 25, 2010.
2 Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965.
3 Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982.
4 McHutchison JG, Lawitz EJ, Shiffman ML, et al; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593.
5 Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.
6 Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).
7 Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW. Aging of hepatitis C virus (HCV)-infected persons in the United States: A multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010;138:513-521.
8 Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009;50(6):1750-1755.
9 Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.
10 Pyenson B, Fitch K, Iwasaki K. Consequences of hepatitis C virus (HCV): Costs of a baby boomer epidemic of liver disease. http://www.natap.org/2009/HCV/051809_01.htm. Updated May 2009. This report was commissioned by Vertex Pharmaceuticals, Inc.
11 Institute of Medicine of the National Academies. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Colvin HM and Mitchell AE, ed. http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx. Updated January 11, 2010. Accessed May 25, 2010.
Vertex Contacts:
Media:
Dawn Kalmar, 617-444-6992
or
Amy Pasqua, 617-444-6992
or
Zachry Barber, 617-444-6992
mediainfo@vrtx.com
or
Investors:
Michael Partridge, 617-444-6108
or
Lora Pike, 617-444-6755
or
Matthew Osborne, 617-444-6057
Source: Vertex Pharmaceuticals
News Provided by Acquire Media
Source
March 8, 2011
Interventional and combined approaches show promise in advanced liver Cancer
03/07/2011
Emerging interventional techniques appear promising for the treatment of hepatic tumours, even those at advanced stages. Attendees at the special focus session on transarterial procedures, taking place today at ECR, will find out just how far these techniques, as well as combined approaches, have gone.
Surgery and liver transplantation are being widely used to treat hepatocellular carcinoma (HCC), incidence of which has increased steadily, particularly due to the spread of the hepatitis C virus.
For around 80% of liver cancer patients, surgical options are no longer viable once the disease has been diagnosed, which means the patients become candidates for interventional approaches. Radiofrequency (RF) ablation is an effective option for patients with early-stage HCC, particularly if the tumour is no larger than 3–5 cm in diameter. For patients at an intermediate or advanced stage, because HCC is highly chemoresistant, the traditional method of classical systemic infusion chemotherapy is not very effective.
Chemotherapeutic agents such as doxorubicin must thus be infused locally in high concentrations into the artery supplying the tumour. After local application using a catheter, arterial flow to the tumour must be blocked by embolisation. This method, transarterial chemo-embolisation (TACE), has shown promise in randomised trials. Furthermore, drug-eluting beads allow small particles to be loaded with the chemotherapeutic agent to transport doxorubicin directly into the tumour, blocking arterial flow at the same time. Results published from a European multicentre randomised study (Johannes Lammer et al, Cardiovasc. Intervent. Radiol. 2009) show improved outcome compared to conventional TACE. Drug-eluting beads used with doxorubicin are now attracting attention as a palliative life-prolonging treatment. Compared with conventional TACE, drug-eluting beads have significantly fewer adverse side effects because the therapeutic agent remains in the tumour and does not circulate in the patient’s body.
“In terms of therapy options, this is likely to be news to many radiologists. It’s important for them to know that even for patients with advanced tumours there is now a viable treatment,” said session moderator Prof. Johannes Lammer, director of cardiovascular and interventional radiology at Vienna’s Medical University.
Another study published last year in Cardiovascular Interventional Radiology by Dr. Katarina Malagari demonstrated that chemo-embolisation using drug-eluting beads was significantly better in terms of subjective patient response and time to progression compared to bland embolisation.
Also under evaluation in large European multicentre studies is another therapeutic option that involves radioembolisation using beta-emitting Yttrium particles injected into the tumour-feeding artery. This highly effective local radiation can kill the tumour cells without damaging the liver. Additionally, therapies combining TACE with drug-eluting beads and RF ablation are being studied in a multicentre randomised trial now in its second year.
“TACE can first reduce the size of the tumour, so that those patients who aren’t candidates for surgery, or whose tumours are a little too large for ablation, can still profit from curative ablation rather than palliative treatment,” Lammer said.
“The efficacy of a combination therapy, including RFA plus the intra-arterial administration of drug-eluting beads has been recently demonstrated, while the use of intravenously administered, thermally sensitive drug carriers is currently being explored,” added Professor Riccardo Lencioni, Director of Diagnostic Imaging and Intervention at Cisanello University Hospital in Pisa. Experimental studies in animal tumour models have shown that lowering the temperature threshold at which cell death occurs by combining sublethal heating with cell exposure to chemotherapeutic agents is an attractive alternate strategy for increasing tumour necrosis.
Despite the advances in local treatment, the long-term outcome of treated patients remains unsatisfactory because new tumours emerge within five years in about 80% of the cases. Adjuvant molecular targeted therapies with anti-angiogenic and anti-proliferative activity may prove useful in preventing early recurrence after successful ablation. Clinical trials of these methods are currently ongoing. Surgery remains the gold standard in HCC therapy. But if research over the next couple of years proves that a combined approach is effective, its routine use in the clinical setting will increase, to the benefit of patients, experts predict.
Source
Emerging interventional techniques appear promising for the treatment of hepatic tumours, even those at advanced stages. Attendees at the special focus session on transarterial procedures, taking place today at ECR, will find out just how far these techniques, as well as combined approaches, have gone.
Surgery and liver transplantation are being widely used to treat hepatocellular carcinoma (HCC), incidence of which has increased steadily, particularly due to the spread of the hepatitis C virus.
For around 80% of liver cancer patients, surgical options are no longer viable once the disease has been diagnosed, which means the patients become candidates for interventional approaches. Radiofrequency (RF) ablation is an effective option for patients with early-stage HCC, particularly if the tumour is no larger than 3–5 cm in diameter. For patients at an intermediate or advanced stage, because HCC is highly chemoresistant, the traditional method of classical systemic infusion chemotherapy is not very effective.
Chemotherapeutic agents such as doxorubicin must thus be infused locally in high concentrations into the artery supplying the tumour. After local application using a catheter, arterial flow to the tumour must be blocked by embolisation. This method, transarterial chemo-embolisation (TACE), has shown promise in randomised trials. Furthermore, drug-eluting beads allow small particles to be loaded with the chemotherapeutic agent to transport doxorubicin directly into the tumour, blocking arterial flow at the same time. Results published from a European multicentre randomised study (Johannes Lammer et al, Cardiovasc. Intervent. Radiol. 2009) show improved outcome compared to conventional TACE. Drug-eluting beads used with doxorubicin are now attracting attention as a palliative life-prolonging treatment. Compared with conventional TACE, drug-eluting beads have significantly fewer adverse side effects because the therapeutic agent remains in the tumour and does not circulate in the patient’s body.
“In terms of therapy options, this is likely to be news to many radiologists. It’s important for them to know that even for patients with advanced tumours there is now a viable treatment,” said session moderator Prof. Johannes Lammer, director of cardiovascular and interventional radiology at Vienna’s Medical University.
Another study published last year in Cardiovascular Interventional Radiology by Dr. Katarina Malagari demonstrated that chemo-embolisation using drug-eluting beads was significantly better in terms of subjective patient response and time to progression compared to bland embolisation.
Also under evaluation in large European multicentre studies is another therapeutic option that involves radioembolisation using beta-emitting Yttrium particles injected into the tumour-feeding artery. This highly effective local radiation can kill the tumour cells without damaging the liver. Additionally, therapies combining TACE with drug-eluting beads and RF ablation are being studied in a multicentre randomised trial now in its second year.
“TACE can first reduce the size of the tumour, so that those patients who aren’t candidates for surgery, or whose tumours are a little too large for ablation, can still profit from curative ablation rather than palliative treatment,” Lammer said.
“The efficacy of a combination therapy, including RFA plus the intra-arterial administration of drug-eluting beads has been recently demonstrated, while the use of intravenously administered, thermally sensitive drug carriers is currently being explored,” added Professor Riccardo Lencioni, Director of Diagnostic Imaging and Intervention at Cisanello University Hospital in Pisa. Experimental studies in animal tumour models have shown that lowering the temperature threshold at which cell death occurs by combining sublethal heating with cell exposure to chemotherapeutic agents is an attractive alternate strategy for increasing tumour necrosis.
Despite the advances in local treatment, the long-term outcome of treated patients remains unsatisfactory because new tumours emerge within five years in about 80% of the cases. Adjuvant molecular targeted therapies with anti-angiogenic and anti-proliferative activity may prove useful in preventing early recurrence after successful ablation. Clinical trials of these methods are currently ongoing. Surgery remains the gold standard in HCC therapy. But if research over the next couple of years proves that a combined approach is effective, its routine use in the clinical setting will increase, to the benefit of patients, experts predict.
Source
Positive Phase 2 Interim Data from First Study of Telaprevir in People Co-Infected with Hepatitis C and HIV Presented at CROI Conference
CROI: Clinical Pharmacology of Boceprevir: Metabolism, Excretion, and Drug-Drug Interactions - (03/2/11)
CROI: Pharmacokinetic Interactions Between Antiretroviral Agents and the Investigational HCV Protease Inhibitor Telaprevir in Healthy Volunteers - (03/2/11)
from Jules of NATAP: the study was done in patients on Reyataz or efavirenz, darunavir and other protease inhibitors are not to be used right now with telaprevir due t drug drug interactions, although darunavir will be revisited, raltegravir interactions will soon be studied but an interaction with telaprevir is not expected.
- Early results from ongoing study showed that the hepatitis C virus was undetectable by week 4 in 70% of people treated with telaprevir-based combination therapy -
BOSTON--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) announced today interim results from an ongoing, two-part (A and B), Phase 2 study evaluating telaprevir in combination with pegylated-interferon and ribavirin compared to pegylated-interferon and ribavirin alone in people who are infected with both genotype 1 hepatitis C virus (HCV) and human immunodeficiency virus (HIV), also known as HCV-HIV co-infection. All people in this study were new to hepatitis C treatment. Part A of the study is evaluating telaprevir in people who are not currently being treated with antiretroviral therapy (ART) for HIV infection. Part B of the study is evaluating telaprevir in people receiving Atripla® or a Reyataz®-based regimen for HIV. These initial HIV regimens were selected based on current HIV treatment guidelines1 and data from drug-drug interaction studies of telaprevir and commonly used ART medicines. Data from the co-infection study were presented today at the 18th Conference on Retroviruses and Opportunistic Infections (CROI) taking place February 27 to March 2, 2011 in Boston.
The primary endpoint of the study is to evaluate the safety and tolerability of telaprevir-based combination therapy in people co-infected with hepatitis C and HIV. The interim analysis was conducted when all patients had reached week 4 of treatment. At that time, 70 percent (n=26/37) of people in the study (Parts A and B) who received telaprevir-based combination therapy had undetectable hepatitis C virus by week 4 (rapid viral response, RVR) compared to 5 percent (n=1/22) of people who received pegylated-interferon and ribavirin alone. HIV viral load and CD4 counts were stable among patients receiving a telaprevir-based regimen. Adverse events that occurred more frequently (≥10% difference) in the telaprevir arms compared to placebo were pruritus, nausea, dizziness, pyrexia, anorexia and vomiting. The majority of adverse events were mild or moderate.
"Research in hepatitis C has shown that people who respond early to treatment have a higher likelihood of achieving a viral cure," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer at Vertex. "These interim results are encouraging because they showed a high proportion of people in the study had a rapid viral response to telaprevir. We will use what we are learning from this study to inform the design of a Phase 3 co-infection study of telaprevir planned for the end of the year."
Interim Study Results
Sixty people were enrolled in this Phase 2 study. At the time of the analysis, all study participants had reached week 4 of treatment and 69 percent of patients (n=41/59) had completed a week 12 assessment. Data on one patient were not available when the analysis was performed. The preliminary results from this study are based on an interim analysis of 59 patients. For the purposes of this analysis, the 12-week results do not include patients who were still on treatment but had not yet reached the 12-week time point in the study.
Atripla (efavirenz, tenofovir disoproxil fumarate and emtricitabine): TVR was dosed at 1,125 mg, every 8 hours (q8h).
Reyataz-based regimen (ritonavir-boosted atazanavir, tenofovir disoproxil fumarate and emtricitabine or lamivudine): TVR was dosed at 750 mg, every 8 hours (q8h).
*RVR: rapid viral response; undetectable (<25IU/mL undetectable by Roche COBAS Taqman HCV test) at week 4. **cEVR: complete early viral response; undetectable (<25IU/mL undetectable by Roche COBAS Taqman HCV test) at week 12.
+12 weeks of telaprevir (TVR), Pegasys® (PEG, pegylated-interferon alfa-2a) and Copegus® (RBV, ribavirin) followed by 36 weeks of only PEG and RBV. ++48 weeks of PEG and RBV only for hepatitis C treatment.
The most common adverse events (≥15% of people) regardless of treatment arm were fatigue, pruritus, nausea, headache, dizziness, pyrexia, anorexia, vomiting, diarrhea and chills. Of these adverse events, pruritus, nausea, dizziness, pyrexia, anorexia and vomiting occurred more frequently in the telaprevir arms (≥10% difference) compared to placebo. The majority of adverse events were mild or moderate. Two people (n=2/14, or 14 percent) in a telaprevir-based treatment arm who were also receiving a Reyataz-based regimen discontinued part or all of the hepatitis C treatment regimen due to adverse events. There were no discontinuations due to adverse events in any of the other treatment arms. Final sustained viral response (SVR, or viral cure) results from this study in all 60 people are expected in 2012.
About the Ongoing Phase 2 Study
This study is a Phase 2, two-part (A and B), randomized, double-blind, placebo-controlled, parallel group, multi-center study in people chronically infected with both genotype 1 hepatitis C virus and human immunodeficiency virus (HIV) who were new to hepatitis C treatment. The study enrolled 60 people. This interim analysis includes 59 people who received at least one dose of telaprevir or placebo and for whom data were available. The primary endpoint of the study is to evaluate the safety and tolerability of telaprevir-based combination therapy in people co-infected with hepatitis C and HIV. A secondary endpoint is to evaluate rates of SVR. The study is being conducted by Vertex in collaboration with Tibotec BVBA.
People in Part A and Part B of the study were randomized to receive either 12 weeks of telaprevir or placebo in combination with peginterferon alfa-2a (Pegasys®) and ribavirin (Copegus®) followed by 36 weeks of peginterferon alfa-2a and ribavirin alone. Part A (n=13) of the study enrolled people who were not receiving antiretroviral therapy (ART) for the treatment of HIV. Part B (n=47) enrolled people who were being treated for HIV with either Atripla (n=24) or a Reyataz-based regimen (n=23). For people in Part B who were receiving Atripla, telaprevir was dosed at 1,125 mg every eight hours (q8h) based on drug-drug interaction data from a Phase 1 study. For people in Part B who were receiving a Reyataz-based regimen telaprevir was dosed at 750 mg every eight hours (q8h). The ART regimens evaluated in this study were selected based on current HIV treatment guidelines from the U.S. Department of Health and Human Services and International AIDS Society and drug-drug interaction studies of telaprevir and HIV medicines.
Additional Data Presented at CROI: Results from Multiple Phase 1 Drug-Drug Interaction Studies
Results from multiple Phase 1 studies evaluating the drug-drug interactions between telaprevir and commonly used HIV medicines were also presented at the CROI conference. The HIV medicines evaluated in these studies included ritonavir, ritonavir-boosted protease inhibitors, a non-nucleoside reverse-transcriptase inhibitor (NNRTI) and a nucleotide analogue reverse-transcriptase inhibitor (NRTI). The ritonavir-boosted protease inhibitors studied were lopinavir, atazanavir, darunavir and fosamprenavir; the NNRTI was efavirenz and the NRTI was tenofovir.
