New On The Blog
It is scheduled to be reviewed by NICE in 2011 with a decision for use in England and Wales expected in 2012. Until then, the availability of Incivo to NHS patients depends on formulary committee decisions made at a local level.
Thousands of hepatitis C patients across the West Midlands are set to benefit from a new treatment, according to research.
Around 18,670 people in the region have been diagnosed with the blood-borne infection that attacks the liver, according to figures.
The disease, which can be spread by sharing needles, a razor, toothbrush, body piercing and tattoos, affects an estimated 216,000 people across the UK, the Hepatitis C in the UK: annual report 2011 from the London Health Protection Agency reveals.
The new treatment Incivo targets those suffering from genotype 1 hepatitis C, one of the hardest to treat types of the disease in the UK.
Genotype 1 affects around 45% of those who are chronically infected with hepatitis C, but current therapies are only effective in treating around 50% of this group.
The new treatment is a protease inhibitor which targets the virus directly rather than attempting to boost the immune system. The drug aims to reduce the virus in about four out of five hepatitis C patients, while current treatments are only able to target between two or three out of five sufferers, research shows.
Charles Gore, chief executive of the Hepatitis C Trust, said: "Hepatitis C can be a devastating disease; however, if treated successfully, patients can avoid life-threatening liver problems such as further liver damage, cirrhosis, liver failure and liver cancer. The arrival of protease inhibitors is the first major treatment advance in more than 10 years and a significant step forward for the hep C community."
Patients will receive a 12-week course of treatment which costs £22,398. The treatment is available on the NHS, if prescribed by a doctor, or privately - it is prescription only, so the treatment must be initiated by a doctor.
It is scheduled to be reviewed by NICE in 2011 with a decision for use in England and Wales expected in 2012. Until then, the availability of Incivo to NHS patients depends on formulary committee decisions made at a local level.
The regional figures have been taken from the commissioning template for estimating hepatitis C virus prevalence by PCT and numbers eligible for treatment; produced by the Immunisation Department, Health Protection Agency Centre for Infections, 2009.
Copyright (c) Press Association Ltd. 2011, All Rights Reserved.
From-NICE
Hepatitis C (genotype 1) - telaprevir
| Status: | In progress |
| Expected date of issue: | June 2012 |
Liver disease and performance of non-invasive fibrosis biomarkers
The most recent issue of the Alimentary Pharmacology & Therapeutics investigates the impact of liver disease etiology and the stages of hepatic fibrosis on the performance of non-invasive fibrosis biomarkers.
Performance of non-invasive fibrosis biomarkers may be influenced by aetiology of chronic liver disease and the stages of hepatic fibrosis, but large-scale studies are pending.
Dr Sebastiani and colleagues from Italy investigated the effect of etiogy and stages of hepatic fibrosis on the performance of fibrosis biomarkers.
A total of 2411 patients with compensated chronic liver disease were consecutively enrolled in 9 centers.
APRI, Forns’index, Lok index, AST-to-ALT ratio, Fib-4, platelets and Fibrotest-Fibrosure were tested against liver biopsy, considered the gold standard.
Etiology is a major factor influencing the performance of liver fibrosis biomarkers
Alimentary Pharmacology & Therapeutics
The effect of the stages of hepatic fibrosis to diagnose significant fibrosis and cirrhosis was investigated through difference between advanced and non-advanced fibrosis stages.
Performance was expressed as observed area under the ROC curve and AUROC adjusted for non-advanced fibrosis stages.
The researchers found that performance of APRI and Fibrotest-Fibrosure was higher than other biomarkers.
In all etiologies, AUROC adjusted for DANA was higher than observed area under the ROC curve.
APRI showed its best performance in HCV monoinfected cases, with an AUROC adjusted for non-advanced fibrosis stages of 0.77 and 0.8 for F2 and F4, respectively.
The research team found that in HBV and non-alcoholic steatohepatitis (NASH) patients, its performance was poor.
Performance of Fibrotest-Fibrosure was good in all etiologies for both F2 and F4, except for F2 in NASH.
The team found that performance of all biomarkers was reduced in HCV cases with normal ALT.
Dr Sebastiani's team concluded, "Etiology is a major factor influencing the performance of liver fibrosis biomarkers."
"Even after correction for DANA, APRI and Fibrotest-Fibrosure exhibit the best performance."
"However, liver biopsy is not replaceable, especially to diagnose F2 and in HCV carriers with normal ALT."
Aliment Pharmacol Ther 2011: 34(10): 1202–1216
21 October 2011
Hepatitis A and B vaccination rates in chronic liver diseases and diabetes in the USA
A study in this month's Hepatology investigates changes in hepatitis A and B vaccination rates in adult patients with chronic liver diseases and diabetes in the population in the USA.
Professional societies recommend hepatitis A and hepatitis B immunization for individuals with chronic liver disease, but the degree of implementation is unknown.
