April 8, 2014

Gilead aims to license hepatitis C drug to 3-4 Indian firms

By Ben Hirschler
LONDON  Tue Apr 8, 2014 11:42am EDT

(Reuters) - Gilead Sciences aims to license its new hepatitis C drug Sovaldi to three or four Indian generic manufacturers to allow sales of the medicine at lower prices in some 60 developing nations.

Clifford Samuel, head of access operations and emerging markets at the U.S. drugmaker, told Reuters he expected to have deals in place shortly with the Indian firms, which would be able to produce the drug in high volumes and at low margins.

Gilead is under pressure to address the high cost of its breakthrough pill, which is the first of a new wave of drugs that have been shown to raise cure rates and cut treatment duration without the side effects of current injections.

"We're in the midst of discussions right now. We're nailing down the geographical scope, and we should have these licenses in place and ready to go in short order," Samuel said on a visit to London for an international liver conference.

He said Gilead was looking to strike deals with firms that had proven experience in producing generic versions of its HIV/AIDS drugs, such as the Indian division of Mylan.

The Foster City, California-based company has been operating a similar voluntary licensing programme for many years for low-cost HIV drugs, which covers 112 countries.

Under the hepatitis C plan, Indian-made generics would be available in most of sub-Saharan Africa, selected Asian countries including India, Pakistan and Myanmar, and some smaller developing nations.

Gilead is also working to establish "tiered pricing" for Sovaldi in other low- and middle-income countries, Samuel said.

The company struck the first such tiered pricing deal last month in Egypt, where it has agreed to supply the government at just over 1 percent of the U.S. price, or $300 for a 28-day bottle against $28,000.

For India, the company is currently discussing a price of $2,000 based on 24 weeks of treatment, although no final deal has been reached, Samuel added.

Egypt has the world's highest prevalence of the liver-destroying hepatitis C virus, which is spread through blood, making it an obvious first market for more affordable, tiered pricing.

"We're targeting key, high-prevalence countries like India, Pakistan and Egypt. We are sitting down with them and looking at differential pricing," Samuel said.

Gilead's tiered pricing will not apply, however, to some large middle-income countries with significant hepatitis C populations such as Ukraine and China, which are viewed as commercial market opportunities.

In the United States, Sovaldi's price tag of $84,000 for a 12-week course of treatment has been described by one health provider as "outrageous", while U.S. lawmakers have written to the firm demanding an explanation of the price.

(Editing by Jane Baird)

Source

Hep C Therapies to Hog Spotlight at EASL

Published: Apr 8, 2014

By Michael Smith, North American Correspondent, MedPage Today

45148

LONDON -- New treatments for hepatitis C virus (HCV) will have most of the limelight this week at the annual meeting of the European Association for the Study of the Liver.

A tidal wave of novel direct-acting agents has been building for several years and is set to break here, according to the association's secretary-general, Markus Peck, MD, of the Medical University of Vienna in Austria.

"What strikes you most," Peck told MedPage Today, "is first of all the number of phase III trials that are being presented ... the most phase III data you will ever see in a liver meeting."

That's because several companies are rushing to get novel regimens approved and into the clinic, he said.

Indeed, of the 18 abstracts in the first three general sessions of the meeting, nine have to do with new treatments for HCV, as do half of the late-breaking oral presentations. There are also several parallel sessions devoted to HCV therapy.

But equally important, he said, are the "consistently positive results ... more or less independent of what kind of patients you are looking at: treatment-naive patients, previously treated patients, patients with advanced liver disease -- it's always working."

"It's fascinating and fantastic at the same time," he said. Even a year ago, Peck added, experts would not have expected to "treat patients for 3 months -- maybe even 2 months -- and cure 95% or 98% of them."

The direct-acting agents are so-called because they work on aspects of the virus itself, unlike the two drugs that until very recently were the mainstays of HCV therapy -- pegylated interferon-alfa and ribavirin.

Peginterferon is a general immune system booster with a range of unpleasant side effects, while ribavirin is a general antiviral drug with its own drawbacks. Cure rates with the combination -- the so-called sustained virologic response or SVR -- vary depending on the HCV genotype of the patient but are generally regarded as low.

A major goal of recent research, including much to be presented here, has been to combine different direct-acting agents in order to avoid using peginterferon. In addition, some of the trials to be reported here have also examined ribavirin-free regimens.

Studies of other forms of viral hepatitis are also being reported here, Peck said, "but nothing can match the success of HCV treatment at the moment."

For instance, there will be data on hepatitis B therapy that is "interesting ... but nothing game-changing" but Peck said future meetings are likely to see more work on HBV once the furor over HCV dies down.

Researchers also will detail some early investigations into hepatitis D and E, he said.

Other aspects of liver disease are also under examination here, including what is touted as the first phase III trial in 20 years for a new drug -- obeticholic acid -- to treat primary biliary cirrhosis.

"This is something that is very new," Peck said. While the condition is not common, it accounts for between 4% and 5% of liver transplant patients, he added, and "everyone who's treating people for liver disease has several patients."

And Spanish researchers are to present data form a phase III trial on the use of statins in patients with portal hypertension that is likely to draw some attention, Peck said, if only because it's something other than viral hepatitis.

In all, more than 1,000 abstracts are to be presented, Peck said.

Source

April 7, 2014

Idenix Announces Promising Clinical Data and Continued Progress in Nucleotide Prodrug Development Programs for the Treatment of Hepatitis C

  • Idenix Reports Positive Proof-of-Concept Data for Lead Nucleotide Prodrug, IDX21437
  • Idenix on Track to Initiate All-Oral Pan-Genotypic Phase II Combination Clinical Study of IDX21437 and Samatasvir in mid-2014
  • Idenix Initiates Phase I Clinical Trial of Follow-on Nucleotide Prodrug, IDX21459
  • Idenix to Host Conference Call / Webcast at 8:00 a.m. ET today

CAMBRIDGE, Mass., April 7, 2014 (GLOBE NEWSWIRE) -- Idenix Pharmaceuticals, Inc. (Nasdaq:IDIX), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today announced continued progress of the Company's program to develop nucleotide prodrug inhibitors for the treatment of hepatitis C virus (HCV) infection. Idenix is reporting potent antiviral activity of mean maximum 4.2-4.3 log10 IU/mL reductions for patients infected with HCV genotype 1, 2 or 3 receiving 300 mg once daily of IDX21437 in the seven-day proof-of-concept portion of a phase I/II clinical trial. Based on this progress, the Company's goal is to initiate a combination clinical trial of IDX21437 and samatasvir, a pan-genotypic NS5A inhibitor, in mid-2014. In addition, Idenix has selected a follow-on uridine-based nucleotide prodrug, IDX21459, from its ongoing nucleotide discovery program and initiated enrollment for the healthy volunteer portion of a phase I clinical trial.

"As more all-oral regimens become available to treat hepatitis C, an increased number of patients will be diagnosed and treated. It will be important to have simple, short duration options for our patients. These early data for IDX21437 support its potential to be part of future treatment combinations." said Professor Edward Gane, MD, Deputy Director and Hepatologist, New Zealand Liver Transplant Unit, Auckland City Hospital in New Zealand, and a clinical investigator in the IDX21437 proof-of-concept study. "Nucleotide-based treatment combinations are favored because of safety, efficacy, high barrier to resistance and low drug-drug interaction potential and we look forward to seeing further results from studies with IDX21437."

"We are very pleased with these positive data for IDX21437 and we are excited to have two nucleotide prodrug candidates in the clinic," said Ron Renaud, Idenix's President and Chief Executive Officer.  "With the initiation of the phase II study of IDX21437 and samatasvir later this year, we will be one of a few companies with an all-oral, pan-genotypic, nucleotide-based combination approach in the clinic. We believe this regimen has the potential to play a significant role in advancing HCV care for the benefit of patients, physicians and payers."

