Wednesday, September 30, 2015

Long-Term Safety Of Medical Cannabis In The Treatment Of Chronic Pain

Canadian multicentre study examines safety of medical cannabis in the treatment of chronic pain 

Montreal — A Canadian research team led by Dr. Mark Ware from the Research Institute of the McGill University Health Centre (RI-MUHC) in Montréal has completed a national multicentre study looking at the safety of medical cannabis use among patients suffering from chronic pain. They found that patients with chronic pain who used cannabis daily for one year, when carefully monitored, did not have an increase in serious adverse events compared to pain patients who did not use cannabis. The results, which have been published online in The Journal of Pain, will serve as a benchmark study on the side effects of cannabis when used in pain management.

“This is the first and largest study of the long term safety of medical cannabis use by patients suffering from chronic pain ever conducted,” says lead author, Dr. Ware, pain specialist at the Montreal General Hospital of the MUHC and associate professor in Family Medicine and Anesthesia at McGill University. “We found that medical cannabis, when used by patients who are experienced users, and as part of a monitored treatment program for chronic pain over one year, appears to have a reasonable safety profile.”

As part of the Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS), that started in 2004, the researchers followed 215 adult patients, with chronic non-cancer pain, who used medical cannabis, and compared them to a control group of 216 chronic pain sufferers who were not cannabis users. The study involved seven clinical centres with pain management expertise across Canada located in Fredericton, Halifax, London, Montreal, Toronto and Vancouver.

The cannabis users were given access to herbal cannabis containing 12.5 per cent THC from a licensed cannabis producer. Cannabis was dispensed through the hospital pharmacy at each site, and patients collected their supply every month after completing the necessary visits and tests. Along with information on adverse effects, subjects underwent lung function and cognitive testing, and were asked about their pain, mood and quality of life over the one year of follow up. A number of the subjects underwent complete panels of blood tests for routine biochemistry, liver and kidney function, and selected hormone levels. The average amount of cannabis used overall was 2.5 grams per day whether smoked, vaporized or taken as edibles.

“Our data show that daily cannabis users had no greater risk than non-users (control group) to experience serious adverse events,’’ explains Dr. Aline Boulanger, director of the pain clinic at the Centre hospitalier de l’Université de Montréal. ‘’We found no evidence of harmful effects on cognitive function, or blood tests among cannabis consumers and we observed a significant improvement in their levels of pain, symptom distress, mood and quality of life compared to controls.

However, the researchers did report an increased risk of non-serious adverse events in medical cannabis consumers such as headache, nausea, dizziness, somnolence, and respiratory problems associated with smoking.

“It is important to note the limitations of the study,” adds Dr. Ware. “Patients were self-selected, not randomized, and most were experienced users. So what we are seeing is that it appears to be a relatively safe drug when used by people who have already determined that it helps them. We cannot draw conclusions about safety issues of new cannabis users”.

About the study
The study was funded by the Canadian Institutes of Health Research (CIHR). The article Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS) is available online.

The sites involved in this study were the Alan Edwards Pain Management Unit at the Montreal General Hospital of the McGill University Health Centre and the Pain clinic at the Centre hospitalier de l’Université de Montréal – Hôtel-Dieu, (Montréal, QC); the QEII Health Sciences Centre (Halifax, NS), the Wasser Pain Management Centre of the Mount Sinai Hospital (Toronto, ON); the London Health Research Institute of St. Joseph’s Health Care (London, ON); the Stan Cassidy Center for Rehabilitation (Fredericton, NB); and the Arthritis Research Center of Canada (Vancouver, BC).

About The Research Institute of the McGill University Health Centre

The Research Institute of the McGill University Health Centre (RI-MUHC) is a world-renowned biomedical and healthcare research centre. The Institute, which is affiliated with the Faculty of Medicine of McGill University, is the research arm of the McGill University Health Centre (MUHC) - an academic health centre located in Montreal, Canada, that has a mandate to focus on complex care within its community. The RI-MUHC supports over 500 researchers, and over 1,200 students, devoted to a broad spectrum of fundamental, clinical and health outcomes research at the Glen and the Montreal General Hospital sites of the MUHC. Our research facilities offer a dynamic multidisciplinary environment that fosters collaboration and leverages discovery aimed at improving the health of individual patients across their lifespan. Over 1,600 clinical research projects and trials are conducted within the organization annually. The RI-MUHC is supported in part by the Fonds de recherche du Québec - Santé (FRQS). www.rimuhc.ca

Media contact:

Julie Robert
Public Affairs & Strategic planning
McGill University Health Centre
julie.robert@muhc.mcgill.ca
(514) 934-1934 ext. 71381

The Future in Liver Medicine: The extinction of chronic viral hepatitis?

Clinical Liver Disease

Volume 6, Issue 3 Pages 55 - 77, September 2015
Special Issue: Liver and the Microbiome, Non-Viral Liver Infections, Non-Cirrhotic Portal Hypertension & The Future in Liver Medicine

Clinical Liver Disease (CLD) is the latest online learning resource of The American Association for the Study of Liver Diseases (AASLD.) CLD blends text, audio, video, webinars, and other interactive content into educational interventions launched every two months. These interventions are designed for any physician or healthcare provider caring for a patient with liver disease.

The latest issue of Clinical Liver Disease is available on Wiley Online Library

The Future in Liver Medicine
Guest Edited by Meena Bansal, MD

The extinction of chronic viral hepatitis? (pages 75–77)
Sonal Kumar and Ira M. Jacobson
Article first published online: 29 SEP 2015 | DOI: 10.1002/cld.502

Reviews
Liver and the Microbiome

Guest Edited by Eamonn Quigley, MD

The gut microbiome in NAFLD and ALD (pages 55–58)
Irina A. Kirpich, Dipendra Parajuli and Craig J. McClain
Article first published online: 29 SEP 2015 | DOI: 10.1002/cld.494


Non-Viral Liver Infections

Guest Edited by Emily A. Blumberg, MD

Schistosomiasis: Clinical management of liver disease (pages 59–62)
Marta Guimarães Cavalcanti, João Marcello de Araujo-Neto and José Mauro Peralta
Article first published online: 29 SEP 2015 | DOI: 10.1002/cld.495

Herpes virus infections (pages 63–66)
Daniel Mueller and Heather Clauss
Article first published online: 29 SEP 2015 | DOI: 10.1002/cld.500

Non-Cirrhotic Portal Hypertension
Guest Edited by Theo Heller, MD, Ohad Etzion, MD, and Christopher Koh, MD

Noncirrhotic portal hypertension: Imaging, hemodynamics, and endovascular therapy (pages 67–71)
Elliot Levy
Article first published online: 29 SEP 2015 | DOI: 10.1002/cld.496

Noncirrhotic portal hypertension: An overview (pages 72–74)
Ohad Etzion, Christopher Koh and Theo Heller
Article first published online: 29 SEP 2015 | DOI: 10.1002/cld.497


Tuesday, September 29, 2015

Full Text: HCV targeting of patients with cirrhosis

October 2015
Volume 63, Issue 4, Pages 1015–1022

HCV targeting of patients with cirrhosis
Peter Ferenci, Karin Kozbial , Mattias Mandorfer , Harald Hofer Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria  

Received: March 11, 2015; Received in revised form: June 9, 2015; Accepted: June 10, 2015; Published Online: June 19, 2015 Article has an altmetric score of 10
DOI: http://dx.doi.org/10.1016/j.jhep.2015.06.003

[Free review] @ Journal Of Hepatology


Summary
Interferon (IFN)-free treatments are now the treatment of choice for patients with chronic hepatitis C. Previously difficult to treat patients by IFN-containing treatments can now be treated safely by IFN-free therapies. More than 90% of hepatitis C genotype 1 and 4 patients with compensated cirrhosis or after orthotopic liver transplantation (OLT) can be cured by sofosbuvir combined with simeprevir, daclatasvir or ledipasvir, or by the paritaprevir/ritona-vir/ombitasvir/±dasabuvir (3D) combination. Addition of ribavirin confers to a minimal, if any, benefit to increase SVR. The need for ribavirin is controversial and remains to be studied. The optimal length of treatment is still unknown, and an individual approach may be needed. Most patients require only 12 weeks of therapy. The safety of these drugs is not fully explored in patients with decompensated cirrhosis (Child-Pugh C), who should not be treated with protease inhibitors. In cirrhosis hepatitis C virus eradication does not necessarily mean a cure of the disease and patients regularly require follow-up. Drug-drug interactions with immunosuppressant in patients after OLT are easier to manage but still require attention. Better drugs are needed for genotype 3 patients

Table 1
Impact of treatment duration and addition of ribavirin on the response to IFN-free treatments in patients with cirrhosis due to HCV-GT1 infection.

