Monday HCV News Ticker:Born Between 1945-1965? Aged-Based Hepatitis Screenings on the Horizon
- File Under HCV News, liver health, Pharmaceuticals, support-hotline
Pavel Tchelitchew. Anatomical Painting, 1946.
New On The Blog
An off-the-shelf cholesterol-lowering drug blocks hepatitis C from gaining entry into the cell.
Podcast- Feb 2012
Source- Nature
In The News
"whether to use and how to use non-invasive makers of fibrosis instead of liver biopsy to determine a patient's need for treatment, and the optimal timing to initiate treatment.....
Management of chronic HCV in the U.S. could be improved by a shift towards strategies that initiate immediate treatment without fibrosis screening or else periodic screening with a non-invasive method followed by treatment for those found likely to have significant fibrosis.....The model did not include possible future advances in treatment in the base case analysis and allow patients to delay treatment for a later date. The analyses also did not include the benefits of fibrosis screening to patients being able to make an informed choice and, therefore, potentially having a stronger commitment to treatment adherence."
Noted by Jules @ NATAP: As we move close to very high cure rates, 90% or more, this discussion becomes increasingly relevant. Should any patient defer HCV therapy if cure rates are 90-100%, even though in HCV mono-infection a patient may not progress over 30 years to serious liver disease? We know even though a specific patient may not develop serious liver disease over such a long span of time or even a lifetime, HCV infection can cause other cormorbid diseases including cancers outside the liver, it affects other bodily organs, in other words the presence of HCV-infection is not innocuous even if liver disease does not progress. And if a patient' chance for cure is 90-100% with a 3-drug all oral therapy taken for 12-24 weeks, should everyone be treated, is this cost-effective, should re-imbursers encourage treatment??? These are discussions that will become increasingly likely to be held. There have been in addition recent presentations of these studies finding successful treatment reduces risk for death, liver cancer, & morbidity....
Read Study and download PDF @ NATAP
Posted by Dr. Stephen Vogt ⋅ February 6, 2012
Deaths due to hepatitis C in the United States have already reached 15,000 deaths each year, according to the Centers for Disease Control and Prevention (CDC). This number is expected to rise to 35,000 hepatitis C deaths per year within the next two decades. Baby Boomers account for 75 percent of hepatitis C virus (HCV) fatalities.
An estimated 1.6 million U.S. adults ages 40-64 are currently infected with the hepatitis C virus but have no idea of their disease state. How could this happen? The answer is partly due to the silent nature of HCV infection: it can be without any symptoms for up to 20 years. The other part of the answer is connected to the current standards that limit HCV screenings to those with conventional high risk factors (such as IV drug use, blood transfusion before 1992, or unprotected sex with a known HCV-infected person). Yet a huge portion of people (many of them Baby Boomers) do not fit this risk factor profile.
As I pointed out last year, in “Call for Wider Hepatitis Screenings ,” we can stem this rising tide of HCV deaths by instituting more HCV screenings, particularly age-based screenings for all Baby Boomers. Today, we are getting one step closer to changing the HCV screening process from the current one based on risk factors to a screening process based on birth year.
The CDC is poised to recommend a one-time age-based screening for all Baby Boomers. A new CDC-funded study took a close look at the cost-effectiveness of an aged-based screening for HCV. It was clear that a one-time screening (followed by treatment for infected individuals) for everyone born from 1945-1965 would pay off both financially and in healthier lives. The cost-effectiveness from widespread HCV screenings would be in line with cervical cancer and cholesterol screenings.
A switch to an aged-based screening couldn’t come at a better time. Screening tests are faster and easier than ever (answers can come back as quick as 20 minutes ) and treatments today clear this virus in greater numbers of infected people, giving a meaningful cure to most patients.
Stephen C Vogt, PharmD
President and CEO
BioPlus SP
President and CEO
BioPlus SP
New national hepatitis C Helpline promises “One call – lots of help”
Project Inform is pleased to announce the launch of a new national helpline, 877-HELP-4-HEP (877-435-7443), run by and for people affected by hepatitis C. This consumer resource is the result of two year-long collaboration among five national nonprofits with a combined 90 years’ experience in phone-based peer counseling, including Project Inform.
Hepatitis C affects nearly 4.5 million Americans, and each year nearly 17,000 people are newly infected. Chronic hepatitis C infection is a leading cause of liver cancer and transplants, and is associated with nearly 12,000 deaths each year. The US currently faces a large population of people in growing need of care and treatment.
Being diagnosed with hepatitis C carries with it many emotional and social challenges. It is especially complicated by the lack of comprehensive medical, mental health and community support services. People with hepatitis C report spending countless hours trying to find reliable support and information.
The launch of 877-HELP-4-HEP has been timed to respond to the growing need for hepatitis C care information and referrals as vastly improved treatments become available.
In 2012, the rollout of a new point-of-contact antibody test will occur, and the Centers for Disease Control will release new Guidelines to screen for the virus. More than one-half of people with hepatitis C do not know they are infected. In 2011, two new drugs came to market that have nearly doubled the cure rate, offering hope to many to live free of the virus. Additionally, President Obama increased federal spending on viral hepatitis by $10 million, and the Department of Health & Human Services announced its Action Plan for the Prevention, Care and Treatment of Viral Hepatitis, both of which elevate the national discourse on hepatitis C infection and treatment. These significant policy developments have occurred, in part, as a result of Project Inform’s advocacy.
These recent changes in hep C care provide ample opportunity for supporting and linking people into care. Unique to 877-HELP-4-HEP are specially trained peer counselors using a structured approach to help callers navigate through screening, diagnosis, medical evaluation and treatment. Follow-up contact by the counselors keeps callers engaged at each step of their journey and helps them follow through with their health decisions.
877-HELP-4-HEP also uses an up-to-date national database of 25,000 referral resources and a secure shared caller database for counseling continuity. 877-HELP-4-HEP is designed to maintain contact with callers to improve health outcomes as well as document and measure the impact of our services.