IDX21437: Topline 7-Day Phase I/II Clinical Results

In January 2014, Idenix initiated the seven-day proof-of-concept portion of a phase I/II clinical trial for IDX21437. The trial completed enrollment of 44 treatment-naïve, genotype (GT) 1, 2 or 3 HCV-infected patients. Patients were randomized to receive once-daily doses of placebo, 50 mg, 150 mg, or 300 mg of IDX21437 for seven days. The topline clinical results include:

  • IDX21437 was well-tolerated with no observed pattern of adverse events or laboratory abnormalities.
  • Treatment with IDX21437 exhibited potent pan-genotypic activity in a dose-dependent manner:
  • In GT 1 HCV-infected patients (n=8), the mean maximal viral load reduction was 4.2 log10 IU/mL in the 300 mg arm.
  • The mean maximal viral load reduction of 4.3 log10 IU/mL was achieved in GT 2 and 3 HCV-infected patients in the 300 mg arm (n=10).
  • More detailed findings are expected to be presented at a future scientific meeting.
  • Based on these findings, the 300 mg dose of IDX21437 has been chosen for the anticipated phase II combination study with samatasvir.

IDX21459: Phase I Clinical Program

In April 2014, Idenix initiated enrollment for the healthy volunteer portion of a phase I clinical trial of IDX21459 in Europe. This portion of the study is expected to enroll approximately 50 healthy volunteers and will evaluate once-daily doses of IDX21459 ranging from 10 mg - 300 mg. The proof-of-concept portion of the study is expected to enroll a total of 40 treatment-naïve, genotype 1 HCV-infected patients who will receive once-daily doses of placebo, 50 - 300 mg of IDX21459 for seven days. IDX21459 has shown a favorable preclinical profile including potent, pan-genotypic activity and favorable safety with respect to cardiac, mitochondrial and genotoxicity assessments.

Additional Nucleotide Candidates

Idenix's primary efforts in nucleotide development will continue to focus on its lead candidate, IDX21437, and follow-on prodrug candidate, IDX21459, as well as earlier-stage nucleotide prodrugs. An important objective for the discovery program is to identify nucleotides offering distinct resistance profiles that can be combined with one of the Company's current nucleotide clinical candidates to treat HCV. Idenix also announced today that the Company has elected not to continue its clinical development program for HCV nucleotide prodrug, IDX20963, previously placed on clinical hold by the U.S. Food and Drug Administration (FDA).

CONFERENCE CALL AND WEBCAST INFORMATION

Idenix management will host a conference call at 8:00 a.m. ET today. To access the call, please dial (877) 640-9809 (U.S./Canada) or (914) 495-8528 (International) and enter passcode 26004979. A live webcast will be available through the Investor section of the Idenix website at www.idenix.com under "Events & Presentations". The archived webcast will be available for two weeks following the call on the Idenix website.

ABOUT IDX21437

IDX21437, Idenix's lead uridine-based nucleotide prodrug inhibitor, has completed the single-dose and seven-day proof-of-concept portions of a phase I/II clinical trial. Extensive preclinical testing for IDX21437 has demonstrated favorable antiviral activity across genotypes 1-6 and a safety profile which supported advancement into clinical trials. Based on this progress, the Company's goal is to initiate an Idenix-sponsored combination clinical trial of IDX21437 and samatasvir in mid-2014.

ABOUT SAMATASVIR

Samatasvir is an NS5A inhibitor with low picomolar, pan-genotypic antiviral activity in vitro. To date, samatasvir has been safe and well-tolerated after single and multiple doses of up to 150 mg in healthy volunteers up to 14 days duration, and in HCV-infected patients up to 12 weeks duration. Samatasvir has demonstrated potent pan-genotypic antiviral activity in HCV-infected patients with mean maximal viral load reductions up to approximately 4.0 log10 IU/mL across HCV genotypes 1-4 in a proof-of-concept, three-day monotherapy study.

Under a non-exclusive collaboration with Janssen Pharmaceuticals, Inc., Idenix is evaluating all-oral, direct-acting antiviral HCV combination regimens including samatasvir, simeprevir (TMC435), a once-daily protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB, and TMC647055/r, a once-daily non-nucleoside polymerase inhibitor boosted with low-dose ritonavir being developed by Janssen. In this program, Idenix is conducting two ongoing phase II 12-week clinical trials, HELIX-1 and HELIX-2.

ABOUT HEPATITIS C

Hepatitis C virus is a common blood-borne pathogen infecting three to four million people worldwide annually. The World Health Organization (WHO) estimates that more than 150 million people worldwide are chronically infected with HCV, representing a nearly 5-fold greater prevalence than human immunodeficiency virus.

ABOUT IDENIX

Idenix Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts, is a biopharmaceutical Company engaged in the discovery and development of drugs for the treatment of human viral diseases. Idenix's current focus is on the treatment of patients with hepatitis C infection. For further information about Idenix, please refer to www.idenix.com.

FORWARD-LOOKING STATEMENTS

This press release contains "forward-looking statements" for purposes of the safe harbor provisions of The Private Securities Litigation Reform Act of 1995, including but not limited to the statements regarding the Company's future business and financial performance. For this purpose, any statements contained herein that are not statements of historical fact may be deemed forward-looking statements. Without limiting the foregoing, the words "expect," "plans," "anticipates," "intends," "will," and similar expressions are also intended to identify forward-looking statements, as are expressed or implied statements with respect to the Company's potential pipeline candidates, including any expressed or implied statements regarding the efficacy and safety of samatasvir, IDX21437, IDX21459 or any other drug candidate; the successful development of novel combinations of direct-acting antivirals for the treatment of HCV; and the likelihood and success of any future clinical trials involving samatasvir, IDX21437, IDX21459 or our other drug candidates. Actual results may differ materially from those indicated by such forward-looking statements as a result of risks and uncertainties, including but not limited to the following: there can be no guarantees that the Company will advance any clinical product candidate or other component of its potential pipeline to the clinic, to the regulatory process or to commercialization; uncertainties relating to, or unsuccessful results of, clinical trials, including additional data relating to the ongoing clinical trials evaluating its product candidates; and the Company's ability to obtain, maintain and enforce patent and other intellectual property protection for its product candidates and its discoveries. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. These and other risks which may impact management's expectations are described in greater detail under the heading "Risk Factors" in the Company's annual report on Form 10-K for the year ended December 31, 2013 as filed with the Securities and Exchange Commission (SEC) and in any subsequent periodic or current report that the Company files with the SEC.

All forward-looking statements reflect the Company's estimates only as of the date of this release (unless another date is indicated) and should not be relied upon as reflecting the Company's views, expectations or beliefs at any date subsequent to the date of this release. While Idenix may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so, even if the Company's estimates change.

CONTACT: Idenix Pharmaceuticals Contact:
Teri Dahlman (617) 995-9807

Source: Idenix Pharmaceuticals

Source

Gilead Announces U.S. FDA Priority Review Designation for Ledipasvir/Sofosbuvir Fixed-Dose Combination Tablet for Chronic Hepatitis C Genotype 1 Infection

PRESS RELEASE  April 7, 2014, 8:35 a.m. ET

-- Final FDA Decision Anticipated by October 10, 2014 --

FOSTER CITY, Calif.--(BUSINESS WIRE)--April 07, 2014--

Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the U.S. Food and Drug Administration (FDA) has granted priority review to the company's New Drug Application (NDA) for a once-daily fixed-dose combination of the NS5A inhibitor ledipasvir (LDV) 90 mg and the nucleotide analog polymerase inhibitor sofosbuvir (SOF) 400 mg for the treatment of chronic hepatitis C genotype 1 infection in adults. Gilead filed the NDA for LDV/SOF on February 10, 2014, and the FDA has set a target action date under the Prescription Drug User Fee Act (PDUFA) of October 10, 2014.

The FDA has also assigned LDV/SOF a Breakthrough Therapy designation. The FDA grants Breakthrough Therapy designation and priority review status to investigational medicines that may offer major advances in treatment over existing options. The data submitted in the NDA are from three Phase 3 studies, ION-1, ION-2 and ION-3, and support the use of LDV/SOF in adults with genotype 1 HCV infection, with a treatment duration of eight or 12 weeks depending on prior treatment history and whether they have cirrhosis. Approximately 75 percent of people infected with HCV in the United States have the genotype 1 strain of the virus.

A marketing application for LDV/SOF is also under review in the European Union, and was validated by the European Medicines Agency (EMA) on March 27, 2014. The agency has accepted Gilead's request for accelerated assessment of LDV/SOF, a designation that is granted to new medicines of major public health interest. If accepted, accelerated assessment could shorten the EMA's review time of LDV/SOF by two months, although it does not guarantee a positive opinion from the Committee for Medicinal Products for Human Use or approval by the European Commission.