Click Image To Enlarge


[Free review] @ Journal Of Hepatology
© 2015 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.

Monday, September 28, 2015

Historical Path of Discovery of Viral Hepatitis

Historical Path of Discovery of Viral Hepatitis

Posted on September 27, 2015 by David T. Wong, Martin C. Mihm, MD, James L. Boyer, MD, and Dhanpat Jain, MD

This article presents an overview of the historical timeline of the gradual discovery of various hepatitis viruses and the pivotal roles of epidemiological observations, human experimentations, and laboratory research in their discovery and containment.

Full Text Article

Abstract

Viral hepatitis is an ongoing global infectious public health problem and a major cause of chronic liver diseases, including liver cancer. Previously described as “epidemic jaundice,” viral hepatitis has been known to exist since ancient civilizations. The contagious nature of the illness was suspected even in the eighth century CE. Records from major military campaigns in different continents from the 18th to 20th centuries, including the American Civil War and the First and Second World Wars, reported that “campaign jaundice” caused significant morbidity of the troops and impacted war strategies. Epidemiological observations from late 19th century and research, including human experimentation in the 20th century, led to the gradual identification of a distinct “infectious hepatitis” agent transmitted by oral-fecal transmission, known later as hepatitis A virus (HAV), and a “serum hepatitis” agent transmitted by inoculation or transfusion of serum, blood or plasma, or sexual contact. Experiments that involved feeding and injecting infected feces, urine, and serum into volunteered military personnel, prisoners, and mentally retarded children raised issues of informed consent and mental competency of the retarded children. Only until the 1960s was one of the causative agents of “serum hepatitis,” the hepatitis B virus (HBV), discovered. Further research led to the discovery of additional hepatitis viruses (HCV, HDV, HEV, and HGV). Breakthroughs in the containment of the hepatitis epidemic included development of hepatitis vaccines and recent therapeutic successes for hepatitis C. This paper presents an overview of the historical timeline of the gradual discovery of the causative agents of viral hepatitis.

Continue reading 

Of Interest - Hepatitis Timeline 
The Origin Of Hepatitis:HCV and HBV






AbbVie's VIEKIRAX Approved In Japan For Genotype 1 Chronic Hepatitis C

AbbVie's VIEKIRAX Approved In Japan For Genotype 1 Chronic Hepatitis C

ABBVIE'S VIEKIRAX® (OMBITASVIR/PARITAPREVIR/RITONAVIR TABLETS) RECEIVES APPROVAL IN JAPAN FOR THE TREATMENT OF GENOTYPE 1 CHRONIC HEPATITIS C

- NEW INTERFERON AND RIBAVIRIN-FREE TREATMENT OPTION FOR PATIENTS WITH MOST COMMON TYPE OF HEPATITIS IN JAPAN, GENOTYPE 1 CHRONIC HEPATITIS C, INCLUDING THOSE WITH COMPENSATED CIRRHOSIS[1]

- VIEKIRAX CONSISTS OF A 12-WEEK, TWO DIRECT-ACTING ANTIVIRAL, FIXED-DOSE COMBINATION OF PARITAPREVIR/RITONAVIR WITH OMBITASVIR, DOSED ONCE DAILY[1]

- APPROXIMATELY 1.5 TO 2 MILLION PEOPLE ARE LIVING WITH HEPATITIS C IN JAPAN, ONE OF THE HIGHEST RATES OF HEPATITIS C INFECTION IN THE INDUSTRIALIZED WORLD[2],[3]

Sep 28, 2015

NORTH CHICAGO, Ill., Sept. 28, 2015 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) approved VIEKIRAX®(ombitasvir/paritaprevir/ritonavir), as a new interferon and ribavirin-free treatment option for adult patients with chronic genotype 1 (GT1) hepatitis C virus (HCV) infection, including those with compensated liver cirrhosis.1 VIEKIRAX consists of a 12-week, two direct-acting antiviral, fixed-dose combination of paritaprevir/ritonavir with ombitasvir, dosed once daily.

"Today's approval represents an important step forward for the treatment of Japanese patients, a population with specific needs based on patient and viral characteristics," said Jean-Michel Pawlotsky, MD, PhD, professor of medicine at the University of Paris-Est, France. "VIEKIRAX is a valuable new addition to a number of treatments that are changing the face of hepatitis C, making it possible to achieve high virologic cure rates, even in patients whose disease has progressed to compensated liver cirrhosis."

Japan has one of the highest rates of hepatitis C infection in the industrialized world, with approximately 1.5 to 2 million people living with HCV.2, 3 Genotype 1 is the most common HCV genotype in Japan with 60 to 70 percent of patients infected and, of those, about 95 percent are infected with the genotype 1b (GT1b) sub-type.4

"We are pleased to provide VIEKIRAX as a new treatment that offers a high probability of virologic cure for GT1b HCV patients and are working to support access to our treatment in Japan," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "We are also prioritizing disease education and awareness by collaborating with stakeholders to identify and address the diverse challenges across Japan, such as supporting screening and diagnosis initiatives, and providing accurate information to the medical community about treatment options."

The approval is supported by the Phase 3 GIFT-I study.1 An overall 95 percent (n=140/148) of treatment-naïve and 94 percent (n=102/109) of treatment-experienced GT1b HCV infected patients achieved SVR12 with VIEKIRAX.1

The primary endpoint was achieved, demonstrating 95 percent (n=106/112) SVR12 in a sub-group of treatment-naïve, non-cirrhotic, adult GT1b HCV infected Japanese patients who were eligible for therapy with interferon (IFN) and had a high viral load. A secondary endpoint in GT1b HCV patients with compensated cirrhosis achieved 91 percent (n=38/42) SVR12.5

Across all treatment arms three patients (n=3/363) experienced on-treatment virologic failure, eight patients (n=8/354) experienced post-treatment relapse and three patients discontinued treatment due to adverse events. The most commonly reported adverse events (>5 percent in any arm) were nasopharyngitis, headache, peripheral edema, nausea, pyrexia and decreased platelet count.5 In April 2015, AbbVie was granted priority review by the MHLW for VIEKIRAX, on the basis of clinical usefulness of the treatment and recognizing the severity and unmet need of the disease in Japan.

About the GIFT-I Study5

GIFT-I comprises 363 patients in two sub-studies.

In sub-study 1, 321 genotype 1b (GT1b) patients without cirrhosis, both treatment-naïve and interferon (IFN) [with or without ribavirin (RBV)] treatment-experienced, were randomized to receive either ombitasvir/paritaprevir/ritonavir (Arm A) [OBV/PTV/r] or placebo (Arm B) [2:1 randomization ratio, stratified by treatment history, past response, viral load and IFN eligibility]. Patients initially randomized to placebo (Arm B) then received OBV/PTV/r for an additional 12 weeks of open-label treatment. Sustained virologic response was assessed 12 weeks post-treatment (SVR12) as a primary efficacy endpoint in a sub-group of previously untreated, non-cirrhotic GT1b patients who were eligible for therapy with IFN and had a high viral load, defined as an HCV RNA level ≥ 100,000 IU/mL and received at least one dose of the double-blind, active study drug.

In sub-study 2, 42 GT1b treatment-naïve and IFN (with or without RBV) treatment-experienced patients with compensated cirrhosis received open-label treatment for 12 weeks (Arm C) with SVR12 and assessed as a secondary efficacy endpoint.