Data were obtained from the National Health and Nutrition Examination Surveys (NHANES) conducted in 1999-2008.
For the entire study population and for those with chronic liver disease and diabetes, Drs Younossi and Stepanova from Virginia, USA determined the rates and independent predictors of history of hepatitis A and hepatitis B (HepA and HepB) vaccinations, of their effectiveness, and of seroprevalence of hepatitis A antibody and anti-HB surface antibody.
In total, 24,871 participants from NHANES were included, of which 14,886 and 9,985.
Of these individuals, 14% had chronic liver disease and 9% had diabetes. During the study period, HepA vaccination in chronic liver disease increased from 13% to 20%.
The research team found that HepB vaccination increased from 23% to 32%.
Of subtypes of chronic liver disease, HepA vaccination rates increased only in nonalcoholic fatty liver disease (NAFLD), whereas HepB vaccination increased for patients with hepatitis C and nonalcoholic fatty liver disease.
In the diabetic cohort, HepA vaccination rates increased from 9% to 15%, and HepB rates increased from 15% to 22%.
The researchers observed that all changes were similar to those observed in the general population.
The quality measure for HepA in the general population decreased from 44% in 1999-2004 to 42% in 2005-2008, and similar changes were noted for all subcohorts.
On the other hand, quality measure for HepB increased from 32% to 41% in the population, whereas no changes in quality measure were noted in any diagnostic cohort except for NAFLD.
Dr Younossi and colleague commented, "Although vaccination rates in chronic liver disease and diabetic cohorts are increasing, they remain low."
"Given the public health implications of acute hepatitis A and hepatitis B in patients with chronic liver disease, better implementation of the vaccination recommendations for these populations is warranted."
Hepatology 2011: 54(4): 1167–1178
21 October 2011
Liver Cancer
From Scope
Radiation traveling in microspheres hits liver cancer where surgery can’t
Michelle Phillips came to Stanford Hospital with all other options exhausted. In 2002, the Sunnyvale mother of two had been diagnosed with a very rare, and malignant, brain tumor. Two surgeries and radiation treatments removed it, but five years later, new tumors appeared in her liver and lungs: thirty in her liver alone. Inoperable, her physicians told her. And they didn’t have any other recommendations.
After long hours of research, Philips and her husband found (.pdf) Stanford’s Daniel Sze, MD, PhD, an interventional radiologist. Sze and his colleagues had made Stanford among a few dozen U.S. hospitals offering patients like Philips a very new form of treatment: microscopic, radiation-loaded spheres sent through the bloodstream to the arteries that feed tumors.
Now, in a new paper in the Journal of Vascular and Interventional Radiology, Sze and his team share the results of their work with 201 patients treated this way between 2004 and 2010. In two separate studies, the team looked at how to deliver the microspheres most effectively. In some patients, tumors had recruited blood vessels from outside the liver to feed them. The Stanford group wanted to see what would happen if they closed off those vessels first before delivering the microspheres. In a second group of patients, the physicians blocked off extra arteries found in almost half the population and used the liver’s own network of vessels to deliver the microspheres.
“Results of these two new studies may be beneficial to patients with liver tumors that cannot be surgically removed,” Sze said in a release (.pdf). “These studies address methods to modify the blood vessels of the liver in order to maximize delivery of tumor-killing material to the targets and to make treatment simpler and safer.” Continue Reading »
Radiology Studies On Yttrium-90 Radioembolization Treatmentfor Liver Cancer Illustrate Ways To Assist In Treating Even The Most Challenging Cases
Oct 21
Finding innovative, minimally invasive ways to treat liver cancer - and being able to tailor that treatment individually to patients - are hallmarks of interventional radiologists. Advances in yttrium-90 (Y-90) radioembolization for liver cancer, a leading cause of cancer deaths worldwide, are reported in studies in the October Journal of Vascular and Interventional Radiology. "Results of these two new studies may be beneficial to patients with liver tumors that cannot be surgically removed," said Daniel Sze, M.D., Ph.D., FSIR, professor of interventional radiology at Stanford University Medical Center, Stanford, Calif. "These studies address methods to modify the blood vessels of the liver in order to maximize delivery of tumor-killing material to the targets and to make treatment simpler and safer," he added.
"Blood supply to tumors can be complex and can present challenges for interventional radiologists," said Riad Salem, M.D., MBA, FSIR, who wrote an accompanying commentary in JVIR. "This research advances the field and provides information that is immediately applicable to all interventional radiologists when treating their cancer patients," said Salem, professor of radiology, medicine and surgery and director of interventional oncology, division of interventional radiology, in the department of radiology at Northwestern University in Chicago, Ill. "Such research allows interventional radiologists to tailor treatments to help even the sickest patients achieve a better quality of life," he explained. Worldwide, primary liver cancer accounts for an estimated 600,000 deaths annually. Last year, it was estimated that 24,120 new cases of primary liver cancer and intrahepatic (within the liver) bile duct cancer would be diagnosed and 18,910 people would die of these cancers in the United States. Primary liver cancer shows the most rapidly increasing incidence of all cancers in this country.