Results from a Phase 1 study of telaprevir and ritonavir (Abstract #629)
· No significant boosting of telaprevir exposure by low-dose ritonavir was observed when telaprevir was given in combination with ritonavir. Results from multiple Phase 1 studies evaluating the interaction between telaprevir and ritonavir-boosted protease inhibitors, NNRTIs and NRTIs (Abstract #119)
· Telaprevir slightly increased the exposure to ritonavir-boosted atazanavir. Ritonavir-boosted atazanavir slightly reduced the exposure to telaprevir. This interaction was not considered to be clinically significant. A HIV regimen that includes ritonavir-boosted atazanavir is being evaluated in an ongoing Phase 2 study of telaprevir-based therapy in people infected with both hepatitis C and HIV.
· An interaction between efavirenz and telaprevir (750 mg, every eight hours) was observed, but a higher dose of telaprevir (1,125 mg, every eight hours) could largely offset the interaction. This higher dose of telaprevir is being evaluated as part of an ongoing Phase 2 study in people co-infected with hepatitis C and HIV who are also receiving efavirenz as part of their HIV treatment.
· Significant interactions were observed between telaprevir and boosted-lopinavir, darunavir and fosamprenavir, such that telaprevir-based combination therapy is not currently being evaluated for people taking these HIV medicines.
About Telaprevir
Telaprevir is an investigational, oral inhibitor that acts directly on the HCV protease, an enzyme essential for viral replication. To date, more than 2,500 people with genotype 1 hepatitis C have received telaprevir in Phase 2 and Phase 3 studies.
Vertex is developing telaprevir in collaboration with Tibotec BVBA and Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America. Through its affiliate, Janssen, Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries.
Telaprevir has been granted priority review by the U.S. Food and Drug Administration (FDA) and by Health Canada and accelerated assessment by the European Medicines Agency for the treatment of people chronically infected with genotype 1 hepatitis C virus (HCV). The applications include data from three registrational studies, ADVANCE, ILLUMINATE and REALIZE, which evaluated telaprevir in people with hepatitis C who were new to treatment as well as those who did not achieve a viral cure after treatment with currently available medicines. For complete information on the clinical trials or a fact sheet on the trial designs visit: www.vrtx.com/press.cfm.
About Hepatitis C and HIV Co-Infection
There are 1 million people living with HIV in the United States.2 It's estimated that up to 30 percent of people living with HIV/AIDS are also infected with hepatitis C. 3 There have been dramatic improvements in the treatment of HIV and the prognosis for people living with HIV. However, liver disease progresses more rapidly in people co-infected with hepatitis C and HIV, with an increased rate of progression to cirrhosis, decompensated liver disease, hepatocellular carcinoma and death.3,4,5
About Hepatitis C
Hepatitis C is a serious liver disease caused by the hepatitis C virus, which is spread through direct contact with the blood of infected people and ultimately affects the liver.6 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.6 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.6 Approximately 60 percent of genotype 1 hepatitis C patients who undergo treatment with an initial 48-week regimen with pegylated-interferon and ribavirin, the currently approved medicines, do not achieve SVR,7,8,9 or viral cure.10 If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.11,12,13,14,15
More than 170 million people worldwide are chronically infected with hepatitis C. In the United States, nearly 4 million people have chronic hepatitis C and 75 percent of them are unaware of their infection.16 The majority of people with hepatitis C in the United States were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.15 Hepatitis C is the leading cause of liver transplantations in the United States and is reported to contribute to 4,600 to 12,000 deaths annually.12 By 2029, total annual medical costs in the United States for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.15 PEGASYS® and COPEGUS® are registered trademarks of Hoffman-LA Roche. Reyataz® is a registered trademark of Bristol-Myers Squibb.
Atripla® is a registered trademark of Bristol-Myers Squibb and Gilead Sciences, LLC.
Special Note Regarding Forward-looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including statements regarding (i) the interim results being encouraging because they showed a high proportion of people in the study had a rapid response to telaprevir; (ii) Vertex's plan to use what it is learning from the study to inform a Phase 3 co-infection study of telaprevir planned for the end of 2011; (iii) expectations that final SVR results from the study will be available in 2012 and (iv) the possibility that a higher dose of telaprevir could largely offset the interaction observed between efavirenz and telaprevir. While Vertex believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, the risks that efforts to develop telaprevir as a treatment for patients co-infected with genotype 1 HCV and HIV may not proceed due to technical, scientific, commercial, financial or other reasons; that final outcomes, including SVR rates, from this clinical trial and any future clinical trials of telaprevir in patients with HCV-HIV co-infection may not be favorable; that RVR and cEVR may not be predictive of SVR in patients with HCV-HIV co-infection and the other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through Vertex's website at http://www.vrtx.com/. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.
About Vertex
Vertex creates new possibilities in medicine. Our team aims to discover, develop and commercialize innovative therapies so people with serious diseases can lead better lives.
Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, epilepsy and other life-threatening diseases.
Founded more than 20 years ago in Cambridge, MA, we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada. For more information and to view Vertex's press releases, please visit http://www.vrtx.com/.
(VRTX - GEN)
References:
1 2010 Guidelines for Antiretroviral Treatment of HIV From the International AIDS Society-USA Panel JAMA. 2010;304(17):1897
2 Centers for Disease Control and Prevention. HIV/AIDS and Viral Hepatitis. Available at http://www.cdc.gov/hepatitis/Populations/hiv.htm. Accessed February 17, 2011.
3 Health Resources and Services Administration. Care and Treatment for Hepatitis C and HIV Co-infection. Available at http://hab.hrsa.gov/tools/coinfection/coinfectionsub.html and http://hab.hrsa.gov/tools/coinfection/index.html Accessed February 28, 2011.
4 Benhamou Y, Bochet M, Di Martino V, Charlotte F, Azria F, Coutellier A, et al. Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients. Hepatology 1999;30(4):1054-58.
5 Martin-Carbonero L, Benhamou Y, Puoti M, Berenguer J, Mallolas J, Quereda C, et al. Incidence and predictors of severe liver fibrosis in human immunodeficiency virus-infected patients with chronic hepatitis C: a European collaborative study. CID 2004;38:128-33.
6Martinez-Sierra C, Arizcorreta A, Diaz F, Roldan R, Martin-Herrera M, Perez- Guzman E, et al. Progression of chronic hepatitis C to liver fibrosis and cirrhosis in patients coinfected with hepatitis C virus and human immunodeficiency virus. CID 2003;36:491-8.
7 Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf. Accessed May 25, 2010.
8 Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965.
9 Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982. 10 McHutchison JG, Lawitz EJ, Shiffman ML, et al; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593.
11 Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.
12 Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).
13 Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW. Aging of hepatitis C virus (HCV)-infected persons in the United States: A multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010;138:513-521.
14Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009;50(6):1750-1755.
15Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007;147: 677-684.
16 Pyenson B, Fitch K, Iwasaki K. Consequences of hepatitis C virus (HCV): Costs of a baby boomer epidemic of liver disease. http://www.natap.org/2009/HCV/051809_01.htm. Updated May 2009. This report was commissioned by Vertex Pharmaceuticals, Inc. Source: Vertex Pharmaceuticals Incorporated
Source
CROI: Pharmacokinetic Interactions Between Antiretroviral Agents and the Investigational HCV Protease Inhibitor Telaprevir in Healthy Volunteers - (03/2/11)
from Jules of NATAP: the study was done in patients on Reyataz or efavirenz, darunavir and other protease inhibitors are not to be used right now with telaprevir due t drug drug interactions, although darunavir will be revisited, raltegravir interactions will soon be studied but an interaction with telaprevir is not expected.
- Early results from ongoing study showed that the hepatitis C virus was undetectable by week 4 in 70% of people treated with telaprevir-based combination therapy -
BOSTON--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) announced today interim results from an ongoing, two-part (A and B), Phase 2 study evaluating telaprevir in combination with pegylated-interferon and ribavirin compared to pegylated-interferon and ribavirin alone in people who are infected with both genotype 1 hepatitis C virus (HCV) and human immunodeficiency virus (HIV), also known as HCV-HIV co-infection. All people in this study were new to hepatitis C treatment. Part A of the study is evaluating telaprevir in people who are not currently being treated with antiretroviral therapy (ART) for HIV infection. Part B of the study is evaluating telaprevir in people receiving Atripla® or a Reyataz®-based regimen for HIV. These initial HIV regimens were selected based on current HIV treatment guidelines1 and data from drug-drug interaction studies of telaprevir and commonly used ART medicines. Data from the co-infection study were presented today at the 18th Conference on Retroviruses and Opportunistic Infections (CROI) taking place February 27 to March 2, 2011 in Boston.
The primary endpoint of the study is to evaluate the safety and tolerability of telaprevir-based combination therapy in people co-infected with hepatitis C and HIV. The interim analysis was conducted when all patients had reached week 4 of treatment. At that time, 70 percent (n=26/37) of people in the study (Parts A and B) who received telaprevir-based combination therapy had undetectable hepatitis C virus by week 4 (rapid viral response, RVR) compared to 5 percent (n=1/22) of people who received pegylated-interferon and ribavirin alone. HIV viral load and CD4 counts were stable among patients receiving a telaprevir-based regimen. Adverse events that occurred more frequently (≥10% difference) in the telaprevir arms compared to placebo were pruritus, nausea, dizziness, pyrexia, anorexia and vomiting. The majority of adverse events were mild or moderate.
"Research in hepatitis C has shown that people who respond early to treatment have a higher likelihood of achieving a viral cure," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer at Vertex. "These interim results are encouraging because they showed a high proportion of people in the study had a rapid viral response to telaprevir. We will use what we are learning from this study to inform the design of a Phase 3 co-infection study of telaprevir planned for the end of the year."
Interim Study Results
Sixty people were enrolled in this Phase 2 study. At the time of the analysis, all study participants had reached week 4 of treatment and 69 percent of patients (n=41/59) had completed a week 12 assessment. Data on one patient were not available when the analysis was performed. The preliminary results from this study are based on an interim analysis of 59 patients. For the purposes of this analysis, the 12-week results do not include patients who were still on treatment but had not yet reached the 12-week time point in the study.
Atripla (efavirenz, tenofovir disoproxil fumarate and emtricitabine): TVR was dosed at 1,125 mg, every 8 hours (q8h).
Reyataz-based regimen (ritonavir-boosted atazanavir, tenofovir disoproxil fumarate and emtricitabine or lamivudine): TVR was dosed at 750 mg, every 8 hours (q8h).
*RVR: rapid viral response; undetectable (<25IU/mL undetectable by Roche COBAS Taqman HCV test) at week 4. **cEVR: complete early viral response; undetectable (<25IU/mL undetectable by Roche COBAS Taqman HCV test) at week 12.
+12 weeks of telaprevir (TVR), Pegasys® (PEG, pegylated-interferon alfa-2a) and Copegus® (RBV, ribavirin) followed by 36 weeks of only PEG and RBV. ++48 weeks of PEG and RBV only for hepatitis C treatment.
The most common adverse events (≥15% of people) regardless of treatment arm were fatigue, pruritus, nausea, headache, dizziness, pyrexia, anorexia, vomiting, diarrhea and chills. Of these adverse events, pruritus, nausea, dizziness, pyrexia, anorexia and vomiting occurred more frequently in the telaprevir arms (≥10% difference) compared to placebo. The majority of adverse events were mild or moderate. Two people (n=2/14, or 14 percent) in a telaprevir-based treatment arm who were also receiving a Reyataz-based regimen discontinued part or all of the hepatitis C treatment regimen due to adverse events. There were no discontinuations due to adverse events in any of the other treatment arms. Final sustained viral response (SVR, or viral cure) results from this study in all 60 people are expected in 2012.
About the Ongoing Phase 2 Study
This study is a Phase 2, two-part (A and B), randomized, double-blind, placebo-controlled, parallel group, multi-center study in people chronically infected with both genotype 1 hepatitis C virus and human immunodeficiency virus (HIV) who were new to hepatitis C treatment. The study enrolled 60 people. This interim analysis includes 59 people who received at least one dose of telaprevir or placebo and for whom data were available. The primary endpoint of the study is to evaluate the safety and tolerability of telaprevir-based combination therapy in people co-infected with hepatitis C and HIV. A secondary endpoint is to evaluate rates of SVR. The study is being conducted by Vertex in collaboration with Tibotec BVBA.
People in Part A and Part B of the study were randomized to receive either 12 weeks of telaprevir or placebo in combination with peginterferon alfa-2a (Pegasys®) and ribavirin (Copegus®) followed by 36 weeks of peginterferon alfa-2a and ribavirin alone. Part A (n=13) of the study enrolled people who were not receiving antiretroviral therapy (ART) for the treatment of HIV. Part B (n=47) enrolled people who were being treated for HIV with either Atripla (n=24) or a Reyataz-based regimen (n=23). For people in Part B who were receiving Atripla, telaprevir was dosed at 1,125 mg every eight hours (q8h) based on drug-drug interaction data from a Phase 1 study. For people in Part B who were receiving a Reyataz-based regimen telaprevir was dosed at 750 mg every eight hours (q8h). The ART regimens evaluated in this study were selected based on current HIV treatment guidelines from the U.S. Department of Health and Human Services and International AIDS Society and drug-drug interaction studies of telaprevir and HIV medicines.
Additional Data Presented at CROI: Results from Multiple Phase 1 Drug-Drug Interaction Studies
Results from multiple Phase 1 studies evaluating the drug-drug interactions between telaprevir and commonly used HIV medicines were also presented at the CROI conference. The HIV medicines evaluated in these studies included ritonavir, ritonavir-boosted protease inhibitors, a non-nucleoside reverse-transcriptase inhibitor (NNRTI) and a nucleotide analogue reverse-transcriptase inhibitor (NRTI). The ritonavir-boosted protease inhibitors studied were lopinavir, atazanavir, darunavir and fosamprenavir; the NNRTI was efavirenz and the NRTI was tenofovir.
Results from a Phase 1 study of telaprevir and ritonavir (Abstract #629)
· No significant boosting of telaprevir exposure by low-dose ritonavir was observed when telaprevir was given in combination with ritonavir. Results from multiple Phase 1 studies evaluating the interaction between telaprevir and ritonavir-boosted protease inhibitors, NNRTIs and NRTIs (Abstract #119)
· Telaprevir slightly increased the exposure to ritonavir-boosted atazanavir. Ritonavir-boosted atazanavir slightly reduced the exposure to telaprevir. This interaction was not considered to be clinically significant. A HIV regimen that includes ritonavir-boosted atazanavir is being evaluated in an ongoing Phase 2 study of telaprevir-based therapy in people infected with both hepatitis C and HIV.
· An interaction between efavirenz and telaprevir (750 mg, every eight hours) was observed, but a higher dose of telaprevir (1,125 mg, every eight hours) could largely offset the interaction. This higher dose of telaprevir is being evaluated as part of an ongoing Phase 2 study in people co-infected with hepatitis C and HIV who are also receiving efavirenz as part of their HIV treatment.
· Significant interactions were observed between telaprevir and boosted-lopinavir, darunavir and fosamprenavir, such that telaprevir-based combination therapy is not currently being evaluated for people taking these HIV medicines.
About Telaprevir
Telaprevir is an investigational, oral inhibitor that acts directly on the HCV protease, an enzyme essential for viral replication. To date, more than 2,500 people with genotype 1 hepatitis C have received telaprevir in Phase 2 and Phase 3 studies.
Vertex is developing telaprevir in collaboration with Tibotec BVBA and Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America. Through its affiliate, Janssen, Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries.