LDV/SOF is an investigational product and its safety and efficacy have not yet been established.

SOF as a single agent was approved by the FDA under the tradename Sovaldi(R) on December 6, 2013 and by the European Commission on January 17, 2014.

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 worldwide. Headquartered in Foster City, California, Gilead has operations in North and South America, Europe and Asia Pacific.

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 the FDA, EMA and other regulatory agencies may not approve LDV/SOF fixed-dose combination in the currently anticipated timelines or at all, and that any marketing approvals, if granted, may have significant limitations on its use. Further, additional studies of LDV/SOF, including results from the 24-week arms of ION-1, may produce unfavorable results. As a result, Gilead may not be able to successfully commercialize LDV/SOF, and may make a strategic decision to discontinue its development if, for example, the market for the product fails to materialize as expected. 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 Annual Report on Form 10-K for the year ended December 31, 2013, as filed with the U.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 is available at www.gilead.com.

Sovaldi is a registered trademark of Gilead Sciences, Inc.

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.

Source

Bristol-Myers Squibb Submits NDAs for Daclatasvir and Asunaprevir to US FDA for the Treatment of Hepatitis C

U.S. application submission marks third major daclatasvir regulatory milestone globally, follows E.U. and Japan

Monday, April 7, 2014 8:00 am EDT

PRINCETON, N.J..--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) "These FDA submissions represent a major step towards offering daclatasvir-based regimens to U.S. HCV patients, many of whom continue to have high unmet medical needs"

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) announced today that they have submitted new drug applications (NDAs) with the U.S. Food and Drug Administration (FDA) for the investigational products daclatasvir (DCV), an NS5A replication complex inhibitor, and asunaprevir (ASV), a NS3 protease inhibitor. The data submitted in the NDAs support the use of DCV+ASV in patients with genotype 1b hepatitis C (HCV). The DCV NDA also seeks approval for use of this compound in combination with other agents for multiple genotypes. The submissions are subject to FDA review for acceptance for filing.

“These FDA submissions represent a major step towards offering daclatasvir-based regimens to U.S. HCV patients, many of whom continue to have high unmet medical needs,” said Brian Daniels, MD, senior vice president, Global Development and Medical Affairs, Research and Development, Bristol-Myers Squibb. “We are excited to have achieved this milestone and, looking forward, will continue to innovate and invest in daclatasvir in a range of patient types and regimens.”

These submissions follow the recent announcement that the FDA granted the investigational DCV Dual Regimen (DCV+ASV) Breakthrough Therapy Designation. In 2013, the investigational all-oral 3DAA Regimen (daclatasvir/asunaprevir/BMS-791325) also received Breakthrough Therapy Designation, and the company anticipates submitting this regimen for FDA review in Q1 2015.

In January 2014, the European Medicines Agency (EMA) validated the company’s marketing authorization application for the use of DCV in combination with other agents for the treatment of adults with HCV with compensated liver disease, including genotypes 1, 2, 3, and 4, and this application is under accelerated review. In addition, NDAs for DCV and ASV are under priority review by Japan’s Pharmaceutical and Medical Devices Agency for patients with chronic HCV genotype 1b, classified as either interferon-ineligible naïve/intolerant or non-responders to interferon and ribavirin.

About Hepatitis C

Hepatitis C is a virus that infects the liver and is transmitted through direct contact with infected blood and blood products. Approximately 170 million people worldwide are infected with hepatitis C, with an estimated 2.7–3.9 million chronically infected in the United States. Up to 90 percent of those infected with hepatitis C will not spontaneously clear the virus and will become chronically infected. According to the World Health Organization, up to 20 percent of people with chronic hepatitis C will develop cirrhosis; of those, up to 25 percent may progress to liver cancer.

About Bristol-Myers Squibb’s HCV Portfolio

Bristol-Myers Squibb’s research efforts are focused on advancing late-stage compounds to deliver the most value to patients with hepatitis C. At the core of our pipeline is daclatasvir (DCV), an investigational NS5A replication complex inhibitor that has been studied in more than 5,500 patients as part of multiple direct-acting antiviral (DAA) based combination therapies. DCV has shown a low drug-drug interaction profile, supporting its potential use in multiple treatment regimens and in people with co-morbidities.

DCV is currently being studied in the ongoing Phase III UNITY Program, where it is being investigated as part of an all-oral 3DAA Regimen (daclatasvir/asunaprevir/BMS-791325). Study populations include non-cirrhotic naïve, cirrhotic naïve and previously treated patients. The 3DAA Regimen is being studied as a fixed-dose-combination treatment with twice daily dosing.

Daclatasvir is also being investigated in combination with sofosbuvir in high unmet need patients, such as pre- and post-transplant patients, HIV/HCV co-infected patients, and patients with genotype 3, as part of the ongoing Phase III ALLY Program.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.

Bristol-Myers Squibb Forward Looking Statement

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that clinical trials of these compounds will support regulatory filings, or that DCV or any other compounds mentioned in this release will receive regulatory approval or, if approved, that they will become commercially successful products. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2013 in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.

Contact:

Bristol-Myers Squibb
Media:
Carrie Fernandez,
Office: +1-609-252-4831; Cell: +1-215-859-2605
carrie.fernandez@bms.com
or
Investors:
Ranya Dajani, 609-252-5330, ranya.dajani@bms.com
Ryan Asay, 609-252-5020, ryan.asay@bms.com

Source

April 4, 2014

Risk Factors for Hepatitis C Infection Among Vietnam Era Veterans Versus Nonveterans: Results from the Chronic Hepatitis Cohort Study (CHeCS)

Journal of Community Health
March 2014

Joseph A. Boscarino, Alexandra Sitarik, Stuart C. Gordon, Loralee B. Rupp, David R. Nerenz, Vinutha Vijayadeva, Mark A. Schmidt, Emily Henkle, Mei Lu

Abstract

Research suggests that Vietnam era veterans have a higher prevalence of hepatitis C virus (HCV) than other veterans and nonveterans. However, the reasons for this are unclear, since this research has been conducted among Department of Veterans Affairs (VA) patients and most veterans do not use the VA. The current study compares HCV risk factors between the Vietnam era veterans and nonveterans seen in 4 large non-VA systems to explain this disparity. A total of 4,636 HCV patients completed surveys in 2011–2012. Vietnam era veterans were defined as those who served in the military any time between 1964 and 1975. Bivariate tests followed by logistic regressions, and multivariable modeling were conducted to study risk factors among Vietnam era veterans and nonveterans. Since few veterans were female (~2 %), they were excluded. Among male respondents (N = 2,638), 22.5 % were classified as Vietnam era veterans. Compared to nonveterans, these patients were older (p < 0.001), more educated (p < 0.001), less often foreign born (p = 0.009), more often married (p < 0.001), less often employed, and less likely to have a history of drug abuse treatment (p < 0.001). Comparison of specific risk factor differences for HCV infection by veteran status suggested that while injection drug use approached statistical significance (nonveterans = 46.1 % vs. Vietnam era veterans = 41.4 %, p = 0.06), only reported sex with men was significant (nonveterans = 2.4 % vs. Vietnam era veterans = 0.6 %, p = 0.013). In multivariate logistic regression controlling for age, education, country of birth, marital status and study site, no HCV risk factor was associated with Vietnam era veteran status. However, veterans were more likely to report “other” exposures were the source of infection than nonveterans (p < 0.001). While Vietnam era veterans seen in non-VA facilities do not report a higher prevalence of common HCV risk factors, such as injection drug use, they are more likely to report “other” exposures, typically associated with military service, as the source of HCV infection.

Source

April 3, 2014

HHS Dr Koh releases update to National Viral Hepatitis Action Plan & highlights 10 big advances propelling progress

Provided by The Huffington Post

Updated Viral Hepatitis Action Plan Released

Dr. Howard K. Koh
Assistant Secretary for Health, U.S. Department of Health and Human Services

Posted: 04/02/2014 4:18 pm EDT Updated: 04/03/2014 9:59 am EDT

Today we are pleased to release an updated version of the nation's first comprehensive cross-governmental action plan to combat chronic viral hepatitis, initially launched in 2011. The Action Plan for the Prevention, Care and Treatment of Viral Hepatitis (2014-2016) builds upon the substantial progress accomplished over the past three years by agencies and offices across the Department of Health and Human Services - as well as within the Departments of Justice and Veterans Affairs. (Read a brief factsheet about the updated plan.)