In addition, roughly ten times as many patients succumb to liver cancers that spread from other sites. Many of these patients may be treated with Y-90 radioembolization. With Y-90 radioembolization treatment, radioactive microspheres (tiny beads) are injected through a catheter from the groin into the liver artery supplying the tumor. The beads become lodged within the tumor vessels, where they emit radiation locally that causes tumor cells to die. This technique allows for a very high local dose of radiation to be delivered, with little danger from radiation to the healthy tissues in the body, said Salem.
While radioembolization is palliative - not curative - the treatment benefits patients by extending lives and by improving symptoms and is associated with fewer side effects than traditional treatments for cancer.
Interventional radiologists have long studied the use of intra-arterial (delivery of treatment via an artery) therapies for cancer and pioneered yttrium-90 radioembolization since its introduction in 2000 to treat liver cancer.
One study showed promising results in a group of 35 patients in whom the "thirsty tumors" had recruited blood vessels from outside the liver, a situation that interferes with complete delivery of Y-90 microspheres to the tumors, explained Sze. "These 'parasitized' blood vessels were successfully embolized, or closed off, before administration of Y-90 microspheres, reestablishing the blood supply from within the liver to enable the successful delivery of the microspheres to the targeted tumors," said Sze, senior author of "Embolization of Parasitized Extrahepatic Arteries to Reestablish Intrahepatic Arterial Supply to Tumors Before Yttrium-90 Radioembolization."
"While large, multicenter studies will be necessary to further confirm the proof of the concept, it is notable because the Stanford University researchers investigated the idea of simplifying blood supply in order to permit a direct injection of microspheres into the tumor," said Salem.
In a related report, "Consolidation of Hepatic Arterial Inflow by Embolization of Variant Hepatic Arteries in Preparation for Yttrium-90 Radioembolization," the same team was able to make treatment simpler and safer by blocking extra (variant) arteries that almost half of normal people have and utilizing collateral (detour) vessels inside the liver to assist in microsphere delivery. "After blocking these variant arteries, we were able to treat nearly 100 percent of tumors through the main hepatic artery - taking advantage of the networks of blood vessels within the liver," reported Sze. "By embolizing small, less important vessels to the tumors, one main arterial channel was created that could treat the entire area in a technically simple and practical way," Salem explained. He also noted that these principles may be applicable to other embolization procedures, such as drug-eluting bead chemoembolization using microspheres that have been impregnated with a chemotherapy agent rather than radioactivity. "Based on this research, more people who are not good candidates for surgery will benefit in several ways," he explained. "Whenever we can administer chemotherapy directly to a tumor, we limit the drug's entrance into the patient's bloodstream and thus lessen the spread throughout the body and the associated consequences and side effects. This method of delivering chemotherapy provides an additional advantage by releasing the drug slowly, destroying the tumor over a greater period of time. The new techniques applied to radioembolization may also be applied to chemoembolization," said Salem.
In "Toxicities Following Radioembolization With Yttrium-90 SIR-Spheres: Incidence and Contributing Risk Factors at a Single Center," Thomas Jefferson University researchers examined the results of liver function tests from 29-571 days following treatment in 81 patients who received 122 Y-90 infusions to treat primary or metastatic liver tumors. "Radioembolization with resin microspheres is a safe treatment for patients with unresectable, or inoperable, hepatic malignancies," concluded Daniel B. Brown, M.D., FSIR, an interventional radiologist and chief of interventional radiology and interventional oncology at Thomas Jefferson University Hospital in Philadelphia, Pa. "More than 90 percent of the individuals in our study who received infusions showed no, or few, changes in liver function. And, generally speaking, almost all patients receiving Y-90 infusions to treat primary or metastatic liver tumors were asymptomatic after treatment," he added.
"JVIR is committed to publishing important research that could be practice-changing," noted JVIR editor-in-chief Ziv J Haskal, M.D., FSIR. "Studies such as these allow interventional radiologists, whose hallmark is minimally invasive, targeted treatment of disease, to tailor treatments to help even those who are not candidates for surgery live longer and achieve a better quality of life," added Haskal, who is also professor of radiology and surgery at the University of Maryland School of Medicine and vice chair of strategic development and chief of vascular and interventional radiology, image-guided therapy and interventional oncology at the University of Maryland Medical Center, both in Baltimore.
European studies on risks of hepatocellular carcinoma
Among known risk factors for hepatocellular cancer, smoking, obesity, and heavy alcohol consumption, along with chronic hepatitis B and C infection, contribute to a large share of the disease burden in Europe, according to a cohort study published online October 21 in the Journal of the National Cancer Institute.