Telaprevir has been granted priority review by the U.S. Food and Drug Administration (FDA) and by Health Canada and accelerated assessment by the European Medicines Agency for the treatment of people chronically infected with genotype 1 hepatitis C virus (HCV). The applications include data from three registrational studies, ADVANCE, ILLUMINATE and REALIZE, which evaluated telaprevir in people with hepatitis C who were new to treatment as well as those who did not achieve a viral cure after treatment with currently available medicines. For complete information on the clinical trials or a fact sheet on the trial designs visit: www.vrtx.com/press.cfm.
About Hepatitis C and HIV Co-Infection
There are 1 million people living with HIV in the United States.2 It's estimated that up to 30 percent of people living with HIV/AIDS are also infected with hepatitis C. 3 There have been dramatic improvements in the treatment of HIV and the prognosis for people living with HIV. However, liver disease progresses more rapidly in people co-infected with hepatitis C and HIV, with an increased rate of progression to cirrhosis, decompensated liver disease, hepatocellular carcinoma and death.3,4,5
About Hepatitis C
Hepatitis C is a serious liver disease caused by the hepatitis C virus, which is spread through direct contact with the blood of infected people and ultimately affects the liver.6 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.6 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.6 Approximately 60 percent of genotype 1 hepatitis C patients who undergo treatment with an initial 48-week regimen with pegylated-interferon and ribavirin, the currently approved medicines, do not achieve SVR,7,8,9 or viral cure.10 If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.11,12,13,14,15
More than 170 million people worldwide are chronically infected with hepatitis C. In the United States, nearly 4 million people have chronic hepatitis C and 75 percent of them are unaware of their infection.16 The majority of people with hepatitis C in the United States were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.15 Hepatitis C is the leading cause of liver transplantations in the United States and is reported to contribute to 4,600 to 12,000 deaths annually.12 By 2029, total annual medical costs in the United States for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.15 PEGASYS® and COPEGUS® are registered trademarks of Hoffman-LA Roche. Reyataz® is a registered trademark of Bristol-Myers Squibb.
Atripla® is a registered trademark of Bristol-Myers Squibb and Gilead Sciences, LLC.
Special Note Regarding Forward-looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including statements regarding (i) the interim results being encouraging because they showed a high proportion of people in the study had a rapid response to telaprevir; (ii) Vertex's plan to use what it is learning from the study to inform a Phase 3 co-infection study of telaprevir planned for the end of 2011; (iii) expectations that final SVR results from the study will be available in 2012 and (iv) the possibility that a higher dose of telaprevir could largely offset the interaction observed between efavirenz and telaprevir. While Vertex believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, the risks that efforts to develop telaprevir as a treatment for patients co-infected with genotype 1 HCV and HIV may not proceed due to technical, scientific, commercial, financial or other reasons; that final outcomes, including SVR rates, from this clinical trial and any future clinical trials of telaprevir in patients with HCV-HIV co-infection may not be favorable; that RVR and cEVR may not be predictive of SVR in patients with HCV-HIV co-infection and the other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through Vertex's website at http://www.vrtx.com/. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.
About Vertex
Vertex creates new possibilities in medicine. Our team aims to discover, develop and commercialize innovative therapies so people with serious diseases can lead better lives.
Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, epilepsy and other life-threatening diseases.
Founded more than 20 years ago in Cambridge, MA, we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada. For more information and to view Vertex's press releases, please visit http://www.vrtx.com/.
(VRTX - GEN)
References:
1 2010 Guidelines for Antiretroviral Treatment of HIV From the International AIDS Society-USA Panel JAMA. 2010;304(17):1897
2 Centers for Disease Control and Prevention. HIV/AIDS and Viral Hepatitis. Available at http://www.cdc.gov/hepatitis/Populations/hiv.htm. Accessed February 17, 2011.
3 Health Resources and Services Administration. Care and Treatment for Hepatitis C and HIV Co-infection. Available at http://hab.hrsa.gov/tools/coinfection/coinfectionsub.html and http://hab.hrsa.gov/tools/coinfection/index.html Accessed February 28, 2011.
4 Benhamou Y, Bochet M, Di Martino V, Charlotte F, Azria F, Coutellier A, et al. Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients. Hepatology 1999;30(4):1054-58.
5 Martin-Carbonero L, Benhamou Y, Puoti M, Berenguer J, Mallolas J, Quereda C, et al. Incidence and predictors of severe liver fibrosis in human immunodeficiency virus-infected patients with chronic hepatitis C: a European collaborative study. CID 2004;38:128-33.
6Martinez-Sierra C, Arizcorreta A, Diaz F, Roldan R, Martin-Herrera M, Perez- Guzman E, et al. Progression of chronic hepatitis C to liver fibrosis and cirrhosis in patients coinfected with hepatitis C virus and human immunodeficiency virus. CID 2003;36:491-8.
7 Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf. Accessed May 25, 2010.
8 Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965.
9 Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982. 10 McHutchison JG, Lawitz EJ, Shiffman ML, et al; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593.
11 Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.
12 Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).
13 Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW. Aging of hepatitis C virus (HCV)-infected persons in the United States: A multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010;138:513-521.
14Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009;50(6):1750-1755.
15Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007;147: 677-684.
16 Pyenson B, Fitch K, Iwasaki K. Consequences of hepatitis C virus (HCV): Costs of a baby boomer epidemic of liver disease. http://www.natap.org/2009/HCV/051809_01.htm. Updated May 2009. This report was commissioned by Vertex Pharmaceuticals, Inc. Source: Vertex Pharmaceuticals Incorporated
Source
February 15, 2011
What Would You Do If You Witnessed AIDS Discrimination?
By MARY BETH LAVENDER
Feb. 15, 2011
Customers React as HIV-Positive Actor Faces Prejudice at Diner in WWYD Scenario
It's been exactly thirty years since AIDS -- the acquired immune deficiency syndrome -- was first recognized in the United States. Since then, more than half a million people have died from the disease in this country alone, and more than a million Americans are currently living with HIV, the virus that causes AIDS.
In the early days of the epidemic, little was known about what caused the illness or how it was transmitted, and rumors soon circulated that it could be spread by sneezing, a handshake, kissing or even sharing utensils. Growing public fear led some to call for a quarantine of those diagnosed with the disease. And in 1985, a 13-year-old boy named Ryan White, who contracted AIDS from a blood transfusion, made headlines when he was banned from attending school. It was just one of many instances of people living with AIDS being stigmatized and ostracized. Three decades later, we wanted to see if people still misunderstood the disease. Would they feel uneasy if they were near an individual who they knew was carrying the AIDS virus? We decided to find out and brought our hidden cameras to the Colonial Diner in Lyndhurst, N.J.
In our first scene, our hired actress playing the waitress engages in conversation with another actor, who is playing a customer who happens to be HIV positive. It's only partly an act: the actor, Daniel Logan, is HIV positive in real life. In conversation, Daniel reveals to the waitress that he is HIV positive. Vince, another actor hired by "WWYD" to play a customer, seated at the next stool at the counter, is alarmed.
"You have AIDS?" Vince asks. "No. That's different, it's HIV," Daniel replies. Vince then gets up from his seat and moves away from Daniel. Reactions like this were not uncommon 30 years ago. So how will it play today? Customer Joe Smith comforts Daniel and encourages him to ignore our rude actor, saying, "Don't talk to him. It doesn't pay. He doesn't understand."
Man Agrees That AIDS Might Be Spread Like Common Cold
But another customer seems to agree with our hypochondriac actor, Vince, who argues that the disease could be spread the same way a common cold or flu is: by sneezing or coughing. "He's right in a way," the customer tells Vince. "Think about it. If I get the flu and I sneeze on you, you're going to get the flu," and he wonders if HIV is spread the same way.
He is not the only one who's not sure how HIV is spread. A recent nationwide study from the Kaiser Family Foundation found that more than a quarter of adults still believe the virus can be transmitted simply by sharing a drinking glass. This, despite decades of scientific evidence that shows that HIV is primarily spread through infected blood.
That lack of awareness doesn't surprise our actor, Daniel, who says he's heard it all. "Growing up in Long Island in the suburbs," says Daniel, "you hear, you know, ignorance like that all the time. I mean there's some people out there that either refuse to accept it and learn about it more," he says.
Back at the diner, as soon as our waitress, Traci, tries handing Vince the same menu Daniel was holding, Vince starts hurling inappropriate comments. This time, the restaurant is all ears.
"C'mon he touched it," Vince complains. "I don't want it."
"You think you can get this from something I touched?" Daniel asks. "I'm just telling you I don't want to take any chances," Vince says.
But not everyone feels the way our actor, Vince, does. In fact, fellow diner Kelly Rivera not only consoles Daniel, she invites him to sit and have lunch with her and her neighbor. Later, she tells John Quinones, "I thought he was being treated really badly, and nobody should be treated like that. That's terrible."
In another scene, we have our female actress play the role of the anxious diner to see how people will react. As she informs other diners sitting nearby that Daniel has AIDS, they seem more irritated with her.
Traci asks, "Nobody has a problem with this?" "No one has a problem with this!" customer Rick Gimello responds. "You should just leave," adds customer Janis Mitchell.
When we caught up with Rick Gimello later to get his thoughts, he tells Quinones, "This is 2011. You know? The world ought to be educated enough to know what's going on."
Source
February 14, 2011
Suicide risk in hepatitis C and during interferon-alpha therapy: a review and clinical update
Journal of Viral Hepatitis
Volume 18, Issue 3, pages 153–160, March 2011
S. Sockalingam 1,2,3, P. S. Links 3,4, S. E. Abbey 1,2,3
Article first published online: 10 NOV 2010
DOI: 10.1111/j.1365-2893.2010.01393.x
© 2010 Blackwell Publishing Ltd
Author Information
1 University Health Network, Toronto General Hospital, Toronto, ON, Canada
2 Medical Psychiatry Program, Toronto, ON, Canada
3 Department of Psychiatry, University of Toronto, Toronto, ON, Canada
4 Arthur Sommer Rotenberg Chair in Suicide Studies, Toronto, ON, Canada
* Correspondence: Sanjeev Sockalingam, University Health Network, Toronto General Hospital, 200 Elizabeth Street – 8EN-228, Toronto, ON M5G 2C4, Canada. E-mail: sanjeev.sockalingam@uhn.on.ca
Abstract
Keywords: depression; hepatitis C; interferon-alpha; suicide
Summary.Chronic hepatitis C (CHC) affects over 170 million individuals worldwide and is a growing public health concern. Despite the availability of CHC treatment, specifically interferon-α and ribavirin, treatment of CHC is limited by concerns about psychiatric side effects including risks of suicide. Although depression has been the focus of neuropsychiatric complications from interferon-alpha (IFNα), emerging evidence has contributed to our understanding of IFNα-induced suicidal ideation and attempts. Using Pubmed, we performed a literature review of all English articles published between 1989 and April 1, 2010 on suicide in untreated and IFNα-treated patients with CHC. References in all identified review articles were scanned and included in our review. A total of 17 articles were identified. Studies have suggested that the first 12 weeks of IFNα therapy are the high-risk period. Moreover, the emergence of suicidal ideation can be linked to neuropsychiatric abnormalities, specifically serotonin depletion. Pretreatment with antidepressant treatment should be reserved for high-risk groups, as this may reduce the risk of depression and thus decrease the suicide risk indirectly. Although there is a paucity of literature on suicide and suicide risk during IFNα therapy for CHC, recent studies on IFNα-induced depression have provided some potential insights into suicide in this patient population. Further research examining the effects of pharmacological and nonpharmacological interventions on suicide risk during IFNα treatment is needed.
Source
Volume 18, Issue 3, pages 153–160, March 2011
S. Sockalingam 1,2,3, P. S. Links 3,4, S. E. Abbey 1,2,3
Article first published online: 10 NOV 2010
DOI: 10.1111/j.1365-2893.2010.01393.x
© 2010 Blackwell Publishing Ltd
Author Information
1 University Health Network, Toronto General Hospital, Toronto, ON, Canada
2 Medical Psychiatry Program, Toronto, ON, Canada
3 Department of Psychiatry, University of Toronto, Toronto, ON, Canada
4 Arthur Sommer Rotenberg Chair in Suicide Studies, Toronto, ON, Canada
* Correspondence: Sanjeev Sockalingam, University Health Network, Toronto General Hospital, 200 Elizabeth Street – 8EN-228, Toronto, ON M5G 2C4, Canada. E-mail: sanjeev.sockalingam@uhn.on.ca
Abstract
Keywords: depression; hepatitis C; interferon-alpha; suicide
Summary.Chronic hepatitis C (CHC) affects over 170 million individuals worldwide and is a growing public health concern. Despite the availability of CHC treatment, specifically interferon-α and ribavirin, treatment of CHC is limited by concerns about psychiatric side effects including risks of suicide. Although depression has been the focus of neuropsychiatric complications from interferon-alpha (IFNα), emerging evidence has contributed to our understanding of IFNα-induced suicidal ideation and attempts. Using Pubmed, we performed a literature review of all English articles published between 1989 and April 1, 2010 on suicide in untreated and IFNα-treated patients with CHC. References in all identified review articles were scanned and included in our review. A total of 17 articles were identified. Studies have suggested that the first 12 weeks of IFNα therapy are the high-risk period. Moreover, the emergence of suicidal ideation can be linked to neuropsychiatric abnormalities, specifically serotonin depletion. Pretreatment with antidepressant treatment should be reserved for high-risk groups, as this may reduce the risk of depression and thus decrease the suicide risk indirectly. Although there is a paucity of literature on suicide and suicide risk during IFNα therapy for CHC, recent studies on IFNα-induced depression have provided some potential insights into suicide in this patient population. Further research examining the effects of pharmacological and nonpharmacological interventions on suicide risk during IFNα treatment is needed.
Source
HIV Regimens Similar but Not Equivalent
By Michael Smith, North American Correspondent, MedPage Today
Published: February 14, 2011
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston.
A large clinical trial fell short of showing that two commonly used approaches to a first anti-HIV treatment regimen are formally equivalent.
But the two -- based on either the ritonavir-boosted protease inhibitor atazanavir (Reyataz) or the non-nucleoside reverse transcriptase inhibitor efavirenz (Sustiva) -- still appeared to have similar efficacy, according to Eric Daar, MD, of Harbor-UCLA Medical Center in Torrance, Calif., and colleagues.
The failure to reach formal equivalence -- as defined before the study started -- was probably the result of a lower than expected rate of virologic failure two years into the study, Daar and colleagues reported online in Annals of Internal Medicine.
But a post-hoc analysis of the data suggested the probability of remaining free of failure differed by less than 10%, a threshold commonly used for defining equivalence, the researchers argued.
Treatment guidelines for initial HIV therapy suggest two nucleoside reverse transcriptase inhibitors combined with either a non-NRTI, a ritonavir-boosted protease inhibitor, or an integrase inhibitor, the researchers noted.
But there are limited data comparing atazanavir/ritonavir with efavirenz, they noted.
To help fill the gap, they conducted a randomized trial, in which the two lead compounds were added to common, once-daily combinations of nucleoside reverse transcriptase inhibitors -- either abacavir/lamivudine (Kivexa) or tenofovir/emtricitabine (Truvada).
The trial ran from September 2005 to November 2007, with a median of 138 weeks of follow-up, and the primary outcomes were time to virologic failure, safety, and tolerability.
All told, 1,857 patients were randomly assigned to one of the four treatment regimens and 1,331 completed the follow-up.
The primary efficacy hypothesis was that, within each of the NRTI arms, boosted atazanavir would be equivalent to efavirenz, Daar and colleagues noted.
The drugs were specified to be equivalent if a Cox proportional hazards model, using efavirenz as the reference, found the two-sided 95% confidence interval for the hazard ratio to be between 0.71 and 1.40.