One patient from each arm (n=3/363) experienced on-treatment virologic failure [Arm A, 0.5% (n=1/215); Arm B, 0.9% (n=1/106); Arm C, 2.4% (n=1/42)]. Across all arms, eight patients (n=8/354) experienced post-treatment relapse [Arm A, 2.4% (n=5/209); Arm B, 1.0% (n=1/105); Arm C, 5.0% (n=2/40)].

AbbVie studied its two direct-acting antiviral treatment regimen without RBV in Japan due to patient and viral characteristics specific to the Japanese population, including high prevalence of GT1b.

About VIEKIRAX in Japan

Indication in Japan

VIEKIRAX is indicated for the improvement of viremia in chronic hepatitis C or compensated hepatic cirrhosis C in patients of serogroup 1 (genotype 1).

Summary of Safety Information

Contraindications

VIEKIRAX is contraindicated in patients with a history of known hypersensitivity to an ingredient in VIEKIRAX, patients with severe hepatic impairment (Child-Pugh C) or patients being treated with the following drugs: azelnidipine, triazolam, iv midazolam, blonanserin, pimozide, ergotamine tartrate, dihydroergotamine mesilate, ergometrine maleate, methylergometrine maleate, sildenafil citrate [Revatio], tadalafil [Adcirca], rivaroxaban, vardenafil hydrochloride hydrate, riociguat, simvastatin, atorvastatin calcium hydrate, carbamazepine, phenytoin, phenobarbital, rifampin, efavirenz, foods containing St. John's Wort (Hypericum perforatum), ethinyl estradiol-containing medicinal products.

Precautions for Use

Positive result for HCV RNA should be confirmed before administering VIEKIRAX and decompensated cirrhosis should be excluded.

When VIEKIRAX is used for patients co-infected with HIV/HCV, administer VIEKIRAX only to patients whose virological suppression has been achieved by anti-HIV therapy as ritonavir may cause resistance against a HIV protease inhibitor.

During the administration of VIEKIRAX, perform liver function tests regularly because hepatic function disorder may occur.

Co-administration of VIEKIRAX with drugs that are substrates of CYP3A4, P-gp, BCRP, OATP1B1 or OATP1B3 may result in increased plasma concentrations of such drugs, potentially requiring dose adjustment or clinical monitoring.

The safety of VIEKIRAX in pregnant women has not been established. VIEKIRAX should be used in pregnant women and women who may possibly be pregnant only if the expected therapeutic benefits outweigh the possible risks associated with treatment.

Do not administer VIEKIRAX to nursing mothers. If VIEKIRAX is administered to a nursing mother by necessity, breast feeding must be discontinued during treatment.

Safety and effectiveness have not been established in children.

Adverse Reactions

Major adverse reactions included peripheral edema in 15 subjects (4.1%), headache in 12 subjects (3.3%) and nausea in 10 subjects (2.8%)

About AbbVie's HCV Clinical Development Program in Japan

AbbVie's HCV clinical development program in Japan focuses on our two direct-acting antiviral treatment and is designed with the goal of achieving high SVR rates in chronic HCV infected patients, including additional genotypes and patients with compensated cirrhosis.

Paritaprevir was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors. Paritaprevir has been developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of hepatitis C.

About AbbVie

AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases. Together with its wholly-owned subsidiary, Pharmacyclics, AbbVie employs more than 28,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit www.abbvie.com. Follow @abbvie on Twitter or view careers on our Facebook or LinkedInpage.

Forward-Looking Statements

Some statements in this news release may be forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry.

Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," in AbbVie's 2014 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

1 VIEKIRAX [package insert]. Tokyo, Japan: AbbVie Ltd; 2015.
2 Kohnodai Hospital. National Center for Global Health and Medicine [cited 20 February 2013]. Available from:http://www.ncgm.go.jp/center/forpatient_hcv.html
3 Gower, E. Global epidemiology and genotype distribution of the hepatitis C virus infection. Journal of Hepatology 2014; 61: S45-S57, Table 2.
4 Hajarizadeh B et al. Nat Rev Gastroenterol Hepatol 2013; 10: 553-562. Available from:http://www.nature.com/nrgastro/journal/v10/n9/fig_tab/nrgastro.2013.107_F1.html
5 Kumada H, et al. Randomized phase 3 trial of ombitasvir/paritaprevir/ritonavir for hepatitis C virus genotype 1b-infected Japanese patients with or without cirrhosis. Hepatology. 2015 Jul 3. doi: 10.1002/hep.27972.

Sunday, September 27, 2015

Liver Enzymes Tell Tale in Hepatitis C Complications

MedPage Today

Liver Enzymes Tell Tale in Hepatitis C Complications
ALT/AST ratio could be useful screen for fatty liver complications

by Mike Bassett
Contributing Writer, MedPage Today

The serum aminotransferase ratio -- commonly used as a measurement of liver health -- is associated with hepatosteatosis in patients with hepatitis C, according to Taiwanese researchers.

According to the study, published online in BMJ Open, patients with a higher ALT/AST ratio had a 1.9-fold greater risk of NAFLD and a 2.44-fold higher risk of a high degree of NAFLD.

There is a high incidence of NAFLD in patients with hepatitis C and that poses a further health risk for patients since it can progress to liver diseases such as nonalcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular cancer.

The problem, according to Lin and his colleagues, is that NAFLD "silently coexists" with hepatitis C and is only diagnosed incidentally.

Friday, September 25, 2015

TGIF Rewind: Big pharmaceuticals and the Hepatitis C drug trail dubbed a 'miracle cure'

Rewind: News and Views

Welcome to TGIF rewinda look back at this weeks hepatitis C headlines with updates from around the web.

In The News

Big pharmaceuticals and the Hepatitis C drug trail dubbed a 'miracle cure'
What would you do if you had a potentially lethal illness, knew of a "miracle" cure which would most likely fix the problem in three months by taking one pill a day, but you couldn't afford to buy the medicine from the drug company which owned the patent? This is the position that "Patient Zero" found himself in. And he, with a doctor and a group of campaigning mates, found an answer – one that they believe costs up to 30 times less than the drug company might expect them to pay.

CDC
State Reporting Requirements for Viral Hepatitis
Former hedge fund manager Martin Shkreli has the Internet ablaze after hiking the price of the drug that's been on the market for decades. Here's what happened. (Gillian Brockell/The Washington Post)

Health Care Industry Mergers Side Effect of Affordable Care Act
Many are worried that the huge consolidations will dampen competition and push up health care prices over time...

Many veterans who fought to protect and defend our country are still fighting to get the support they need from the federal government...

Why people don't trust drug makers
Insurers and pharmacy benefit managers - not drug companies - are the ones who determine what patients pay for medications. Consider the controversy surrounding the hepatitis C drug Sovaldi. When the medicine came on the market, it quickly became ...

Rhode Island Medicaid Denied 65% of Hep C Treatment Requests in 2015
It's a move that, while saving the state millions of dollars, is keeping hundreds of sick patients from accessing a cure.

Concern about drug costs has been particularly acute for state Medicaid programs, which face both limited budgets and high Hepatitis C prevalence among beneficiaries (higher than in the general population). And perhaps with good reason: In 2014, the ...

September 23, 2015 
A once-daily, fixed-dose combination of sofosbuvir (SOF) plus velpatasvir (VEL) had high success rates for the treatment of all six genotypes of hepatitis C virus, manufacturer Gilead Sciences reported.

In three of four phase III trials (ASTRAL-1ASTRAL-2, and ASTRAL-3), 1,035 HCV patients were given the drug combination for 12 weeks. In the fourth trial (ASTRAL-4), 267 HCV patients with decompensated cirrhosis were randomized to receive either the SOF/VEL combination for 12 weeks with or without ribavirin or 24 weeks of just SOF/VEL. The primary efficacy endpoint for all studies was a sustained virological response at 12 weeks, the company said in a statement.