While a causal link between hepatitis B and C and hepatocellular cancer has been known for a few decades, tobacco smoking, obesity, and alcohol consumption are common risk factors, albeit with lower relative risks, that also contribute to the development of the disease. In fact, there were many more Europeans with hepatocellular cancer who were smokers than carriers of hepatitis virus infections. Previous studies have not explored the contribution of each risk factor.
To determine the contribution of each of these risk factors to hepatocellular carcinoma, Dimitrios Trichopoulos, Ph.D., of the Harvard School of Public Health, and colleagues, used data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, which was established to investigate the role of biological, dietary, lifestyle and environmental factors in the etiology of cancer and other diseases in several European countries. The researchers matched 115 patients with hepatocellular carcinoma to 229 control subjects.
The researchers found that 47.6% of the cases of hepatocellular carcinoma in the cohort were associated with smoking, 20.9% with hepatitis C, 16.1% with obesity, 13.2% with hepatitis B, and 10.2% with heavy alcohol intake. They write, "We have shown that hepatocellular carcinoma, one of the most lethal human cancers, is largely amenable to primary prevention with existing knowledge and technology," noting that "although chronic infection with HBV and/or HCV was the strongest risk factor for hepatocellular carcinoma, tobacco smoking was responsible for more cases of hepatocellular carcinoma than either or both these viruses in the population."
In an accompanying editorial, Morris Sherman, M.D., and Josep M. Llovet, M.D., of the Mount Sinai School of Medicine write that this study's results are consistent with those from other epidemiological studies, but that the numbers need to be put into context.
Specifically, the editorialists caution against giving too much importance to smoking as a risk factor of hepatocellular carcinoma, since in this cohort, smoking was present in a large proportion of the population, thereby making the attributable risk more substantial than it might have otherwise been. If fact, they point out that no studies to date support the notion that smoking is a stand-alone risk factor for liver cancer. They also stress that the study does not explore combinations of risk factors in defining disease risk. Still, the data on smoking are noteworthy, they conclude. "We should be counseling our patients who have other risk factors for hepatocellular carcinoma to quit smoking. Of course, there are many other health reasons to stop smoking. Here is one more."
A second study on hepatocellular carcinoma in this issue of the Journal confirms the association between hepatitis B and hepatocellular carcinoma among a population cohort in Greenland. However, the study also finds that the Greenlanders studied have a relatively low incidence of hepatocellular carcinoma compared to those in other parts of the world, suggesting that a more benign course of Hepatitis B infection is prevalent in Greenland and accounts for the lower incidence of hepatocellular carcinoma there.
Marlene M. Børresen, M.D., Ph.D., of the Department of Epidemiology Research at Statens Serum Institut in Copenhagen, and colleagues, looked at a population of 8879 Greenlanders enrolled in populated-based serum surveys in 1987 and in 1998, who were followed until 2010. The researchers checked them for hepatitis B status, and found that those who were HBV positive had a much higher rate of hepatocellular carcinoma than those who were HBV negative. However, they also found that the incidence of hepatocellular carcinoma was much lower in Greenland than parts of the world that had a similarly high prevalence of hepatitis B.
The authors write that this finding could be attributable to a number of factors: for example, that the infection is transmitted typically during adolescence and adulthood, whereas infection during childhood carries a stronger risk for developing hepatocellular carcinoma; and that the strains of HBV that are associated with high risk of hepatocellular carcinoma are less common in Greenland than elsewhere. Furthermore, low smoking rates and alcohol consumption in Greenland may account for the lower rates of hepatocellular carcinoma, along with the relatively young age of the cohort studied (average age at recruitment was 33.4 years, with follow-up occurring in the mid-fifties.)
In an accompanying editorial, Morris Sherman, M.D., and Josep M. Llovet, M.D., of the Mount Sinai School of Medicine concur with the authors that genotype differences may in part account for the lower prevalence of hepatocellular carcinoma amongst those with HBV. The editorialists note that in Greenland, the D and B6 genotypes of HVB are most common, and that "the incidence of hepatocellular carcinoma in people infected by genotype B6 has not been documented." They add that viral load and infection by mutants of HBV are also risk factors of hepatocellular carcinoma that this study did not investigate.
Contacts:
Article: Dimitrios Trichopolous, dtrichop@hsph.harvard.edu ; +30 697 3 88 63 88; or Todd Datz, tdatz@hsph.harvard.edu ; 617-432-8413
rticle: Malene Landbo Børresen, MLB@ssi.dk; +45 3268 3268
Editorial: Josep Llovet, Josep.Llovet@mssm.edu; 212-659-9503
Diabetes
New Insights Into Insulin Resistance Could Lead to Better Drugs for Diabetics
ScienceDaily (Oct. 20, 2011) — Research published in the October Molecular and Cellular Biology moves us closer to developing drugs that could mitigate diabetes.