But analysis showed:
• Among those randomized to the abacavir/lamivudine arms, the hazard ratio for time to virologic failure was 1.13 with a 95% confidence interval from 0.82 to 1.56. The difference was not statistically significant, at P=0.147.
• For those assigned to the tenofovir/emtricitabine arms, the hazard ratio was 1.01 with a 95% confidence interval from 0.70 to 1.46, which again was not significant, at P=0.37.
Although neither hazard ratio showed a significant difference, "neither met prespecified equivalence boundaries," the researchers reported.
However, analysis also showed that the probability of remaining free of virologic failure at week 96 was 83.4% for boosted atazanavir and 85.3% for efavirenz when they were combined with abacavir/lamivudine. The difference was -1.9 with a 95% confidence interval from -6.8 to 2.9, or 9.7 percentage points.
Values in the tenofovir/emtricitabine arms were 89% for boosted atazanavir and 89.8% for efavirenz, with a difference of -0.8 and a 95% confidence interval from -4.9 to 3.3, or 8.2 percentage points, the researchers reported.
Although the results did not meet the specified equivalence mark, the results suggest "for the first time in a large randomized study" that the two drugs have similar efficacy, the researchers argued.
They also found that safety and tolerability were slightly better for atazanavir than efavirenz when combined with abacavir/lamivudine, but there were no differences when they were combined with tenofovir/emtricitabine.
Daar and colleagues cautioned that when the study started it was not routine practice to test for HLA-B*5701 before using abacavir -- something that might have affected safety and tolerability results.
They also noted that study limitations include baseline drug resistance testing in only 40% to 50% of patients because of changing practices over time, premature unblinding of the NRTIs in the group of patients with high baseline viral loads, and change or discontinuation of the third drug in almost a third of patients.
The study was supported by the National Institute of Allergy and Infectious Diseases, and the National Center for Research Resources. Abbott Pharmaceuticals, Bristol-Myers Squibb, Gilead Sciences, and GlaxoSmithKline provided the study medications.
Daar reported financial links with Abbott Laboratories, Merck Laboratories, GlaxoSmithKline, Pfizer, Gilead Sciences, Bristol Myers Squibb, Tibotec, Schering-Plough, and Ardea Biosciences. Several authors reported being employed by the companies that supplied the study drugs.
Primary source: Annals of Internal Medicine
Source reference:
Daar ES, et al "Atazanavir plus ritonavir or efavirenz as part of a three drug regimen for initial treatment of HIV-1: A randomized trial " Ann Intern Med 2011.
Source
Published: February 14, 2011
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston.
A large clinical trial fell short of showing that two commonly used approaches to a first anti-HIV treatment regimen are formally equivalent.
But the two -- based on either the ritonavir-boosted protease inhibitor atazanavir (Reyataz) or the non-nucleoside reverse transcriptase inhibitor efavirenz (Sustiva) -- still appeared to have similar efficacy, according to Eric Daar, MD, of Harbor-UCLA Medical Center in Torrance, Calif., and colleagues.
The failure to reach formal equivalence -- as defined before the study started -- was probably the result of a lower than expected rate of virologic failure two years into the study, Daar and colleagues reported online in Annals of Internal Medicine.
But a post-hoc analysis of the data suggested the probability of remaining free of failure differed by less than 10%, a threshold commonly used for defining equivalence, the researchers argued.
Treatment guidelines for initial HIV therapy suggest two nucleoside reverse transcriptase inhibitors combined with either a non-NRTI, a ritonavir-boosted protease inhibitor, or an integrase inhibitor, the researchers noted.
But there are limited data comparing atazanavir/ritonavir with efavirenz, they noted.
To help fill the gap, they conducted a randomized trial, in which the two lead compounds were added to common, once-daily combinations of nucleoside reverse transcriptase inhibitors -- either abacavir/lamivudine (Kivexa) or tenofovir/emtricitabine (Truvada).
The trial ran from September 2005 to November 2007, with a median of 138 weeks of follow-up, and the primary outcomes were time to virologic failure, safety, and tolerability.
All told, 1,857 patients were randomly assigned to one of the four treatment regimens and 1,331 completed the follow-up.
The primary efficacy hypothesis was that, within each of the NRTI arms, boosted atazanavir would be equivalent to efavirenz, Daar and colleagues noted.
The drugs were specified to be equivalent if a Cox proportional hazards model, using efavirenz as the reference, found the two-sided 95% confidence interval for the hazard ratio to be between 0.71 and 1.40.
But analysis showed:
• Among those randomized to the abacavir/lamivudine arms, the hazard ratio for time to virologic failure was 1.13 with a 95% confidence interval from 0.82 to 1.56. The difference was not statistically significant, at P=0.147.
• For those assigned to the tenofovir/emtricitabine arms, the hazard ratio was 1.01 with a 95% confidence interval from 0.70 to 1.46, which again was not significant, at P=0.37.
Although neither hazard ratio showed a significant difference, "neither met prespecified equivalence boundaries," the researchers reported.
However, analysis also showed that the probability of remaining free of virologic failure at week 96 was 83.4% for boosted atazanavir and 85.3% for efavirenz when they were combined with abacavir/lamivudine. The difference was -1.9 with a 95% confidence interval from -6.8 to 2.9, or 9.7 percentage points.
Values in the tenofovir/emtricitabine arms were 89% for boosted atazanavir and 89.8% for efavirenz, with a difference of -0.8 and a 95% confidence interval from -4.9 to 3.3, or 8.2 percentage points, the researchers reported.
Although the results did not meet the specified equivalence mark, the results suggest "for the first time in a large randomized study" that the two drugs have similar efficacy, the researchers argued.
They also found that safety and tolerability were slightly better for atazanavir than efavirenz when combined with abacavir/lamivudine, but there were no differences when they were combined with tenofovir/emtricitabine.
Daar and colleagues cautioned that when the study started it was not routine practice to test for HLA-B*5701 before using abacavir -- something that might have affected safety and tolerability results.
They also noted that study limitations include baseline drug resistance testing in only 40% to 50% of patients because of changing practices over time, premature unblinding of the NRTIs in the group of patients with high baseline viral loads, and change or discontinuation of the third drug in almost a third of patients.
The study was supported by the National Institute of Allergy and Infectious Diseases, and the National Center for Research Resources. Abbott Pharmaceuticals, Bristol-Myers Squibb, Gilead Sciences, and GlaxoSmithKline provided the study medications.
Daar reported financial links with Abbott Laboratories, Merck Laboratories, GlaxoSmithKline, Pfizer, Gilead Sciences, Bristol Myers Squibb, Tibotec, Schering-Plough, and Ardea Biosciences. Several authors reported being employed by the companies that supplied the study drugs.
Primary source: Annals of Internal Medicine
Source reference:
Daar ES, et al "Atazanavir plus ritonavir or efavirenz as part of a three drug regimen for initial treatment of HIV-1: A randomized trial " Ann Intern Med 2011.
Source
New hepatitis C drug
14 February 2011
Scientists in the UK have developed a compound to combat the hepatitis C virus that could be taken as a pill.
David Pryde and his team from Pfizer Global Research and Development, Sandwich, have made new compounds to activate a protein in the immune system called TLR7 - toll-like receptor 7 - which fights the infection. Toll-like receptors identify foreign DNA, such as a virus, and produce proteins that inhibit the virus' replication.
300 million people suffer from hepatitis C worldwide. The virus that causes the disease resides in the liver and can lead to cirrhosis, with some sufferers requiring liver transplants. Current treatments only cure half of patients and are administered intravenously. Recent research has focused on increasing the effectiveness of the drugs and on developing oral treatments.
Pryde's team made heterocyclic analogues based on the structure of purines, known activators of TLR7 and the basis of current oral drugs. 'The most potent TLR7 agonists are purine-based,' explains Pryde. 'But we wanted to design potent non-purine based agonists to maximise the chances of avoiding any unwanted off-target pharmacology.'
The compounds activate a protein in the immune
When they tested the compounds against a hepatitis C cell line, the team found that one of the compounds, a trifluoromethyl derivative, was highly selective for TLR7. The agonist also had comparable performance to injected alternatives at doses below 50mg.
'Medicinal chemistry is often castigated for surrendering synthetic elegance in order to gain compound access. Pryde elegantly repudiates this, accomplishing both elegance and access,' says Adam McCluskey, an expert in drug design and discovery from the University of Newcastle, Australia.
Pryde and his team hope to make the agonist more soluble and to increase its potency further before moving on to human trials.
Catherine Bacon
Link to journal articleThe discovery of a novel prototype small molecule TLR7 agonist for the treatment of hepatitis C virus infection
David C. Pryde, Thien-Duc Tran, Peter Jones, Gemma C. Parsons, Gerwyn Bish, Fiona M. Adam, Mya C. Smith, Donald S. Middleton, Nick N. Smith, Frederick Calo, Duncan Hay, Michael Paradowski, Katie J. W. Proctor, Tanya Parkinson, Carl Laxton, David N. A. Fox, Nigel J. Horscroft, Giuseppe Ciaramella, Hannah M. Jones, Jonathan Duckworth, Neil Benson, Anthony Harrison and Rob Webster, Med. Chem. Commun., 2011
DOI: 10.1039/c0md00197j
Source
Scientists in the UK have developed a compound to combat the hepatitis C virus that could be taken as a pill.
David Pryde and his team from Pfizer Global Research and Development, Sandwich, have made new compounds to activate a protein in the immune system called TLR7 - toll-like receptor 7 - which fights the infection. Toll-like receptors identify foreign DNA, such as a virus, and produce proteins that inhibit the virus' replication.
300 million people suffer from hepatitis C worldwide. The virus that causes the disease resides in the liver and can lead to cirrhosis, with some sufferers requiring liver transplants. Current treatments only cure half of patients and are administered intravenously. Recent research has focused on increasing the effectiveness of the drugs and on developing oral treatments.
Pryde's team made heterocyclic analogues based on the structure of purines, known activators of TLR7 and the basis of current oral drugs. 'The most potent TLR7 agonists are purine-based,' explains Pryde. 'But we wanted to design potent non-purine based agonists to maximise the chances of avoiding any unwanted off-target pharmacology.'
The compounds activate a protein in the immune
system, which fights hepatitis C
'Medicinal chemistry is often castigated for surrendering synthetic elegance in order to gain compound access. Pryde elegantly repudiates this, accomplishing both elegance and access,' says Adam McCluskey, an expert in drug design and discovery from the University of Newcastle, Australia.
Pryde and his team hope to make the agonist more soluble and to increase its potency further before moving on to human trials.
Catherine Bacon
Link to journal articleThe discovery of a novel prototype small molecule TLR7 agonist for the treatment of hepatitis C virus infection
David C. Pryde, Thien-Duc Tran, Peter Jones, Gemma C. Parsons, Gerwyn Bish, Fiona M. Adam, Mya C. Smith, Donald S. Middleton, Nick N. Smith, Frederick Calo, Duncan Hay, Michael Paradowski, Katie J. W. Proctor, Tanya Parkinson, Carl Laxton, David N. A. Fox, Nigel J. Horscroft, Giuseppe Ciaramella, Hannah M. Jones, Jonathan Duckworth, Neil Benson, Anthony Harrison and Rob Webster, Med. Chem. Commun., 2011
DOI: 10.1039/c0md00197j
Source
Success rates for experimental drugs falls: study
By Bill Berkrot
NEW YORK
Mon Feb 14, 2011 8:09am EST
NEW YORK (Reuters) - The success rate in bringing new medicines to market in recent years is only about half of what it had been previously, but biotech drugs are twice as likely to gain U.S. approval than more traditional chemical drugs, according to a new study released on Monday.
And while oncology has been one of the hottest and most active therapeutic areas for drug development, drugmakers may want to take note of a finding that new cancer drugs have proven far more difficult to gain approval than medicines for infectious and autoimmune diseases.
Drugmakers have been complaining about the difficulty of bringing new products to market in a regulatory climate that has become increasingly unpredictable and more likely to err on the side of safety in deciding risk/benefit ratios of experimental medicines.
Data from this new study appears to bear that out.
"It ain't getting any easier to develop new therapies." said Alan Eisenberg, head of emerging companies and business development for the biotech trade group Biotechnology Industry Organization (BIO), putting the findings succinctly.
"Knowing more about the magnitude of risk can lead to smarter drug development as well as smarter investing," he said.
The study, covering 2004 through 2010, found the overall success rate for drugs moving from early stage Phase I clinical trials to FDA approval is about one in 10, down from one in five to one in six seen in reports involving earlier years.
The study, conducted by BIO and BioMedTracker, which collects data on drugs in development, reviewed more than 4,000 drugs from companies large and small and both publicly traded and private. It was released in conjunction with the annual BioCEO and Investor conference in New York.
Adding weight to the desire by major pharmaceutical companies to become increasingly involved in biotechnology was a finding that biologics had a 15 percent chance of going from Phase I through to FDA approval, compared with a 7 percent success rate for traditional small molecule chemical drugs.
When broken down by therapeutic categories, the highest overall success rate from Phase 1 through likelihood of approval was infectious diseases, such as hepatitis and HIV drugs, at 12 percent, followed by endocrine system drugs, featuring diabetes treatments, at 10.4 percent, and autoimmune diseases, such as rheumatoid arthritis, at 9.4 percent, the study found.
John Craighead, BIO's managing director for investor relations, said clinical trial goals and the approval pathways for infectious diseases and diabetes drugs are clear and very well-established.
"The Phase II results are very predictive of the Phase III outcomes and very predictive of approval," he said.
"The overall success rate in oncology was the lowest of the therapeutic areas that we looked at," he said, noting that cancer studies vary dramatically in design and extending survival sets a high bar for approval.
The cancer drug success rate was a mere 4.7 percent, with cardiovascular drugs second-worst at 5.7 percent, as regulators are increasingly demanding proof that heart drugs reduce heart attacks and strokes rather than just lower a risk factor, such as cholesterol levels.
The largest dropout rate along the clinical pathway came in advancing drugs from mid-stage Phase II studies to late-stage Phase III testing.
Some 63 percent of drugs in Phase I testing advanced to Phase II, but only 33 percent of Phase II drugs made it to Phase III, which requires a commitment to larger and much more expensive clinical trials. Phase III is typically the final stage of human testing before a new drug is submitted to regulators for an approval decision.
Not surprisingly, the numbers increase after that as the drugs had already shown success in the clinic.
Approval applications were filed for 55 percent of the drugs that made it to Phase III testing, and 80 percent of those gained eventual approval, although only about half were approved on their initial FDA review.
The 80 percent approval rate, while seemingly high, is down from 93 percent seen in studies of earlier years.
Source
NEW YORK
Mon Feb 14, 2011 8:09am EST
NEW YORK (Reuters) - The success rate in bringing new medicines to market in recent years is only about half of what it had been previously, but biotech drugs are twice as likely to gain U.S. approval than more traditional chemical drugs, according to a new study released on Monday.
And while oncology has been one of the hottest and most active therapeutic areas for drug development, drugmakers may want to take note of a finding that new cancer drugs have proven far more difficult to gain approval than medicines for infectious and autoimmune diseases.
Drugmakers have been complaining about the difficulty of bringing new products to market in a regulatory climate that has become increasingly unpredictable and more likely to err on the side of safety in deciding risk/benefit ratios of experimental medicines.
Data from this new study appears to bear that out.
"It ain't getting any easier to develop new therapies." said Alan Eisenberg, head of emerging companies and business development for the biotech trade group Biotechnology Industry Organization (BIO), putting the findings succinctly.
"Knowing more about the magnitude of risk can lead to smarter drug development as well as smarter investing," he said.