The FDA has designated the SOF/VEL combination as “breakthrough therapy” status, granted to “investigational medicines that may offer major advances in treatment over existing options,” the statement said.Results showed that 98% of patients in the first three trials achieved the efficacy endpoint. In the ASTRAL-4 study, 94% of patients in the SOF/VEL plus ribavirin group achieved sustained virological response at 12 weeks. The rates of success in patients receiving the SOF/VEL combination for 12 or 24 weeks were 83% and 86%, respectively. The most common adverse effects were fatigue, nausea, and headache.

Press Release
Gilead Announces SVR12 Rates from Four Phase 3 Studies Evaluating Fixed-Dose Sofosbuvir/Velpatasvir (GS-5816) Pan-Genotypic

The Food and Drug Administration (FDA) announced that Rebetol(ribavirin; Merck) capsules and PegIntron (peginterferon alfa-2b; Merck) for Injection are being discontinued. The decision is business-related and not due to safety or efficacy issues with the drugs.

Rebetol is a nucleoside analogue indicated for chronic hepatitis C in combination with interferon alfa-2b (pegylated and nonpegylated), in patients ≥3 years of age with compensated liver disease. It is supplied as 200mg capsules in 56-, 70-, and 84-count bottles. The Rebetol discontinuation is effective February 1, 2016.

PegIntron is an antiviral indicated for treatment of chronic hepatitis C in patients with compensated liver disease. It is supplied as 50mcg/0.5mL, 80mcg/0.5mL, 120mcg/0.5mL, and 150mcg/0.5mL single-use vials and single-use pre-filled pens. No effective date is available for the PegIntron discontinuation.

For more information call (888) 463-6332 or visit FDA.gov.
Source
http://www.empr.com/safety-alerts-and-recalls/rebetol-pegintron-to-be-discontinued/article/440426/

Conatus Announces emricasan Phase 2 study reduces liver portal hypertension predominantly due to NASH or HCV

A player in J&J's hep C cocktail helps hustle a quick cure 
September 17, 2015 | By John Carroll
Gilead has already made a megablockbuster fortune out of its hepatitis C cure. But the race to cure patients faster (and probably cheaper) is still on. And Achillion today posted some new data from small studies that show its NS5A inhibitor odalasvir (or ACH-3102) could feature prominently in one of the new cocktail therapies now in development at Johnson & Johnson...

Around The Web

Hepatitis C virus infection: a risk factor for Parkinson's disease
"In summary, our study not only demonstrated a significantly positive association between HCV infection and Parkinson's disease (PD) from a large population-based epidemiological study but also proved the dopaminergic neuronal toxicity by HCV in vitro at the molecular level through an increase in cytokines induced by HCV. Epidemiologically, we found that anti-HCV(+) patients had statistically significant increased risk of developing PD in the population-based study. 

Revolutionary new drugs to cure hepatitis C virus (HCV) infection represent one of the most important breakthroughs in clinical medicine in recent decades. However, high pricing of these well-tolerated, highly efficacious all-oral regimens and high demand (actual or anticipated) has led many payers in the United States and other countries to exclude people who have recently used illicit drugs, injectable drugs or alcohol (with the definitions of "use" varying by jurisdiction) from access to these treatments

Correspondence
N Engl J Med 2015; 373:1279-1281 September 24, 2015 
DOI: 10.1056/NEJMc1506108
To the Editor:
The cure rates associated with sofosbuvir, a new treatment for hepatitis C virus (HCV), have been remarkable.1 However, the high cost of the drug has raised concerns,2 particularly in regard to socioeconomically disadvantaged populations with a high prevalence of HCV infection, such as Medicaid beneficiaries. Demand for new HCV drugs in Medicaid populations drove historic surges in spending on drugs in 2014, the first full year during which sofosbuvir was available since its approval by the Federal Drug Administration (FDA) in late 2013.3 Given its recent introduction to the market, little is known about state-level utilization and spending patterns for sofosbuvir...

Healio 
NICE recommends software to diagnose, monitor liver fibrosis
“As well as meaning that people with chronic hepatitis B or C could avoid having invasive liver biopsies, the associated savings of more than £400 per person ...

Interferon-based therapy still common for HCV among veterans
In a retrospective study, researchers found that the uptake of direct-acting antivirals, specifically Victrelis and Incivek, increased among veterans with HCV over time…

Editorial
The guidelines for hepatitis C have been updated twice in the month of August.
The first update incorporated the approval of daclatasvir (Daklinza, Bristol-Myers Squibb) in the United States and, based on that approval, modified treatment recommendations for most of the treatment groups..

Lucinda Porter
Hepatitis C: The Evolution of Treatment
Last week I discussed the history of hepatitis C. This week I focus on the evolution of hepatitis C treatment...

Healthy You

Green Tea Hidden Dangers: Teen Contracts Acute Hepatitis After Drinking Three Cups Per Day
A young woman has contracted hepatitis after drinking three cups of Chinese green tea per day.
Doctors have now warned of the hidden dangers of consuming too much of the herbal tea, which they believe was to blame for the teenager contracting acute hepatitis...

Over long term, diet and exercise are best to prevent diabetes
In a head-to-head comparison over 15 years, diet and exercise outperformed the drug metformin in preventing people at high risk for diabetes from developing the disease.

Metformin Link to Vitamin B12 Deficiency, Neuropathy, in Diabetes
Researchers link 4 years of metformin use to a net worsening of peripheral neuropathy in type 2 diabetes, even after accounting for improvements from HbA1c lowering.
Medscape Medical News, September 25, 2015 
Explore calculators, interactive worksheets, and more that will help you take a look at your drinking habits and understand how they may affect your health...

Off Topic

Should Dr Oz, a Prominent Surgeon, Be Fired for Quackery?
Last spring, 10 physicians wrote to Columbia University, where Dr Mehmet Oz is employed, demanding his removal for promoting quack remedies on TV. Should he be? See what your colleagues think.

Scientists stop and search malware hidden in shortened URLs on Twitter
Intelligent system created to stop and search malware links
Engineering and Physical Sciences Research Council

Cyber-criminals are taking advantage of real-world events with high volumes of traffic on Twitter in order to post links to websites which contain malware.

To combat the threat, computer scientists have created an intelligent system to identify malicious links disguised in shortened urls on Twitter. They will test the system in the European Football Championships next summer. The research is co-funded by the Engineering and Physical Sciences Research Council (EPSRC) and the Economic and Social Research Council (ESRC).

In the recent study the Cardiff University team identified potential cyber-attacks within five seconds with up to 83% accuracy and within 30 seconds with up to 98% accuracy, when a user clicked on a URL posted on Twitter and malware began to infect the device.

The scientists collected tweets containing URLs during the 2015 Superbowl and cricket world cup finals, and monitored interactions between a website and a user's device to recognise the features of a malicious attack. Where changes were made to a user's machine such as new processes created, registry files modified or files tampered with, these showed a malicious attack.

The team subsequently used system activity such as bytes and packets exchanged between device and remote endpoint, processor use and network adapter status to train a machine classifier to recognise predictive signals that can distinguish between malicious and benign URLs.

Dr Pete Burnap, Director of the Social Data Science Lab at Cardiff University, and lead scientist on the research, said: "Unfortunately the high volume of traffic around large scale events creates a perfect environment for Cyber-criminals to launch surreptitious attacks. It is well known that people use online social networks such as Twitter to find information about an event.

"Attackers can hide links to malicious servers in a post masquerading as an attractive or informative piece of information about the event.

"URLs are always shortened on Twitter due to character limitations in posts, so it's incredibly difficult to know which are legitimate. Once infected the malware can turn your computer into a zombie computer and become part of a global network of machines used to hide information or route further attacks.

"In a 2013 report from Microsoft these 'drive-by downloads' were identified as one of the most active and commercial risks to Cyber security.

"At the moment many existing anti-virus solutions identify malware using known code signatures, which make it difficult to detect previous unseen attacks."

Professor Omer Rana, Principal investigator on the project which is also includes Royal Holloway, University of London, City University London, the University of Plymouth and Durham University said:

"We are trying to build systems that can help law enforcement authorities make decisions in a changing Cyber Security landscape. Social media adds a whole new dimension to network security risk. This work contributes to new insight into this and we hope to take this forward and develop a real-time system that can protect users as they search for information about real-world events using new forms of information sources.