877-HELP-4-HEP (877-435-7443) operates Monday through Friday 9am to 7pm EST. To learn more, visit www.help4hep.org or email info@help4hep.org.
Hepatitis C affects nearly 4.5 million Americans, and each year nearly 17,000 people are newly infected. Chronic hepatitis C infection is a leading cause of liver cancer and transplants, and is associated with nearly 12,000 deaths each year. The US currently faces a large population of people in growing need of care and treatment.
Being diagnosed with hepatitis C carries with it many emotional and social challenges. It is especially complicated by the lack of comprehensive medical, mental health and community support services. People with hepatitis C report spending countless hours trying to find reliable support and information.
The launch of 877-HELP-4-HEP has been timed to respond to the growing need for hepatitis C care information and referrals as vastly improved treatments become available.
In 2012, the rollout of a new point-of-contact antibody test will occur, and the Centers for Disease Control will release new Guidelines to screen for the virus. More than one-half of people with hepatitis C do not know they are infected. In 2011, two new drugs came to market that have nearly doubled the cure rate, offering hope to many to live free of the virus. Additionally, President Obama increased federal spending on viral hepatitis by $10 million, and the Department of Health & Human Services announced its Action Plan for the Prevention, Care and Treatment of Viral Hepatitis, both of which elevate the national discourse on hepatitis C infection and treatment. These significant policy developments have occurred, in part, as a result of Project Inform’s advocacy.
These recent changes in hep C care provide ample opportunity for supporting and linking people into care. Unique to 877-HELP-4-HEP are specially trained peer counselors using a structured approach to help callers navigate through screening, diagnosis, medical evaluation and treatment. Follow-up contact by the counselors keeps callers engaged at each step of their journey and helps them follow through with their health decisions.
877-HELP-4-HEP also uses an up-to-date national database of 25,000 referral resources and a secure shared caller database for counseling continuity. 877-HELP-4-HEP is designed to maintain contact with callers to improve health outcomes as well as document and measure the impact of our services.
877-HELP-4-HEP (877-435-7443) operates Monday through Friday 9am to 7pm EST. To learn more, visit www.help4hep.org or email info@help4hep.org.
Anaerobic threshold, as determined by submaximal cardiopulmonary exercise testing, may have value in predicting 90-day post-transplant survival for patients undergoing liver transplantation, according to a study published in the February issue of Liver Transplantation.
James M. Prentis, M.B.B.S., M.R.C.P., of the Freeman Hospital in Newcastle upon Tyne, U.K., and colleagues utilized preoperative submaximal CPET data for prediction of 90-day post-liver transplant survival. A total of 182 patients underwent CPET preoperatively, and 165 completed it successfully (defined as the ability to determine the AT). Ninety-day post-transplant survival, critical care length of stay, and overall length of hospital stay were evaluated during the post-transplant follow-up.
The researchers found that 33 percent of the patients underwent liver transplantation, and the mortality rate was 10 percent. The mean AT values were significantly higher for survivors compared with those who did not survive. On multivariate analysis, AT was the only significant predictor of mortality. In the receiver operating curve analysis, the sensitivity and specificity of AT was 90.7 and 83.3 percent, respectively, and the area under the receiver operating characteristic curve was 0.92. The optimal AT level for survival was established as greater than 9.0 mL/minute/kg. Substitution of ideal weight for actual body weight of a patient with refractory ascites improved the predictive value.
"Our results demonstrate that patients with good cardiopulmonary reserve (according to an exercise test before liver transplantation) have a higher survival rate and use less critical care resources postoperatively," the authors write.
Abstract
Full Text (subscription or payment may be required)
Copyright © 2012 HealthDay. All rights reserved.
Laparoscopy for liver malignancy oncologically safe: study
NEW YORK (Reuters Health) - Laparoscopic liver resections for cancer are oncologically safe and efficient, with survival rates similar to open surgery - at one U.K. center, at least, doctors there say.
There's continuous debate over whether laparoscopy is a viable alternative to open surgery for liver tumors, especially for complex cases or major resections, Dr. Mohammed Abu Hilal of the University Hospital Southampton NHS Foundation Trust and his colleagues write.
In their series of 133 surgeries, reported this month in Archives of Surgery, patients did well, they say.
In an invited critique, Dr. Jake Krige and Dr. Delawir Kahn of the University of Cape Town in South Africa say the "relatively large" experience confirms laparoscopic liver resection is similar to open surgery in terms of oncological safety and efficacy.
But, they warn, "For the moment, the laparoscopic technique for major liver resections should be confined to those centers that have both substantive experience with liver resection surgery and advanced laparoscopic skills."
And it's not likely to be feasible in all patients, they add.
Dr. Abu Hilal and his team reviewed perioperative results and survival for 128 patients treated at their center between 2003 and 2010. Their analysis included 133 surgeries in all, because two patients had two-stage operations and three had repeated resections for recurrent disease.
Eighty-three patients were being treated for colorectal metastases. Other indications for surgery included hepatocellular carcinoma (HCC; 18 patients), neuroendocrine tumor (NET) metastasis (17 patients), non-colorectal metastasis (11 patients), and two patients each with lymphoma and intrahepatic cholangiosarcoma.
The median operative time was 210 minutes, and the median length of stay was four days. Seven patients needed conversion to open surgery, while four required conversion to a laparoscopic-assisted procedure. Sixteen patients had major postoperative complications; one patient died in the hospital.
None of the patients developed port-site metastasis, and no peritoneal seeding was observed.
Two-year overall survival was 80% for patients with colorectal metastases, 77% for patients with HCC, and 92% for the NET patients.
Most of the NET patients were treated with debulking and cytoreductive surgery. Six of the 17 had positive microscopic resection margins. Out of the remaining 116 resections, microscopic resection margins were negative in 112.
Some fear that NET manipulation during laparoscopic surgery could lead to excessive hormone release and "life-threatening carcinoid crisis," the researchers note. They say all patients in this series received perioperative octreotide infusion, and there were no carcinoid crises.