The study, covering 2004 through 2010, found the overall success rate for drugs moving from early stage Phase I clinical trials to FDA approval is about one in 10, down from one in five to one in six seen in reports involving earlier years.
The study, conducted by BIO and BioMedTracker, which collects data on drugs in development, reviewed more than 4,000 drugs from companies large and small and both publicly traded and private. It was released in conjunction with the annual BioCEO and Investor conference in New York.
Adding weight to the desire by major pharmaceutical companies to become increasingly involved in biotechnology was a finding that biologics had a 15 percent chance of going from Phase I through to FDA approval, compared with a 7 percent success rate for traditional small molecule chemical drugs.
When broken down by therapeutic categories, the highest overall success rate from Phase 1 through likelihood of approval was infectious diseases, such as hepatitis and HIV drugs, at 12 percent, followed by endocrine system drugs, featuring diabetes treatments, at 10.4 percent, and autoimmune diseases, such as rheumatoid arthritis, at 9.4 percent, the study found.
John Craighead, BIO's managing director for investor relations, said clinical trial goals and the approval pathways for infectious diseases and diabetes drugs are clear and very well-established.
"The Phase II results are very predictive of the Phase III outcomes and very predictive of approval," he said.
"The overall success rate in oncology was the lowest of the therapeutic areas that we looked at," he said, noting that cancer studies vary dramatically in design and extending survival sets a high bar for approval.
The cancer drug success rate was a mere 4.7 percent, with cardiovascular drugs second-worst at 5.7 percent, as regulators are increasingly demanding proof that heart drugs reduce heart attacks and strokes rather than just lower a risk factor, such as cholesterol levels.
The largest dropout rate along the clinical pathway came in advancing drugs from mid-stage Phase II studies to late-stage Phase III testing.
Some 63 percent of drugs in Phase I testing advanced to Phase II, but only 33 percent of Phase II drugs made it to Phase III, which requires a commitment to larger and much more expensive clinical trials. Phase III is typically the final stage of human testing before a new drug is submitted to regulators for an approval decision.
Not surprisingly, the numbers increase after that as the drugs had already shown success in the clinic.
Approval applications were filed for 55 percent of the drugs that made it to Phase III testing, and 80 percent of those gained eventual approval, although only about half were approved on their initial FDA review.
The 80 percent approval rate, while seemingly high, is down from 93 percent seen in studies of earlier years.
Source
Caring Ambassadors Program Launches Unique New DVD Series "Hepatitis C: Choices in Care"
Feb 14, 2011 11:31 ET
OREGON CITY, OR--(Marketwire - February 14, 2011) - The Caring Ambassadors Program (CAP) proudly announces the release of the new DVD series "Hepatitis C: Choices in Care -- Distinctive Viewpoints on Choices for Your Hepatitis C Journey." The 2-disc set offers over nine hours of leading expert physician interviews, patient consultations, panel discussions, Power Point presentations and 30 minutes of Qi Gong exercises specifically geared towards people living with hepatitis C.
About five million Americans are infected with HCV, making hepatitis C the most common chronic blood-borne viral illness in the U.S. HCV is the leading cause of chronic liver disease and liver cancer in the U.S. and the most common indication for liver transplantation. In January 2010, the Institute of Medicine (IOM) released its report, "Hepatitis and Liver Cancer, A National Strategy for the Prevention and Control of Viral Hepatitis." The committee found that many health care providers lack an adequate knowledge of HCV and that chronic hepatitis C patients are often confused about their treatment and disease management options.
The DVD series addresses these knowledge gaps by providing a shorter version of the book, Hepatitis C Choices, 4th Edition. The book presents evidence-based conventional and alternative treatment options and is the collective effort of leading medical experts and hepatitis C patient advocates. It is still the only book, and now DVD, of its kind.
"I was scared and did not know which way to turn when I was diagnosed with hepatitis C. I had a lot of unanswered questions," said Randy Dietrich, Board Chair of the Caring Ambassadors Program. "This information combined with the book was what I wanted to make an informed decision about my care."
The Caring Ambassadors Program produced "Hepatitis C: Choices in Care" to educate the public and health care community about hepatitis C. CAP believes it is vitally important that everyone with hepatitis C virus (HCV) know their disease status and have accurate and ample information to make the best health care decisions. Education is essential for making informed choices and taking charge of one's health.
"Hepatitis C: Choices in Care" is available for free viewing at the Caring Ambassadors Program Hepatitis C website at http://www.hepcchallenge.org/. The entire DVD series "Hepatitis C: Choices in Care" can also be purchased for $10.00 plus shipping and handling.
Contact:
Lorren Sandt
503-632-9030
Lorren@HepCChallenge.org
Source
OREGON CITY, OR--(Marketwire - February 14, 2011) - The Caring Ambassadors Program (CAP) proudly announces the release of the new DVD series "Hepatitis C: Choices in Care -- Distinctive Viewpoints on Choices for Your Hepatitis C Journey." The 2-disc set offers over nine hours of leading expert physician interviews, patient consultations, panel discussions, Power Point presentations and 30 minutes of Qi Gong exercises specifically geared towards people living with hepatitis C.
About five million Americans are infected with HCV, making hepatitis C the most common chronic blood-borne viral illness in the U.S. HCV is the leading cause of chronic liver disease and liver cancer in the U.S. and the most common indication for liver transplantation. In January 2010, the Institute of Medicine (IOM) released its report, "Hepatitis and Liver Cancer, A National Strategy for the Prevention and Control of Viral Hepatitis." The committee found that many health care providers lack an adequate knowledge of HCV and that chronic hepatitis C patients are often confused about their treatment and disease management options.
The DVD series addresses these knowledge gaps by providing a shorter version of the book, Hepatitis C Choices, 4th Edition. The book presents evidence-based conventional and alternative treatment options and is the collective effort of leading medical experts and hepatitis C patient advocates. It is still the only book, and now DVD, of its kind.
"I was scared and did not know which way to turn when I was diagnosed with hepatitis C. I had a lot of unanswered questions," said Randy Dietrich, Board Chair of the Caring Ambassadors Program. "This information combined with the book was what I wanted to make an informed decision about my care."
The Caring Ambassadors Program produced "Hepatitis C: Choices in Care" to educate the public and health care community about hepatitis C. CAP believes it is vitally important that everyone with hepatitis C virus (HCV) know their disease status and have accurate and ample information to make the best health care decisions. Education is essential for making informed choices and taking charge of one's health.
"Hepatitis C: Choices in Care" is available for free viewing at the Caring Ambassadors Program Hepatitis C website at http://www.hepcchallenge.org/. The entire DVD series "Hepatitis C: Choices in Care" can also be purchased for $10.00 plus shipping and handling.
Contact:
Lorren Sandt
503-632-9030
Lorren@HepCChallenge.org
Source
February 13, 2011
HCV: Genotype & Quasispecies
Alan Franciscus Editor-in-Chief
Hepatitis C Support project
HCV Advocate
The term genotype refers to different genetic variations or strains of hepatitis C. The variance in genetic differences is approximately 1/3 between the different genotypes. There are six major groups or genotypes numbered 1 to 6 although some experts believe that there may be as many as 11. Within each genotype are further divisions called subtypes (for example 1a and 1b) and quasispecies.
HCV constantly changes and mutates as it replicates—more than 1 trillion hepatitis C virions replicate each day. During the replication process, the hepatitis C virus will make ‘bad’ copies or errors in the genetic make-up of the newly replicated viruses. The process of constant mutation helps the virus evade the body’s immune response---when the dominant quasi-species is eradicated, another quasi-species emerges. This requires the immune system to constantly identify and kill the newly emerged variants. This is one of the reasons why so many people develop chronic disease. Scientists believe there are literally millions of different HCV quasispecies in everyone infected with hepatitis C, which are unique to everyone because of the individual’s immune response to HCV and quasispecies constantly change over time. In addition, it has been suggested that quasispecies play a role in disease progression and treatment response, but this is still controversial and more studies are needed to fully appreciate the role of quasi-species.
This variability (genotype, subtypes and quasispecies) of hepatitis C has made it difficult to treat and to develop a vaccine that will protect against all HCV strains although recent advances in vaccine development have been encouraging.
Testing for Genotype, Subtype & Quasispecies
A blood test is required for the genotype test. Generally, a quasispecies test is only performed for research purposes. HCV genotype testing is only done once since the genotype does not change.
Genotype Distribution
HCV genotypes and subtypes are distributed differently in different parts of the world, and certain genotypes predominate in certain areas. Genotypes 1-3 are widely distributed throughout the world. Subtype 1a is prevalent in North and South America, Europe, and Australia. Subtype 1b is common in North America and Europe, and is also found in parts of Asia. Genotype 2 is present in most developed countries, but is less common than genotype 1. Some studies suggest that different types of HCV may be associated with different transmission routes. Subtype 3a appears to be prevalent among injection drug users and it is believed that they were introduced into North American and the United Kingdom with the widespread use of heroin in the 1960s.
Importance of Genotype Information
HCV Genotype information is important because of the role it plays in predicting HCV medical treatment response, treatment duration and the dose of ribavirin. However, it should never be used as a reason to deny treatment.
Prediction of Treatment Response
Genotype information is important because it can be used as a predictor of a positive treatment outcome or response. The sustained virological response rates for pegylated interferon plus ribavirin are much higher in genotype 2 and 3 compared with genotype 1.
Other predictors of treatment response include:
• Age of Patient – younger patients respond more favorably especially people under 30 years old.
• Sex of Patient – women are more likely to respond to therapy than men
• Histological (health of the liver) – people with minimal damage respond better to treatment
• Viral Load – the lower the viral load (less than 800,000 IU/mL) the more likely one is to respond to current medications
• Obesity or high Body Mass Index is associated with lower treatment response rates
• Steatosis or fatty liver reduces the chance of responding to treatment.
• Race—Caucasians and Asians respond better to current HCV medications.
Genotype and Treatment Response
Genotype 1 is considered the most difficult to treat with current HCV medications. However, treatment response rates with the newer forms of pegylated interferon plus ribavirin have been remarkably high--up to a 51% sustained virological response rate (SVR – undetectable viral load six months post treatment). Genotype 2 and 3 respond even better to current medications—up to 80%. There is some evidence that genotype 2 responds better to current HCV therapies than genotype 3, but this needs to be confirmed in prospective studies. The reason that a particular genotype responds to treatment differently is unknown, but it is speculated that specific genotypes of the hepatitis C virus live longer or shorter than others. For example, it has been theorized that genotype 2 and 3 of the hepatitis C virus do not live as long (viral lifecycle) as genotype 1 thus making eradication of genotype 2 and 3 easier.
Genotype and Treatment Duration
Genotype is also a factor in the period of time required to treat with current HCV medications. Generally, genotype 1 is treated for 48 weeks and genotype 2 and 3 are treated for 24 weeks. However, there are studies underway to determine the most optimal treatment duration based on certain factors. For instance, some experts believe that people with genotype 1, high viral load should be treated for 72 weeks instead of 48 weeks to maximize treatment response rates. There are also studies evaluating treating people with genotype 2 for 12 weeks and genotype 3 for 48 weeks.
Genotype and HCV Medication Dosage
Genotype information is also important for establishing the appropriate dose of ribavirin. For instance, people with genotype 2 and 3 are given 800 mg a day of ribavirin (flat dose), whereas the ribavirin dose for people with genotype 1 is dosed by body weight.
Mixed Genotypes
A person can become infected with more than one genotype. Data is almost non-existent on being infected with more than one genotype, but some experts believe it may effect treatment response and HCV disease progression.
Steatosis and Genotype
Steatosis (fatty infiltrates of the liver) is a well recognized feature of hepatitis C infection. Steatosis can contribute to HCV disease progression and lower treatment response although the exact mechanism is not completely understood. People with HCV genotype 3 are more likely to develop steatosis and it is believed that HCV genotype 3 is an independent risk factor and may actually play a direct role in the development of steatosis. It has been reported that when genotype 3 individuals are successful treated that steatosis will generally improve and for some steatosis will disappear.
Genotype and HCV Disease Progression
In regards to genotype and HCV disease progression, early limited data suggested that genotype 1b was associated with a more severe disease progression than in genotype 1a or 2, but further studies have not been able to confirm this observation.
Genotype and Liver Transplantation
Genotype 1 (especially 1b) has been associated with a more rapid fibrosis progression in people who have received a liver transplant.
Source
Hepatitis C Support project
HCV Advocate
The term genotype refers to different genetic variations or strains of hepatitis C. The variance in genetic differences is approximately 1/3 between the different genotypes. There are six major groups or genotypes numbered 1 to 6 although some experts believe that there may be as many as 11. Within each genotype are further divisions called subtypes (for example 1a and 1b) and quasispecies.
HCV constantly changes and mutates as it replicates—more than 1 trillion hepatitis C virions replicate each day. During the replication process, the hepatitis C virus will make ‘bad’ copies or errors in the genetic make-up of the newly replicated viruses. The process of constant mutation helps the virus evade the body’s immune response---when the dominant quasi-species is eradicated, another quasi-species emerges. This requires the immune system to constantly identify and kill the newly emerged variants. This is one of the reasons why so many people develop chronic disease. Scientists believe there are literally millions of different HCV quasispecies in everyone infected with hepatitis C, which are unique to everyone because of the individual’s immune response to HCV and quasispecies constantly change over time. In addition, it has been suggested that quasispecies play a role in disease progression and treatment response, but this is still controversial and more studies are needed to fully appreciate the role of quasi-species.
This variability (genotype, subtypes and quasispecies) of hepatitis C has made it difficult to treat and to develop a vaccine that will protect against all HCV strains although recent advances in vaccine development have been encouraging.
Testing for Genotype, Subtype & Quasispecies
A blood test is required for the genotype test. Generally, a quasispecies test is only performed for research purposes. HCV genotype testing is only done once since the genotype does not change.
Genotype Distribution
HCV genotypes and subtypes are distributed differently in different parts of the world, and certain genotypes predominate in certain areas. Genotypes 1-3 are widely distributed throughout the world. Subtype 1a is prevalent in North and South America, Europe, and Australia. Subtype 1b is common in North America and Europe, and is also found in parts of Asia. Genotype 2 is present in most developed countries, but is less common than genotype 1. Some studies suggest that different types of HCV may be associated with different transmission routes. Subtype 3a appears to be prevalent among injection drug users and it is believed that they were introduced into North American and the United Kingdom with the widespread use of heroin in the 1960s.
Importance of Genotype Information
HCV Genotype information is important because of the role it plays in predicting HCV medical treatment response, treatment duration and the dose of ribavirin. However, it should never be used as a reason to deny treatment.
Prediction of Treatment Response
Genotype information is important because it can be used as a predictor of a positive treatment outcome or response. The sustained virological response rates for pegylated interferon plus ribavirin are much higher in genotype 2 and 3 compared with genotype 1.
Other predictors of treatment response include:
• Age of Patient – younger patients respond more favorably especially people under 30 years old.
• Sex of Patient – women are more likely to respond to therapy than men
• Histological (health of the liver) – people with minimal damage respond better to treatment
• Viral Load – the lower the viral load (less than 800,000 IU/mL) the more likely one is to respond to current medications
• Obesity or high Body Mass Index is associated with lower treatment response rates
• Steatosis or fatty liver reduces the chance of responding to treatment.
• Race—Caucasians and Asians respond better to current HCV medications.