"We have the European Football Championships coming up next summer, which will provide a huge spike in Twitter traffic and we expect to stress-test our system using this event."

Professor Philip Nelson, Chief Executive, EPSRC said: "Using social media is an integral part of modern life, vital to organisations, businesses and individuals. The UK needs to operate in a resilient and secure environment and this research will help combat these criminal Cyber-attacks."

Hope everyone has a wonderful weekend.
Tina



Thursday, September 24, 2015

Two HCV Drugs to Be Discontinued

Two HCV Drugs to Be Discontinued

The Food and Drug Administration (FDA) announced that Rebetol (ribavirin; Merck) capsules and PegIntron (peginterferon alfa-2b; Merck) for Injection are being discontinued. The decision is business-related and not due to safety or efficacy issues with the drugs.

Rebetol is a nucleoside analogue indicated for chronic hepatitis C in combination with interferon alfa-2b (pegylated and nonpegylated), in patients ≥3 years of age with compensated liver disease. It is supplied as 200mg capsules in 56-, 70-, and 84-count bottles. The Rebetol discontinuation is effective February 1, 2016.

PegIntron is an antiviral indicated for treatment of chronic hepatitis C in patients with compensated liver disease. It is supplied as 50mcg/0.5mL, 80mcg/0.5mL, 120mcg/0.5mL, and 150mcg/0.5mL single-use vials and single-use pre-filled pens. No effective date is available for the PegIntron discontinuation.

For more information call (888) 463-6332 or visit FDA.gov.
Source
http://www.empr.com/safety-alerts-and-recalls/rebetol-pegintron-to-be-discontinued/article/440426/


Conatus Announces emricasan Phase 2 study reduces liver portal hypertension predominantly due to NASH or HCV

Press Release

Conatus Announces Top-line Results From Multicenter Phase 2 Portal Hypertension Clinical Trial in Patients With Liver Cirrhosis

September 23, 2015 16:01 ET | Source: Conatus Pharmaceuticals

- Emricasan Significantly Lowered Portal Pressure in Patients With Severe Portal Hypertension -

- Conference Call and Webcast Presentation at 8:30 a.m. ET on Thursday, September 24 -

SAN DIEGO, Sept. 23, 2015 (GLOBE NEWSWIRE) -- Conatus Pharmaceuticals Inc. (NASDAQ:CNAT) today announced that the company's exploratory Phase 2 Portal Hypertension (PH) clinical trial of emricasan, a first-in-class, orally active pan-caspase inhibitor, met the following primary endpoints: a) a clinically meaningful and statistically significant change from baseline in hepatic venous pressure gradient (HVPG), a measurement of pressure in the portal vein, in patients with liver cirrhosis and severe portal hypertension (HVPG ≥12 mmHg); and b) a statistically significant change from baseline in cleaved Cytokeratin 18 (cCK18), a mechanism-specific biomarker of excessive cell death that contributes to chronic inflammation, in the total evaluable liver cirrhosis patient population.

The open-label PH trial was conducted at nine U.S. sites and enrolled 23 patients (22 evaluable) with portal hypertension and compensated liver cirrhosis that was predominantly due to nonalcoholic steatohepatitis (NASH) or hepatitis C virus (HCV), including patients with active HCV infection and patients who had a sustained viral response (SVR) to antiviral therapy. Portal hypertension, or elevated blood pressure in the major vein feeding into the liver, was confirmed by HVPG measurement >5 mmHg at baseline and measured again after treatment with 25 mg of emricasan orally twice daily for 28 days. Patients were divided according to the HVPG therapeutic threshold of 12 mmHg, which indicates more severe portal hypertension. Reducing the HVPG to below 12 mmHg or reducing HVPG by ≥10% or ≥20% has been strongly associated with clinical benefit in this patient population.

The HVPG endpoint was analyzed in: a) patients with baseline HVPG values ≥12 mmHg (N=12); b) patients with baseline HVPG values <12 mmHg (N=10); and c) all evaluable patients (N=22). HVPG measurement was standardized, and tracings were evaluated by a single expert reader not otherwise involved in the PH trial. HVPG decreased by a mean of 3.7 mmHg from the mean baseline of 20.6 mmHg in the higher baseline HVPG group (p<0.003), with 8 of 12 achieving a ≥10% decrease, 4 of 12 achieving a ≥20% decrease, and 2 of 12 achieving reductions below 12 mmHg. The changes from baseline HVPG were not statistically significant in the lower baseline HVPG group (+1.9 mmHg mean increase from mean baseline of 8.1 mmHg; p=0.12) or the total evaluable patient population (–1.1 mmHg from mean baseline of 15.2 mmHg; p=0.26). The cCK18 endpoint, analyzed in the total evaluable patient population, showed a statistically significant reduction (p<0.03) from baseline. Consistent with results from prior trials, emricasan was safe and well tolerated in the PH trial, with no dose-limiting toxicities and no drug-related serious adverse events. Detailed results are expected to be presented in a future scientific forum.

As liver cirrhosis progresses, portal pressure increases and hepatic function is eventually lost. Importantly, portal hypertension is largely responsible for events of hepatic decompensation including variceal bleeding, ascites, and encephalopathy, which contribute substantially to morbidity and mortality in these patients. By lowering elevated portal pressures, emricasan has the potential to decrease the risk of hepatic decompensation in liver cirrhosis patients over the short term, and may improve both liver function and structure over the long term through anti-inflammatory and anti-fibrotic effects.

David T. Hagerty, M.D., Executive Vice President of Clinical Development at Conatus, said, "We were excited to demonstrate that a drug candidate with the potential to achieve long-term resolution of fibrosis and cirrhosis also has the ability to induce a rapid and clinically meaningful reduction of severe portal hypertension. The reduction of portal pressure over a relatively short time frame in the patients with therapeutically relevant portal hypertension may reflect the initial impact of emricasan on the hyperdynamic circulation that is the predominant contributor to portal hypertension as cirrhosis progresses and/or a direct effect upon intrahepatic vasculature resistance. Future studies will be needed to assess the relative contribution of these mechanisms to the observed clinical effect. Decreasing HVPG has been identified by the FDA (U.S. Food and Drug Administration) as a validated, objective measure that may be acceptable as a surrogate endpoint for clinical trials of patients with liver cirrhosis. These results set the stage for future Phase 2b clinical trials in patients with cirrhosis and therapeutically relevant portal hypertension."

"These results demonstrate that emricasan can cause a clinically meaningful improvement in portal hypertension in the liver cirrhosis patients who need it most," said Conatus co-founder, President and Chief Executive Officer Steven J. Mento, Ph.D. "Specifically, patients with therapeutically relevant baseline portal hypertension showed meaningful decreases in HVPG. We believe the results from this trial establish the near-term effects of emricasan on portal hypertension. We are evaluating emricasan's potential longer-term effects on liver function and liver structure in our other two ongoing clinical trials: the Phase 2 Liver Cirrhosis (LC) trial and the Phase 2b post-transplant trial."

"Even though the number of patients in this trial was small," added Dr. Hagerty, "Conatus was encouraged by the consistency of responses in patients with portal hypertension and cirrhosis due primarily to NASH or HCV. These results further support our view that apoptosis and inflammation are important common mechanisms for progressive liver disease across multiple etiologies, and that treatment with emricasan is likely to provide both short- and long-term clinical benefits."

Conference Call/Webcast/Presentation

Conatus will host a conference call and webcast at 8:30 a.m. Eastern Time on Thursday, September 24, to discuss the top-line results and provide a mechanism-focused overview of liver cirrhosis and portal hypertension. To access the conference call, please dial 877-312-5857 (domestic) or 970-315-0455 (international) at least five minutes prior to the start time and refer to conference ID 45793794. An associated presentation and live and archived audio webcast of the call will be available in the Investor Center of the company's website at http://ir.conatuspharma.com/events.cfm.