Diabetes afflicts an estimated 26 million Americans, while 79 million have prediabetes. In other words, one in three Americans confronts this disease. Diabetes raises the risk of heart disease and stroke by as much as fourfold, and it is the leading cause of blindness among adults 20-74. It is also the leading cause of kidney failure.
In earlier research, four years ago another team of researchers showed that they could boost insulin sensitivity in experimental rodents by giving the animals a drug called myriocin. People with diabetes have a condition called insulin resistance, which renders them poorly able to process sugar. That results in high blood sugar, which damages the blood vessels, leading to many of diabetes' ills. In their study, that team, led by Johannes M. Aerts of the University of Amsterdam, observed a decrease in a compound called ceramide, which sits on cell membranes in the circulatory system, which they postulated was responsible for the rise in insulin sensitivity.
In the new study, Xian-Cheng Jiang of Downstate Medical Center, Brooklyn, NY, and his collaborators set out to confirm this earlier work, using a genetic approach.
The new research provides strong evidence that ceramide was not causing insulin sensitivity, but that another membrane-bound compound, sphingomyelin, might be doing so.
Ceramide is the substrate for the last step in a five step cascade that produces sphingomyelin. In that step an enzyme called sphingomyline synthase 2 (SMS2) cleaves ceramide to produce sphingomyelin. The first enzyme in this pathway is called serine palmitoyltransferase (SPT).
To test the hypothesis that ceramide is involved in modulating insulin resistance the researchers used knockout mice for each of these enzymes. They postulated that (partially) knocking out the first enzyme in the cascade would decrease ceramide levels while knocking out the last enzyme in the sphingomyelin pathway would boost ceramide levels, since that enzyme uses ceramide to produce sphingomyelin. Thus, SPT knockout mice would have greater insulin sensitivity, while SMS knockout mice would have reduced insulin sensitivity.
Surprisingly, while ceramide levels changed as predicted, that change did not influence insulin sensitivity, which was higher in both groups.
The research has important implications for drug development for mitigating diabetes. Myriocin proved highly toxic and major efforts to modify the drug to reduce that toxicity have been fruitless. Myriocin's toxicity probably stems from the fact that it inhibits the first step of the sphingomyelin biosynthetic pathway, affecting all the downstream biology, says Jiang. The discovery that knocking out the last step in the biosynthetic pathway improves insulin sensitivity means that drug treatments could target that last enzyme, SMS, leaving the rest of that biosynthetic pathway to function normally.
Pharmaceuticals
RPT-UPDATE 1-Vertex CEO sees "historic launch" for Hep-C drug
* CEO says uptake of Incivek very strong
* CEO says will be very proud to show results
* Says does not know if latest IMS data is correct
* Shares rise as much as 6 percent
By Ros Krasny
BOSTON, Oct 20 (Reuters) - The chief executive of Vertex Pharmaceuticals Inc , Matthew Emmens, said on Thursday that adoption of its recently launched hepatitis C drug, Incivek, has been "very, very fast."
The first full quarter of U.S. sales of Incivek will emerge when the biotechnology company reports its quarterly earnings later this month.
"We'll be very proud at what we show you," said Emmens, speaking at a Greater Boston Chamber of Commerce breakfast.
The Incivek launch "will be a historic launch in terms of acceptance."
Vertex shares rose as much as 6 percent following his comments.
"I think reading between the lines of his comments there's an indication that expectations for Incivek sales are below where Vertex will actually report," said Brian Skorney, an analyst at Brean Murray, Carret & Co.
Analysts are on average expecting Incivek sales in the quarter of about $250 million, Skorney said. He himself expects a number closer to $400 million.
Vertex shares have lurched recently after IMS Health, which provides prescription data and other services to the pharmaceutical industry, revised its estimates of the number of prescriptions written in late September.
Initially, investors thought demand was flattening. It then emerged IMS had failed to include certain data, which sent the prescription number up again.
Emmens declined to comment on the error, or speculate on whether IMS now has correct figures.
"I'm confident of our internal data and that's how we drive the company," he said.
Incivek is one of two new breakthrough hepatitis C drugs to be launched recently. The other is Victrelis, made by Merck & Co . Both drugs promise a higher cure rate for the disease, which infects the liver and can lead eventually to cirrhosis and liver failure.
Vertex shares closed more than 5 percent higher at $42.28 in trading on Nasdaq. They briefly traded as high as $42.65.Pharmasset Falls on Rival Abbott Hepatitis C Therapy Results
By Pat Wechsler
(Adds analyst comments in fourth paragraph.)
Oct. 21 (Bloomberg) -- Pharmasset Inc., developer of anti- viral medicines, plunged the most ever after Abbott Laboratories said interim study results of its rival experimental hepatitis C therapy showed high cure rates.