Genotype and Treatment Response
Genotype 1 is considered the most difficult to treat with current HCV medications. However, treatment response rates with the newer forms of pegylated interferon plus ribavirin have been remarkably high--up to a 51% sustained virological response rate (SVR – undetectable viral load six months post treatment). Genotype 2 and 3 respond even better to current medications—up to 80%. There is some evidence that genotype 2 responds better to current HCV therapies than genotype 3, but this needs to be confirmed in prospective studies. The reason that a particular genotype responds to treatment differently is unknown, but it is speculated that specific genotypes of the hepatitis C virus live longer or shorter than others. For example, it has been theorized that genotype 2 and 3 of the hepatitis C virus do not live as long (viral lifecycle) as genotype 1 thus making eradication of genotype 2 and 3 easier.
Genotype and Treatment Duration
Genotype is also a factor in the period of time required to treat with current HCV medications. Generally, genotype 1 is treated for 48 weeks and genotype 2 and 3 are treated for 24 weeks. However, there are studies underway to determine the most optimal treatment duration based on certain factors. For instance, some experts believe that people with genotype 1, high viral load should be treated for 72 weeks instead of 48 weeks to maximize treatment response rates. There are also studies evaluating treating people with genotype 2 for 12 weeks and genotype 3 for 48 weeks.
Genotype and HCV Medication Dosage
Genotype information is also important for establishing the appropriate dose of ribavirin. For instance, people with genotype 2 and 3 are given 800 mg a day of ribavirin (flat dose), whereas the ribavirin dose for people with genotype 1 is dosed by body weight.
Mixed Genotypes
A person can become infected with more than one genotype. Data is almost non-existent on being infected with more than one genotype, but some experts believe it may effect treatment response and HCV disease progression.
Steatosis and Genotype
Steatosis (fatty infiltrates of the liver) is a well recognized feature of hepatitis C infection. Steatosis can contribute to HCV disease progression and lower treatment response although the exact mechanism is not completely understood. People with HCV genotype 3 are more likely to develop steatosis and it is believed that HCV genotype 3 is an independent risk factor and may actually play a direct role in the development of steatosis. It has been reported that when genotype 3 individuals are successful treated that steatosis will generally improve and for some steatosis will disappear.
Genotype and HCV Disease Progression
In regards to genotype and HCV disease progression, early limited data suggested that genotype 1b was associated with a more severe disease progression than in genotype 1a or 2, but further studies have not been able to confirm this observation.
Genotype and Liver Transplantation
Genotype 1 (especially 1b) has been associated with a more rapid fibrosis progression in people who have received a liver transplant.
Source
Loving your liver: Organ crucial to good health
Published: Friday, February 11, 2011
By Dr. Allen Yudovich
Henry Ford Health System
Of all the body’s vital organs, the heart is the one that gets the most attention this month. But right underneath it is one of the hardest-working organs we have, our liver. It doesn’t carry the touch of romance the heart does, but it is crucial to our well-being.
Our livers change food into nutrients and filter out harmful substances. The vital functions it performs include:
• converting nutrients into energy, hormones and other essential chemicals;
• cleansing toxic substances (including alcohol) from the blood, then neutralizing or rerouting them for disposal;
• processing drugs;
• storing vitamins, minerals, sugars and iron;
• regulating fat and cholesterol; and
• manufacturing bile -- a fluid that helps digest food.
The liver is also generally very good at keeping itself healthy. When it stops functioning well, the term liver disease is often used. But there are actually many forms of liver disease. When symptoms appear, they may include jaundice (a yellowing of the skin or eyes), abdominal pain, lose of appetite and weight loss, dark urine and pale bowel movements. Sometimes the first indication of a problem is found in the results of liver function tests ordered by a physician.
Cirrhosis
Some forms of liver disease are more common in older adults. Cirrhosis most frequently develops after years of alcohol abuse, although moderate drinkers sometimes develop it as well. Over time, the liver becomes scarred and loses its ability to do what it was designed to. Other liver diseases, including hepatitis B, C and D, can also lead to cirrhosis.
As the disease progresses, symptoms that may develop include nausea, fatigue, itching, vomiting blood and a swollen abdomen.
When cirrhosis is caused by excessive drinking, avoiding alcohol and eating a healthy diet may be beneficial because of the liver’s ability to regenerate itself. Medication is used to treat cirrhosis caused by viral hepatitis.
Cirrhosis is also one of the risk factors for liver cancer, which most often affects people older than 40. It also affects men more frequently than women. Other risk factors include smoking, heavy drinking, hepatitis B and C and cancer in another area of the body.
Liver cancer
Liver cancer can be either primary (meaning it started in the liver) or secondary (beginning elsewhere in the body and spreading to the liver). Secondary liver cancer is far more common than primary, because blood that may carry cancer cells is filtered through the liver.
Symptoms include abdominal pain or swelling, jaundice and weight loss, but these rarely appear in the early stages of the disease. Various tests are used to confirm a cancer diagnosis. These may include a biopsy, CT scan, an MRI, ultrasound and blood tests.
Treatment options include surgery, chemotherapy and radiation, along with newer treatments such as radiofrequency ablation, which uses heat to destroy tumors, and cryosurgery, which uses cold to do the same thing. A liver transplant could also be necessary.
Treatment is most successful when the cancer is diagnosed in an earlier stage and when the patient does not also have cirrhosis.
Hepatitis
All forms of hepatitis are inflammations of the liver. The symptoms are similar to other forms of liver disease, but are often mild. A blood test is needed to confirm a hepatitis diagnosis. Treatment ranges from bed rest and avoiding alcohol to medication, depending on the form of hepatitis someone has.
Primary biliary cirrhosis
This is a chronic inflammation of the liver’s bile ducts that affects women more than men. Those who contract it are usually between 40 and 60 years old. It can lead to cirrhosis and eventually destroy the bile ducts. A healthy diet and medication can alleviate the symptoms, which include itching, fatigue and jaundice. A liver transplant may eventually be recommended.
Alcoholic liver disease
As its name implies, this disease is tied to alcohol abuse, although not all heavy drinkers develop it. Alcoholic liver disease generally develops over a period of years and leads to cirrhosis. Symptoms often don’t appear in the early stages of the disease. When they are present they may include abdominal pain, jaundice, fever, excessive thirst and a loss of appetite. They may also worsen after heavy drinking.
All of the above symptoms could also be indicators of a different illness. Anyone who experiences these symptoms should discuss them with their physician.
Allen Yudovich, M.D., is a gastroenterologist at the Henry Ford Medical Center - Fairlane in Dearborn. For an appointment call (800) HENRYFORD.
Source
By Dr. Allen Yudovich
Henry Ford Health System
Of all the body’s vital organs, the heart is the one that gets the most attention this month. But right underneath it is one of the hardest-working organs we have, our liver. It doesn’t carry the touch of romance the heart does, but it is crucial to our well-being.
Our livers change food into nutrients and filter out harmful substances. The vital functions it performs include:
• converting nutrients into energy, hormones and other essential chemicals;
• cleansing toxic substances (including alcohol) from the blood, then neutralizing or rerouting them for disposal;
• processing drugs;
• storing vitamins, minerals, sugars and iron;
• regulating fat and cholesterol; and
• manufacturing bile -- a fluid that helps digest food.
The liver is also generally very good at keeping itself healthy. When it stops functioning well, the term liver disease is often used. But there are actually many forms of liver disease. When symptoms appear, they may include jaundice (a yellowing of the skin or eyes), abdominal pain, lose of appetite and weight loss, dark urine and pale bowel movements. Sometimes the first indication of a problem is found in the results of liver function tests ordered by a physician.
Cirrhosis
Some forms of liver disease are more common in older adults. Cirrhosis most frequently develops after years of alcohol abuse, although moderate drinkers sometimes develop it as well. Over time, the liver becomes scarred and loses its ability to do what it was designed to. Other liver diseases, including hepatitis B, C and D, can also lead to cirrhosis.
As the disease progresses, symptoms that may develop include nausea, fatigue, itching, vomiting blood and a swollen abdomen.
When cirrhosis is caused by excessive drinking, avoiding alcohol and eating a healthy diet may be beneficial because of the liver’s ability to regenerate itself. Medication is used to treat cirrhosis caused by viral hepatitis.
Cirrhosis is also one of the risk factors for liver cancer, which most often affects people older than 40. It also affects men more frequently than women. Other risk factors include smoking, heavy drinking, hepatitis B and C and cancer in another area of the body.
Liver cancer
Liver cancer can be either primary (meaning it started in the liver) or secondary (beginning elsewhere in the body and spreading to the liver). Secondary liver cancer is far more common than primary, because blood that may carry cancer cells is filtered through the liver.
Symptoms include abdominal pain or swelling, jaundice and weight loss, but these rarely appear in the early stages of the disease. Various tests are used to confirm a cancer diagnosis. These may include a biopsy, CT scan, an MRI, ultrasound and blood tests.
Treatment options include surgery, chemotherapy and radiation, along with newer treatments such as radiofrequency ablation, which uses heat to destroy tumors, and cryosurgery, which uses cold to do the same thing. A liver transplant could also be necessary.
Treatment is most successful when the cancer is diagnosed in an earlier stage and when the patient does not also have cirrhosis.
Hepatitis
All forms of hepatitis are inflammations of the liver. The symptoms are similar to other forms of liver disease, but are often mild. A blood test is needed to confirm a hepatitis diagnosis. Treatment ranges from bed rest and avoiding alcohol to medication, depending on the form of hepatitis someone has.
Primary biliary cirrhosis
This is a chronic inflammation of the liver’s bile ducts that affects women more than men. Those who contract it are usually between 40 and 60 years old. It can lead to cirrhosis and eventually destroy the bile ducts. A healthy diet and medication can alleviate the symptoms, which include itching, fatigue and jaundice. A liver transplant may eventually be recommended.
Alcoholic liver disease
As its name implies, this disease is tied to alcohol abuse, although not all heavy drinkers develop it. Alcoholic liver disease generally develops over a period of years and leads to cirrhosis. Symptoms often don’t appear in the early stages of the disease. When they are present they may include abdominal pain, jaundice, fever, excessive thirst and a loss of appetite. They may also worsen after heavy drinking.
All of the above symptoms could also be indicators of a different illness. Anyone who experiences these symptoms should discuss them with their physician.
Allen Yudovich, M.D., is a gastroenterologist at the Henry Ford Medical Center - Fairlane in Dearborn. For an appointment call (800) HENRYFORD.
Source
New Opportunities in Anti-Hepatitis C Virus Drug Discovery: Targeting NS4B
Antiviral Res. 2011 Feb 1. [Epub ahead of print]
Rai R, Deval J.
Alios BioPharma, South San Francisco, USA.
Abstract
Current therapy for chronic hepatitis C virus (HCV) infection constitutes a combination of pegylated interferon alfa-2a or alpha-2b and ribavirin. Although successful for many patient populations, this regimen has numerous limitations, including non-response, relapse, poor tolerability and long duration of treatment. To address these shortcomings, new small molecule agents are advancing in clinical development. Most of the current clinical candidates act by directly inhibiting key enzymes in the viral life-cycle: the NS5B polymerase, or the NS3/4A protease. Less well-studied, the non-structural 4B (NS4B) protein has recently emerged as an alternative target for Direct-acting Antiviral Agents (DAAs). NS4B is a 27-kDa membrane protein that is primarily involved in the formation of membrane vesicles-also named membranous web-used as scaffold for the assembly of the HCV replication complex. In addition, NS4B contains NTPase and RNA binding activities, as well as anti-apoptotic properties. This review summarizes the current understanding of the structure and functions of NS4B, an essential component of the replication machinery of HCV. In this literature and patent review, we report the recent developments in anti-NS4B drug discovery. These advances open the possibility for future combination therapies with other DAAs.
Copyright © 2011. Published by Elsevier B.V.
PMID: 21295075 [PubMed - as supplied by publisher]
Source
Rai R, Deval J.
Alios BioPharma, South San Francisco, USA.
Abstract
Current therapy for chronic hepatitis C virus (HCV) infection constitutes a combination of pegylated interferon alfa-2a or alpha-2b and ribavirin. Although successful for many patient populations, this regimen has numerous limitations, including non-response, relapse, poor tolerability and long duration of treatment. To address these shortcomings, new small molecule agents are advancing in clinical development. Most of the current clinical candidates act by directly inhibiting key enzymes in the viral life-cycle: the NS5B polymerase, or the NS3/4A protease. Less well-studied, the non-structural 4B (NS4B) protein has recently emerged as an alternative target for Direct-acting Antiviral Agents (DAAs). NS4B is a 27-kDa membrane protein that is primarily involved in the formation of membrane vesicles-also named membranous web-used as scaffold for the assembly of the HCV replication complex. In addition, NS4B contains NTPase and RNA binding activities, as well as anti-apoptotic properties. This review summarizes the current understanding of the structure and functions of NS4B, an essential component of the replication machinery of HCV. In this literature and patent review, we report the recent developments in anti-NS4B drug discovery. These advances open the possibility for future combination therapies with other DAAs.
Copyright © 2011. Published by Elsevier B.V.
PMID: 21295075 [PubMed - as supplied by publisher]
Source
Cirrhosis Patients at Increased Risk of Extrahepatic Cancer
Last Updated: February 07, 2011
Patients with liver cirrhosis have more than double the risk of developing extrahepatic cancer than the general population, and they also have a significantly increased risk of hepatocellular carcinoma, according to a study published in the February issue of Clinical Gastroenterology and Hepatology.
MONDAY, Feb. 7 (HealthDay News) -- Patients with liver cirrhosis have more than double the risk of developing extrahepatic cancer than the general population, and they also have a significantly increased risk of hepatocellular carcinoma (HCC), according to a study published in the February issue of Clinical Gastroenterology and Hepatology.
Evangelos Kalaitzakis, M.D., of the University of Gothenburg in Sweden, and colleagues investigated the incidence of malignant neoplasms in patients diagnosed with cirrhosis between 1994 and 2005. Of the 1,019 patients, 68 percent were men, 48 percent had alcoholic liver disease (ALD), 10 percent had hepatitis C virus (HCV), and 12 percent had both ALD and HCV.
The researchers found that, compared to the general population, patients with cirrhosis were at increased risk of HCC (26-fold); cholangiocarcinoma (13-fold); colorectal cancer (four-fold); and cancers of the esophagus (eight-fold), pancreas (five-fold), and lung (five-fold). HCC occurred more frequently among patients with HCV than other diseases, and the risk of HCC among patients with HCV was similar whether they had ALD or not. Patients with non-ALD cirrhosis were at increased risk for cholangiocarcinoma; whereas, the risk for extrahepatic cancers increased mainly among patients with ALD and cirrhosis.
"This study confirms the association of liver cirrhosis with HCC and further indicates that non-HCC malignant neoplasms may be more common in patients with cirrhosis compared with the general population," the authors write.
Abstract
Full Text (subscription or payment may be required)
Source
Patients with liver cirrhosis have more than double the risk of developing extrahepatic cancer than the general population, and they also have a significantly increased risk of hepatocellular carcinoma, according to a study published in the February issue of Clinical Gastroenterology and Hepatology.
MONDAY, Feb. 7 (HealthDay News) -- Patients with liver cirrhosis have more than double the risk of developing extrahepatic cancer than the general population, and they also have a significantly increased risk of hepatocellular carcinoma (HCC), according to a study published in the February issue of Clinical Gastroenterology and Hepatology.
Evangelos Kalaitzakis, M.D., of the University of Gothenburg in Sweden, and colleagues investigated the incidence of malignant neoplasms in patients diagnosed with cirrhosis between 1994 and 2005. Of the 1,019 patients, 68 percent were men, 48 percent had alcoholic liver disease (ALD), 10 percent had hepatitis C virus (HCV), and 12 percent had both ALD and HCV.