"The excellent 92 percent 2-year overall survival in the NET metastasis group justified the aggressive management and confirms the efficacy of the laparoscopic approach," Dr. Abu Hilal and colleagues write.
In their critique, Dr. Krige and Dr. Kahn say, "For now, LLR appears to be as good as the open technique. Whether it is better can only be addressed in a randomized controlled trial."
SOURCE: http://bit.ly/wiQUEH
Arch Surg 2012;147:42-48.
In Case You Missed It
SVR Achieved With Two Direct-acting Antivirals in Absence of Interferon in Small Study
t-acting antiviral agents (DAAs)—asunaprevir and daclatasvir—suppressed hepatitis C virus (HCV) genotype 1 infection in a majority of patients who had previously not responded to treatment, according to results from a small Phase II study published in the Jan. 19 issue of The New England Journal of Medicine (Lok AS et al. 2012;366:216-224).
Success rates were 100% in patients who received the drugs in combination with peginterferon alfa-2a (Peg-IFN) and ribavirin (RBV).
And, most notably, even in patients who received daclatasvir and asunaprevir without Peg-IFN and RBV, sustained virologic response (SVR) was achieved in 36% of patients, making this the first published study to show that SVR can be achieved with an IFN-free treatment in previous null responders.
“The response in some patients to the combination of daclatasvir and asunaprevir alone showed proof-of-concept that a sustained virologic response can be achieved without peginterferon and ribavirin therapy,” concluded the research team, led by Anna S. Lok, MD, professor of internal medicine in the Division of Gastroenterology, University of Michigan Medical School, Ann Arbor.
In an editorial accompanying the study, Raymond T. Chung, MD, director of hepatology and medical director of the liver transplant program at Massachusetts General Hospital, Boston, called the study a “watershed moment in the annals of HCV therapy.
“It shows that sustained virologic response can be achieved without interferon. Implicit in this finding is the concept that two potent agents with complementary resistance profiles, given for a sufficient duration, can impose a stranglehold on viral replication and result in clearance of the virus.”
In this Phase II study, 10 patients received the experimental drugs in combination with Peg-IFN and RBV for 24 weeks. All 10 patients had undetectable viral loads at the end of treatment and at 12 weeks after stopping treatment. Nine patients continued to exhibit SVR at 48 weeks after treatment, whereas one patient had HCV RNA of less than 25 IU/mL at post-treatment week 48 and undetectable HCV RNA 13 days later.
In a separate arm of the study, 11 patients received asunaprevir and daclatasvir alone, without the addition of Peg-IFN and RBV.
Of these, four patients (36%) achieved an SVR at 12 and 24 weeks after treatment. Six patients (55%) had viral breakthrough during treatment, with resistance mutations to both antiviral agents. Breakthroughs occurred as early as treatment week 3 and as late as treatment week 12.
Although only one-third of the patients given the two-drug combination without Peg-IFN and RBV achieved an SVR, investigators and other hepatologists say the finding is “very promising.”
“For years, the concept of IFN-free therapy was hotly debated. Now, we’re very quickly moving toward IFN-free therapy. It’s potentially just around the corner,” said Donald M. Jensen, MD, professor of medicine and director of the Center for Liver Diseases, University of Chicago Medical Center.
“For patients who can wait, they might just have to wait a few more years until IFN-free therapy is on the market,” he said.
Daclatasvir is a first-in-class, highly selective HCV NS5A replication complex inhibitor that has shown picomolar potency in vitro. Asunaprevir is a highly active HCV NS3 protease inhibitor. Both drugs produce robust declines in HCV RNA levels in patients with HCV genotype 1 infection and, taken in combination, there is no clinically meaningful pharmacokinetic interaction.
Hepatologists say that treatment of HCV infection is entering a new era, highlighted by combinations of second-generation DAAs. As more DAAs are developed with non-overlapping resistance profiles, they may reduce dependence on treatment with IFN.
“These data are very encouraging because peginterferon-alfa and ribavirin are associated with many side effects and many patients with hepatitis C choose not to receive treatment for fear that they cannot tolerate those drugs,” said Dr. Lok, in a statement.
The participants in Dr. Lok’s study had previously failed to respond to Peg-IFN and RBV treatment, meaning they represent a difficult-to-treat population with poor expected outcomes. Previous null responders typically do not respond to retreatment with Peg-IFN and RBV and also tend to have a poor response to triple-combination therapy with Peg-IFN and RBV plus a protease inhibitor.
This combination of new DAAs, if supported by larger studies, could help the large number of patients who have not responded to previous treatment.
“Because of this high unmet medical need, there is a necessity for new combination regimens that can increase response rates in that population,” said Dr. Lok.
Study Details
In the current study, investigators screened 56 patients and ultimately enrolled 21 patients in an exploratory cohort to assess the safety and antiviral activity of the new DAAs. All patients were between the ages of 18 and 70 years, had a chronic HCV genotype 1 infection with an HCV RNA level of 105 IU/mL or higher, showed no evidence of cirrhosis and exhibited no response to previous HCV therapy. Of these patients, 90% had interleukin 28B (IL28B) genotype CT or TT, both of which are associated with poor response to Peg-IFN and RBV, and most patients had HCV genotype 1a infection.
Daclatasvir was administered orally at a dose of 60 mg once daily and asunaprevir at a dose of 600 mg twice daily, with no dose reductions permitted. Ten patients also received Peg-IFN 180 mcg per week, administered subcutaneously, and RBV, administered orally twice daily, with doses determined according to body weight.
Investigators believe that the combination of two DAAs increases the resistance barrier, particularly for patients with HCV genotype 1b infection. In this study, all viral breakthroughs occurred in patients with HCV genotype 1a infection.
This study appears to confirm the results of a recent Japanese study, which showed a high SVR rate among patients with HCV genotype 1b infection in a pilot study of 10 previous non-responders who received combination therapy with asunaprevir and daclatasvir (Chayama K et al. Hepatology 2011 Oct 10; 10.1002/hep.24724 [Epub ahead of print]).