Pharmasset declined 15 percent to $67.33 at 1:32 p.m. New York time. Earlier, the stock fell 21 percent to $63 in the biggest intraday drop since the Princeton, New Jersey-based company first sold shares in April 2007.
Abbott, based in Abbott Park, Illinois, told investors and analysts today in New York that study results of its hepatitis C drug combination found that patients with the liver infection can be cured without adding interferon to treatment. Investors had expected that Pharmasset’s treatment wouldn’t have competition from a therapy that didn’t use interferon, said Howard Liang, an analyst at Leerink Swann in Boston.
“We are seeing there is another way of achieving a regimen without interferon that looks like it will be competitive,” said Liang in a telephone interview. “It will eventually all boil down to who has the better data.”
New Pharmasset data isn’t expected to be available until April, Liang said.
Abbott released early results of its trial, dubbed PILOT, at the conference. The study found the hepatitis C virus was reduced to undetectable levels in 41 of 42 patients after they were treated with Abbott’s drug combination for three months. At six months, nine of the 10 patients still being monitored showed no sign of the virus.
Abbott Results
Abbott’s hepatitis C therapy promises to “dramatically change the treatment landscape” for the disease, Richard Gonzalez, the company’s executive vice president for pharmaceuticals, said at the investor conference. “We’re on track to show patient cure rates in the 90 percent range.”
The drugmaker told investors it would be able to get its drug combination approved and to market by 2015. Pharmasset hasn’t given a date for release. Abbott has four drugs in its combination therapy and Pharmasset has two.
“The two-drug combination has a better chance of a very clean safety profile,” Brian Skorney, an analyst at Brean Murray Carret & Co. LLC in New York, said in a telephone interview. I continue to believe Pharmasset’s will be better.”
--With assistance from Alex Nussbaum in New York. Editor: Angela Zimm, Bruce Rule
To contact the reporter on this story: Angela Zimm in Boston at azimm@bloomberg.net
To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net
Related;
HIV/HCV
Preview: Hot Topics of Clinical Interest at IDSA 2011
Hello. This is Paul Auwaerter from Johns Hopkins University speaking for Medscape Infectious Diseases today on the jam-packed annual meeting of the Infectious Diseases Society of America in Boston in October 2011. Given the short period of time that I have today, this is a capricious list, but I thought I would highlight a couple of interesting trends and observations and perhaps studies that could be of interest to you as a clinician.
The first is an interesting vaccine debate: HPV [human papillomavirus] immunization in males.[1] Recently, HPV immunization has taken a bit of a political tack in the Republican debate, but the vaccine, although effective in male patients, raises issues as to whether its effectiveness is worth the cost or potential consequences as part of vaccine policy. There is no doubt that it is effective, and this session by Kevin Ault will address those issues.
The second is a late-breaking abstract.[2] By conflict of interest I should mention that the author, Mark Sulkowski, is from Johns Hopkins, but this abstract is important because it looks at the new HCV [hepatitis C vaccine] drug boceprevir in co-infected patients with HIV and HCV when combined with pegylated interferon and ribavirin. There have been precious little data in co-infected patients. This study looked at 100 patients who were randomly assigned to a boceprevir or a nonboceprevir arm. The conclusions were that patients who received boceprevir tolerated it well, and these patients were also on suppression ART [antiretroviral therapy] programs for HIV. At week 12, approximately 60% had undetectable HCV viral load -- a 33% higher response rate in patients taking boceprevir. This is obviously a smaller study but important news for anybody who has HIV-infected patients who also have HCV infection.
The balance of my comments point to the growing issues with respect to antimicrobial resistance. Clearly gram negatives are among the greatest worries, with many presentations and posters looking at epidemiology, resistance, and potentials for treatment as well as drug shortages. I would like to point out 3 interesting issues. One is an oral abstract, number 161,[3] which looked at a survey of infectious diseases (ID) clinicians and whether they experienced drug shortages in the last 2 years. Of 503 ID clinicians responding, 78% said that they had to alter their practice in the last 2 years. The top 4 offenders (probably no surprise to any of you) are trimethoprim/sulfamethoxazole, amikacin, aztreonam, and foscarnet. Respondees commented that when they had to use different drugs, it resulted in toxicities; unnecessary use of broader-spectrum agents; increased coughs; increased length of stay; and 30% cited that their patients had inadequate response to treatment. Obviously, this is a survey rather than a strict study, but certainly it portends to problems that we are dealing with -- not only the resistant organisms, but we often don't have the right drugs to treat them.