About Emricasan Clinical Development

To date, emricasan has been studied in over 600 subjects in fifteen clinical trials across a broad range of liver disease etiologies and stages of progression. In multiple clinical trials, emricasan has demonstrated statistically significant, rapid and sustained reductions in elevated levels of key biomarkers of inflammation and apoptosis that are implicated in the severity and progression of liver disease. Importantly, these key biomarkers are known to be elevated and to have prognostic value in multiple hepatic indications that Conatus is currently pursuing. The company's ongoing Phase 2 LC trial is evaluating emricasan's potential medium-term effect on liver function using two other potential surrogate clinical endpoints – Model for End-Stage Liver Disease (MELD) score and Child-Pugh-Turcotte (CPT) status. The company also is evaluating emricasan's potential longer-term effects on liver structure in its ongoing Phase 2b clinical trial in post-orthotopic liver transplant (POLT) recipients who have reestablished liver fibrosis or cirrhosis post-transplant as a result of recurrent HCV infection and have successfully achieved a SVR following HCV antiviral therapy (POLT-HCV-SVR). The company currently is developing a strategy for initial registration of emricasan as a potential treatment for patients with liver cirrhosis.

About Conatus Pharmaceuticals

Conatus is a biotechnology company focused on the development and commercialization of novel medicines to treat liver disease. Conatus is developing its lead compound, emricasan, for the treatment of patients with chronic liver disease. Emricasan is a first-in-class, orally active pan-caspase inhibitor designed to reduce the activity of enzymes that mediate inflammation and apoptosis. Conatus believes that by reducing the activity of these enzymes, emricasan has the potential to interrupt the disease progression across the spectrum of liver disease. For additional information, please visit www.conatuspharma.com.

Forward-Looking Statements
This press release contains forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical facts contained in this press release are forward looking statements, including statements regarding: presenting detailed results of the PH trial in a future scientific forum; emricasan's potential to decrease risk of hepatic decompensation; emricasan's potential to improve both liver function and structure through anti-inflammatory and anti-fibrotic effects; emricasan's potential to achieve long-term resolution of fibrosis and cirrhosis; emricasan's potential impact on hyperdynamic circulation and/or intrahepatic vasculature resistance; the acceptability of HVPG as a surrogate endpoint for clinical trials of patients with liver cirrhosis; whether the results from the PH trial establish the near-term effects of emricasan on portal hypertension or allow for future Phase 2b clinical trials in patients with cirrhosis and therapeutically relevant portal hypertension; emricasan's longer-term effects on liver function and liver structure; the importance of apoptosis as a common mechanism for progressive liver disease and that inhibiting apoptosis with emricasan is likely to be of both short- and long-term clinical benefit; the utility of MELD and CPT as potential surrogate clinical endpoints; the potential for emricasan to be a treatment for liver cirrhosis patients; and emricasan's potential to interrupt the disease progression across the spectrum of liver disease. In some cases, you can identify forward-looking statements by terms such as "may," "will," "should," "expect," "plan," "anticipate," "could," "intend," "target," "project," "contemplates," "believes," "estimates," "predicts," "potential" or "continue" or the negative of these terms or other similar expressions. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, including: Conatus' ability to initiate and successfully complete current and future clinical trials; Conatus' ability to evaluate emricasan's potential medium-term and longer-term effects on liver function and liver structure in its other two ongoing clinical trials; Conatus' ability to develop a registration strategy and pathway for emricasan; Conatus' dependence on its ability to obtain regulatory approval for, and then successfully commercialize emricasan, which is Conatus' only drug candidate; Conatus' reliance on third parties to conduct its clinical trials, enroll subjects, manufacture its preclinical and clinical drug supplies and manufacture commercial supplies of emricasan, if approved; the potential that earlier clinical trials may not be predictive of future results; potential adverse side effects or other safety risks associated with emricasan that could delay or preclude its approval; results of future clinical trials of emricasan; the potential for competing products to limit the clinical trial enrollment opportunities for emricasan in certain indications; the uncertainty of the FDA's and other regulatory agencies' approval processes and other regulatory requirements; Conatus' ability to fully comply with numerous federal, state and local laws and regulatory requirements applicable to it; Conatus' limited operating history and its ability to operate successfully as a public company; Conatus' ability to obtain additional financing in order to complete the development and commercialization of emricasan; and those risks described in Conatus' prior press releases and in the periodic reports it files with the Securities and Exchange Commission. The events and circumstances reflected in Conatus' forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Except as required by applicable law, Conatus does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.MEDIA: David Schull Russo Partners, LLC (858) 717-2310 INVESTORS: Alan Engbring Conatus Pharmaceuticals Inc. (858) 376-2637

Rational Drug Pricing

Rational Drug Pricing
Jeffrey Sachs
Earth Institute at Columbia University

Drug pricing has taken center stage in U.S. politics, and it's high time that it should. The soaring prices for drugs like Sovaldi ($1,000 a pill) and the recent hike of Deraprim from $13.50 to $750 a pill after the supplier was bought by a shady hedge-fund manager, have caused white-hot fury in the public. Corporate lobbyists and their friends in the media spout free-market platitudes about why the sky-high prices are necessary to promote innovation. It's time for a serious understanding of the policy issues. 
Drug pricing is not like the pricing of apples and oranges, clothing, or furniture that well and good should be left to the marketplace. There are two major reasons. First, the main cost of drug production is not the cost of manufacturing the tablet but the cost of producing the knowledge embedded in the tablet. Second, there is often a life-and-death stake in access to the drug, so society should take steps to ensure that the drug is affordable and accessible.

Continue reading... 

In The News


Monday, September 21, 2015

Gilead Announces SVR12 Rates from Four Phase 3 Studies Evaluating Fixed-Dose Sofosbuvir/Velpatasvir (GS-5816) Pan-Genotypic

Gilead's new pan-genotype hep C combo scores stellar results in PhIII
September 21, 2015 | By John Carroll
Gilead has proved once again that it knows how to cure hepatitis C for a heavy concentration of patients, posting some stellar pangenotype data from a slate of four late-stage studies that combined its blockbuster Sovaldi with the experimental NS5A inhibitor velpatasvir. And the Big Biotech says it's ready to step up with new marketing applications with an eye to continuing its domination.

Press Release
Gilead Announces SVR12 Rates from Four Phase 3 Studies Evaluating a Once-Daily, Fixed-Dose Combination of Sofosbuvir (SOF) and Velpatasvir (VEL) (GS-5816) for the Treatment of All Six Hepatitis C Genotypes

If Approved, SOF/VEL Would be the First All-Oral Pan-Genotypic Single Tablet Regimen for Chronic HCV-

- U.S. NDA and European MAA Submissions Planned for Q4 2015 -

FOSTER CITY, Calif.--(BUSINESS WIRE)--Sep. 21, 2015-- Gilead Sciences, Inc.(Nasdaq:GILD) today announced topline results from four international Phase 3 clinical studies (ASTRAL-1, ASTRAL-2, ASTRAL-3 and ASTRAL-4) evaluating a once-daily, fixed-dose combination of the nucleotide analog polymerase inhibitor sofosbuvir (SOF) with velpatasvir (VEL), an investigational pangenotypic NS5Ainhibitor, for the treatment of genotype 1-6 chronic hepatitis C virus (HCV) infection.

In the ASTRAL-1, ASTRAL-2, and ASTRAL-3 studies, 1,035 patients with genotype 1-6 HCV infection received 12 weeks of SOF/VEL. Among these patients, 21 percent had compensated cirrhosis and 28 percent had failed prior treatments. The ASTRAL-4 study randomized 267 patients with decompensated cirrhosis (Child-Pugh class B) to receive 12 weeks of SOF/VEL with or without ribavirin (RBV), or 24 weeks of SOF/VEL. The primary endpoint for all studies was SVR12.

The intent-to-treat SVR12 rates observed in the ASTRAL studies are summarized in the table below. Complete results from all four studies will be presented at future scientific conferences.


Of the 1,035 patients treated with SOF/VEL for 12 weeks in the ASTRAL-1, ASTRAL-2 and ASTRAL-3 studies, 1,015 (98 percent) achieved the primary efficacy endpoint of SVR12. Of the 20 patients who did not achieve SVR12, 13 patients (1.3 percent) experienced virologic failure and seven did not complete an SVR12 visit (e.g., lost to follow-up). Twelve of the 13 virologic failure patients relapsed (two genotype 1 HCV-infected patients and 10 genotype 3 HCV-infected patients). There was one patient with documented reinfection. No patients with genotype 2, 4, 5 or 6 HCV infection had virologic failure.