The researchers found that, compared to the general population, patients with cirrhosis were at increased risk of HCC (26-fold); cholangiocarcinoma (13-fold); colorectal cancer (four-fold); and cancers of the esophagus (eight-fold), pancreas (five-fold), and lung (five-fold). HCC occurred more frequently among patients with HCV than other diseases, and the risk of HCC among patients with HCV was similar whether they had ALD or not. Patients with non-ALD cirrhosis were at increased risk for cholangiocarcinoma; whereas, the risk for extrahepatic cancers increased mainly among patients with ALD and cirrhosis.
"This study confirms the association of liver cirrhosis with HCC and further indicates that non-HCC malignant neoplasms may be more common in patients with cirrhosis compared with the general population," the authors write.
Abstract
Full Text (subscription or payment may be required)
Source
HIV-Infected Men at Ongoing Risk for HCV Seroconversion, Study Finds
Norra MacReady
February 7, 2011 — Even with conscientious care and state-of-the-art medication, HIV-infected men are at risk for hepatitis C virus (HCV) seroconversion and should have access to ongoing HCV surveillance, the authors of a new study say. Their findings were published online January 31 and appear in the February print issue of Clinical Infectious Diseases.
HCV has become "a leading cause of non-AIDS related morbidity and mortality for HIV-infected persons in the highly active antiretroviral therapy (HAART) era," lead author Lynn E. Taylor, MD, from Brown University, Providence, Rhode Island, and coauthors write. They estimate that up to 30% of HIV-infected people in the United States are coinfected with HCV.
At this time, the US Public Health Service recommends testing for HCV when a patient is initially diagnosed with HIV infection, but not thereafter. However, reports are now surfacing of acute HCV outbreaks in Europe, Australia, New York, and California among HIV-infected men who have sex with other HIV-infected men and engage in potentially traumatic practices such as unprotected anal sex, use of sex toys, multiple partners, and manual insertion, which may involve some exchange of blood. Because HCV treatment is most effective during the acute stages of infection, "it is vital to diagnose incident HCV infection in HIV-infected persons," the authors say.
For a better idea of the risk for acute HCV infection among HIV-infected men, the researchers studied behavioral and demographic factors associated with HCV antibody seroconversion in men participating in the AIDS Clinical Trial Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) study. The ACTG was established in 1987 by the US Department of Health and Human Services, the National Institute of Allergy and Infectious Diseases, and the National Institutes of Health Division of AIDS, and is the largest HIV clinical trials organization in the world. ALLRT is a randomized cohort study of the long-term immunologic, virologic, pharmacologic, and clinical outcomes associated with the use of HAART by HIV-1-seropositive patients. It was started by ACTG in 2000.
Starting in 2002, patients participating in ALLRT have been tested for HCV on entry, with follow-up testing every 96 weeks beginning in 2006. Seventeen other ACTG-funded trials also test patients for HCV on entry and at various follow-up intervals, between 1996 and 2002. The authors determined the incidence of HCV infection from 1996 to 2008 among men participating in these studies. Of those 2848 patients, 2629 had at least 1 HCV antibody test result, with 264 (10%) of those individuals testing positive at baseline. Of the remaining 2365 patients, 1830 had at least 1 subsequent HCV antibody test and were included in this analysis. Their mean age at the time of the initial negative HCV antibody result was 42 years; other demographic information is shown in the table. The mean interval for HCV testing was 2.8 years for HCV seroconverters and 2.6 years for nonseroconverters.
Table
Characteristic Percentage
Race
* White 57%
* Black 22%
* Hispanic 18%
* Asian/Pacific Islander 2%
* Native American 1%
College-educated 70%
Using HAART 94%
Current or prior injection drug use at study entry 6%
HCV seroconversion occurred in 36 of the men studied (2%), for an overall incidence of .51 cases per 100 person-years. Twenty-five percent of the seroconverters reported a history of injection drug use compared with 5% of patients who remained seronegative (P < .001). However, the authors write, "compared with men with initial HCV antibody positivity, seroconverters were more likely to be white and less likely to be black and were more likely to have never injected drugs and to have attended college."
Patients who seroconverted also were more likely to have an HIV RNA level greater than 400 copies/mL compared with those who did not seroconvert. There is an association between less adherence to the HAART regimen and participation in risky sexual practices, and both of these may have figured in the higher seroconversion rate among patients with a higher viral load, the authors suggest. People in the acute stages of HCV infection are also less tolerant of HAART, which may have contributed to their poor compliance.
There were several study limitations. Only half of the participants underwent follow-up HCV testing at intervals shorter than 3 years, so the authors could not determine exactly when seroconversion occurred in these patients, making it impossible to report incidence trends over time. In addition, 23% of the participants did not undergo any follow-up HCV screening, which raises the possibility of selection bias. However, there was no difference in baseline data between those patients and the patients who did have follow-up testing, so "it is likely that the HCV seroconversions represent the true incidence among HIV-infected patients in care," the authors write.
These findings suggest that HIV-infected patients should undergo regular screening for HCV, the researchers conclude. Early detection "may permit more successful treatment and provide opportunity for intervention to mitigate disease spread among drug-using or sexual partners and education to limit liver damage."
This study was supported in part by the AIDS Clinical Trials Group funded by the National Institute of Allergy and Infectious Diseases; National Institute on Drug Abuse; Lifespan/Tufts/Brown Center for AIDS Research; Center for Drug Abuse and AIDS Research; and the National Institutes of Health. The Miriam Hospital is one of the Clinical 340 Research Sites under Harvard/Partners Clinical Trials Unit. Study authors report various financial relationships with Roche, Vertex, Genentech, BMS, Merck, SciClone, GlaxoSmithKline, Three Rivers, Johnson & Johnson, Regulus, and Tibotec.
Clin Infect Dis. Published online January 31, 2011.
Source
February 7, 2011 — Even with conscientious care and state-of-the-art medication, HIV-infected men are at risk for hepatitis C virus (HCV) seroconversion and should have access to ongoing HCV surveillance, the authors of a new study say. Their findings were published online January 31 and appear in the February print issue of Clinical Infectious Diseases.
HCV has become "a leading cause of non-AIDS related morbidity and mortality for HIV-infected persons in the highly active antiretroviral therapy (HAART) era," lead author Lynn E. Taylor, MD, from Brown University, Providence, Rhode Island, and coauthors write. They estimate that up to 30% of HIV-infected people in the United States are coinfected with HCV.
At this time, the US Public Health Service recommends testing for HCV when a patient is initially diagnosed with HIV infection, but not thereafter. However, reports are now surfacing of acute HCV outbreaks in Europe, Australia, New York, and California among HIV-infected men who have sex with other HIV-infected men and engage in potentially traumatic practices such as unprotected anal sex, use of sex toys, multiple partners, and manual insertion, which may involve some exchange of blood. Because HCV treatment is most effective during the acute stages of infection, "it is vital to diagnose incident HCV infection in HIV-infected persons," the authors say.
For a better idea of the risk for acute HCV infection among HIV-infected men, the researchers studied behavioral and demographic factors associated with HCV antibody seroconversion in men participating in the AIDS Clinical Trial Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) study. The ACTG was established in 1987 by the US Department of Health and Human Services, the National Institute of Allergy and Infectious Diseases, and the National Institutes of Health Division of AIDS, and is the largest HIV clinical trials organization in the world. ALLRT is a randomized cohort study of the long-term immunologic, virologic, pharmacologic, and clinical outcomes associated with the use of HAART by HIV-1-seropositive patients. It was started by ACTG in 2000.
Starting in 2002, patients participating in ALLRT have been tested for HCV on entry, with follow-up testing every 96 weeks beginning in 2006. Seventeen other ACTG-funded trials also test patients for HCV on entry and at various follow-up intervals, between 1996 and 2002. The authors determined the incidence of HCV infection from 1996 to 2008 among men participating in these studies. Of those 2848 patients, 2629 had at least 1 HCV antibody test result, with 264 (10%) of those individuals testing positive at baseline. Of the remaining 2365 patients, 1830 had at least 1 subsequent HCV antibody test and were included in this analysis. Their mean age at the time of the initial negative HCV antibody result was 42 years; other demographic information is shown in the table. The mean interval for HCV testing was 2.8 years for HCV seroconverters and 2.6 years for nonseroconverters.
Table
Characteristic Percentage
Race
* White 57%
* Black 22%
* Hispanic 18%
* Asian/Pacific Islander 2%
* Native American 1%
College-educated 70%
Using HAART 94%
Current or prior injection drug use at study entry 6%
HCV seroconversion occurred in 36 of the men studied (2%), for an overall incidence of .51 cases per 100 person-years. Twenty-five percent of the seroconverters reported a history of injection drug use compared with 5% of patients who remained seronegative (P < .001). However, the authors write, "compared with men with initial HCV antibody positivity, seroconverters were more likely to be white and less likely to be black and were more likely to have never injected drugs and to have attended college."
Patients who seroconverted also were more likely to have an HIV RNA level greater than 400 copies/mL compared with those who did not seroconvert. There is an association between less adherence to the HAART regimen and participation in risky sexual practices, and both of these may have figured in the higher seroconversion rate among patients with a higher viral load, the authors suggest. People in the acute stages of HCV infection are also less tolerant of HAART, which may have contributed to their poor compliance.
There were several study limitations. Only half of the participants underwent follow-up HCV testing at intervals shorter than 3 years, so the authors could not determine exactly when seroconversion occurred in these patients, making it impossible to report incidence trends over time. In addition, 23% of the participants did not undergo any follow-up HCV screening, which raises the possibility of selection bias. However, there was no difference in baseline data between those patients and the patients who did have follow-up testing, so "it is likely that the HCV seroconversions represent the true incidence among HIV-infected patients in care," the authors write.
These findings suggest that HIV-infected patients should undergo regular screening for HCV, the researchers conclude. Early detection "may permit more successful treatment and provide opportunity for intervention to mitigate disease spread among drug-using or sexual partners and education to limit liver damage."
This study was supported in part by the AIDS Clinical Trials Group funded by the National Institute of Allergy and Infectious Diseases; National Institute on Drug Abuse; Lifespan/Tufts/Brown Center for AIDS Research; Center for Drug Abuse and AIDS Research; and the National Institutes of Health. The Miriam Hospital is one of the Clinical 340 Research Sites under Harvard/Partners Clinical Trials Unit. Study authors report various financial relationships with Roche, Vertex, Genentech, BMS, Merck, SciClone, GlaxoSmithKline, Three Rivers, Johnson & Johnson, Regulus, and Tibotec.
Clin Infect Dis. Published online January 31, 2011.
Source
Triplex nucleic acid testing detected HBV, HIV, HCV before seroconversion
Posted February 8, 2011
Stramer S. N Engl J Med. 2011;364:236-247.
A triplex nucleic acid assay detected potentially infectious hepatitis B virus, hepatitis C virus and HIV after analyzing the serologic, biochemical and molecular features of 3.7 million blood donations, according to study findings.
All blood donations in the US have been screened for hepatitis B surface antigen, but the researchers said a small proportion of donors with antibodies against hepatitis B core antigen in the absence of hepatitis B surface antigen have circulating hepatitis B virus (HBV) DNA and may have a risk of infectivity. Additionally, blood collected during the early window period of HBV infection is highly infectious, but the risk decreases as hepatitis B develops.
In 2008, 2,137,275 donors made a total of 3,694,858 donations. Using the Ultrio assay (Gen-Probe), researchers discovered 26 confirmed infections (nine HBV, 15 hepatitis C virus [HCV] and two HIV), giving the assay a positive predictive value of 35%.
The nine patients with HBV had seronegative HBV DNA-positive samples, and all but one was detected on mini-pool nucleic acid testing. Researchers had expected to find no more than four seronegative HBV DNA-positive samples.
Six infected donors had been vaccinated for HBV. Researchers said routine screening for hepatitis B surface antigen or antibodies against hepatitis B core antigen would not have uncovered those infections.
They said the infections were of “inconsequential clinical significance, but their potential for transmission remains unresolved.”
“Our findings show the efficacy of the HBV vaccine for the prevention of clinical disease but not infection, and the cost of interdicting donations that contain HBV DNA from seronegative donors is high in the face of unknown benefit,” they wrote.
Source
Stramer S. N Engl J Med. 2011;364:236-247.
A triplex nucleic acid assay detected potentially infectious hepatitis B virus, hepatitis C virus and HIV after analyzing the serologic, biochemical and molecular features of 3.7 million blood donations, according to study findings.
All blood donations in the US have been screened for hepatitis B surface antigen, but the researchers said a small proportion of donors with antibodies against hepatitis B core antigen in the absence of hepatitis B surface antigen have circulating hepatitis B virus (HBV) DNA and may have a risk of infectivity. Additionally, blood collected during the early window period of HBV infection is highly infectious, but the risk decreases as hepatitis B develops.
In 2008, 2,137,275 donors made a total of 3,694,858 donations. Using the Ultrio assay (Gen-Probe), researchers discovered 26 confirmed infections (nine HBV, 15 hepatitis C virus [HCV] and two HIV), giving the assay a positive predictive value of 35%.
The nine patients with HBV had seronegative HBV DNA-positive samples, and all but one was detected on mini-pool nucleic acid testing. Researchers had expected to find no more than four seronegative HBV DNA-positive samples.
Six infected donors had been vaccinated for HBV. Researchers said routine screening for hepatitis B surface antigen or antibodies against hepatitis B core antigen would not have uncovered those infections.
They said the infections were of “inconsequential clinical significance, but their potential for transmission remains unresolved.”
“Our findings show the efficacy of the HBV vaccine for the prevention of clinical disease but not infection, and the cost of interdicting donations that contain HBV DNA from seronegative donors is high in the face of unknown benefit,” they wrote.
Source
Inhibitex Receives Fast Track Designation for INX-189 for the Treatment of Chronic Hepatitis C Infections
Posted on: Fri, 11 Feb 2011 07:00:01 EST
ATLANTA, Feb 11, 2011 (BUSINESS WIRE) --
Inhibitex, Inc. (Nasdaq: INHX
PowerRating) today reported that the U.S. Food and Drug Administration ("FDA") has designated the investigation of INX-08189 ("INX-189"), a potent guanosine nucleotide polymerase inhibitor for the treatment of chronic hepatitis C viral infection, as a Fast Track development program. Under the FDA Modernization Act of 1997, Fast Track programs are designed to facilitate the development and expedite the review of new drugs that are intended to treat serious or life threatening conditions and that demonstrate the potential to address unmet medical needs. The characteristics of INX-189 that contributed to it being granted Fast Track status include a high genetic barrier to resistance, its pan-genotypic activity, and once-daily oral dosing.
"The FDA's fast track designation for INX-189 is reflective of its unique features and the need for novel antiviral drugs that demonstrate the potential to provide better clinical outcomes and improved tolerability for the millions of individuals suffering from chronic hepatitis C infection," commented Dr. Joseph Patti, Inhibitex's Chief Scientific Officer and Senior Vice President of Research and Development.
The Company reported interim data from the first two cohorts of its ongoing Phase 1b clinical trial of INX-189 on January 9, 2011 and anticipates completing this trial by the end of the first quarter of 2011.
About HCV and INX-189
Hepatitis C is a disease of the liver caused by HCV. It is estimated that over 4 million Americans and 170 million individuals worldwide are infected with HCV, the majority of which represent chronic infections that can cause liver disease, cirrhosis and cancer. Chronic hepatitis C is the leading cause of liver transplants in the United States.
Inhibitex is developing a series of proprietary nucleotide inhibitors that target the RNA-dependent RNA polymerase (NS5b) of HCV. INX-189 is a protide of a 2'-C-methylguanosine analogue. The Company believes that preclinical and clinical studies of INX-189 completed to-date support its potential as a potent, once-daily, low dose oral therapy amenable to combination with other antivirals for the treatment of patients with all known genotypes of HCV.