Chronic viral hepatitis (hepatitis B [HBV] and hepatitis C [HCV]) is a largely preventable and treatable disease. Yet it affects between 3.5 and 5.3 million Americans, most of them unaware of their infection. As a result, untreated chronic viral hepatitis represents the leading cause of liver cancer and the most common reason for liver transplantation in the United States. In addition, it is a leading infectious cause of death in the U.S., claiming the lives of 12,000-18,000 Americans each year.

But we are making progress against this "silent epidemic." The release of the first Action Plan has galvanized progress on many fronts. Here are just 10 of the recent accomplishments in the field:

1. Establishment of National Hepatitis Testing Day. The original Action Plan called for the establishment of this annual observance, which we've now observed on May 19th each year since 2012. National Hepatitis Testing Day raises greater awareness among both health care providers and communities and we look forward to another outstanding observance next month.

2. New hepatitis C testing recommendations. Both the CDC and the U.S. Preventive Services Task Force have issued recommendations to test all individuals born between 1945 and 1965. As these so-called "Baby Boomers" are five times more likely to be infected with hepatitis C, this single recommendation could save over 120,000 lives. The alignment of these CDC and USPSTF recommendations and their widespread dissemination were called for in the 2011 Action Plan.

3. Expanded, culturally appropriate hepatitis B outreach and educational materials. Produced by CDC in partnership with community organizations, the Know Hep B campaign materials, available in several Asian languages, enable health care providers and community organizations to reach more individuals at risk about the importance of testing for HBV.

4. Greater attention to hepatitis C among persons who inject drugs (PWID). Of new cases of HCV infection reported to the CDC, injection drug use represents the most commonly identified risk factor. An estimated 64 percent of PWID are chronically infected with HCV, and 2.7-11 percent are chronically infected with HBV. Recent consultations and research funding announcements are strengthening our understanding of this problem. We are identifying better ways to prevent new infections in this vulnerable population.

5. Opposing discrimination against health care professionals and students with chronic hepatitis. In a great example of the cross-agency collaboration fostered by the Action Plan, the Offices of Civil Rights from the Departments of Justice, Education, and Health and Human Services sent a joint letter last year to health professions schools. The letter highlighted new CDC guidance on the management of health care professionals and students with chronic HBV and outlined steps to eliminate discrimination against those infected.

6. Greater attention to the elimination of perinatal hepatitis B transmission. We have the tools to further reduce the number of infants perinatally infected with HBV. Motivated and active partners have engaged to ensure the administration of a dose of HBV vaccine to all newborns before discharge from hospitals or birthing centers.

7. New hepatitis C treatments. Late last year, the FDA approved two new HCV treatments, which are simpler to use, require a shorter treatment duration, and have fewer side effects than earlier treatment regimens. These treatments lead to a cure in more than 90 percent of patients who complete them - a major advance. Our FDA colleagues are working along with the pharmaceutical industry to make new HCV therapies available safely and as quickly as possible by using the Fast Track program. This special designation facilitates development and review of drugs with the potential to address unmet medical needs in those with serious conditions.

8. Affordable Care Act. The Affordable Care Act is contributing to efforts to combat chronic viral hepatitis in the U.S. For example, because the law prohibits most plans from denying health coverage based on preexisting conditions, those with chronic viral hepatitis who had previously been uninsured will now have the opportunity to get covered and obtain access to needed prevention, care and treatment services. Moreover, hepatitis vaccinations and testing for HBV for pregnant women are among the covered preventive services that must be offered free of cost-sharing or co-pays. Later this year, one-time HCV screening for persons born between 1945 and 1965 will be added to this list. In addition, the law calls for a substantial investment in the HHS community health center program, which is a vital partner in delivering viral hepatitis prevention, diagnosis, care and treatment to vulnerable populations.

9. World Hepatitis Day proclamations from the President. President Obama has lent his support to the global observance of World Hepatitis Day for the past three years, issuing annual proclamations. The White House has also hosted events to commemorate these observances, helping to raise awareness and mobilize action to address viral hepatitis not only in the U.S. but around the globe.

10. An updated Action Plan for the Prevention, Care, & Treatment of Viral Hepatitis. Now, the updated Action Plan will build upon all the important advances noted above, and identify further opportunities for public and private sector stakeholders. So many can engage in efforts to break the silence surrounding viral hepatitis and improve prevention, diagnosis, care and treatment.

New partners have joined in launching the updated Action Plan. We are pleased that from the federal government, the Department of Housing and Urban Development and the White House Office of National Drug Control Policy have joined our efforts along with the HHS Office of Disease Prevention and Health Promotion, Office of Population Affairs, and our Regional Health Administrators. Many others can join as well. As my colleague Dr. Ronald Valdiserri, Deputy Assistant Secretary for Health, Infectious Diseases observes, "Active involvement by a broad mix of partners from various sectors, both public and private, is essential to fully realizing the potential of this plan. The updated plan provides a framework around which all of us can engage in aligned and focused action."

I hope you, too, will join us in this important moment. It is a critical time. We have the potential to save many lives. The era of health care reform provides a historic setting to strengthen the rapid progress we're making in the diagnosis and treatment of chronic hepatitis. Working together, we can successfully leverage all of our resources to help the nation become fully committed to combating the silent epidemic of viral hepatitis.

Share your ideas about how you or your organization can contribute to this national effort in the comments section below or on social media using the hashtag #ViralHepAction.

Follow Dr. Howard K. Koh on Twitter: www.twitter.com/@HHS_DrKoh

Source

Also See: Updated Action Plan to Combat Viral Hepatitis Released

The next frontier in 3-D printing: Human organs

By Brandon Griggs, CNN
updated 9:43 AM EDT, Thu April 3, 2014

(CNN) -- The emerging process of 3-D printing, which uses computer-created digital models to create real-world objects, has produced everything from toys to jewelry to food.

Soon, however, 3-D printers may be spitting out something far more complex, and controversial: human organs.

For years now, medical researchers have been reproducing human cells in laboratories by hand to create blood vessels, urine tubes, skin tissue and other living body parts. But engineering full organs, with their complicated cell structures, is much more difficult.

Enter 3-D printers, which because of their precise process can reproduce the vascular systems required to make organs viable. Scientists are already using the machines to print tiny strips of organ tissue. And while printing whole human organs for surgical transplants is still years away, the technology is rapidly developing.

"The mechanical process isn't all that complicated. The tricky part is the materials, which are biological in nature," said Mike Titsch, editor-in-chief of 3D Printer World, which covers the industry. "It isn't like 3-D printing plastic or metal. Plastic doesn't die if you leave it sitting on an open-air shelf at room temperature for too long."

140327123641-printed-ear-cornell-story-body

Lawrence Bonassar, a professor of biomedical engineering at Cornell University, with an artificial ear made via 3-D printing and injectable molds.

The idea of printing a human kidney or liver in a lab may seem incomprehensible, even creepy. But to many scientists in the field, bioprinting holds great promise. Authentic printed organs could be used for drug or vaccine testing, freeing researchers from less accurate methods such as tests on animals or on synthetic models.

Then there's the hope that 3-D printers could someday produce much-needed organs for transplants. Americans are living longer, and as we get deeper into old age our organs are failing more. Some 18 people die in the United States each day waiting in vain for transplants because of a shortage of donated organs -- a problem that Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine and a pioneer in bioprinting, calls "a major health crisis."

An 'exciting new area of medicine'

Bioprinting works like this: Scientists harvest human cells from biopsies or stem cells, then allow them to multiply in a petri dish. The resulting mixture, a sort of biological ink, is fed into a 3-D printer, which is programmed to arrange different cell types, along with other materials, into a precise three-dimensional shape. Doctors hope that when placed in the body, these 3-D-printed cells will integrate with existing tissues.

The process already is seeing some success. Last year a 2-year-old girl in Illinois, born without a trachea, received a windpipe built with her own stem cells. The U.S. government has funded a university-led "body on a chip" project that prints tissue samples that mimic the functions of the heart, liver, lungs and other organs. The samples are placed on a microchip and connected with a blood substitute to keep the cells alive, allowing doctors to test specific treatments and monitor their effectiveness.