Patients treated with SOF/VEL for 12 weeks in these three studies had similar adverse events compared with placebo-treated patients in ASTRAL-1. Two patients (0.2 percent) treated with SOF/VEL for 12 weeks, one each in ASTRAL-1 and ASTRAL-2, discontinued treatment due to adverse events. The most common adverse events were headache, fatigue and nausea.

In ASTRAL-4, patients with Child-Pugh class B cirrhosis receiving SOF/VEL+RBV achieved higher SVR12 rates than patients receiving SOF/VEL for 12 or 24 weeks. Among genotype 1 and 3 patients treated with SOF/VEL+RBV for 12 weeks, the SVR12 rates were 96 percent and 85 percent, respectively.

The most common adverse events across all arms of ASTRAL-4 were fatigue, nausea and headache. Anemia, a common side effect associated with RBV, was reported in 31 percent of patients in the SOF/VEL+RBV arm and in 4 percent and 3 percent of patients treated with SOF/VEL for 12 or 24 weeks, respectively. Treatment emergent serious adverse events occurred in 18 percent of patients and nine patients died. The majority of serious adverse events and deaths were associated with advanced liver disease.

“The ASTRAL study results demonstrate that a 12-week course of therapy with the first fixed-dose combination of two pan-genotypic compounds can provide high cure rates for patients with all HCV genotypes,” said Norbert Bischofberger, Ph.D., Executive Vice President of Research and Development and Chief Scientific Officer at Gilead. “We are pleased to have now brought forward our second single tablet regimen for HCV infection that complements Harvoni, our first single tablet regimen approved specifically for patients with genotype 1 infection and which could eliminate the need for HCV genotype testing. We look forward to advancing the regulatory submissions for the SOF/VEL fixed-dose combination.”

The U.S. Food and Drug Administration has assigned the SOF/VEL fixed-dose combination a Breakthrough Therapy designation, which is granted to investigational medicines that may offer major advances in treatment over existing options.

The SOF/VEL fixed-dose combination is an investigational product and its safety and efficacy have not yet been established.

About the ASTRAL Studies

The double-blind, placebo-controlled ASTRAL-1 trial enrolled 740 patients with chronic genotype 1, 2, 4, 5 or 6 HCV infection randomized to SOF/VEL or placebo for 12 weeks.

The open-label ASTRAL-2 study evaluated the use of SOF/VEL or SOF+RBV for 12 weeks in 266 genotype 2 HCV-infected patients.

The open-label ASTRAL-3 study evaluated the use of SOF/VEL for 12 weeks or SOF+RBV for 24 weeks in 552 genotype 3 HCV-infected patients.

The ASTRAL-1 study met its primary endpoint of statistical superiority to the pre-specified SVR12 goal of 85 percent (p<0.001). ASTRAL-2 and ASTRAL-3 also met their respective endpoints. In ASTRAL-2, the SVR12 rate among genotype 2 HCV-infected patients receiving SOF/VEL for 12 weeks was statistically superior to the SVR12 rate for patients receiving SOF+RBV for 12 weeks (p=0.018). In ASTRAL-3, the SVR12 rate among genotype 3 HCV-infected patients receiving SOF/VEL for 12 weeks was statistically superior to that of patients treated with SOF+RBV for 24 weeks (p<0.001).

The open-label ASTRAL-4 study evaluated the use of SOF/VEL with or without RBV for 12 weeks and SOF/VEL for 24 weeks in 267 HCV-infected patients with Child-Pugh class B cirrhosis, regardless of genotype.

About Gilead Sciences

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases. Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California.

Forward-Looking Statement
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the risk that Gilead may be unable to file for U.S. regulatory approval of the SOF/VEL fixed-dose combination in the currently anticipated timelines. In addition, the FDA and other regulatory agencies may not approve the SOF/VEL fixed-dose combination, and any marketing approvals, if granted, may have significant limitations on its use. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2015, as filed with theU.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

U.S. full Prescribing Information for Sovaldi and Harvoni are available atwww.gilead.com.

Sovaldi and Harvoni are registered trademarks of Gilead Sciences, Inc. or its related companies.

For more information on Gilead Sciences, please visit the company’s website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

View source version on businesswire.com:
http://www.businesswire.com/news/home/20150921005402/en/

Source: Gilead Sciences, Inc.

Gilead Sciences, Inc.
Investors
Patrick O’Brien, 650-522-1936
or
Media
Cara Miller, 650-522-1616

Saturday, September 19, 2015

Hepatitis C Weekend Review

Weekend Recap

Welcome to Weekend Reading, hope you are all enjoying the weekend!

For me Saturday is a great day to catch up on any HCV news or research I missed during the week. If you have the time click on today's topics for general information about hepatitis C, the cost of treatment, other health news, as well as interim study results using all-oral direct-acting antiviral therapy for the treatment of chronic hepatitis C.

Weekend recap provided by; Lucinda Porter, NATAP, Healio, HCV Advocate, Hepatitis Resource Center Blog, World Journal Of Hepatology, and The Body, along with media news and headlines from across the web.

Lucinda Porter 
What We Talk About When We Talk About Hepatitis C
Since 2007, more people have died every year from hepatitis C than from HIV. Fortunately, the latest hepatitis C medications can cure nearly everyone in a relatively quick, easy fashion. 

NATAP
Paritaprevir, ombitasvir, and dasabuvir are direct-acting antivirals for treatment of chronic hepatitis C virus (HCV) infection. The aim of this study was to characterize the effects of mild, moderate, and severe hepatic impairment on the pharmacokinetics of these drugs.

Patients with recurrent hepatitis C (HCV) infection post liver-transplant can be difficult to treat safely and effectively. A prior (COSMOS) study in non-transplant HCV patients, using sofosbuvir plus simeprevir, had high efficacy and tolerability in treating HCV genotype 1 patients, even prior non-responders to interferon therapy and those with cirrhosis. Our aim was to evaluate the efficacy of sofosbuvir and simeprevir in genotype 1 HCV post-liver transplant patients.
In this large-scale trial that evaluated the efficacy of all-oral direct-acting antiviral therapy in patients with HCV genotype 1 and decompensated cirrhosis, and post-transplant patients with cirrhosis, 12 or 24 weeks of treatment with ledipasvir-sofosbuvir and ribavirin resulted in high rates of response.

Increased incidence of cancer and cancer-related mortality among persons with chronic hepatitis C infection, 2006-2010 
Incidence and mortality of many types of non-liver cancers were higher, and age at diagnosis and death younger, in patients with chronic HCV infection compared to the general population.

Healio
Odalasvir/Sovaldi yields 100% SVR in HCV genotype 1
Achillion announced additional interim results of its phase 2 pilot study of odalasvir in combination with Sovaldi, in which 100% of patients with hepatitis C virus…

September Issue of HCV Next
HCV Next provides an overview of current hepatitis C topics, as well as content on all forms of viral hepatitis, and other liver related disease.
Topic Highlights
Pediatric HCV: Small Patients, Big DecisionsHCV Guidelines: A Living Breathing Document
Caffeine Decreases Risk of Hepatic Fibrosis in Male HCV Patients
Liver Disease Expected to Increase in Switzerland Over Time
HCV may Increase Risk for Coronary Atherosclerosis in MSM
SVR Leads to Survival Benefit Among HCV Patients

HCV Advocate 
September Mid-Month Newsletter
by Alan Franciscus, Editor-in-Chief
This month’s column is about cirrhosis—the causes, how it develops, the tests to identify it, the symptoms of cirrhosis and effect of hepatitis C treatment on cirrhosis and the effect of cirrhosis on treatment.