Another interesting issue is addressed in poster 256.[4] What do you do when you have KPC [Klebsiella pneumoniae carbapenemase]-resistant organisms as well as colistin-resistant organisms at a very high level? This is an issue that very few of us know anything about. Annie Farrell and colleagues from Pittsburgh did in vitro studies using checkerboard analyses and found that the combined use of colistin, doripenem, and ertapenem all yielded 100% synergistic response rates. They postulated that this could be because KPC's high affinity for ertapenem allowed other drugs to work. They found that, to a lesser degree, doripenem and doxycycline as well as doripenem and rifampin were also effective. Obviously, these aren't in vivo results, but perhaps something that might be considered if you are faced with such a terrible organism.
Lastly, a late-breaking abstract (number 279) by Helen Boucher[5] looks at what is coming down the pipeline: 9 drugs in various stages of development for gram-negative organisms. Of importance are a number of beta-lactamase inhibitors that are complexed with other drugs such as ceftaroline, as well as a new aminoglycoside and 4 new completely novel compounds that might represent good and effective new drug classes. Clearly, none of these are yet in clinical use but represent perhaps some hope on the pipeline. Obviously, this will be a big meeting with lots of information well done by the organizers and the many presenters. Thanks for listening.
Hepatitis treatmentThe group writing the section on hepatitis B and C was chaired by Professor Jürgen Rockstroh of the University of Bonn. These involve new, clarified flowcharts for the initiation and management of hepatitis C treatment and also include the management of hepatitis delta (hepatitis D) in patients with hepatitis B.
The writing group of this section had a dilemma: two hepatitis C protease inhibitor drugs (boceprevir and telaprevir) are now licensed for treatment of patients with hepatitis who do not have HIV, and considerably increase the speed and efficacy of treatment, but are not licensed for patients with HIV. The printed version of the guidelines, on the basis of 12 weeks’ interim results of telaprevir in HIV/hepatitis C coinfected patients, recommends that physicians can choose to add telaprevir to standard therapy for twelve weeks. The online version may include a similar recommendation for boceprevir if positive results are received at next month’s AASLD Liver Meeting. They note that atazanavir and efavirenz are so far the only two non-NRTI drugs that have been evaluated for drug interactions with telaprevir.
Read more....
FDA
Oct 21, 2011 (Food and Drug Administration Documents and Publications/ContentWorks via COMTEX) -- Recall -- Firm Press Release FDA posts press releases and other notices of recalls and market withdrawals from the firms involved as a service to consumers, the media, and other interested parties. FDA does not endorse either the product or the company.Insight Pharmaceuticals Issues A Voluntary Nationwide Recall Of "Nostrilla Nasal Decongestant" Due To Bacterial Contamination Contact: Consumer: 1-877-546-9059 Media: Robyn Ungar 610-228-2131 FOR IMMEDIATE RELEASE - October 19, 2011 - Insight Pharmaceuticals, LLC of Langhorne, Pa., is recalling one lot (34,092 bottles) of Nostrilla Nasal Decongestant nasal spray to the consumer level, because it may contain the bacteria Burkholderia cepacia.
Burkholderia cepacia may cause serious infection in individuals with a compromised immune system or chronic lung condition (i.e. cystic fibrosis). However, the possibility of infection is remote in healthy individuals.
Nostrilla Nasal Decongestant, lot #11G075, UPC Code 6373673005, was distributed nationwide through normal retail outlets and pharmacies. The product comes in a 1/2 ounce, plastic bottle marked with lot #11G075 on the label and with an expiration date of 05/2014 stamped on the side. No illnesses have been reported to date in connection with this problem.
The recall was initiated following internal investigations which determined the potential presence of a microbial contaminant that exceeds the product specifications and may consequently result in a subpar product. This contaminant has been found sporadically throughout only the respective manufacturing lot, #11G075.
Consumers who have purchased "Nostrilla Decongestant, lot #11G075" are urged to return the product and contact the company at 1-877-546-9059 Monday through Friday from 9 am-5 pm EST time zone. Consumers should contact their physician or healthcare provider if they have experienced any problems that may be related to taking or using this product Adverse reactions or quality problems experienced with the use of this product may be reported to the FDA's MedWatch Adverse Event Reporting program either online, by regular mail or by fax.
*Online:www.fda.gov/medwatch/report.htm1 *Regular Mail: use postage-paid, pre-addressed Form FDA 3500 available at: www.fda.gov/MedWatch/getforms.htm2. Mail to address on the pre-addressed form.
*Fax: 1-800-FDA-0178 This recall is being conducted with the knowledge of the U.S. Food and Drug Administration.
"It is our commitment to our customers to provide them with products they can rely on as safe and effective for their FDA-approved uses," says Gary R. Downing, CEO of Insight Pharmaceuticals, LLC. "Through our standard testing procedures and protocols, we discovered the potential presence of a bacterial contaminant in one lot of Nostrilla, and reported it to the FDA. Consumer safety is our #1 priority, and we'll take all necessary action to ensure Nostrilla, as well as all of our products, comply with FDA regulations and requirements.