"This is an exciting new area of medicine. It has the potential for being a very important breakthrough," said Dr. Jorge Rakela, a gastroenterologist at the Mayo Clinic in Phoenix and a member of the American Liver Foundation's medical advisory committee.

140325153416-3d-bioprinting-story-body

One of Organovo's engineers oversees the construction of a vascular tissue construct on a Novotel bioprinter.

"Three-D printing allows you to be closer to what is happening in real life, where you have multiple layers of cells," he said. With current 2-D models, "if you grow more than one or two layers, the cells at the bottom suffocate from lack of oxygen."

To accelerate the development of bioprinted organs, a Virginia foundation that supports regenerative medicine research announced in December it will award a $1 million prize for the first organization to print a fully functioning liver.

One early contender for the prize is Organovo, a California start-up that has been a leader in bioprinting human body parts for commercial purposes. Using cells from donated tissue or stem cells, Organovo is developing what it hopes will be authentic models of human organs, primarily livers, for drug testing.

The company has printed strips of human liver tissue in its labs, although they are still very small: four by four by one millimeter, or about one-fourth the size of a dime. Each strip takes about 45 minutes to print, and it takes another two days for the cells to grow and mature, said Organovo CEO Keith Murphy. The models can then survive for about 40 days.

Organovo has also built models of human kidneys, bone, cartilage, muscle, blood vessels and lung tissue, he said.

"Basically what it allows you to do is build tissue the way you assemble something with Legos," Murphy said. "So you can put the right cells in the right places. You can't just pour them into a mold."

Ethical concerns

Not everyone is comfortable with this bold new future of lab-built body parts, however.

A research director at Gartner Inc., the information-technology research and advisory firm, believes 3-D bioprinting is advancing so quickly that it will spark a major ethical debate by 2016.

140402151231-cornell-3d-printed-ear-story-body

A 3-D printer at Cornell University produces an artificial ear.

"Three-D bioprinting facilities with the ability to print human organs and tissue will advance far faster than general understanding and acceptance of the ramifications of this technology," Pete Basiliere said in a recent report.

"These initiatives are well-intentioned, but raise a number of questions that remain unanswered," Basiliere added. "What happens when complex 'enhanced' organs involving nonhuman cells are made? Who will control the ability to produce them? Who will ensure the quality of the resulting organs?"

Bioprinted organs are also likely to be expensive, which could put them out of reach of all but the wealthiest patients.

Murphy said Organovo only uses human cells in creating tissues, and doesn't see any ethical problems with what his company is doing.

"People used to worry about doing research on cadavers ... and that dissipated very quickly," he said. "We don't think there's any controversy if you're producing good data and helping people with health conditions."

Most experts, including Wake Forest's Atala, don't think we'll see complex 3-D-printed organs, suitable for transplants, for years if not decades. Instead, they believe the next step will be printing strips of tissue, or patches, that could be used to repair livers and other damaged organs.

140325154104-3d-bioprinter-story-body

Organovo also uses the Nuveen MMX Bio printer, which is small enough to fit into a cabinet.

"We are very eager to put pieces of tissue to work for surgical transplants," said Organovo's Murphy, who hopes his company will be ready to begin clinical trials within five years.

Of course, any use of 3-D-printed tissue in surgical procedures would require approval by the U.S. Food and Drug Administration. That review process could take up to a decade.

By then, the notion of a surgeon putting a 3-D-printed kidney into a patient may not seem so bizarre. Then again, this swiftly evolving technology may create new moral conundrums.

"The ethical questions are bound to be the same concerns we have seen in the past. Many major medical breakthroughs have suffered moral resistance, from organ transplants to stem cells," said Titsch of 3D Printer World.

"Will only the rich be able to afford it? Are we playing God? In the end, saving lives tends to trump all objections."

Source

Updated Action Plan to Combat Viral Hepatitis Released

FOR IMMEDIATE RELEASE
April 3, 2014

Contact: HHS Press Office
(202) 205-0143

A statement by Deputy Assistant Secretary for Health, Infectious Diseases,
Ronald O. Valdiserri, MD, MPH

Today, federal partners launched an updated Action Plan for the Prevention, Care and Treatment of Viral Hepatitis (2014-2016), building upon the nation’s first comprehensive cross-agency action plan to combat viral hepatitis.

The three-year renewal of the Action Plan builds upon the substantial progress accomplished since 2011 by agencies and offices from across the Department of Health and Human Services, as well as with our partners at the Departments of Justice, Housing and Urban Development, and Veterans Affairs, to prevent new infections and improve the diagnosis, care and treatment of individuals living with chronic hepatitis C in the United States.

Between 3.5 and 5.3 million Americans are living with chronic viral hepatitis, and most of them do not know that they are infected. Viral hepatitis is the leading cause of liver cancer and the most common reason for liver transplantation in the United States. In addition, it is a leading infectious cause of death in the U.S., claiming the lives of 12,000–18,000 Americans each year.

In recent years we have made significant progress in addressing these challenges.  With the new advances in hepatitis C treatment, more widespread availability of safe and effective vaccines for hepatitis A and B, and more opportunities for testing for hepatitis C under the Affordable Care Act, we have arrived at a critical moment. By harnessing these and other developments, we have the potential to reduce the toll of viral hepatitis in the U.S. and save many lives.

Thanks to the outstanding commitment of our public and private partners, we are closer than ever to realizing the potential of this plan.

To access the full Action Plan for the Prevention Care and Treatment of Viral Hepatitis (2014-2016) visit www.aids.gov/hepatitis.

For more information on viral hepatitis, see http://www.cdc.gov/hepatitis/.

Follow the conversation on social media using #ViralHepAction.

###

Note: All HHS press releases, fact sheets and other news materials are available at http://www.hhs.gov/news.

Like HHS on Facebook , follow HHS on Twitter @HHSgov , and sign up for HHS Email Updates.

Follow HHS Secretary Kathleen Sebelius on Twitter @Sebelius .

Last revised: April 3, 2014

Source

Also See: Updated Action Plan to Combat Viral Hepatitis Released

FDA approves new hand-held auto-injector to reverse opioid overdose

FDA NEWS RELEASE

For Immediate Release: April 3, 2014
Media Inquiries: Sandy Walsh, 301-796-4669, sandy.walsh@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA

First naloxone treatment specifically designed to be given by family members or caregivers

The U.S. Food and Drug Administration today approved a prescription treatment that can be used by family members or caregivers to treat a person known or suspected to have had an opioid overdose. Evzio (naloxone hydrochloride injection) rapidly delivers a single dose of the drug naloxone via a hand-held auto-injector that can be carried in a pocket or stored in a medicine cabinet.

It is intended for the emergency treatment of known or suspected opioid overdose, characterized by decreased breathing or heart rates, or loss of consciousness.

Drug overdose deaths, driven largely by prescription drug overdose deaths, are now the leading cause of injury death in the United States – surpassing motor vehicle crashes. In 2013, the Centers for Disease Control and Prevention reported the number of drug overdose deaths had steadily increased for more than a decade.

Naloxone is a medication that rapidly reverses the effects of opioid overdose and is the standard treatment for overdose. However, existing naloxone drugs require administration via syringe and are most commonly used by trained medical personnel in emergency departments and ambulances.

“Overdose and death resulting from misuse and abuse of both prescription and illicit opioids has become a major public health concern in the United States,” said Bob Rappaport, M.D., director of the Division of Anesthesia, Analgesia, and Addiction Products in the FDA’s Center for Drug Evaluation and Research. “Evzio is the first combination drug-device product designed to deliver a dose of naloxone for administration outside of a health care setting. Making this product available could save lives by facilitating earlier use of the drug in emergency situations.”

Evzio is injected into the muscle (intramuscular) or under the skin (subcutaneous). Once turned on, the device provides verbal instruction to the user describing how to deliver the medication, similar to automated defibrillators. Family members or caregivers should become familiar with all instructions for use before administering to known or suspected persons to have had an opioid overdose. Family members or caregivers should also become familiar with the steps for using Evzio and practice with the trainer device, which is included along with the delivery device, before it is needed. 

Because naloxone may not work as long as opioids, repeat doses may be needed. Evzio is not a substitute for immediate medical care, and the person administering Evzio should seek further, immediate medical attention on the patient’s behalf.