Newly Diagnosed
Have you recently found out that you have hepatitis C? Being diagnosed with this brings up a lot of feelings and questions about hepatitis C. In this guide you will find information to help you find answers to your questions. This information is basic and assumes that you have very little knowledge about hepatitis C. Hopefully it reassures you. How can information about a disease be reassuring? We believe that once you get the facts, the future will look a little brighter.

Hepatitis Resource Center Blog
Hepatitis C-Salvage Study Grazoprevir and Elbasvir Plus Ribavirin: Final 24-week Follow-up Results
In the C-SALVAGE study, an interferon free combination of grazoprevir (an NS3/4A protease inhibitor) and elbasvir (an NS5A inhibitor) with ribavirin was used to treat patients with chronic HCV genotype 1 infection who had previously failed triple therapy with pegylated interferon and ribavirin plus an earlier-generation protease inhibitor.

Recent Posts
New HCV Peer-Reviewed PDFs For Free!
HCV Drug Costs: A Treatment Access Barrier
Tx Options for HCV GT 1 or 4 Non-responders
Two DAA regimen in cirrhotic HCV GT1b patients

World Journal Of Hepatology
Psychosocial assessment and monitoring in the new era of non-interferon-alpha hepatitis C virus treatments
The recently Food and Drug Administration approved direct-acting antiviral regimens for hepatitis C virus (HCV), ledipasvir/sofosbuvir regimen and the ombitasvir/paritaprevir/ritonavir and dasabuvir regimen, have demonstrated great efficacy, and thus far seem to have short treatment timelines and relatively benign side effect profiles. Depression has not emerged as a side effect of these treatments. With efficacious regimens that include no interferon-alpha and no ribavirin, there may no longer be a need for strong psychosocial assessment and monitoring built into the routine of HCV treatment. Good history-taking, strong pharmaceutical review, and reliable consultative relationships should be adequate for meeting psychosocial needs in HCV treatment

Assessing cardiovascular risk in hepatitis C: An unmet need.
Chronic hepatitis C is associated with significant morbidity and mortality, as a result of the progression towards cirrhosis and hepatocellular carcinoma. Furthermore, hepatitis C virus seems to be an independent risk factor for cardiovascular diseases due to its association with insulin resistance, diabetes and steatosis. The advent of new direct acting antiviral therapy has dramatically increased the sustained virological response rates of hepatitis C infection. In this scenario, the cardiovascular risk has emerged and represents a major concern after achieving the eradication of the virus.

Of Interest
Novel plan to curb drug costs seeks candidates' attention
The outcry gained momentum after the introduction last year of a $1,000-a-pill cure for hepatitis C. The 45-page plan seeks to rein in the overall cost of drugs ...

2015 Kelly Report: Health Disparities In America
History has shown us that the lack of access to healthcare, health insurance, and health providers has contributed to the gaps we observe in national health outcomes.

Big Pharma
Summary - Gilead Sciences at the Morgan Stanley Global Healthcare Conference
Gilead Provides An Update: Review And Analysis Of Wednesday's Q&A
Next-gen hep C combo plans clarified
Apparently we will have to wait until November, the month of the AASLD meeting, for details of the combo of Sovaldi with GS-5816 (sofosbuvir/velpatasvir), rather than this quarter. It appears that GILD is planning to go with this combo as a 12-week treatment for genotypes 2-6 in developed countries, and for all genotypes in regions where genotyping is not readily available..

Over the last two years, hepatitis C has produced the most epic drug launches in history. But as the fanfare dies down, investors face a key question: How much longer can this drug pipeline pop?

Healthy You And The Flu
Hepatitis C or No Hepatitis C, Get a Flu Shot
I have opinions on various issues, but when it comes to scientific proof, I don't waste my time arguing facts. The earth is round, and it travels around the sun. The only place where humans and dinosaurs coexisted was on the Flintstones. I just got my flu shot.

WASHINGTON (AP) -- Give flu vaccine another chance: This year's version got a recipe change that should make it more effective after last winter's misery from a nasty surprise strain of virus....

Americans urged to get annual influenza vaccine
WASHINGTON, D.C. ― Everyone 6 months of age and older should receive an annual influenza vaccine, health officials advised at a press conference held by the National Foundation for Infectious Diseases.

In addition to flu vaccines, the panel also recommended pneumococcal vaccines for people aged 65 and older and for adults aged 19-64 with certain chronic health conditions, such as diabetes or heart disease.

Acetaminophen
Health Canada proposes new liver damage labeling for acetaminophen
Health Canada announced it is requesting input from clinicians and other healthcare professionals on proposed revisions to the labeling standard for nonprescription acetaminophen products, in an effort to encourage consumers to use them more safely, according to a press release from Health Canada.

Insulin Pens
Shake, shake, shake your NPH insulin pen before injecting
(Reuters Health) - A warning for people who use insulin pens: Not shaking your NPH insulin pen before injecting can result in wide variations in your insulin level and blood sugar control, researchers from Italy report.

Recall
California dairy recalls soft cheeses due to possible Listeria link
- California company Karoun Dairies has recalled a number of soft cheese products due to possible association with Listeria cases over five years in nine states, the U.S. Centers for Disease Control and Prevention said on Friday.

Awareness
If a simple blood test could improve your long-term health or possibly save your life, would you have it done? The answer for most people is a resounding “Yes.” Testing for hepatitis C which entails a basic blood draw and analysis, can be the difference between serious health complications later in life or a manageable — in some cases curable — condition.

In The News
Homeless Veteran Stand Down an infusion of hope for veterans in ...
Prescott Daily Courier-10 hours ago
Free haircuts, HIV and Hepatitis C screenings, pet care facilities, and three hot meals, were just a sample of what these in-need veterans were able to obtain on ...

- 100% SVR12 reported for all patients treated for six- (n=18) or eight-weeks (n=12)
- Odalasvir (ACH-3102) is the subject of an exclusive, worldwide development and commercialization license granted to Janssen

FDA Grants Fast Track Designation to Can-Fite's CF102 in the Treatment of Liver Cancer
U.S. Food and Drug Administration (FDA) has granted the Company's drug candidate CF102 Fast Track designation as a second line treatment for hepatocellular carcinoma (HCC), the most common form of liver cancer. CF102 had already received the FDA's Orphan Drug designation.

Clinical Thought - How I Use Resistance Testing to Guide Management of Patients With Chronic Hepatitis C
Recently, I have begun to hear many questions from colleagues and trainees regarding the use of resistance testing in the management of HCV-infected patients. To be honest, my answers to their questions are not always straightforward, as this is a rapidly evolving area of discussion in the field and I am confident that my opinion will evolve along with the data.

Study Shows Increase in Hepatitis C Rate Among Some HIV-Positive Men 
Researchers conducted an analysis of studies that spanned more than two decades and found that outbreaks of sexually transmitted hepatitis C is increasing among men who are HIV positive and have sex with other men

Redoing the Math: New York State Revises Its Estimate of People With HIV
The NYS Plan to End AIDS relies on increasing the number of HIV-positive people in the state who have an undetectable viral load, since being virally suppressed both improves their health and lowers the chance of HIV transmission to their partners.

Mathematical models estimate that to achieve the state's goal of only 750 new HIV infections per year, the percent of people virally suppressed will need to be over 80%. Since only an estimated 42% were virally suppressed in 2013, the state had a long way to go to achieve its goal.

But NYS recently lowered its estimate of the number of people with HIV in the state, which significantly increases the percent who are virally suppressed. Let's examine how that was done.

Feel Good Video
Sophia just wants to dance, but she found that difficult to do when she was diagnosed with scoliosis and was forced to wear a brace for 23 hours a day. Two years ago, a large tumor was found growing on her spinal cord, and she had major surgery at St. Jude Children's Research Hospital in Memphis to remove it. A year later, the tumor returned and Sophia underwent radiation and advanced proton therapy. Her physician at Willis Knighton Proton Therapy Center, Dr. Ben Wilkinson, promised Sophia he would learn the dance to Watch Me (Whip/Nae Nae) once radiation and therapy were complete. Dr. Wilkinson went one step further and surprised the 12-year-old with a flash mob from the staff. Now that's how you celebrate!



Whenever I watch videos like this I cry, do you?
See you all soon.
Tina