The key benefit of treatment with Peg-IFN and RBV appears to be prevention of viral breakthrough. No patient who received the four-drug combination in the current study experienced a viral breakthrough, whereas six patients in the group that received the DAAs alone had viral breakthroughs. All patients who had a viral breakthrough received and initially responded to Peg-IFN and RBV as rescue therapy. Most ultimately had therapeutic failure.
The high frequency of resistance sends a strong cautionary note about these therapies, said investigators. Future studies of combinations of DAAs without Peg-IFN and RBV in patients with HCV genotype 1a infection should proceed carefully, said the investigators.
But, they added, further research on combinations of DAAs, with or without Peg-IFN and RBV, should be encouraged.
The most common adverse events in this study were diarrhea, fatigue, headache and nausea, which were mild or moderate in all cases. Grade 3 or 4 neutropenia occurred in six patients, all of whom were receiving Peg-IFN and RBV in addition to the two DAAs. No grade 3 or 4 events related to hemoglobin levels or platelet counts were observed.
“This is an exciting study that means care will be better for patients,” said Andrew J. Muir, MD, clinical director of hepatology, Duke University Health System, Durham, N.C., who was not involved with the study.
“For the first time, patients were cured of HCV without interferon-a. Interferon-a has always been the backbone of HCV therapy but has many side effects that make treatment too difficult for many patients.”
Bristol-Myers Squibb, manufacturer of asunaprevir and daclatasvir, funded this study. Dr. Lok has received consulting fees from Abbott Laboratories, Bristol-Myers Squibb and Gilead Sciences, and grant support from Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Merck–Schering-Plough and Roche. Dr. Muir has received grant support from Bristol-Myers Squibb, Gilead Sciences, Merck–Schering-Plough, Roche and Vertex Pharmaceuticals. Dr. Jensen has served on advisory committees or review panels for Abbott Laboratories, Boehringer Ingelheim, Genentech/Roche, GlobeImmune, Human Genome Sciences, Merck, Pfizer, Pharmasset, Tibotec and Vertex Pharmaceuticals; he has received consulting fees from Abbott Laboratories, Bristol-Myers Squibb, Genentech/Roche and Vertex Pharmaceuticals; and he has received grant/research support from Boehringer Ingelheim, Genentech/Roche, Tibotec and Vertex Pharmaceuticals.
In Case You Missed It
Daclatasvir and Asunaprevir Without Peg-IFN and RBV
,
,
SVR Achieved With Two Direct-acting Antivirals in Absence of Interferon in Small Study
ISSUE: FEBRUARY 2012 | VOLUME: 63:2
by Christina Frangou
A combination therapy including two investigational direct-acting antiviral agents (DAAs)—asunaprevir and daclatasvir—suppressed hepatitis C virus (HCV) genotype 1 infection in a majority of patients who had previously not responded to treatment, according to results from a small Phase II study published in the Jan. 19 issue of The New England Journal of Medicine (Lok AS et al. 2012;366:216-224).
Success rates were 100% in patients who received the drugs in combination with peginterferon alfa-2a (Peg-IFN) and ribavirin (RBV).
And, most notably, even in patients who received daclatasvir and asunaprevir without Peg-IFN and RBV, sustained virologic response (SVR) was achieved in 36% of patients, making this the first published study to show that SVR can be achieved with an IFN-free treatment in previous null responders.
“The response in some patients to the combination of daclatasvir and asunaprevir alone showed proof-of-concept that a sustained virologic response can be achieved without peginterferon and ribavirin therapy,” concluded the research team, led by Anna S. Lok, MD, professor of internal medicine in the Division of Gastroenterology, University of Michigan Medical School, Ann Arbor.
In an editorial accompanying the study, Raymond T. Chung, MD, director of hepatology and medical director of the liver transplant program at Massachusetts General Hospital, Boston, called the study a “watershed moment in the annals of HCV therapy.
“It shows that sustained virologic response can be achieved without interferon. Implicit in this finding is the concept that two potent agents with complementary resistance profiles, given for a sufficient duration, can impose a stranglehold on viral replication and result in clearance of the virus.”
In this Phase II study, 10 patients received the experimental drugs in combination with Peg-IFN and RBV for 24 weeks. All 10 patients had undetectable viral loads at the end of treatment and at 12 weeks after stopping treatment. Nine patients continued to exhibit SVR at 48 weeks after treatment, whereas one patient had HCV RNA of less than 25 IU/mL at post-treatment week 48 and undetectable HCV RNA 13 days later.
In a separate arm of the study, 11 patients received asunaprevir and daclatasvir alone, without the addition of Peg-IFN and RBV.
Of these, four patients (36%) achieved an SVR at 12 and 24 weeks after treatment. Six patients (55%) had viral breakthrough during treatment, with resistance mutations to both antiviral agents. Breakthroughs occurred as early as treatment week 3 and as late as treatment week 12.
Although only one-third of the patients given the two-drug combination without Peg-IFN and RBV achieved an SVR, investigators and other hepatologists say the finding is “very promising.”
“For years, the concept of IFN-free therapy was hotly debated. Now, we’re very quickly moving toward IFN-free therapy. It’s potentially just around the corner,” said Donald M. Jensen, MD, professor of medicine and director of the Center for Liver Diseases, University of Chicago Medical Center.
“For patients who can wait, they might just have to wait a few more years until IFN-free therapy is on the market,” he said.
Daclatasvir is a first-in-class, highly selective HCV NS5A replication complex inhibitor that has shown picomolar potency in vitro. Asunaprevir is a highly active HCV NS3 protease inhibitor. Both drugs produce robust declines in HCV RNA levels in patients with HCV genotype 1 infection and, taken in combination, there is no clinically meaningful pharmacokinetic interaction.
Hepatologists say that treatment of HCV infection is entering a new era, highlighted by combinations of second-generation DAAs. As more DAAs are developed with non-overlapping resistance profiles, they may reduce dependence on treatment with IFN.