In one pharmacokinetic study of 30 patients, a single Evzio injection provided equivalent naloxone compared to a single dose of naloxone injection using a standard syringe. The use of Evzio in patients who are opioid dependent may result in severe opioid withdrawal. Abrupt reversal of opioid depression may result in nausea, vomiting, sweating, accelerated heart rate (tachycardia), increased blood pressure, uncontrollable trembling (tremulousness), seizures and cardiac arrest.

The FDA reviewed Evzio under the agency’s priority review program, which provides for an expedited review of drugs that appear to provide safe and effective therapy when no satisfactory alternative therapy exists, or offer significant improvement compared to marketed products. The product was granted a fast-track designation, a process designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need.

Evzio is being approved ahead of the product’s prescription drug user fee goal date of June 20, 2014, the date the agency was originally scheduled to complete review of the drug application.

Evzio’s approval is also the result of efforts by several federal agencies. Naloxone has been a part of the White House’s Office of National Drug Control Policy’s National Drug Control Strategy since 2012. The FDA co-chairs an HHS inter-departmental working group on naloxone, which helped coordinate an April 12, 2012, meeting regarding access to naloxone products.

Evzio is manufactured for kaléo, Inc., of Richmond, Va. 
For more information:

Information on Opioid Medications

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April 2, 2014

Exclusive: Costs to public of $84,000 hep C drug ‘outrageous' - Kaiser

By Deena Beasley
LOS ANGELES  Wed Apr 2, 2014 3:41pm EDT

(Reuters) - Kaiser Permanente, the biggest U.S. health maintenance organization, said it is using Gilead Sciences' new hepatitis C drug, Sovaldi, even though its $84,000 treatment price is "outrageous."

The medication is widely viewed as a breakthrough that can cure a majority of hepatitis C patients, often within 12 weeks. Analysts project 2017 sales of $9.1 billion, according to Thomson Reuters Pharma.

But Gilead has come under fire, from insurers and Congress, for Sovaldi's $1,000-a-pill price at a time when U.S. healthcare spending is under scrutiny and President Barack Obama's Affordable Care Act aims to make health coverage accessible to everyone.

The company says Sovaldi should create huge savings for the healthcare system over time by preventing complications from liver disease and transplants, but declined requests for evidence to back up those claims. A Gilead executive told Reuters last week that it had an agreement to discount the drug for the Kaiser network, based on their recognition of the long-term benefits.

In an interview, Kaiser officials disputed that view. Kaiser is using Sovaldi "not because we see this as a high-value, cost-effective approach," said Dr. Sharon Levine, associate director of the Permanente Medical Group. "It's because this is a therapy that represents a substantial improvement over existing therapies ... It's an outrageous price for a therapy that has huge public health implications."

She called Kaiser's discount on Sovaldi "modest" and said state Medicaid programs and private health insurers "are going to have to make very serious tradeoffs just based on a single manufacturer's decision on pricing a drug because they can."

Gilead officials declined to comment.

Hepatitis C, estimated to infect about 3.2 million Americans, is a blood-borne virus that can cause severe liver damage.

LAWMAKERS SEEK PRICING INFORMATION

Democratic lawmakers in the House of Representatives, led by California's Henry Waxman, have asked Gilead to explain Sovaldi's pricing. The company said it met with committee staff on Monday.

The public call to Gilead from Congress has sent shock waves through the biotech investment community, raising concerns that other leading drugmakers could face pressure on pricing new medicines. Over the past month the Nasdaq Biotechnology Index has fallen more than 8 percent.

Insurers and state officials running the Medicaid health program for the poor fear a multibillion-dollar tab from Sovaldi alone.

Investment bank Leerink Partners estimates the drug's cost could trim as much as 10 percent from the earnings of publicly traded health insurers.

Kaiser, a nonprofit, said Sovaldi will be a material portion of its drug budget - a cost ultimately born by members and employers who pay insurance premiums.

"It comes back to the question of who benefits at a time when there is enormous pressure to ensure that the cost of healthcare, the cost of providing access to cures doesn't bankrupt all of the rest of the investments that the country needs to make," Levine said.

(Reporting by Deena Beasley; Editing by Michele Gershberg and Prudence Crowther)

Source

Gilead Announces Results From Phase 3 Study of Sofosbuvir Among Hepatitis C Patients in Japan

– Results Confirm Efficacy and Safety of All-Oral Sofosbuvir-Based Regimen for Genotype 2 HCV Patients –

– Japanese Regulatory Filing Planned for Mid-Year –

FOSTER CITY, Calif.--(BUSINESS WIRE)--Apr. 2, 2014-- Gilead Sciences, Inc. (Nasdaq:GILD) today announced topline results from a Phase 3 clinical trial (Study GS-US-334-0118) in Japan evaluating the once-daily nucleotide analog polymerase inhibitor sofosbuvir in combination with ribavirin (RBV) for the treatment of genotype 2 chronic hepatitis C virus (HCV) infection. The study met its primary efficacy endpoint of superiority compared to a predefined historical control sustained virologic response (SVR) rate. In the study, 97 percent (n=148/153) of genotype 2 HCV-infected patients receiving 12 weeks of an all-oral regimen of sofosbuvir plus RBV achieved a sustained virologic response 12 weeks after completing therapy (SVR12). SVR12 rates among treatment-naïve and treatment-experienced patients were 98 percent (n=88/90) and 95 percent (n=60/63), respectively. Of the 153 patients who received treatment, 11 percent (n=17) had documented cirrhosis.

Japan has one of the highest rates of liver cancer of any industrialized country, and the majority of cases are due to chronic HCV infection. An estimated two million people in Japan are living with HCV infection, and approximately 20-30 percent have the genotype 2 strain of the virus. Current treatment options for genotype 2 HCV infection in Japan involve up to 48 weeks of therapy with pegylated interferon injections, which may not be suitable for certain patients.

In Study GS-US-334-0118, 153 patients (100%) became HCV undetectable by treatment Week 4 and remained undetectable through the remainder of the 12-week treatment period. Post-treatment relapse accounted for five virologic failures. There were no treatment discontinuations due to adverse events and all patients completed the 12 week post-treatment follow-up visit. The most common side effects observed in the study, consistent with the population and safety profile of RBV, included nasopharyngitis, anemia, headache, malaise and pruritis. Full study results will be presented at a future scientific meeting.

“This study confirms the high efficacy of all-oral therapy with sofosbuvir among genotype 2 hepatitis C patients in Japan, regardless of whether they are treatment experienced or new to treatment,” said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer, Gilead Sciences. “Based on these trial results, Gilead anticipates submitting a New Drug Application for sofosbuvir to the Japanese Pharmaceutical and Medical Devices Agency (PMDA) by mid-2014.”

Gilead established operations in Japan with the formation of Gilead K.K. in Tokyo in September 2013. If approved by the PMDA, sofosbuvir would be the first product to be launched and marketed by Gilead in Japan.

Gilead is also conducting a Phase 3 study in Japan evaluating the efficacy and safety of a once-daily fixed-dose combination of the NS5A inhibitor ledipasvir 90 mg and sofosbuvir 400 mg with and without ribavirin for the treatment of patients with genotype 1 chronic HCV infection, the most common strain of HCV in Japan. SVR12 results are expected in the second half of 2014.

Sofosbuvir is an investigational product in Japan and its safety and efficacy has not yet been established. The compound has been approved by regulatory authorities in the United States, European Union and Canada and is commercialized under the tradename Sovaldi®. The ledipasvir/sofosbuvir fixed-dose combination is an investigational product and its safety and efficacy has not yet been established.

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 worldwide. Headquartered in Foster City, California, Gilead has operations in North and South America, Europe and Asia Pacific.

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 possibility of unfavorable results from additional clinical trials involving sofosbuvir or the ledipasvir/sofosbuvir fixed-dose combination in Japan, and the possibility we may not file for regulatory approval of sofosbuvir in Japan in the currently anticipated timelines. Further, the PMDA may not approve these products in Japan, 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 Annual Report on Form 10-K for the year ended December 31, 2013, as filed with the U.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 is available at www.Gilead.com

Sovaldi is a registered trademark of Gilead Sciences, Inc.

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.

Source: Gilead Sciences, Inc.