Healthy You
Featured Article
November 2011
The Sight-Saving Diet?
A look behind the eye-health claims made for foods and supplements
No one knows how to prevent the eye disorders that often come with aging, though not smoking and avoiding strong sunlight may help reduce the risk of cataracts. That’s why there has been so much interest in the role of nutrition in eye health, which has generated hundreds of studies in recent years—and many promising leads.
It’s clear that malnutrition harms vision. A shortage of vitamin A, for example, causes night blindness and other problems. Thus, carrots really are good for your eyes, since they’re rich in beta carotene, which the body converts into vitamin A. Vitamin deficiencies can also cause eye disorders such as cataracts in lab animals.
Other nutrients and plant compounds may help protect vision, perhaps by acting as antioxidants and reducing inflammation. These include two other carotenoids, lutein and zeaxanthin, which are antioxidant pigments in many vegetables and fruits. Lutein and zeaxanthin are also found in the retina of the healthy eye, specifically in the macula (the part of the retina responsible for detailed central vision), where they act as a filter against ultraviolet radiation and other harmful components of sunlight—sort of like built-in sunglasses.
Nearly half of us will eventually develop cataracts, a clouding of the lens that is easily corrected with outpatient surgery. Less common but also less treatable is age-related macular degeneration (AMD), the leading cause of blindness among older people. Certain nutrients appear to play a role in preventing AMD—or at least delaying it—and possibly cataracts. And there is one supplement formula that can help slow the progression of AMD if you do develop it (see box below).
Eye on research
Here are the nutrients and supplements most often promoted as ways to preserve vision in healthy people and prevent AMD and/or cataracts, along with what the research shows:
• Lutein and zeaxanthin. Most (but not all) observational studies have found that people with high dietary intakes or high blood levels of these carotenoids have a reduced risk of AMD and cataracts. Some small short-term clinical trials have also suggested protective effects in people with healthy eyes, as well as benefits in those who already have AMD. More research is needed.
• Vitamin C and E, selenium, beta carotene and other antioxidants. Again, some studies have found that people who consume plant foods rich in such antioxidants are at reduced risk for cataracts and AMD. For instance, a recent British study found that older vegetarians are 30 to 40 percent less likely to develop cataracts, compared to daily meat eaters.
But there’s little evidence that antioxidant supplements have this effect. Last year a large eight-year Harvard study of male doctors found that vitamin C and E supplements, alone or in combination, did not reduce the risk of cataracts. And a review by the Cochrane Collaboration in 2009 concluded that vitamin E and beta carotene pills do not reduce the risk of AMD. Moreover, high doses of beta carotene increase the risk of cancer in smokers.
• Zinc. This mineral, essential to good vision, is found in the retina, and it may protect eye tissue from the damaging effects of light and from inflammation. But supplemental zinc has never been found to be beneficial to healthy eyes. In addition, high doses (more than 50 milligrams daily, as in many eye supplements) can have adverse effects. Unless you have AMD (see box), get zinc from food.
• Omega-3 fats. Several large observational studies have linked fish intake (in particular, fish rich in omega-3 fats) to reduced AMD incidence and progression, and possibly to reduced risk of cataracts. The most recent study, in the Archives of Ophthalmology in June, found that women who consumed the most omega-3s from fish were 40 percent less likely to develop AMD than those with the lowest intake.
• Herbal supplements, such as bilberry and ginkgo. Many herbs show up in various eye supplements, often combined with high doses of vitamins. Bilberries contain carotenoids and other pigments (anthocyanins) that may be good for vision.
Despite the many claims and some promising lab research, so far there’s no convincing evidence that any herb or eye supplement can keep your eyes healthy.
Focus on diet
Some research, including data from the well-known Women’s Health Initiative, suggests that a healthy diet (as opposed to individual nutrients) can protect against eye disorders. In fact, it seems that the dietary habits that contribute to cardiovascular health—and that may protect the brain and help prevent some cancers—are also good for your eyes. Here are the basics:
• Emphasize colorful fruits and vegetables. In particular, leafy greens such as kale and spinach are rich in carotenoids and may protect against AMD and cataracts. Blueberries, blackberries, beets, broccoli and carrots are also excellent choices. Colorful foods—deep green, orange, yellow, purple, red, blue—contain the most carotenoids and other healthy pigments.
• Opt for healthy fats, as in fish and nuts, which may benefit the retina.
• Get more zinc, which is plentiful in foods. Meat, seafood (especially oysters) and liver are the richest sources. Brewer’s yeast, milk and other dairy products, beans, wheat germ and whole grains also supply some zinc.
Other tips: Smoking endangers your eyes—so if you smoke, this is another reason to quit. Stay out of smoky rooms. Get regular eye exams—once every three to five years starting at age 39, more often as you get older, depending on your health and on professional advice
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