“These data are very encouraging because peginterferon-alfa and ribavirin are associated with many side effects and many patients with hepatitis C choose not to receive treatment for fear that they cannot tolerate those drugs,” said Dr. Lok, in a statement.
The participants in Dr. Lok’s study had previously failed to respond to Peg-IFN and RBV treatment, meaning they represent a difficult-to-treat population with poor expected outcomes. Previous null responders typically do not respond to retreatment with Peg-IFN and RBV and also tend to have a poor response to triple-combination therapy with Peg-IFN and RBV plus a protease inhibitor.
This combination of new DAAs, if supported by larger studies, could help the large number of patients who have not responded to previous treatment.
“Because of this high unmet medical need, there is a necessity for new combination regimens that can increase response rates in that population,” said Dr. Lok.
Study Details
In the current study, investigators screened 56 patients and ultimately enrolled 21 patients in an exploratory cohort to assess the safety and antiviral activity of the new DAAs. All patients were between the ages of 18 and 70 years, had a chronic HCV genotype 1 infection with an HCV RNA level of 105 IU/mL or higher, showed no evidence of cirrhosis and exhibited no response to previous HCV therapy. Of these patients, 90% had interleukin 28B (IL28B) genotype CT or TT, both of which are associated with poor response to Peg-IFN and RBV, and most patients had HCV genotype 1a infection.
Daclatasvir was administered orally at a dose of 60 mg once daily and asunaprevir at a dose of 600 mg twice daily, with no dose reductions permitted. Ten patients also received Peg-IFN 180 mcg per week, administered subcutaneously, and RBV, administered orally twice daily, with doses determined according to body weight.
Investigators believe that the combination of two DAAs increases the resistance barrier, particularly for patients with HCV genotype 1b infection. In this study, all viral breakthroughs occurred in patients with HCV genotype 1a infection.
This study appears to confirm the results of a recent Japanese study, which showed a high SVR rate among patients with HCV genotype 1b infection in a pilot study of 10 previous non-responders who received combination therapy with asunaprevir and daclatasvir (Chayama K et al. Hepatology 2011 Oct 10; 10.1002/hep.24724 [Epub ahead of print]).
The key benefit of treatment with Peg-IFN and RBV appears to be prevention of viral breakthrough. No patient who received the four-drug combination in the current study experienced a viral breakthrough, whereas six patients in the group that received the DAAs alone had viral breakthroughs. All patients who had a viral breakthrough received and initially responded to Peg-IFN and RBV as rescue therapy. Most ultimately had therapeutic failure.
The high frequency of resistance sends a strong cautionary note about these therapies, said investigators. Future studies of combinations of DAAs without Peg-IFN and RBV in patients with HCV genotype 1a infection should proceed carefully, said the investigators.
But, they added, further research on combinations of DAAs, with or without Peg-IFN and RBV, should be encouraged.
The most common adverse events in this study were diarrhea, fatigue, headache and nausea, which were mild or moderate in all cases. Grade 3 or 4 neutropenia occurred in six patients, all of whom were receiving Peg-IFN and RBV in addition to the two DAAs. No grade 3 or 4 events related to hemoglobin levels or platelet counts were observed.
“This is an exciting study that means care will be better for patients,” said Andrew J. Muir, MD, clinical director of hepatology, Duke University Health System, Durham, N.C., who was not involved with the study.
“For the first time, patients were cured of HCV without interferon-a. Interferon-a has always been the backbone of HCV therapy but has many side effects that make treatment too difficult for many patients.”
Bristol-Myers Squibb, manufacturer of asunaprevir and daclatasvir, funded this study. Dr. Lok has received consulting fees from Abbott Laboratories, Bristol-Myers Squibb and Gilead Sciences, and grant support from Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Merck–Schering-Plough and Roche. Dr. Muir has received grant support from Bristol-Myers Squibb, Gilead Sciences, Merck–Schering-Plough, Roche and Vertex Pharmaceuticals. Dr. Jensen has served on advisory committees or review panels for Abbott Laboratories, Boehringer Ingelheim, Genentech/Roche, GlobeImmune, Human Genome Sciences, Merck, Pfizer, Pharmasset, Tibotec and Vertex Pharmaceuticals; he has received consulting fees from Abbott Laboratories, Bristol-Myers Squibb, Genentech/Roche and Vertex Pharmaceuticals; and he has received grant/research support from Boehringer Ingelheim, Genentech/Roche, Tibotec and Vertex Pharmaceuticals.
Infectious Disease
Review Article
200th Anniversary Article
N Engl J Med 2012; 366:454-461
February 2, 2012
Among the many challenges to health, infectious diseases stand out for their ability to have a profound impact on the human species. Great pandemics and local epidemics alike have influenced the course of wars, determined the fates of nations and empires, and affected the progress of civilization, making infections compelling actors in the drama of human history.1-11 For 200 years, the Journal has captured the backdrop to this human drama in thousands of articles about infectious diseases and about biomedical research and public health efforts to understand, treat, control, and prevent them.An unanticipated outcome of the explosion of information concerning the microbial world is the recognition that a growing number of chronic diseases that were once attributed to host, environmental, or lifestyle factors or to unknown causes are actually directly or indirectly caused by infectious agents that potentially can be controlled through prevention and treatment.
For example, liver cancer and cirrhosis are complications of hepatitis B and C infections, cervical cancer is a complication of human papillomavirus (HPV) infection, and gastric and duodenal ulcers may result from Helicobacter pylori infection.70-72 Vaccines against two of these agents, hepatitis B and HPV, are already in use, exemplifying the concept of cancer-preventing vaccines. H. pylori infection can be cured with antibiotics, and chronic hepatitis B and C infections are being treated by means of antiviral regimens with growing success rates. Certain autoimmune conditions have also been attributed to infections. For example, enteric microbes have been associated with inflammatory arthritides, and Campylobacter jejuni and certain viruses have been associated with the Guillain–BarrĂ© syndrome.73
In addition, with new technologies and approaches, scientists are exploring new facets of microbiology, including the role of the human microbiome in maintaining homeostasis in the ecosystems of our bodies and its possible relationship to conditions such as obesity and inflammatory bowel disease.