About Inhibitex
Inhibitex, Inc. is a biopharmaceutical company focused on developing products to prevent and treat serious infectious diseases. In addition to INX-189, the Company's clinical stage antiviral pipeline includes FV-100, a bicyclic nucleoside inhibitor in Phase II development for the prevention and reduction of shingles-associated pain. The Company also has additional HCV nucleotide polymerase inhibitors in various stages of preclinical development and has licensed the use of its proprietary MSCRAMM(R) protein platform to Pfizer for the development of active staphylococcal vaccines. For additional information about the Company, please visit www.inhibitex.com.
Safe Harbor Statement
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties. All statements, other than historical facts included in this press release, including statements regarding the Company's belief that the results of preclinical and clinical studies of INX-189 to-date support its potential as a highly potent, once-daily, oral therapy amenable to combination with other anti-virals for the treatment of patients with all known genotypes of HCV, are forward looking statements. These intentions, expectations, or results may not be achieved in the future and various important factors could cause actual results or events to differ materially from the forward-looking statements that the Company makes, including the risk that; the results of ongoing or future preclinical or clinical studies of INX-189 alone or in combination with other anti-viral compounds not supporting its further development for lack of safety, tolerability, anti-viral activity, or any other reason; either the Company, the FDA, a data safety monitoring board or an investigational review board suspending or terminating the clinical development of INX-189 at any time for lack of safety, tolerability, anti-viral activity, or any other reason; obtaining, maintaining and protecting the intellectual property incorporated into and supporting the commercial viability of the Company's product candidates; and other cautionary statements contained elsewhere herein and in its Annual Report on Form 10-K for the year ended December 31, 2009, as filed with the Securities and Exchange Commission, or SEC, on March 26, 2010, and its Quarterly Report on Form 10-Q for the quarter ended September 30, 2010, as filed with the SEC on November 15, 2010. Given these uncertainties, you should not place undue reliance on these forward-looking statements, which apply only as of the date of this press release.
There may be events in the future that the Company is unable to predict accurately, or over which it has no control. The Company's business, financial condition, results of operations and prospects may change. The Company may not update these forward-looking statements, even though its situation may change in the future, unless it has obligations under the Federal securities laws to update and disclose material developments related to previously disclosed information. The Company qualifies all of the information contained in this press release, and particularly its forward-looking statements, by these cautionary statements.
Inhibitex(R) and MSCRAMM(R) are registered trademarks of Inhibitex, Inc.
SOURCE: Inhibitex, Inc.
Inhibitex, Inc.
Russell H. Plumb, Chief Executive Officer, 678-746-1136
rplumb@inhibitex.com
or
The Trout Group
Lee M. Stern, CFA, 646-378-2922
lstern@troutgroup.com
Source
ATLANTA, Feb 11, 2011 (BUSINESS WIRE) --
Inhibitex, Inc. (Nasdaq: INHX
PowerRating) today reported that the U.S. Food and Drug Administration ("FDA") has designated the investigation of INX-08189 ("INX-189"), a potent guanosine nucleotide polymerase inhibitor for the treatment of chronic hepatitis C viral infection, as a Fast Track development program. Under the FDA Modernization Act of 1997, Fast Track programs are designed to facilitate the development and expedite the review of new drugs that are intended to treat serious or life threatening conditions and that demonstrate the potential to address unmet medical needs. The characteristics of INX-189 that contributed to it being granted Fast Track status include a high genetic barrier to resistance, its pan-genotypic activity, and once-daily oral dosing.
"The FDA's fast track designation for INX-189 is reflective of its unique features and the need for novel antiviral drugs that demonstrate the potential to provide better clinical outcomes and improved tolerability for the millions of individuals suffering from chronic hepatitis C infection," commented Dr. Joseph Patti, Inhibitex's Chief Scientific Officer and Senior Vice President of Research and Development.
The Company reported interim data from the first two cohorts of its ongoing Phase 1b clinical trial of INX-189 on January 9, 2011 and anticipates completing this trial by the end of the first quarter of 2011.
About HCV and INX-189
Hepatitis C is a disease of the liver caused by HCV. It is estimated that over 4 million Americans and 170 million individuals worldwide are infected with HCV, the majority of which represent chronic infections that can cause liver disease, cirrhosis and cancer. Chronic hepatitis C is the leading cause of liver transplants in the United States.
Inhibitex is developing a series of proprietary nucleotide inhibitors that target the RNA-dependent RNA polymerase (NS5b) of HCV. INX-189 is a protide of a 2'-C-methylguanosine analogue. The Company believes that preclinical and clinical studies of INX-189 completed to-date support its potential as a potent, once-daily, low dose oral therapy amenable to combination with other antivirals for the treatment of patients with all known genotypes of HCV.
About Inhibitex
Inhibitex, Inc. is a biopharmaceutical company focused on developing products to prevent and treat serious infectious diseases. In addition to INX-189, the Company's clinical stage antiviral pipeline includes FV-100, a bicyclic nucleoside inhibitor in Phase II development for the prevention and reduction of shingles-associated pain. The Company also has additional HCV nucleotide polymerase inhibitors in various stages of preclinical development and has licensed the use of its proprietary MSCRAMM(R) protein platform to Pfizer for the development of active staphylococcal vaccines. For additional information about the Company, please visit www.inhibitex.com.
Safe Harbor Statement
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties. All statements, other than historical facts included in this press release, including statements regarding the Company's belief that the results of preclinical and clinical studies of INX-189 to-date support its potential as a highly potent, once-daily, oral therapy amenable to combination with other anti-virals for the treatment of patients with all known genotypes of HCV, are forward looking statements. These intentions, expectations, or results may not be achieved in the future and various important factors could cause actual results or events to differ materially from the forward-looking statements that the Company makes, including the risk that; the results of ongoing or future preclinical or clinical studies of INX-189 alone or in combination with other anti-viral compounds not supporting its further development for lack of safety, tolerability, anti-viral activity, or any other reason; either the Company, the FDA, a data safety monitoring board or an investigational review board suspending or terminating the clinical development of INX-189 at any time for lack of safety, tolerability, anti-viral activity, or any other reason; obtaining, maintaining and protecting the intellectual property incorporated into and supporting the commercial viability of the Company's product candidates; and other cautionary statements contained elsewhere herein and in its Annual Report on Form 10-K for the year ended December 31, 2009, as filed with the Securities and Exchange Commission, or SEC, on March 26, 2010, and its Quarterly Report on Form 10-Q for the quarter ended September 30, 2010, as filed with the SEC on November 15, 2010. Given these uncertainties, you should not place undue reliance on these forward-looking statements, which apply only as of the date of this press release.
There may be events in the future that the Company is unable to predict accurately, or over which it has no control. The Company's business, financial condition, results of operations and prospects may change. The Company may not update these forward-looking statements, even though its situation may change in the future, unless it has obligations under the Federal securities laws to update and disclose material developments related to previously disclosed information. The Company qualifies all of the information contained in this press release, and particularly its forward-looking statements, by these cautionary statements.
Inhibitex(R) and MSCRAMM(R) are registered trademarks of Inhibitex, Inc.
SOURCE: Inhibitex, Inc.
Inhibitex, Inc.
Russell H. Plumb, Chief Executive Officer, 678-746-1136
rplumb@inhibitex.com
or
The Trout Group
Lee M. Stern, CFA, 646-378-2922
lstern@troutgroup.com
Source
FDA removes full clinical hold on Idenix's HCV drug
Wed Feb 9, 2011 6:12pm EST
* Says to stop development of IDX320
* Says FDA places partial clinical hold on IDX184
* Says HIV drug licensed to Glaxo also put on hold (Adds details)
Feb 9 (Reuters) - Idenix Pharmaceuticals Inc (IDIX.O) said U.S. health regulators have removed the full clinical hold on one of its two experimental hepatitis C drugs, and it ceased the development of the other drug because of a toxicity issue.
In September, the U.S. Food and Drug Administration halted all trials of the experimental drugs after detecting liver function abnormalities in three healthy volunteers during an early-stage study of a combination of the compounds IDX184 and IDX320. [ID:nSGE6860G7]
The company said the observed toxicity in the drug-drug interaction study was likely caused by IDX320.
Idenix, which focuses on treating viral diseases, said the FDA has placed the IDX184 program on partial clinical hold.
It said it expects to initiate a Phase IIb trial of IDX184 in combination with pegylated interferon and antiviral pill ribavirin in the second half of 2011.
The company also said its HIV drug -- licensed to GlaxoSmithKline's (GSK.L) unit ViiV Healthcare -- was placed on a clinical hold by the FDA.
Idenix shares closed at $75.04 Wednesday on Nasdaq. (Reporting by Anand Basu in Bangalore; Editing by Joyjeet Das)
Source
* Says to stop development of IDX320
* Says FDA places partial clinical hold on IDX184
* Says HIV drug licensed to Glaxo also put on hold (Adds details)
Feb 9 (Reuters) - Idenix Pharmaceuticals Inc (IDIX.O) said U.S. health regulators have removed the full clinical hold on one of its two experimental hepatitis C drugs, and it ceased the development of the other drug because of a toxicity issue.
In September, the U.S. Food and Drug Administration halted all trials of the experimental drugs after detecting liver function abnormalities in three healthy volunteers during an early-stage study of a combination of the compounds IDX184 and IDX320. [ID:nSGE6860G7]
The company said the observed toxicity in the drug-drug interaction study was likely caused by IDX320.
Idenix, which focuses on treating viral diseases, said the FDA has placed the IDX184 program on partial clinical hold.
It said it expects to initiate a Phase IIb trial of IDX184 in combination with pegylated interferon and antiviral pill ribavirin in the second half of 2011.
The company also said its HIV drug -- licensed to GlaxoSmithKline's (GSK.L) unit ViiV Healthcare -- was placed on a clinical hold by the FDA.
Idenix shares closed at $75.04 Wednesday on Nasdaq. (Reporting by Anand Basu in Bangalore; Editing by Joyjeet Das)
Source
Medivir Announces Start of Phase 1a Trial of the Hepatitis C Polymerase Inhibitor TMC649128
HUDDINGE, Sweden, February 10, 2011 /PRNewswire/ -- Medivir AB (OMX: MVIR), the emerging research-based specialty pharmaceutical company focused on infectious diseases, today announces the start of a phase 1a clinical trial with TMC649128 intended for the treatment of chronic hepatitis C virus infection.
TMC649128 is a nucleoside NS5B polymerase inhibitor that has already demonstrated an attractive pre-clinical profile. It is anticipated that this profile would see TMC649128 be used in combination with HCV directly acting antiviral agents, given their high genetic barrier to resistance and antiviral activity across multiple HCV genotypes.
In pre-clinical studies, TMC649128 displayed in vitro activity across multiple HCV genotypes and a high genetic barrier to resistance.
The phase 1a trial is a double-blind, randomized, placebo-controlled single-ascending dose trial to assess the safety, tolerability and pharmacokinetics in healthy volunteers and will be conducted in Belgium. TMC649128 is being developed in collaboration with Tibotec Pharmaceuticals.
Milestone payment
Medivir entered a Research and Development agreement in the field of hepatitis C virus polymerase with Ortho Biotech Products LP, an affiliate of Tibotec in May 2008. The development of TMC649128 falls under this agreement and by entering clinical development, a milestone payment of Euro 7 million has been triggered for payment to Medivir.
"We are extremely excited to see TMC649128, our first HCV nucleoside inhibitor, move into clinical development", stated Bertil Samuelsson, CSO of Medivir. "The start of this phase 1a trial underlines Medivir's commitment to the development of novel and innovative hepatitis C treatments. We view nucleoside inhibitors as cornerstone components of future HCV treatment paradigms in combination with directly acting antiviral agents and a TMC649128 component could set them apart from other HCV drug classes."
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's Commitment of the HCV Area
Medivir and Tibotec are also jointly developing the once daily protease inhibitor TMC435 for treatment of hepatitis C virus infections (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. Medivir has a strong R&D portfolio and has recently launched its first product Xerese(TM)/Xerclear(R). Medivir's key pipeline asset, TMC435, a protease inhibitor, is in phase 2b clinical development for Hepatitis C and is partnered with Tibotec Pharmaceuticals.
Xerese(TM)/Xerclear(R) is an innovative treatment for cold sores, which has been approved in both the US and Europe. It is partnered with GlaxoSmithKline to be sold OTC in Europe and Russia and with Meda AB in North America. Medivir has retained the Rx rights for Xerclear(R) in Sweden and Finland.
For more information about Medivir, please visit the Company's website: http://www.medivir.se/
For more information about Medivir, please contact;
Medivir (http://www.medivir.se/)
Rein Piir, CFO & VP Investor Relations
Mobile: +46-708-537-292
M:Communications
Europe: Mary-Jane Elliott / Amber Bielecka /
Nick Francis
Medivir@mcomgroup.com
+44(0)20-7920-2330
USA: Jason Marshall
+1-212-897-5497
SOURCE Medivir
Source
TMC649128 is a nucleoside NS5B polymerase inhibitor that has already demonstrated an attractive pre-clinical profile. It is anticipated that this profile would see TMC649128 be used in combination with HCV directly acting antiviral agents, given their high genetic barrier to resistance and antiviral activity across multiple HCV genotypes.
In pre-clinical studies, TMC649128 displayed in vitro activity across multiple HCV genotypes and a high genetic barrier to resistance.
The phase 1a trial is a double-blind, randomized, placebo-controlled single-ascending dose trial to assess the safety, tolerability and pharmacokinetics in healthy volunteers and will be conducted in Belgium. TMC649128 is being developed in collaboration with Tibotec Pharmaceuticals.
Milestone payment
Medivir entered a Research and Development agreement in the field of hepatitis C virus polymerase with Ortho Biotech Products LP, an affiliate of Tibotec in May 2008. The development of TMC649128 falls under this agreement and by entering clinical development, a milestone payment of Euro 7 million has been triggered for payment to Medivir.
"We are extremely excited to see TMC649128, our first HCV nucleoside inhibitor, move into clinical development", stated Bertil Samuelsson, CSO of Medivir. "The start of this phase 1a trial underlines Medivir's commitment to the development of novel and innovative hepatitis C treatments. We view nucleoside inhibitors as cornerstone components of future HCV treatment paradigms in combination with directly acting antiviral agents and a TMC649128 component could set them apart from other HCV drug classes."
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's Commitment of the HCV Area
Medivir and Tibotec are also jointly developing the once daily protease inhibitor TMC435 for treatment of hepatitis C virus infections (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. Medivir has a strong R&D portfolio and has recently launched its first product Xerese(TM)/Xerclear(R). Medivir's key pipeline asset, TMC435, a protease inhibitor, is in phase 2b clinical development for Hepatitis C and is partnered with Tibotec Pharmaceuticals.
Xerese(TM)/Xerclear(R) is an innovative treatment for cold sores, which has been approved in both the US and Europe. It is partnered with GlaxoSmithKline to be sold OTC in Europe and Russia and with Meda AB in North America. Medivir has retained the Rx rights for Xerclear(R) in Sweden and Finland.
For more information about Medivir, please visit the Company's website: http://www.medivir.se/
For more information about Medivir, please contact;
Medivir (http://www.medivir.se/)
Rein Piir, CFO & VP Investor Relations
Mobile: +46-708-537-292
M:Communications
Europe: Mary-Jane Elliott / Amber Bielecka /
Nick Francis
Medivir@mcomgroup.com
+44(0)20-7920-2330
USA: Jason Marshall
+1-212-897-5497
SOURCE Medivir
Source
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