Gilead Sciences, Inc.
Patrick O’Brien, Investors, 650-522-1936
Cara Miller, Media (U.S.), 650-522-1616

Source

Hepatitis C Drug Trials to Take Spotlight at Liver Congress

Miriam E. Tucker
April 02, 2014

New all-oral interferon-free treatment regimens for hepatitis C will take center stage at the European Association for the Study of the Liver (EASL) International Liver Congress 2014, with an unprecedented number of phase 3 trials demonstrating cure rates of up to 100%.

The congress will take place April 9 to 13 in London, United Kingdom.

"There are a lot of very important things being discussed, but I think what really stands out are the remarkable results achieved in several trials on the treatment of hepatitis C, particularly genotype 1, which is the most difficult to treat," explained Giorgina Mieli-Vergani, MD, who is honorary president of the EASL.

"Hepatitis C is a major killer in the world, and doctors have been trying for a long time to find the best way of treating it. Now we are very close to being able to treat it very effectively — this is a major, major thing coming out of this congress," Dr. Mieli-Vergani told Medscape Medical News.

In fact, "we've never had this many phase 3 studies in one conference before, said Markus Peck-Radosavljevic, MD, secretary-general of the EASL. "They will be changing clinical practice."

Dr. Markus Peck-Radosavljevic

The studies will show that "without interferon, by combining 2 or 3 drugs, you can cure hepatitis C in 95% and 99% of cases, which means essentially you can cure everybody with very little side effect," said Dr. Peck-Radosavljevic told Medscape Medical News.

Moving "Very, Very Fast"

Some of the most highly anticipated phase 3 results are from the SAPPHIRE trials, which evaluated 12-week regimens of ribavirin plus ABT-450/r, ABT-267, and ABT-333, under development by AbbVie, in patients with genotype 1 hepatitis C. SAPPHIRE I involves treatment-naïve patients and SAPPHIRE II involves treatment-experienced patients.

Also anticipated are results from the ION-2 study, which evaluated the fixed-dose combination of sofosbuvir plus ledipasvir (Gilead Sciences), with and without ribavirin, in treatment-naïve and treatment-experienced patients with genotype 1 hepatitis C.

Dr. Giorgina Mieli-Vergani

The once-daily sofosbuvir/ledipasvir pill appears to work in a short period of time in the most difficult-to-treat patients, and with far fewer adverse effects than regimens containing pegylated interferon. Dr. Mieli-Vergani called the results "amazing."

"I am a pediatrician, and this is exceedingly exciting for me," she told Medscape Medical News. "The current oral drug regimens require up to 12 pills a day, which is impossible for a child. There are no trials in children yet, but they will follow." Although hepatitis C is much less common in children than in adults, 6% to 7% of infected mothers pass along the infection to their infants, she explained.

New treatment guidelines for hepatitis C from the World Health Organization — primarily addressing the developing world — will be presented at the meeting.

Also presented will be EASL guidelines on hepatitis C. Although they were published online in December 2013, they are already outdated, Dr. Peck-Radosavljevic told Medscape Medical News (J Hepatol. 2014;60:392-420).

"Things are moving very, very fast. We will definitely need to update again within a year," he said. The organization will probably stop printing the guidelines on paper and only house them online so that they can be continually updated, he said.

Hallway Conversation

Not officially on the agenda but sure to be discussed is the high cost of new drugs for hepatitis C. "How all people who need it are going to be able to have it, I don't know," said Dr. Mieli-Vergani.

Dr. Peck-Radosavljevic pointed out that "companies have to recover their cost of development and satisfy their investors." But, he added, "you have a drug curing a deadly disease in 100% of patients. If you put that into perspective, the pricing is not outrageous."

Both he and Dr. Mieli-Vergani predict that the prices will eventually drop, as was the case with the HIV drugs.

Beyond Hepatitis C

Beyond hepatitis C, new information on numerous liver disease-related topics, including hepatitis B and D, nonalcoholic fatty liver disease, hepatocellular carcinogenesis, liver regeneration, and noninvasive assessment of liver disease, will be featured, and beginner and advanced sonography workshops will be offered.

Of note, phase 3 data will be presented on the use of obeticholic acid (Intercept Pharmaceuticals) for the treatment of primary biliary cirrhosis.

"This is a new type of drug. It's very interesting because it's the first time in many years we will have a new drug that works in primary biliary cirrhosis," said Dr. Peck-Radosavljevic.

The current treatment, ursodeoxycholic acid, has been on the market for about 40 years. "It helps, but doesn't work for all patients, so it is really quite important to have something new here," he said.

Primary biliary cirrhosis is an autoimmune liver disease of major interest to Dr. Mieli-Vergani. She is looking forward to meeting with 40 to 50 fellow members of an international ad hoc autoimmune hepatitis interest group that meets every year at the EASL and major liver meetings, she told Medscape Medical News.

"Autoimmune liver disease is a small part of the meeting, but a very intense and important part," she said.

Another "small but important" topic is children with liver disease. They are by and large surviving into adulthood now and transitioning to adult hepatology care, Dr. Mieli-Vergani explained.

"When I started doing pediatric hepatology 40 years ago, 60% of my patients died within 2 years of diagnosis. There were many conditions we didn't understand or know how to treat. Transplantation didn't exist. Nowadays, it's about 5%," she reported.

It is challenging for adult hepatologists, she said, because these patients are very different from those who develop liver disease in adulthood. In the United Kingdom, efforts have been made to ease the transition by having pediatric, adolescent, and adult specialists coordinate care for the patient during a transition period.

"Pediatrics is a very small part of the meeting, but the fact that they have me as the honorary president is a very nice sign," she told Medscape Medical News.

Dr. Mieli-Vergani reports receiving research funding from Roche, and being a consultant for Roche, Bristol Myers Squibb, and Novartis. Dr. Peck-Radosavljevic reports consulting for or receiving speaker honoraria from BMS, AbbVie, Gilead, Merck, Roche, Lilly, Bayer, Boehringer, and GlaxoSmithKline.

Source

Two phase III trials evaluating once-daily Simeprevir and Sofosbuvir in hepatitis C infected patients have been initiated

logga-top-enkel-se

Stockholm, Sweden — Medivir AB (OMX: MVIR) today announces that two phase III trials are recruiting patients to examine the efficacy and safety of the NS3/4A protease inhibitor simeprevir in combination with the nucleotide inhibitor sofosbuvir for the treatment of chronic genotype 1 hepatitis C virus (HCV) infection in treatment-naïve and treatment-experienced patients with and without cirrhosis.

“Positive safety and efficacy results have previously been demonstrated in genotype 1 HCV infected patients with the interferon- and ribavirin free combination of simeprevir and sofosbuvir in the phase II COSMOS study. The OPTIMIST trials aim to further consolidate these data and to explore a shorter treatment duration of eight weeks to potentially further simplify this promising treatment option,” says Charlotte Edenius, EVP Development, Medivir AB

Study design
OPTIMIST-1

The first trial, called OPTIMIST-1 or TMC435HPC3017, is a phase III, open-label, randomized study investigating the efficacy and safety of simeprevir 150 mg in combination with sofosbuvir 400 mg.
The combination will be administered once daily for 8 or 12 weeks in chronic HCV genotype 1 infected patients without cirrhosis who are HCV treatment naïve or treatment experienced. This study will enroll approximately 300 patients in the U.S. and Canada.

OPTIMIST-2
The second trial, called OPTIMIST-2 or TMC435HPC3018, is a phase III, open-label, single-arm study investigating the efficacy and safety of simeprevir 150 mg in combination with sofosbuvir 400 mg.
The combination will be administered once daily for 12 weeks in HCV genotype 1 infected patients with cirrhosis who are HCV treatment naïve or treatment experienced. This study will enroll approximately 100 patients in the U.S. and Canada.

Ribavirin will not be administered in the OPTIMIST trials. The primary efficacy endpoint in each study is the proportion of patients achieving sustained virologic response 12 weeks after the end of treatment (SVR12).

For additional information, including inclusion and exclusion criteria for these trials, please visit www.clinicaltrials.gov

COSMOS study
The combination of simeprevir and sofosbuvir was previously evaluated in the phase II COSMOS trial.
The final cohort 1 study results (SVR12) in patients without fibrosis or cirrhosis (METAVIR score of F0-2) and the interim cohort 2 study results (SVR4) in patients with fibrosis or cirrhosis (METAVIR score of F3-4) from the COSMOS study were presented at the American Association for the Study of Liver Diseases (AASLD) Annual Meeting 2013 in Washington, D.C.