Read Full Article From The New England Journal Of Medicine Here
Stem Cells
06 February 2012
By
Appeared in BioNews 643
A clinic in California has announced that its doctors are licensed and trained to carry out a stem cell treatment for chronic pain. Meanwhile, the US Food and Drug Administration (FDA) is pursuing a lawsuit against Regenerative Sciences, the company that developed the technique.
Regenerative Sciences claims that the procedure, called Regenexx, is an alternative to potentially painful surgery for injuries such as bone fractures and torn tendons. Doctors take stem cells from the bone marrow of a patient, and process them in a solution, so that they strengthen and multiply. They are then injected into the injured joints, helping to rebuild damaged tissue.
The FDA states that stem cell treatments are a type of medication, and so fall under its jurisdiction. It says the safety of the procedure has not been sufficiently tested, and inspections showed that facilities offering the treatment do not meet its standards. It has insisted that Regenerative Sciences stop performing the Regenexx procedure until the case is resolved.
Regenerative Sciences counter that because stem cells are produced by the body, they are not drugs, so the treatment does not need FDA approval. The group claims to have treated more than 1,000 patients and spent over $500,000 on testing. Regenerative Sciences also point out that the California clinic uses a modified version of the technique that does not include a growth enhancer, a crucial part of the FDA's lawsuit.
Dr Christopher Centeno, director of Regenerative Sciences, says that the FDA is pursuing the case because it fears that Regenexx will become a successful alternative to pain medication, and threaten the FDA's control of a lucrative market. 'Unfortunately, in many cases, it's the clients suffering the most that we can't treat now', he told 5280 - the Denver Magazine.
However, Professor George Muschler, an orthopedic surgeon at Case Western Reserve University in Ohio is concerned by the medical risks of Regenexx after reviewing the published case studies. The procedure 'may be degenerating into an undisciplined and unfocused and even groping and wishful fishing expedition', he told ABC7 News.
The FDA's lawsuit was filed in August 2010 but may not reach a federal court until 2013.
Regenerative Sciences claims that the procedure, called Regenexx, is an alternative to potentially painful surgery for injuries such as bone fractures and torn tendons. Doctors take stem cells from the bone marrow of a patient, and process them in a solution, so that they strengthen and multiply. They are then injected into the injured joints, helping to rebuild damaged tissue.
The FDA states that stem cell treatments are a type of medication, and so fall under its jurisdiction. It says the safety of the procedure has not been sufficiently tested, and inspections showed that facilities offering the treatment do not meet its standards. It has insisted that Regenerative Sciences stop performing the Regenexx procedure until the case is resolved.
Regenerative Sciences counter that because stem cells are produced by the body, they are not drugs, so the treatment does not need FDA approval. The group claims to have treated more than 1,000 patients and spent over $500,000 on testing. Regenerative Sciences also point out that the California clinic uses a modified version of the technique that does not include a growth enhancer, a crucial part of the FDA's lawsuit.
Dr Christopher Centeno, director of Regenerative Sciences, says that the FDA is pursuing the case because it fears that Regenexx will become a successful alternative to pain medication, and threaten the FDA's control of a lucrative market. 'Unfortunately, in many cases, it's the clients suffering the most that we can't treat now', he told 5280 - the Denver Magazine.
However, Professor George Muschler, an orthopedic surgeon at Case Western Reserve University in Ohio is concerned by the medical risks of Regenexx after reviewing the published case studies. The procedure 'may be degenerating into an undisciplined and unfocused and even groping and wishful fishing expedition', he told ABC7 News.
The FDA's lawsuit was filed in August 2010 but may not reach a federal court until 2013.
Liver Health
Posted on February 6, 2012 - 07:37 by Emma Woollacott
ShareObesity could be - quite literally - contagious, say Yale scientists, who have discovered that it can be triggered by changes in microbes in the stomach.
Along with chronic liver disease, they say, obesity can be caused by a family of proteins that alter populations of intestinal microbes.
"When healthy mice were co-housed with mice that had altered gut microbes, the healthy mice also developed a susceptibility for development of liver disease and obesity," says Richard A. Flavell, professor of immunobiology at Yale School of Medicine.
The proteins in question, inflammasomes, are responsible for launching the immune system’s inflammatory response, and act as sensors and regulators of the microbial environment of the intestines.
And the Yale team found that a deficiency in components of two particular inflammasomes in mice led to an increase in bacteria which determined the severity of non-alcoholic fatty liver disease (NAFLD) and obesity in the mice.
NAFLD is the result of metabolic syndrome, a collection of disorders that includes obesity and diabetes, and is the leading cause of chronic liver disease in the western world.
Up to 30 million people are believed to suffer from NAFLD in the US alone. Twenty percent of sufferers develop chronic liver inflammation, placing them at risk for cirrhosis and liver cancer - and, until now, nobody has known why.
The next step, says Flavell, is to extend this research to humans and to identify more precisely the bacteria involved in the progression to liver disease.
"We found, in mice, that targeted antibiotic treatment brought the microbial composition back to normal, and thus eased the liver disease," he says.
"Our hope is that our findings may eventually lead to a treatment for humans."
Healthy You
Sugar Wars: The Public vs. the Personal
Author: Marsha Hallet
Published: February 04, 2012 at 6:12 am
No matter where you sprinkle it, the consumption of sugar is up. Researchers at the University of California Medical School, San Francisco are so concerned about the health risks from sugar that they are advocating that sugar be regulated like tobacco and alcohol.
This is serious stuff. Remember Prohibition? They remind us that alcohol is fermented sugar and that many of the diseases related to chronic ethanol exposure are the same as those related to chronic exposure to fructose.
Obesity was the disease that I keyed in on. But, for the more medically astute they also mention hypertension, myocardial infarction, pancreatitis, hepatic dysfunction, and habituation if not addiction. The good news, fetal alcohol syndrome and cirrhosis of the liver are not sugar related.
Their paper suggests that many of the interventions that were used to control the consumption of alcohol and tobacco could be used to control sugar. Think taxes, licensing requirements, advertising bans, etc. Can you just imagine the Bureau of Alcohol, Tobacco, Firearms and SUGAR? I cannot, and in protest I am enjoying a bowl of ice cream as I write this blog.
Robert Lustig, MD, who likes to use hyperbole, says in his video "The Toxic Truth About Sugar" that sugar is the biggest health crisis in the history of the world and that "sugar is toxic beyond calories." Laura Schmidt, PhD, MSW, MPH another author of the study says, "We’re not talking prohibition. We’re not advocating a major imposition of the government into people’s lives. We’re talking about gentle ways to make sugar consumption slightly less convenient, thereby moving people away from the concentrated dose." But Claire Brindis, DPH and third author, states the opposite, that "effective interventions can’t rely solely on individual change, but instead on environmental and community-wide solutions, similar to what has oGreen tea could be secret to healthy old ageccurred with alcohol and tobacco, that increase the likelihood of success."
In conclusion, there are probably many good reasons to eat less sugar besides the obvious one that sugar contains approximately 4 calories per gram and can make us fat. The public should be informed about any emerging science that has health consequences. But what we do with that information should not require government intervention.
Behind The Headines-Miracle Foods-Special Report
What is Behind the Headlines?
We give you the facts without the fiction. Professor Sir Muir Gray, founder of Behind the Headlines, explains more...
We give you the facts without the fiction. Professor Sir Muir Gray, founder of Behind the Headlines, explains more...
Curry could save your life.” “Beetroot can fight dementia.” “Asthma risk linked to burgers.” Every day there’s a new crop of seemingly life-changing headlines about how the food we eat affects our health.
Food stories are one of the most common topics that Behind the Headlines covers, accounting for about one in five of our appraisals. Often, news stories have claimed that foods can offer remarkable health benefits, such as fighting disease or slowing ageing.
Our special report: Miracle foods: myths and the media (PDF, 2Mb: opens in new window) looks at some of the foods that regularly appear in the news and examines whether the reports match the scientific evidence behind them.
Pharmaceuticals
NEW YORK (AP) — Shares of Gilead Sciences Inc. jumped Friday after the company reported further progress of GS-7977, a newly-acquired hepatitis C treatment still in clinical testing.
THE SPARK: Gilead said Thursday that in a clinical trial, two groups of patients who were treated with GS-7977 had undetectable levels of the hepatitis C virus after four weeks. The patients took GSI-7977 and ribavirin, an older treatment for the virus, and they had either failed to respond to previous therapies or had not been treated before. In November, Pharmasset Inc. — which developed the drug and was acquired by Gilead in January — said 100 percent of patients in a study responded to the drug.
THE BIG PICTURE: Gilead, of Foster City, Calif., bought Pharmasset to get the rights to that drug and other compounds Pharmasset was developing. The GS-7977 pill may be the most promising of several experimental therapies for hepatitis C, which helps explain why Gilead paid $11.1 billion for Pharmasset — a figure that on a per-share basis amounted to more than twice what Pharmasset's stock was trading at before Gilead made its offer.
Gilead also reported its fourth-quarter results after the market closed on Thursday. Its profit of 97 cents per share fell short of Wall Street estimates, and the company also forecast disappointing revenue in 2012.
THE ANALYSIS: Cowen and Co. analyst Phil Nadeau said Gilead's quarterly results were somewhat disappointing because the company is spending more money on drug development, but key drugs like the HIV therapies Atripla, Viread, and Truvada met expectations. Nadeau said he believes that investors are paying more attention to Gilead's drug pipeline than its current results.
"With '7977 continuing to look like the next standard of care in hepatitis C, we think investors are less focused on Gilead's near-term fundamentals," he wrote.
The Food and Drug Administration is scheduled to make a decision on Gilead's four-in-one "Quad" HIV pill by Aug. 27.
Merck’s Victrelis sold just $87 million in Q4 2011. That makes the share split for Q4 about 84 percent for Vertex; 16 percent for Merck....
| BioLineRx In-Licenses Second Oral Hepatitis C Treatment |
| 06 Feb 2012 | |
BL-8030 is a potent and selective second generation NS3 protease inhibitor. The NS3 protease is essential for the replication of the Hepatitis C virus (HCV) and is an important target for HCV therapies. BL-8030 has been shown to have excellent antiviral activity against various HCV genotypes. Pre-clinical studies have demonstrated an improved resistance profile against common protease inhibitor mutants, resulting in a lower probability that the virus will develop resistance to treatment. In addition, BL-8030 has demonstrated a good toxicity profile in pre-clinical studies, exhibiting specificity only to the viral protease and lack of activity against a relevant panel of human proteases as well as a clean profile versus human liver enzymes, which is expected to lead to less drug-drug interactions. BL-8030 was invented by Professor Philippe Halfon and his team at Genoscience and co-developed with assistance from scientists at RFS Pharma, LLC. Prof. Halfon, Co-Founder and President of Genoscience, is a specialist in molecular virology and infectious diseases, especially HIV, HPV (Human Papilloma Virus) and Hepatitis. In addition he is the founder of several biotechnology companies focusing on antiviral drug discovery and development including ACTgene, Alphabio and Genoscience. RFS Pharma was founded by Professor Raymond F. Schinazi; he currently serves as the Frances Winship Walters Professor of Pediatrics at Emory University. He is also a founder of Pharmasset, Idenix, Triangle and ActivBiotics Pharma. Prof. Philippe Halfon said, "We were impressed by the drug development expertise of the BioLineRx team and are very pleased to collaborate with them on a second HCV project. There is clearly a huge unmet medical need in finding a safe and effective treatment for HCV, and based on pre-clinical results, we believe that our product, especially when combined with other available Hepatitis C drugs, has the potential to become an important addition to HCV combination therapies and bring remedy to millions suffering from this devastating disease." “We worked closely with the group at Genoscience to determine the optimum characteristic that led to the discovery of BL-8030 and related protease inhibitors,” said Dr. Steven