Final cohort 2 results (SVR12) have been accepted for presentation at the European Association for the Study of the Liver (EASL) International Liver Congress 2014 on April 12.

For more information please contact:
Rein Piir, EVP Corporate Affairs & IR, mobile: +46 708 537 292

Medivir is required under the Securities Markets Act to make the information in this press release public. The information was submitted for publication at 13.00 CET on 2 April 2014.

About Simeprevir
Simeprevir is an NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB and indicated for the treatment chronic hepatitis C infection in combination with pegylated interferon and ribavirin in HCV genotype 1 and 4 infected patients with compensated liver disease, including cirrhosis.

Janssen is responsible for the global clinical development of simeprevir and has exclusive, worldwide marketing rights, except in the Nordic countries. Medivir AB will retain marketing rights for simeprevir in these countries under the marketing authorization held by Janssen-Cilag International NV. The treatment was approved for the treatment of genotype 1 hepatitis C in September 2013 in Japan and in November 2013 in Canada and the U.S. and in March 2014 in Russia. The Committee for Medicinal Products for Human Use (CHMP) recently recommended Marketing Authorisation in the European Union for the use of Simeprevir in combination with other medicinal products for the treatment of chronic hepatitis C (CHC) in adult patients. An approval is expected during Q2-2014.

About Medivir
Medivir is an emerging research-based pharmaceutical company focused on infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company’s key pipeline asset is simeprevir, a novel protease inhibitor for the treatment of hepatitis C that is being developed in collaboration with Janssen R&D Ireland. The company is also working with research and development in other areas, such as bone disorders and neuropathic pain. Medivir has also a broad product portfolio with prescription pharmaceuticals in the Nordics.

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April 1, 2014

Screening for liver cancer in patients with cirrhosis

Provided by MedicalXpress

April 1, 2014

In a systematic review and meta-analysis of 47 studies with 15,158 patients, Amit Singal (University of Texas Southwestern Medical Center) and colleagues found that patients with cirrhosis who underwent surveillance (via liver ultrasound with or without measurement of serum alpha fetoprotein) for hepatocellular carcinoma (HCC) had cancers detected at an earlier stage, were more likely to receive curative instead of palliative treatment, and had longer survival. Across all the studies, the pooled 3-year survival rate was 50.8% among the 4735 patients who underwent HCC surveillance, compared to 27.9% among the 6115 patients without prior surveillance (p<0.001).

The finding of longer survival persisted after the authors limited their review to studies that took into account lead time bias. Lead time bias, as it applies to this study, is the time between when a disease would normally be diagnosed without screening and when the disease is diagnosed with screening. Detecting disease earlier through screening can sometimes appear to increase survival when instead it only prolongs the time the person has the diagnosis. However, in this case, studies that accounted for lead time bias statistically still found that screening increased survival. Among the 6 studies that adjusted for lead time bias, those who underwent HCC surveillance had 3-year survival rates of 39.7%, vs. 29.1% among those who did not (p<0.001).

The authors note that while screening for HCC in patients with hepatitis B virus (HBV) infection is supported by a large randomized trial, no such randomized trials exist for patients with cirrhosis. Therefore the authors systematically reviewed published research that evaluated whether screening was associated with improved patient outcomes. While guidelines of the American Association for the Study of Liver Diseases and European Association for the Study of the Liver recommend surveillance with ultrasound every 6 months in high-risk patients (which includes those with chronic HBV infection and/or cirrhosis), the authors note that studies have shown that surveillance in the US is performed in less than 20% of these patients nationally, with lower rates among primary care physicians than gastroenterologists/hepatologists (physicians who specialize in caring for patients with liver disease).

A limitation of the study is that the studies were quite heterogeneous, suggesting benefits of surveillance may not be uniform among all patients, and studies did not include functional status, an important factor in determining appropriate treatment.

The authors conclude, "the preponderance of data that consistently demonstrate benefits should provide sufficient rationale to recommend HCC surveillance, even in the absence of a randomized controlled trial among patients with cirrhosis."

More information: Singal AG, Pillai A, Tiro J (2014) Early Detection, Curative Treatment, and Survival Rates for Hepatocellular Carcinoma Surveillance in Patients with Cirrhosis: A Meta-analysis. PLoS Med 11(4): e1001624. DOI: 10.1371/journal.pmed.1001624

Provided by Public Library of Science

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Low sodium levels pre-transplant does not affect liver transplant recipient survival

PUBLIC RELEASE DATE: 1-Apr-2014 Contact: Dawn Peters
sciencenewsroom@wiley.com
781-388-8408
Wiley

Researchers report that low levels of sodium, known as hyponatremia, prior to transplantation does not increase the risk of death following liver transplant. Full findings are published in Liver Transplantation, a journal of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

Medical evidence shows that low sodium concentration is common in patients with end stage liver disease (ESLD), with roughly half of those with cirrhosis having sodium levels below the normal range of 135-145 mmol/L. Moreover, previous research suggests that hyponatremia is linked to complications including bacterial infections, kidney failure and encephalopathy, and increases mortality in patients with ESLD. Following liver transplantation sodium levels will return to normal.

"There is much debate within the transplant community about whether to incorporate measures of serum sodium in the organ allocation system in the U.S.," explains lead author Dr. W. Ray Kim from Stanford University in Calif., and formerly with the Mayo Clinic where the research took place. "Understanding the impact of sodium concentrations in patients prior to and following liver transplantation is an important contribution to this debate."

Using data from the Organ Procurement and Transplantation Network (OPTN) researchers identified 19,537 patients 18 years of age or older who received a liver transplant in the U.S. between 2003 and 2010. Subjects were split into three groups: those with hyponatremia (sodium levels less than 130 mEq/L); normal sodium levels (serum sodium between131-145mEq/L); and hypernatremia (high sodium levels great than 145mEq/L).

"While our findings confirm that low sodium levels prior to transplant were a strong risk factor for waitlist mortality it was not associated with higher death risk following liver transplantation," concludes Dr. Kim. "Our data suggests that using serum sodium levels to determine organ allocation priority will not impact survival following a liver transplant."

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This study is published in Liver Transplantation. Media wishing to receive a PDF of the article may contact sciencenewsroom@wiley.com

Full citation: "The Effect of Pretransplant Serum Sodium Concentration on Outcome Following Liver Transplantation." Michael D. Leise, Byung Cheol Yun, Joseph J. Larson, Joanne T. Benson, Ju DongYang, Terry M. Therneau, Charles B. Rosen, Julie K. Heimbach, Scott W. Biggins and W. Ray Kim.Liver Transplantation; (DOI: 10.1002/lt.23860).

URL: http://doi.wiley.com/10.1022/lt.23860

About the Journal

Liver Transplantation is published by Wiley on behalf of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. Since the first application of liver transplantation in a clinical situation was reported more than twenty years ago, there has been a great deal of growth in this field and more is anticipated. As an official publication of the AASLD and the ILTS, Liver Transplantation delivers current, peer-reviewed articles on surgical techniques, clinical investigations and drug research — the information necessary to keep abreast of this evolving specialty. For more information, please visit http://wileyonlinelibrary.com/journal/lt.

About Wiley

Wiley is a global provider of content-enabled solutions that improve outcomes in research, education, and professional practice. Our core businesses produce scientific, technical, medical, and scholarly journals, reference works, books, database services, and advertising; professional books, subscription products, certification and training services and online applications; and education content and services including integrated online teaching and learning resources for undergraduate and graduate students and lifelong learners.

Founded in 1807, John Wiley & Sons, Inc. (NYSE: JWa, JWb), has been a valued source of information and understanding for more than 200 years, helping people around the world meet their needs and fulfill their aspirations. Wiley and its acquired companies have published the works of more than 450 Nobel laureates in all categories: Literature, Economics, Physiology or Medicine, Physics, Chemistry, and Peace. Wiley's global headquarters are located in Hoboken, New Jersey, with operations in the U.S., Europe, Asia, Canada, and Australia. The Company's website can be accessed at http://www.wiley.com.

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