J. Coats, Senior Director of Chemistry at RFS Pharma. “We are privileged and fortunate to partner with two world class groups in the development of viral therapeutics," said Dr. Kinneret Savitsky, CEO of BioLineRx. "Two years ago, we took a strategic decision to enter the dynamic and rapidly growing field of Hepatitis C. Since that time, we have evaluated numerous projects in the field. A year ago, we identified and decided to focus on the in-licensing of the two most promising candidates: BL-8020, which we've recently licensed, and now BL-8030. We will do our utmost to develop these promising drugs as swiftly as possible for the benefit of Hepatitis C infected individuals around the world.” About Hepatitis C Hepatitis C is a blood borne infection of the liver caused by the Hepatitis C virus (HCV) which becomes chronic in about 85% of cases. According to the World Health Organization (WHO), up to 170 million people worldwide are chronically infected with HCV. In addition, HCV infection is the leading cause of liver transplantation and is a risk factor for liver cancer. The Hepatitis C market is growing rapidly and is forecasted to reach $16 billion in 2015 in the seven major markets (US, France, Germany, Italy, Spain, UK and Japan). About BioLineRx BioLineRx Ltd. is a publicly-traded biopharmaceutical development company. It is dedicated to building a portfolio of products for unmet medical needs or with advantages over currently available therapies. BioLineRx’s current portfolio consists of five clinical stage candidates: BL-1020 for schizophrenia has commenced a Phase II/III study; BL-1040, for prevention of pathological cardiac remodeling following a myocardial infarction, is currently undergoing a pivotal CE-Mark registration trial and has been out-licensed to Ikaria Inc. for a total deal value of $282.5 million, in addition to sales royalties; BL-5010 for non-surgical removal of skin lesions has completed a Phase I/II study; BL-1021 for neuropathic pain is in Phase I development and BL-7040 for treating Inflammatory Bowel Disease (IBD) has completed Phase I. In addition, BioLineRx has 13 products in various pre-clinical development stages for a variety of indications, including central nervous system diseases, oncology, infectious diseases, cardiovascular and autoimmune diseases. BioLineRx’s business model is based on acquiring molecules mainly from biotechnological incubators and academic institutions. The Company performs feasibility assessment studies and development through pre-clinical and clinical stages, with partial funding from the Israeli Government’s Office of the Chief Scientist (OCS). The final stage includes partnering with medium and large pharmaceutical companies for advanced clinical development (Phase III) and commercialization. For more information on BioLineRx, please visit www.biolinerx.com. About Genoscience Genoscience, a biopharmaceutical company located in Marseille, France, is focused on the development of new drugs for the treatment of viral diseases as HCV. Genoscience’s innovative technology platform, which combines internal expertise in resistance with unique molecular modeling through its proprietary software (GenMol™), allows for the development of highly targeted molecules, taking into account the phenomenon of resistance. For further information about Genoscience, please refer to http://www.genosciencepharma.com. About RFS Pharma, LLC RFS Pharma, LLC was founded in September 2004 and is located in a 26,500 sq. ft. state-of-the-art research facility in Tucker, Georgia. RFS Pharma is a privately owned biotech company committed to the discovery and development of antiviral agents and other human therapeutics. The company capitalizes on its expertise in nucleoside chemistry to develop drugs to combat infections caused by drug-resistant HIV and hepatitis viruses. RFS Pharma’s lead product candidate is amdoxovir, which is in advanced Phase 2 clinical studies for the treatment of HIV-1 infections. In addition, the company has identified promising, early stage compounds for hepatitis infections, analogs that are effective against noroviruses, and has a proprietary novel nucleoside prodrug technology. For further information about RFS Pharma, please refer to our website, www.rfspharma.com. SOURCE: BioLineRx |
By Kim Tae-gyu-Korea Times
A total of 17 local drug makers were caught last year for having offered illegal rebates of nearly 100 billion won to doctors and pharmacists between 2006 and 2010.
The Fair Trade Commission (FTC) said Sunday that the 17 players including Sanofi-aventis Korea, Yansen Korea and Novartis Korea combined to present 97 billion won in unlawful kickbacks.
More than 8,500 hospitals and pharmacies across the country were found to have pocketed such payments and few believe all of the violators have been investigated by the anti-trust watchdog.
``On average just a couple of cases were probed a year before 2010 but a host of cases appeared on our radar last year thanks to the new policy of rewarding whistle-blowers,’’ an FTC official said.
``However, I think that the 17 drug producers are just the tip of the iceberg. We have dropped so many probes due to a lack of material evidence despite firm belief of their wrongdoings.’’
Drug companies employed various ways to encourage doctors or pharmacies to prescribe or sell their brand of medicines.
On top of providing under-the-table cash or gift certificates, some treated doctors or pharmacists at expensive restaurants, financially sponsored golf games and bought them computers or TVs.
A company paid around 5 million won to a doctor for delivering lectures each of nine times. The doctor read drafts for some 10~20 minutes at restaurants in front of a few people before dining. All of this is paid for by the company.
The anonymous FTC official declined to estimate the total amount of rebates but market observers predict that trillions of won were spent every year in such manner.
``The market norm of rebates is known to be about 20 percent of the price of the drug. Yet, some latecomers suggested even 25 to 30 percent in order to gain market share,’’ an insider at a domestic drug firm said.
``Because the overall size of the Korean medicine market is approximately 16 trillion won, the consensus is that trillions of won is channeled toward rebates every year. Some put the figure at 3 trillion won.’’
Indeed, the medicine industry spends up to 35 percent of its revenue on marketing or related activities, which is way above the average 12 percent of other businesses. A substantial portion of these expenses is believed to be connected to the rebates, according to the insider.
In order to weed out the problematic practice, the FTC phased in the policy of rewarding whistle-blowers in 2010 and started punishing both rebate providers and recipients last year.
Previously, merely providers were subject to punishments, thus exempting doctors or pharmacists from any legal responsibilities no matter how much they received.
0 comments: