Tuesday, December 31, 2013

Grading Pharma In 2013: Gilead's hepatitis C collaboration with Bristol had ethical issues

Grading Pharma In 2013: 16 Drug Companies Ranked

I gave one A+, to Bristol-Myers Squibb, based on its overall performance and its pioneering development of cancer drugs that work by priming the immune system. Gilead Sciences would have gotten one two were it not for the ethical issues surrounding its stopped collaboration with Bristol in hepatitis C, which I think hurt some patients. I am giving no Ds or Fs. There were no big drug disasters on a par with the recall of Merck’s Vioxx or Pfizer’s Bextra this year. Not even close. 
Companies are sorted by the letter grade I gave them, and, where there was a tie, by stock performance. Let me know what I got right – and what I got wrong. 
The Best Drug Companies 
1. Bristol-Myers Squibb CompanyMarket capitalization: $87 billionStock appreciation: +61.4%Grade: A+ 
Sure, the big-cap biotechs delivered better stock performance. But Big Pharmas don’t trade like this, and Bristol’s transformation, started under James Cornelius and continuing under current chief Lamberto Andreotti, has simply been amazing. (Former R&D head Elliot Sigal deserves credit, too.) Bristol is leading the way when it comes to cancer immunotherapy, which Science Magazine named as the breakthrough of the year. It’s smartly jettisoning its diabetes business to focus on what is working. And it is a player in hepatitis C............

Continue Reading @ Forbes

Friday, December 27, 2013

Top 10 Highlights From The Liver Meeting - A Future Without Hepatitis C

 Medscape Medical News from:
The Liver Meeting 2013: American Association for the Study of Liver Diseases (AASLD)

This coverage is not sanctioned by, nor a part of, the American Association for the Study of Liver Diseases.

Medscape Gastroenterology

Top 10 Highlights From The Liver Meeting
A Glimpse of the Future

William F. Balistreri, MD
December 27, 2013


A Future Without Hepatitis C
The successful development of targeted therapies for patients with chronic hepatitis C virus (HCV) was clearly evident. Several companies are jockeying to be the first to offer an all-oral, interferon (IFN)-free strategy. On the near horizon is the promise that a cocktail of agents, constructed on the basis of synergistic mechanisms of action, will be available for clinicians to wisely, effectively, and safely treat patients with HCV infection. A major advance, in my opinion, is the validation of regimens that are devoid of IFN and, in some cases, ribavirin.
Chayama and colleagues[1] documented the safety and efficacy of an IFN/ribavirin-free, all-oral therapy with daclatasvir (60 mg once daily) and asunaprevir (100 mg twice daily) in IFN-ineligible, -naive, or -intolerant patients and in those who did not respond to standard treatment for HCV genotype 1b.
Daclatasvir is a novel NS5A replication complex inhibitor with pangenotypic antiviral activity. Asunaprevir is a potent NS3 protease inhibitor with antiviral activity against genotypes 1, 4, 5, and 6. This regimen was associated with high (87%) sustained virologic response (SVR) rates after 12 weeks in both groups of patients. Treatment with this dual therapy was well tolerated.
Another all-oral triple combination -- daclatasvir, asunaprevir, and BMS-791325 (a nonnucleoside NS5B inhibitor) -- achieved SVR rates > 90% in pilot cohorts of noncirrhotic patients with HCV genotype 1 infection. Everson and colleagues[2] evaluated this regimen in larger cohorts that included cirrhotic patients. Patients received a twice-daily regimen of daclatasvir (30 mg), asunaprevir (200 mg), and BMS-791325 (either 75 mg or 150 mg) for 12 weeks. This investigational combination, which likewise avoids the use of both IFN and ribavirin, allowed a high percentage (92%) of patients infected with HCV to achieve SVR, including 87% of cirrhotic patients. The most frequent adverse effects in both groups were headache, diarrhea, fatigue, and nausea.
Lawitz and colleagues[3] reported successful results with another strategy. They administered the investigational combination of ABT-450, an HCV NS3/4A protease inhibitor (150 mg, dosed with ritonavir 100 mg), with ABT-267, an NS5A inhibitor (25 mg). Both compounds have shown potent antiviral activity in vitro against HCV genotypes 1-4 and 6. This combination, given once daily for 12 weeks, reduced viral loads to undetectable levels 12 weeks after the end of treatment in 95% of treatment-naive patients and in 90% of patients who had been previously treated but did not respond. The regimen was generally well tolerated. There were no serious adverse events related to the study drugs, and no patients stopped treatment because of adverse events.
Other reported regimens included a once-daily combination of simeprevir plus sofosbuvir (2 novel agents that were recently approved by the US Food and Drug Administration), with or without ribavirin, in patients with cirrhosis and noncirrhotic HCV genotype 1 treatment-naive and previous null responders.[4] One study[5] reported the effect of sofosbuvir and ribavirin for the treatment of recurrent HCV infection after liver transplantation, and another study[6] reported that sofosbuvir and ribavirin can be administered before transplant to prevent recurrence of HCV infection after liver transplantation.

Topic Highlights:

  • A Rapid Pace of Progress in Hepatology
  • Screening Specific Populations for HCV
  • Outcomes of Chronic HCV Infection
  • Reactivation of Hepatitis B Attendant to Immune Suppression
  • Insight Into the Mechanism, Diagnosis, and Treatment of NAFLD
  • Pathophysiology of Acute Liver Failure
  • Herbal and Dietary Supplement-Induced Liver Injury

  • Continue reading @ Medscape

    Thursday, December 26, 2013

    HCV Updates-HCV F1/F2 Treat Now Or Wait? and The best interferon-free combinations

    Hello Folks,
    I hope everyone had a festive and peaceful Christmas. This year my grandchildren were horribly sick with an "adenovirus" infection.

    After taking one very sick child to see their doctor, and the youngest child 24 hours later to the emergency room, some 48 hours after that Mr. and Mrs. Santa Clause were so sick the presents almost didn't make it under the tree. Our seasonal flu shot offered no protection against this nasty virus.

    The entire family is still recuperating from a sore throat, upper respiratory infection, ear infections and a few other complications. Oh my, it was so bad we postponed Christmas until this Saturday. My poor little babies.

    I just had to keep myself busy today, so for those of you with some free time over the holiday - here are a few updates.  

    News and Updates

    December 29
    People With HCV Die Decades Earlier Then Persons Without The Disease
    Recently, researchers set out to investigate the most frequent causes of death in people with viral hepatitis. In the study persons who shared the same cause of death were examined; one group of people with viral hepatitis and one without the infection. In the group of individuals with HBV or HCV, researchers found people died 22–23 years earlier than persons without the disease. Study results were released late in 2013, now the full text is available for viewing.

    Interferon-free combinations
    The best interferon-free combinations
    Based on the recent encouraging results from the widely studied IFN-free regimens in non-GT1 infection, it is possible that in the future, HCV may be the first chronic viral infection to be eradicated worldwide with one or more antiviral drug

    FDA warns consumers not to use muscle growth product
    Product marketed as a dietary supplement contains potentially harmful synthetic steroids
    The U.S. Food and Drug Administration is advising consumers to immediately stop using a product called Mass Destruction, marketed as a dietary supplement for muscle growth. The product is labeled to contain at least one synthetic anabolic steroid and has been linked to at least one reported serious illness.

    The FDA was alerted by the North Carolina Department of Health and Human Services of a serious injury associated with use of Mass Destruction. The report described a previously healthy 28-year-old male with liver failure requiring transplant after several weeks of product use. Liver injury is generally known to be a possible outcome of using products that contain anabolic steroids and steroid-like substances. The product’s ingredients are undergoing further analysis by the FDA.

    2014/HCV Multimedia: Videos and Podcast
    Three new videos from Lucinda Porter, RN., author and hepatitis C advocate.
    For people starting treatment Ms. Porter offers valuable tips on everything from the first time you inject (interferon), to keeping well hydrated during HCV therapy.

    Website and blog of Lucinda Porter, RN

    2014 - HCV F1/F2 Treat Now Or Wait?
    Topics Include:
    Genotypes 1-6
    Mixing and Matching Antiviral Agents

    Investment Commentary
    The Most Important New Drug Of 2013
    Gilead Sciences’ Sovaldi, for hepatitis C, was the most important new medicine approved this year. It heralds the hope that a viral disease that afflicts more than 3 million Americans, can be treated with a few pills– or even one – and that doctors and scientists may be able to dramatically reduce the toll of the infection, which can cause liver failure and death.

    Coffee, chocolate linked to improved liver health in HIV/HCV patients
    Patients coinfected with HIV and hepatitis C may experience a reduction in abnormal liver enzymes and an overall improvement in liver function with increased consumption of coffee and chocolate, a study determined.

    Cinnamon might help in nonalcoholic fatty liver disease

    By David Douglas
    NEW YORK (Reuters Health) - Cinnamon may help remedy lipid profiles and have therapeutic benefits in patients with nonalcoholic fatty liver disease (NAFLD), according to a new Iranian trial.

    2014-Hepatitis C Full Text Articles
    Comprehensive review of full text articles covering important aspects of hepatitis C and hepatitis B management.

    Hepatitis C Treatment Side-Effects: Interferon-Free and Triple Therapy
    Links with a quick summary highlighting common adverse events seen in triple therapy and interferon-free regimens.

    See you all soon!

    Sunday, December 22, 2013

    Hepatitis C: 2013 A Year In Review

      Welcome To Hepatitis C: 2013 A Year In Review 

    The Big Story Of 2013?

    The biggest story thus far is the FDA approval of Olysio (simeprevir) and Solvadi (sofosbuvir), two new oral drugs to treat hepatitis C, or is it?

    In 2013 we found ourselves with a prolific HCV pipeline of direct-acting anti-viral agents which have improved: 1. Efficacy - overall 90% cure rates, 2. Tolerability - less side effects and 3. Convenience - shorter treatment duration, less pill burden. Wow. 

    In this short 2013 review we count down twelve months of news, research and breakthroughs that made a significant difference in the lives of people living with hepatitis C.


    BMS-986094 Lawsuit

    We heard more on the lawsuit involving 15 patients who were tragically hurt - one died- during the company-sponsored clinical trials of the hepatitis C drug BMS-986094. The Wall Street Journal reported that Bristol-Myers Squibb agreed to pay $80 million to 15 patients who either died or were hospitalized while participating in the study.

    The Canadian Liver Foundation (CLF) recommended hepatitis C screening among all persons born between 1945 and 1965

    The Canadian Liver Foundation (CLF) urged general practitioners (GPs) to immediately begin recommending a one-time blood test for all adults born between 1945 and 1975.

    2013-Guide to Clinical Trials for People with Hepatitis C

    The Treatment Action Group (TAG) published an insightful second edition guide to hepatitis C clinical trials, written by Tracy Swan and Matt Sharp.

    Pegylated interferon- Pegasys, PegIntron similarly effective for chronic HCV genotype 1

    *Pegylated interferon alfa-2a (Pegasys) and alfa-2b (PegIntron)
    A paper published in BMC suggested standard doses of pegylated interferon alfa-2a and alfa-2b, administered with ribavirin, were similarly effective in patients with chronic hepatitis C genotype 1.

    Updated Practice Guideline: Treatment of Genotype 1 Chronic HCV Virus Infection

     In 2011 the American Association for the Study of Liver Diseases released "An Update on Treatment of Genotype 1 Chronic Hepatitis C Virus Infection" in January a new section was added to the guidelines entitled "Use and Interpretation of HCV RNA Results During Triple Therapy."


    Sexual transmission of HCV rare among long-term, monogamous couples

    (The HCV partners study)

    Patients with chronic hepatitis C in long-term, monogamous relationships are at a very low risk for transferring the virus to their partner via sexual contact.

    The study, published in Hepatology is available at NATAP, this past April Drs. Stephen A. Harrison and Norah A. Terrault discussed the article: Sexual transmission of hepatitis C virus among monogamous heterosexual couples: The HCV partners study, below in this podcast.

    Idenix drops development of 2 hepatitis C drugs

    The company has elected not to continue its clinical development program for IDX184, a nucleotide polymerase inhibitor in phase IIb testing for the treatment of hepatitis C virus (HCV) infection, or to continue its development of IDX19368, an HCV nucleotide polymerase inhibitor

    The two Idenix drugs, IDX184 and IDX19368, as well as another drug from Bristol-Myers Squibb Co. called BMS-986094, work in similar ways. All three products are nucleotide inhibitors, meaning they are designed to prevent the hepatitis C virus from making copies of itself.

    In August *2012 Bristol-Myers halted testing of BMS-986094 after one patient in the clinical trial died of heart failure following treatment. The drugmaker eventually abandoned development of the product.

     Idenix has said there are important differences between the drugs, but the Food and Drug Administration placed IDX184 on clinical hold Aug. 16. At the time, it was Idenix's most advanced experimental drug. The FDA also had placed a hold on IDX19368, which hadn't begun patient dosing.


    Mortality risk greater among patients with HCV who moderately drank alcohol

    For people with the chronic liver infection hepatitis C, heavy drinking is an obvious no-no, but a new study links even modest alcohol consumption with an increased risk of death - and not just from liver disease.

    "What this study shows is... truly, even what might be considered a moderate and safe amount of alcohol use in people without hepatitis C is dangerous to your health if you have hepatitis C," said Rae Jean Proeschold-Bell, a hepatitis C researcher at Duke University in Durham, North Carolina, who was not involved in the study.

    Of Interest
    6 Booze-Free Ways to Toast the Holidays with Hepatitis C
    If you have hepatitis C, your doctor probably told you, “No alcohol.” If you like to drink, this is hard news to bear, particularly around the holidays. Alcohol seems to be everywhere this time of year, even in grandma’s fruitcake. It may be alluring to the mouth, but it is like adding fertilizer to hepatitis C.........

    April 2013

    FDA Approves FibroScan for Noninvasive Liver Diagnosis

    A painless alternative to liver biopsy for evaluating the stage of liver fibrosis.

    video platformvideo managementvideo solutionsvideo player

    The new machine called a fibroscan is a timely and welcome alternative to a needle biopsy as diseases of the liver increase.

    EASL 2013

    The International Liver Congress 2013 of the European Association for the Study of the Liver (EASL), took place April 24 to 28 in Amsterdam, The Netherlands.

    EASL 2013 - Internet Symposium: Watch Advances in Chronic Hepatitis C Management and Treatment - Interferon  Free, All Oral Regimens Are Highlighted

    Watch - Best of the EASL 2013 on hepatitis C - webcast with Dr Andrew Muir


    Hepatologist Urges caution among clinicians in the administration of telaprevir

    Dr. Maheshwari urges caution among clinicians in the administration of telaprevir, and stresses the need for rigorous side-effect management protocol and adequate long-term follow-up for patients with HCV receiving this treatment.

    In December 2012 telaprevir included a “black box” warning that fatal and non-fatal serious skin reactions have been reported in patients taking INCIVEK

    DDW 2013 - May 18-21, 2013 - Orlando, FL

    Digestive Disease Week - The conference will showcase the latest advances in GI research, medicine and technology in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery
    View Media and DDW Updates

    DDW 2013 - Coverage @ GI & Hepatology News
    Aug 12 2013 - DDW 2013 The AGA Report
    Download PDF | Digital Edition


    US Preventive Services Task Force recommended hepatitis C screening among all persons born between 1945 and 1965

    In June 2013, the US Preventive Services Task Force updated recommendations to include hepatitis C screening among all persons born between 1945 and 1965.

    The USPSTF had initially recommended a "C" rating for this birth cohort (1945 and 1965) in a draft proposal, conflicting with the CDC recommendation and creating confusion in the primary care community. The change from a "C" to a "B" rating gives primary care clinicians the absolute clarity of the hepatology community -- early detection of HCV allows for the drastically greater possibility of treatment success for patients. The new "B" rating allowed for testing without a copayment by  both Medicare and private insurers.

    The recommendation statement was published online June 24 in the Annals of Internal Medicine.

    A Science First: Japanese researchers grow human liver using stem cells

    It could herald a giant leap forward for the field of human regenerative medicine.Japanese researchers say they have grown a tiny human liver, only five millimetres long,from reprogrammed human skin cells.


    JAMA - Deaths from liver disease increased from 1990 to 2010

    The most common causes of both cirrhosis and liver cancer are viral hepatitis, alcoholism, and obesity-related fatty liver disease. However, it is hepatitis C that is the most likely cause of the emergence of liver disease as a growing threat to American lives.

     According to a July 10, 2013 article published in the Journal of The American Medical Association – “The State of US Health, 1990-2010: Burden of Diseases, Injuries, and Risk Factors”  deaths from liver disease increased from 1990 to 2010. Liver disease also rose as a contributor to premature mortality.

    Cirrhosis -- damaged liver tissue and the loss of liver function due to a variety of liver diseases -- has risen substantially from the 14(th) most frequent cause of death in 1990 to the 8(th) most frequent cause of death in 2010. In the same time period, liver cancer went from the 39(th) to the 30(th) most frequent cause of death in the US. The prognosis of liver cancer is particularly poor with the medical community's limited ability to treat patients with liver cancer, with death most often occurring within six months.


    Documentary - Breaking the Silence: Voices of Chronic Hepatitis C

    As once a hepatitis C patient myself, I was deeply touched while viewing this awe inspiring documentary from Janssen Therapeutics. For 17 minutes the viewer with hepatitis C is not alone, for 17 minutes normal people just like you and me share their story, diagnosis and family struggles. Support of family and friends is critical, but no matter how much our loved ones may empathize with us - connecting with other people living with the virus is invaluable.

    **View the video or read the transcript here.

    Diet And Liver Health

    There isn't really a diet for people with hepatitis C, but research has shown people with HCV that are obese have a higher risk for developing fibrosis, scarring, and cirrhosis of the liver.

    In the August issue of "Nutrition Journal" researchers suggest exercise, low-fat or low-calorie diets can improve fibrosis, steatosis and insulin resistance in people living with chronic hepatitis C.

    For the hands on reader, in this September video Dr. Galati answers the common question about diet and liver health.

    Additionally, a podcast on the effects of acetaminophen and alcohol on the liver is hosted by Dr. Galati, check out Part One and Part Two 


    Surgeons at New York-Presbyterian/Columbia University Medical Center Report Successful Laparoscopic Living Donor Liver Retrieval for Adult Recipients

    A team of surgeons at New York-Presbyterian/Columbia University Medical Center is the first in the country to report a fully laparoscopic hepatectomy — the removal of a portion of the liver — from a living adult donor for adult and teenage recipients. The procedure advances transplant surgery and offers hope for addressing the significant shortage of liver donors.


    Hepatitis C Treatment One Step at a Time

    Ms. Lucinda K. Porter the author of "Free from Hepatitis C" has graced the HCV community with a second book "Hepatitis C Treatment One Step at a Time".

    The timing of the book couldn't be more perfect. With screening strategies in place by the CDC and Task Force which recommend all people born from 1945 through 1965 get tested one time for hepatitis C, and new drugs moving through the final stages of FDA approval - the need for a guide during HCV therapy is paramount.

    This comprehensive book provides tips for people starting hepatitis C treatment while slowly dissipating the fear of the unknown.


    OLYSIO™ Simeprevir FDA Approved 

    OLYSIO™ (simeprevir) Receives FDA Approval for Combination Treatment of Chronic Hepatitis C
    Johnson & Johnson's protease inhibitor OLYSIO (Simeprevir) is approved for the treatment of HCV genotype 1, in combination with peginterferon alfa and ribavirin in adults with compensated liver disease, including cirrhosis, who are treatment-naïve or who have failed previous interferon therapy (pegylated or non‑pegylated) with ribavirin.

    OLYSIO™ (simeprevir) not effective in patients with HCV Q80K variant

    OLYSIO improved tolerability, has a lower pill burden and appears to be slightly more effective than the standard of care, curing 80 percent of treatment-naïve patients, but there are some drawbacks. Before starting treatment patients with HCV genotype 1a need to be screened for Q80K polymorphism, alternative therapy should be considered for people with the mutation, according to simeprevir prescribing information

    Healio; Screening available for HCV Q80K polymorphism

    Hepatitis C: Boehringer Ingelheim's faldaprevir granted accelerated assessment from European Medicines Agency

    “Faldaprevir* has been studied with pegylated interferon and ribavirin in a broad range of more than 3,300 patients typical of those that doctors see in every day clinical practice. Faldaprevir* has demonstrated strong efficacy and a robust safety profile while also offering the convenience of once-daily dosing and no food restrictions,” said Professor Klaus Dugi, Corporate Senior Vice President Medicine at Boehringer Ingelheim. “The acceptance for accelerated assessment by the EMA supports our position that if approved, faldaprevir* will provide an important alternative to currently available hepatitis C treatments.”

    For full results see the STARTVerso™ press release here.

    The 64th Annual Meeting of the American Association for the Study of Liver Diseases

    The meeting took place in Washington, DC; November 1-5, 2013, highlights include new data on FDA approved and experimental therapies for hepatitis C.

    AASLD Coverage - Clinical Care Options CCO

    AASLD In Review

    In HCV Advocate's December newsletter, information on key breakthough therapies presented at this years AASLD is offered in an easy to digest summary. 

    AASLD 2013 Internet Symposium

     AASLD 2013 Internet Symposium -ViralEd
    The 1.5 hour symposium discussing key studies on current and HCV future drugs, featuring 4 well-known and recognized thought leaders in the HCV field; Fred Poordad, MD ( looking hot in his bow tie), K. Rajender Reddy, MD., Mark Sulkowski, MD., and Nezam H. Afdhal, MD.

    Just Released

    Best of HCV From AASLD 2013 @ Medscape 
    Andrew Muir, MD; Michael P. Manns, MD
    CME Released: 12/23/2013
    Faculty will be discussing information about pharmaceutical agents that is outside of U.S. Food and Drug Administration approved labeling. The following off-label uses are discussed: simeprevir, sofosbuvir, daclatasvir, asunaprevir, ABT-450, ABT-267, MK-5172, MK-8742, faldaprevir, deleobuvir, PPI-668, and ledipasvir

    Published December 27
    Top 10 Highlights From The Liver Meeting - A Future Without Hepatitis C
    A Future Without Hepatitis C
    The successful development of targeted therapies for patients with chronic hepatitis C virus (HCV) was clearly evident. Several companies are jockeying to be the first to offer an all-oral, interferon (IFN)-free strategy. On the near horizon is the promise that a cocktail of agents, constructed on the basis of synergistic mechanisms of action, will be available for clinicians to wisely, effectively, and safely treat patients with HCV infection. A major advance, in my opinion, is the validation of regimens that are devoid of IFN and, in some cases, ribavirin.
    Continue reading @ Medscape

    Daclatasvir plus Asunaprevir HCV Regimen: No Interferon, No Ribavirin, No Problem

    Patients who failed to respond to standard treatment for hepatitis C virus (HCV) infection achieved greater than 80% sustained virologic response at 24 weeks with an all-oral regimen that eschewed both interferon and ribavirin, researchers reported here.

    Among 135 patients who were either ineligible for interferon therapy or who were intolerant of the treatment, 87.4% achieved a sustained virologic response -- basically a treatment cure, reported Kazuaki Chayama, MD, PhD, professor of medicine and director of Hiroshima University Hospital.

    In his plenary session report at the annual meeting of the American Association for the Study of Liver Diseases, Chayama also reported that 80.5% of 87 previous non-responders or partial responders achieved a sustained virologic response at 24 weeks.

    The two investigative agents attack the virus in different ways. Daclatasvir is a potent NS5A replication complex inhibitor with pan-genotypic antiviral activity. Asunaprevir is a potent NS3 protease inhibitor with antiviral activity against genotypes 1, 4, 5, and 6. Chayama said the phase III study he described follows successful phase II studies showing a strong impact on patients with genotype 1b.

    The median age of the 222 participants in the trial was 62.5, about 35% were men, and about 10% were diagnosed with cirrhosis. Baseline factors, including male gender, advanced age, high baseline hepatitis C virus RNA, and cirrhosis, did not appear to have an impact on response rates, Chayama said.

    The Japanese population mainly had genotype 1b infections, he said. Yet the success rate in achieving sustained virologic response was greater than 80%. "When I first started treating hepatitis C virus infection in the 1990s we were getting sustained virologic response rate in the 7% area, and to be getting response in the 80% to 90% levels we are seeing today is phenomenal."

    He acknowledged that historically genotype 1 hepatitis C infection has been considered a more difficult disease to treat than genotypes 2 or 3, but in studies presented at The Liver Meeting 2013, "What has emerged is that genotype 3 is the new genotype 1. With these new drugs I think there has been a surprise that we get suboptimal results with genotype 3."

    Read the article @ MedPage Today

    Finally we make it to December


    Gilead's Sovaldi (Sofosbuvir) Is FDA Approved

    On December 6, 2013, Sovaldi, a polymerase inhibitor was approved to treat HCV genotypes 1 and 4 treatment-naïve adults in combination with PEG-IFN and ribavirin and the first approved interferon-free treatment regimen for people with HCV genotypes 2 and 3. Overall cure rates are at 80%, response rates and treatment duration varies, depending on genotype, viral and host factors.

    Gilead states that Sovaldi in combination with ribavirin alone for 24 weeks can be considered for patients with genotype 1 infection who are interferon ineligible. Additionally, Sovaldi should be used in combination with ribavirin for treatment of HCV patients with hepatocellular carcinoma awaiting liver transplantation for up to 48 weeks or until liver transplantation to prevent post-transplant hepatitis C infection.

    See PDF - For Full Prescribing Information.

    The Cost?

    High price for Hep C drug sparks controversy

    Lynda Dee, co-chair of Fair Pricing Coalition, called Sovaldi a “very safe and highly effective drug” but noted that it must be used in combination with other drugs to treat different Genotypes, or strains, of Hepatitis C.

    She said that although the other drugs – pegylated interferon and ribavirin – are not as expensive as Sovaldi, the price tag for combination therapy with Sovaldi comes to $93,000 and $168,000 for various treatment regimens for a single person living with Hepatitis C.

    “Gilead has set the bar dangerously high as other companies determine prices for similar Hepatitis C drugs as they enter the market,” Dee said.

    In a statement released at the time the U.S. Food and Drug Administration approved Sovaldi for patient use on Dec. 6, Gilead said it had put in place a patient assistance program to ensure that people with Hepatitis C have access to Sovaldi regardless of their ability to pay for it.

    Continue reading.....

    Sovaldi Website
    PDF - FAQ about Sovaldi
    Patient Information
    Support And Patient Assistance Program
    PDF - Full Prescribing Information

    Best treatment options for HCV genotype 1: All of them contain sofosbuvir, all are expensive

    Paul E. Sax, MD, Editor-in-Chief - HIV and ID Observations, wrote an article suggesting the best possible treatment opinion as of December 8, 2013, for genotype 1 patients, listing the PROS and CONS  (cost estimates approximate):

    1. Simeprevir + sofosbuvir for 12 weeks.PROS: More than 90% cure rate in the COSMOS study.

    Two pills once daily (it’s amazing even to write that.)

    CONS: The COSMOS study was very small. Simeprevir can lead to photosensitivity and has many drug-drug interactions. The Q80K polymorphism may reduce response to simeprevir.

    This regimen is not “FDA approved.” Cost = $145,000.

    2. Sofosbuvir + ribavirin for 24 weeks.

    PROS: Cured 76% of HIV/HCV co-infected patients in the PHOTON-1 study. May well do better in HCV mono-infected. Regimen is “FDA approved” for interferon-ineligible patients, which could help get insurance coverage.

    CONS. Ribavirin, and all its side effects. 24 weeks seems long compared to 12 weeks. Response rate is lower than other options listed here, which would require re-treatment.

    Cost (not including ribavirin) = $160,000.

    3. Sofosbuvir + interferon + ribavirin for 12 weeks:

    PROS: 90% cure rate in the NEUTRINO study. Only 12 weeks of interferon and ribavirin.

    Cost = $90,000. CONS: Interferon. Ribavirin. Enough said.

    All are a lot better than what we had just last week. All of them contain sofosbuvir. And all are expensive.

    The Next Big Thing Is Sofosbuvir and Ledipasvir

    Sofosbuvir and Ledipasvir Amazing Late-stage Hepatitis C Data 

    The excitement builds with the one pill two trick pony. Can I say that? Well I did.

    The buzzword is "nukes", the drug is Sovaldi, a nucleotide analog polymerase inhibitor that works by blocking an enzyme the hepatitis C virus needs to copy itself, the drug is potent and has antiviral activity against HCV genotypes 1-6. Ledipasvir, an NS5A inhibitor, has potency against genotypes 1a and 1b.

    SVR12 Rates From Three Phase 3 Studies Evaluating a Once-Daily Fixed-Dose Combination of Sofosbuvir and Ledipasvir for Genotype 1 Hepatitis C Patients

    Gilead tested its promising combination pill - consisting of both agents, Sovaldi and Ledipasvir in various treatment durations, with and without ribavirin. Physicians and patients were excited to see high cure rates without ribavirin. A drug that has side effects including rash, cough and anemia.  Here are those SVR rates;

    In ION-1, which looked at 865 treatment-naïve patients, including 136 participants in the study with cirrhosis, after 12 weeks of therapy 97.7 percent  reached SVR- or 97.7 percent of patients were cured.

    In ION 2 - the study included 440 treatment-experience or difficult to treat patients, these participants failed therapy in the past. Included in the trial were 88 people with cirrhosis - SVR rates were at 93.6 percent after 12 weeks of therapy - while the cure rate rose to 99.1 percent with 24 weeks of treatment.

    Finally, in ION-3 - 647 treatment-naïve patients without cirrhosis were treated for 8 weeks, 94 percent achieved SVR. In patients who treated longer, for 12 weeks, SVR was a bit higher at 95.4 percent.

    AbbVie Demonstrates 96 percent SVR(12) in its Phase III Study of Treatment-Experienced Patients with Genotype 1 Hepatitis C

    Next up we have AbbVie, results of  phase III trials were recently released for a three drug regimen plus ribavirin which consists of boosted protease inhibitor ABT-450/ritonavir, NS5A inhibitor ABT-267, and non-nucleoside polymerase inhibitor ABT-333.

    In the 394-patient SAPPHIRE-II study 96 percent of genotype 1 patients with no evidence of liver cirrhosis who previously failed standard treatment, including approximately 49 percent prior null responders, achieved sustained virologic response (SVR12) with the 12-week regimen.

    An important factor here is that the majority of patients were genotype 1a, which is considered a difficult-to-treat subtype. The SVR12 rate for genotype 1a and genotype 1b were at 96 percent and 97 percent, respectively. 

    Virologic relapse or breakthrough was seen in 2 percent of patients receiving the regimen. In addition, the discontinuation rate due to adverse events was 1 percent.

    In TURQUOISE-II naïve and experienced patients with compensated cirrhosis are included, those results are expected in January 2014.

    Faldaprevir effective even in patients with HCV Q80K variant

    Hepatitis C: Phase III data show Boehringer Ingelheim’s faldaprevir* is effective even in patients with common drug-resistant viral variant

    Summary: Naturally occurring mutations in the hepatitis C virus (HCV) are common and many lead to reduced efficacy of antiviral treatments. Faldaprevir* has now been shown to be effective even in patients with the common HCV Q80K variant,1 which affects an estimated 700,0002,3,4 patients in the USA alone. Faldaprevir* is being studied in combinations both with and without interferon. The EMA recently granted accelerated assessment for faldaprevir* as part of an interferon-based regimen and a decision on marketing authorisation is anticipated next year.5,6
    Read press release here....

    'Serial Infector' Gets 39 Years

    The FBI released a story this month describing the criminal investigation into the HCV outbreak at Exeter Hospital.
    David M. Kwiatkowski, a former healthcare worker at Exeter Hospital stole syringes intended for hospital patients containing the narcotic Fentanyl. After injecting himself with the narcotic, he replaced the syringes of Fentanyl with saline to use on future patients, 45 people became infected because of the drug diversion tactic. Kwiatkowski pleaded guilty to diverting and obtaining the controlled substance fentanyl as well as to product tampering.  He was sentenced earlier this month to 39 years in prison.

    Its Not The First Time Fentanyl Was Diverted By Healthcare Workers

    Similar to the Exeter Hospital outbreak, from 2008-2010 three case scenarios of drug diversion took place at the following medical facilities: Rose Medical Center in Denver, Mayo Clinic in Florida and Riverside Regional in Virginia, a complete summary is available here on this blog.

    At the three facilities employees admitted to stealing syringes filled with Fentanyl, injecting themselves with the drug and replacing the syringes with saline to be used on future unsuspecting patients. The employees, like Kwiatkowski, also traveled around taking jobs at various clinics and hospitals.

    EASL - Revised clinical practice guidelines for management of hepatitis C 

    Management of Hepatitis C: Revised Version December 2013
    3.28 mb | Revised Edition
    Based on a systematic review of existing literature, the CPGs provide best practice recommendations on a number of key areas:

    Current standard of care and developing therapies;
    Diagnosis of acute and chronic hepatitis C;
    Goals and endpoints of HCV therapy;
    Indications for treatment and who should be treated;
    Treatment strategies for different viral genotypes;
    Treatment monitoring including virological response-guided triple, and dual therapy;
    Monitoring treatment safety; and
    Treatment of special groups including HIV co-infection, hepatitis B co-infection and patients with other co-morbidities such as severe liver disease

    Learn More?

    An interactive course on hepatitis C was launched online this year which offers newly diagnosed patients an opportunity to learn more about the management of HCV, to take part in the learning activity, begin here.

    *The project is brought to you from the University of Washington and includes a collaboration with the International Antiviral Society-USA (IAS-USA). Funded by a grant from the Centers for Disease Control and Prevention

    Well, that's all folks

    Wishing You All A Very Merry Christmas And A Safe New Year !

    New drug approved by FDA offers hope for hepatitis C patients

    New drug approved by FDA offers hope for hepatitis C patients 

    The Dallas Morning News
    Special Contributor
    Published: 21 December 2013

    Patrizia Cazzaniga of East Dallas enrolled in a hepatitis C drug trial in May. “Everybody says I look much better than I did,” she said. “I feel free and very happy.”
    Patrizia Cazzaniga suffered stomachaches, tiredness and nausea for months before going to her doctor. The 57-year-old East Dallas resident was shocked to find out that she had hepatitis C, a virus she had probably been infected with 30 years earlier through a blood transfusion she received during childbirth.
    But a new pill, approved by the U.S. Food and Drug Administration this month, actually cures hepatitis C. Sofosbuvir cured 89 percent of hepatitis C patients in only 12 weeks in clinical trials. Patients suffered fewer side effects than with older treatments and didn’t have to endure weekly injections. But at $84,000 for a 12-week course, or $1,000 a pill, the cure doesn’t come cheap.   
    “It’s a game changer,” said Dr. William L. Lee, a liver disease specialist at UT Southwestern Medical Center. Lee has treated hundreds of patients using the older medications, interferon and ribavirin, and has had varied success.
    Cost is a big barrier,” Lee said. The new treatments cost about four times more than the current drugs. Patient assistance programs offered by the pharmaceutical companies provide help to some who need assistance with the cost of medications. 
    But Lee worries that many patients will rely on Medicaid and that the state’s Medicaid program won’t fund the treatment.

    Continue reading...

    Photo Credit - Nathan Hunsinger/Staff Photographer
    Sovaldi Website
    PDF - FAQ about Sovaldi
    Patient Information
    Support And Patient Assistance
    PDF - Full Prescribing Information

    Friday, December 20, 2013

    HCV Therapy: Who to Treat Now, When to Wait, and What to Wait For

    Nothing gets me more excited than listening to Ira M. Jacobson, M.D., discuss HCV, you too?

    In this awesome new "Interactive Virtual Presentation" made available today over at CCO, we, the audience, are prompted to answer the million dollar question - rather to treat HCV now or wait.

    The activity is an enabled response presentation, and based on various patient scenarios, but it gets even better, the good doctor offers his commentary after each slide, or case study.

    Let me tempt you all with a few slides from the online CME. The first slide is for genotype 1 patients with a quick patient history, second slide offers a few treatment choices, and finally reader and expert results.

    Patient Scenario
    Genotype 1, never treated HCV before, stage 2 fibrosis, willing and able to take interferon, for a reasonable amount of time.

    Pick One Any One
    How should this patient be managed? (A) Treat with boceprevir, or telaprevir + Peginterferon/Ribavirin P/R, (B) simeprevir or sofosbuvir + P/R (C) treat with IFN-free off -label therapy based on simeprevir and/or sofosbuvir  (D) or wait and treat with IFN-free options approved for this genotype.
    Which One Would You Pick?

    Reader Response Results
    The participants voted for (C) treat with IFN-free off -label therapy based on simeprevir and/or sofosbuvir.
    Don't miss the in-depth commentary offered by Dr. Jacobson.  

    Expert Results
    Three experts voted to wait and treat when IFN-free options are approved for HCV genotype 1. Two experts voted to treat with the new agents simeprevir or sofosbuvir plus peginterferon and ribavirin. 
    Dr. Jacobson noted in his commentary that SVR rates for sofosbuvir + P/R are high in genotype 1 patients, plus treatment duration is only 12 weeks.
    Other commentary included what we already know, patient preference is the deciding factor. The bottom line is left up to us folks. When considering therapy - do you treat now, or wait?  A difficult decision to be sure, one made only with your own physician, and with an acquired knowledge of new agents - which begin, here.

    Present Approaches to HCV Therapy: Who to Treat Now, When to Wait, and What to Wait For
    Compare your strategies for timing of treatment with HCV experts.
    Source: Treat Now or Later in HCV? Expert Guidance for Individual Scenarios
    Faculty: Ira M. Jacobson MD
    Released: 12/20/2013

    Present Approaches to HCV Therapy: Who to Treat Now, When to Wait, and What to Wait for
    Ira Jacobson, MD, reviews the key factors in deciding to treat or wait in HCV, then walks through several patient scenarios.
    Source: Treat Now or Later in HCV? Expert Guidance for Individual Scenarios
    Date Posted: 12/20/2013

    Protein links liver cancer with obesity, alcoholism, and hepatitis

     Protein links liver cancer with obesity, alcoholism, and hepatitis

    Obesity, alcoholism, and chronic hepatitis all increase the risk of getting liver cancer, which is the third leading cause of cancer death worldwide. Obesity in particular is driving a significant increase in liver cancer in the United States. These three health problems also increase cellular stress in the liver, but until now it has not been clear if there is a direct biological link between cellular stress and the development of liver cancer.

    In a new study, University of Iowa researchers have identified an unexpected molecular link between liver cancer, cellular stress, and these health problems that increase the risk of developing this cancer.

    The study, published Dec. 19 in the journal PLOS Genetics, shows that a protein called CHOP, which had previously been thought to generally protect against cancer, actually promotes liver cancer in mice and may do the same in humans.

    "Obesity, alcoholism, and viral hepatitis are all known independently to cause cellular stress and to induce expression of CHOP," says Thomas Rutkowski, Ph.D., assistant professor of anatomy and cell biology in the UI Carver College of Medicine and senior study author. "So this finding suggests a biological pathway that links those 'upstream' health problems to liver cancer at the end."

    CHOP is a transcription factor that is produced when cells experience certain kinds of stress. It is known to promote cell death, or apoptosis. Usually, factors that promote cell death protect against cancer by causing damaged cells to die.

    The study shows that, despite its role in cell death, CHOP actually is elevated in liver tumor cells in mice. Furthermore, mice without CHOP are partially protected from liver cancer, developing fewer and smaller tumors than the normal mice in response to liver cancer-causing drugs. The mice without CHOP also had less liver scarring and inflammation than mice with the protein.

    Tissue samples from human patients show that CHOP also is elevated in human liver tumors compared to surrounding non-tumor tissue from the same patients.

    "We turned out to be completely wrong about CHOP. We found that it contributes to the development of liver cancer in mice and is associated with liver cancer in humans," Rutkowski says. "CHOP is indeed killing cells, just as we thought it would, but we think the consequence of this killing is not the prevention of tumors, but instead the stimulation of inflammatory signals in the liver that cause excessive proliferation of other cells," he explains.

    Rutkowski notes that although this proposed mechanism is not proven yet, it is consistent with what is known about the role of CHOP.

    Collaboration was critical to the success of the study, Rutkowski adds. Postdoctoral researcher Diane McCabe in his lab performed most of the experiments, and McCabe and Rutkowski worked closely with cancer biology expert Adam Dupuy, Ph.D., UI associate professor of anatomy and cell biology, and his graduate student Jesse Riordan. Another collaboration with Michael Icardi, M.D., UI associate professor of pathology, gave Rutkowski access to liver tissue samples from patients that allowed the team to show the association between elevated CHOP and human liver cancer.

    Having implicated CHOP as a contributing factor in liver cancers associated with obesity, alcoholism, and hepatitis, Rutkowski next wants to learn whether CHOP acts early in the process of tumor formation or if it plays a role in helping established tumors to grow. He also is interested in identifying the other proteins that partner with CHOP to promote liver cancer.

    "This discovery opens up an avenue into a new pathway that promotes liver cancer," he says. "Once we know what those other genes are that interact with CHOP, then maybe we can find a 'druggable' target molecule. The hope is that down the line scientists will be able to convert that finding into something therapeutically useful for patients.

    "Federal funding is the backbone of this kind of research, which has the potential to make unexpected discoveries that, in this case, could help improve cancer treatment," he adds.

    The work was funded by grants from the National Institute of Diabetes, Digestive, and Kidney Disorders of the National Institutes of Health.

    Source: University of Iowa

    Thursday, December 19, 2013

    Hepatitis C Update: What's Happened In 2013 and Taking Medications as Directed

    December Newsletter Update

    Christmas is just around the corner, have you finished your shopping yet?

    While shopping feverishly for a fairy doll that flies, have you heard of it? Anyhoo, I ran into Santa, he asked me to update this months index of HCV newsletters - of course I said yes!

    The American Liver Foundation just published their December Newsletter with a focus on hepatitis C. One featured topic is the importance of taking prescription medications as directed, also included is information on both newly approved HCV drugs, Sovaldi and Olysio.

    Over at  Hepatitis C News, a video looking back at what's happened in 2013 is now available for your viewing pleasure.

    At my house, a new fairy doll is wrapped and under the tree for the little people in my life.

    Merry Christmas!

    *All December newsletters, information on future and current direct-acting antivirals including a quick summary of Gilead's clinical trial data can found here.


    American Liver Foundation

    Living With Hepatitis C: Importance of Taking Medications as Directed
    Prescription drugs can provide important benefits to individuals living with hepatitis C, but taking these medications as prescribed can be difficult. Some individuals struggle with drug side effects and costs while others may forget to take medication on time or order refills. Fortunately there are steps that can help address these challenges and better manage this condition through medication.


    American Liver Foundation Hails Promise of Cure Signaled by Approval of New Hepatitis C Treatments
    The FDA has approved two new treatments for hepatitis C: Sovaldi, to be used in combination with other anti‐virals; and Olysio, the first once-daily protease inhibitor. Welcoming the approval of these breakthrough drugs, American Liver Foundation National Board Chair Tom Nealon said: "This is the beginning of a new, gentler, era in the treatment of hepatitis.”


    The Year in Pictures
    Here’s a sampling of pictures to illustrate how we promoted the need for liver disease awareness during 2013. One of the highlights: A photo showing members of our Run for Research Team symbolically completing the Boston Marathon nearly three weeks after the event was the site of a shocking bombing. Their message: “We are Boston Strong!”

    For the festive season, when you get a moment to relax, find out how much you know about the liver. This multiple choice quiz poses intriguing questions such as: Where did the first successful liver transplant take place? And why would we ask a question where the answer could be Michael Jackson, Ray Charles, John Lennon or Frank Sinatra?

    Looking to cook up something healthy and out of the ordinary for the holidays? The American Liver Foundation has the answer! Two celebrated chefs, who are involved with our annual Flavors events, suggest these mouthwatering recipes: Chestnut Stuffing (Chef Beau MacMillan) and Soup of Red Bell Pepper (Chef Christopher Gross). Happy cooking…and eating!

    Hepatitis C News
    Visit HepatitisCNews.com, an online community for those living with hepatitis C
    The December edition of Hepatitis C News, where we take at look at what's happened in 2013

    See You Soon

    Wednesday, December 18, 2013

    Gilead's Sofosbuvir and Ledipasvir Outstanding Late-stage Hepatitis C Data

    Of interest
    Feb 10 2014
    Gilead Files for U.S. Approval:Ledipasvir/Sofosbuvir Fixed-Dose Combo For Genotype 1 Hepatitis C

    Dec 19
    Gilead's $1,000 Pill Could Eradicate Hepatitis C, But Ethical And Financial Challenges Loom

    Matthew Herper
    Forbes Staff
    Gilead Sciences' GILD -0.37% two-drug combo pill against hepatitis C is so effective, Wall Street analysts say, that it’s possible that public health officials could begin thinking about eradicating the liver-damaging virus, which may afflict 3.2 million Americans and is spread mostly through sharing needles and needle stick injuries, according to the Centers for Disease Control & Prevention. In some of them, like the musician Lou Reed, it leads to liver failure and death. Gilead’s pill could become one of the best-selling medicines in history.....

    Stellar hepatitis C data puts Gilead farther ahead of pack

    By Ransdell Pierson and Bill Berkrot

    Wed Dec 18, 2013 1:34pm EST

    (Reuters) - Gilead Sciences Inc released impressive late-stage data for its once-daily combination pill to treat hepatitis C, advancing its lead in the race to develop new, all-oral treatments for the liver disease, and pushed up its timeline for seeking U.S. approval.

    Gilead on Wednesday unveiled initial results from three Phase III studies that demonstrated cure rates well in excess of 90 percent with as little as 8 weeks of treatment for some patients.

    The findings were achieved without the use of either injectable interferon, which causes miserable flu-like symptoms, or ribavirin, an antiviral pill that carries its own troublesome side effects.

    The tough-to-tolerate older drugs have led thousands of patients to delay treatment for the potentially fatal disease and await new options.

    "The results certainly raise the bar and dim the outlook for competitors such as AbbVie, Bristol and Boehringer Ingelheim," Sanford Bernstein analyst Geoffrey Porges has said of rival all-oral programs in development that require more drugs and more pills than Gilead's to achieve similarly high cure rates.

    Porges, saying the new data could spell the end of ribavirin use and greatly expand the number of people seeking treatment, raised his peak sales forecast for Gilead's combination to an eye-popping $16 billion in 2016, declining to $6.8 billion by 2020 as the backlog of patients awaiting treatment declines.

    Gilead said it would file in the first quarter of 2014 for U.S. approval of the combination treatment that pairs its just-approved Sovaldi (sofosbuvir) and its experimental ledipasvir. The company previously said it would seek marketing approval in the first half of next year.

    The Phase III trials tested the combination pill in subjects with the most common, but hardest to treat, genotype 1 strain of the liver virus in both previously untreated patients and those who had failed to be helped by prior treatment. They also included difficult to treat patients with cirrhosis, who tend to be farther along in the liver-destroying disease.

    Gilead shares rose more than 2 percent on the favorable new data and the likelihood of a speedier approval from the U.S. Food and Drug Administration.

    "We see (trial) results and a more-convenient regimen bolstering Gilead's market prospects over rivals, and expect FDA approval for this regimen before the end of 2014," S&P Capital IQ said in a research report.


    Sovaldi, which costs about $84,000 for a course of treatment, belongs to a class of drugs known as nucleotide analog polymerase inhibitors, or "nukes," designed to block an enzyme the hepatitis C virus needs to copy itself. Ledipasvir belongs to a promising new class of drugs that work by blocking the NS5A protein, which the virus also needs to replicate.

    Current standard regimens include both interferon and ribavirin and must be taken for 24 to 48 weeks, curing about 75 percent of patients.

    Gilead tested its combo pill at a variety of treatment durations both with and without ribavirin. But the high cure rates without ribavirin, which can cause rash, anemia and other side effects, are likely to grab most of the attention of physicians and investors.

    In a study of 647 previously untreated patients without cirrhosis called ION-3, 94 percent achieved sustained virologic response (SVR), which is considered cured, after just 8 weeks of treatment, rising to 95.4 percent with a 12-week regimen.

    In ION 2 - a trial of 440 more difficult to treat patients who were not cured by prior treatment, including 88 cirrhotics - 93.6 percent were cured by the once daily pill after 12 weeks, while the cure rate rose to 99.1 percent with 24 weeks of treatment.

    In ION-1, which looked at 865 previously untreated patients, including 136 with cirrhosis, the Gilead pill cured 97.7 percent with 12 weeks of therapy.

    "In general, the data position Gilead to dominate the genotype 1 landscape," ISI Group analyst Mark Schoenebaum said in a research note. He noted that Gilead's ribavirin-free regimen involved one pill once a day, while AbbVie's is six pills a day with ribavirin and four pills without, and includes a medicine that may interact with other drugs.

    Genotype 1 accounts for about 70 percent of U.S. infections. Hepatitis C affects an estimated 170 million people worldwide, and if left untreated can lead to cirrhosis, liver cancer, or the need for a new liver.

    Bernstein's Porges has said given the convenience and cure rates of the new drugs, the hepatitis C conversation is likely to change from disease management to eradication.

    "This is going to be very tempting for people to say, 'We can lick this'," Porges said. But he noted that demand for the drug will eventually decline as patients are cured.

    "The long-term economics of curing patients is not good for the drug industry, but it's totally great for society."

    (Additional reporting by Caroline Humer; Editing by Gerald E. McCormick, Theodore d'Afflisio and Cynthia Osterman)


    Press Release

    Gilead Announces SVR12 Rates From Three Phase 3 Studies Evaluating a Once-Daily Fixed-Dose Combination of Sofosbuvir and Ledipasvir for Genotype 1 Hepatitis C Patients

    -- High Cure Rates Observed with Single Tablet Regimen May Eliminate Interferon and Ribavirin from HCV Therapy for Genotype 1 Patients -- 

     -- U.S. NDA Submission Planned for Q1 2014--
    FOSTER CITY, Calif.--(BUSINESS WIRE)--Dec. 18, 2013-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced topline results from three Phase 3 clinical trials (ION-1, ION-2 and ION-3) evaluating the investigational once-daily fixed-dose combination of the nucleotide analog polymerase inhibitor sofosbuvir (SOF) 400 mg and the NS5A inhibitor ledipasvir (LDV) 90 mg, with and without ribavirin (RBV), for the treatment of genotype 1 chronic hepatitis C virus (HCV) infection.
    Across the three studies, 1,952 patients with genotype 1 HCV infection were randomized to receive SOF/LDV with or without RBV for eight, 12 or 24 weeks of therapy. Of these, 1,512 patients were treatment-naïve, 440 were treatment experienced and 224 had compensated cirrhosis.
    The intent-to-treat SVR12 rates observed to date in the ION studies are summarized in the table below. Results of the 24-week arms from ION-1 will be available in the first quarter of 2014 and will be presented at a future scientific meeting. 

    Of the 1,518 patients randomized to the 12-week arms of ION-1 and to all arms of ION-2 and ION-3, 1,456 patients (95.9 percent) achieved the primary efficacy endpoint of SVR12. Of the 62 patients (4.1 percent) who failed to achieve SVR12, 36 patients (2.4 percent) experienced virologic failure: 35 due to relapse and only one patient due to on-treatment breakthrough (with documented non-compliance). Twenty-six patients (1.7 percent) were lost to follow-up or withdrew consent.  

    Fewer adverse events were observed in the RBV-free, fixed-dose combination arms compared to the RBV-containing arms in all ION studies. Adverse events observed in those taking the SOF/LDV tablet were generally mild and included fatigue and headache. In the RBV-containing arms of the ION studies, the most common adverse events were fatigue, headache, nausea and insomnia. Anemia, which is a common side effect associated with RBV, was reported in 0.5 percent of patients in the SOF/LDV arms versus 9.2 percent of patients in the RBV-containing arms. Less than 1 percent of patients in the studies discontinued treatment due to treatment-emergent adverse events.

    “The results of the ION studies demonstrate that a simple, safe and short course of therapy with a single tablet regimen of sofosbuvir/ledipasvir can provide high cure rates among patients with genotype 1 HCV infection, while eliminating the need for both interferon and ribavirin,” said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer. “With the availability of these results, Gilead is finalizing its regulatory filing for sofosbuvir/ledipasvir, with the goal of submitting a New Drug Application in the first quarter of 2014.”    

    The FDA has assigned the SOF/LDV fixed-dose combination a Breakthrough Therapy designation, which is granted to investigational medicines that may offer major advances in treatment over existing options. Sofosbuvir was approved as Sovaldi™ in the United States on December 6 and in Canada on December 13. Applications are pending in the European Union, Australia and New Zealand, Switzerland and Turkey.    

    About the ION Studies

    The Phase 3 ION studies are randomized, open-label Phase 3 clinical trials evaluating the efficacy and safety of a once-daily fixed-dose combination of SOF/LDV for 8, 12 or 24 weeks, with and without RBV, among 1,952 genotype 1 HCV patients. The studies included patients who were treatment-naïve or who had failed previous treatment, including protease inhibitor-based regimens. The primary endpoint for each study was SVR12. Complete results from all three studies will be presented at a future scientific conference.    

    In ION-1, 865 treatment-naïve genotype 1 HCV patients, including those with cirrhosis, received SOF/LDV with or without RBV for 12 or 24 weeks. In March 2013, a planned review by the study’s Data and Safety Monitoring Board (DSMB) of interim safety and efficacy data from an initial enrollment of patients concluded that the trial should continue without modification. Enrollment of the remaining patients was completed in May 2013. Prior to the DSMB meeting, the statistical analysis plan was amended to allow for the analysis of the primary efficacy endpoint for the two 12-week arms, independent of the 24-week arms. Per the amendment, if SVR12 rates in the 12-week arms were >90 percent (including among those with cirrhosis), early regulatory filings could be pursued, given that longer treatment durations would not be able to show statistically significantly higher SVR12 rates.    

    The ION-2 study evaluated 440 treatment-experienced genotype 1 HCV patients who had failed past therapy with regimens containing Peg-IFN (including Peg-IFN plus a protease inhibitor). Patients received SOF/LDV with or without RBV for 12 or 24 weeks.

    In ION-3, 647 non-cirrhotic treatment-naïve genotype 1 HCV patients received SOF/LDV with or without RBV for 8 weeks or without RBV for 12 weeks.

    The SOF/LDV 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 risk that Gilead may be unable to file for U.S. regulatory approval of the SOF/LDV fixed-dose combination in the currently anticipated timelines. In addition, the FDA and other regulatory agencies may not approve the SOF/LDV fixed-dose combination, and any marketing approvals, if granted, may have significant limitations on its use. Additional clinical studies of sofosbuvir and the SOF/LDV fixed-dose combination, including results from the 24-week arms of ION-1, may not produce favorable results. As a result, Gilead may not be able to successfully commercialize the SOF/LDV fixed-dose combination, 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 Quarterly Report on Form 10-Q for the quarter ended September 30, 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.Sovaldi.com.

    Sovaldi is a trademark 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.

    - See more at:

    Tuesday, December 17, 2013

    High-Fat Diet Linked to Fewer Gallstones

    High-Fat Diet Linked to Fewer Gallstones

    Published: Dec 17, 2013 | Updated: Dec 17, 2013

    By Cole Petrochko, Staff Writer
    MedPage Today

    Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

    Patients undergoing rapid weight loss who either received ursodeoxycholic acid (Ursodiol) or ate a high-fat diet had a reduced risk of gallstones, researchers found.

    Action Points
    In a meta-analysis of randomized controlled trials of participants undergoing weight loss, ursodeoxycholic acid use was associated with a reduced risk of gallstones.

    Diets high in fat content also were associated with fewer gallstones, compared with those with low fat content

    Compared with control treatments, risk for gallstones was significantly reduced among patients who received daily supplements of ursodeoxycholic acid (RR 0.33, 95% CI 0.18-0.60), according to Frank Lammert, MD, of Saarland University Hospital in Homburg, Germany, and colleagues.

    There was also a significant reduction in gallstone formation in patients who consumed a high-fat diet versus a low-fat diet (RR 0.09, 95% CI 0.01-0.61), they wrote online in the journal Clinical Gastroenterology and Hepatology.

    A study printed in the journal Hepatology in July 2013 showed a causal relationship between high body mass index (BMI) and gallstones, particularly among women.

    Similar findings were reported in the Journal of Pediatric Gastroenterology and Nutrition in August 2012 among overweight or obese children and teens; those who were moderately obese had more than four-fold risks for gallbladder disease compared with normal-weight pediatric patients.

    The authors noted that these risks were also present in patients who underwent rapid weight loss or who underwent weight cycling.

    The authors reviewed randomized controlled trials of nonsurgical gallbladder stone preventive interventions in adult patients who underwent rapid weight loss through bariatric surgery or with diet alone, an analysis that included 13 studies and 1,837 obese participants combined.

    Outcomes included in the analysis were formation of ultrasonically-verified gallstones, mortality, and adverse events. Secondary outcomes included quality of life, cholecystectomy, bile lithogenicity, and weight loss.

    Control interventions included placebo treatment, no intervention, or pharmacological and nonpharmacological interventions.

    Low- versus high-fat diets were examined in two studies, which included groups receiving 3 g versus 12.2 g of fat, and 2 g versus 30 g of fat, each in daily quantities. Participants in the remaining 11 studies received 300 to 1,200 mg daily of ursodeoxycholic acid at a median 750 mg per day.

    Participants were treated from 6 weeks to 18 months and were followed up with for 6 weeks to 24 months.

    In the studies of ursodeoxycholic acid, 5% of those in a treatment arm developed gallstones versus 23% of those in the control arm. No deaths occurred in either arms of the studies. Treatment with ursodeoxycholic acid was associated with a reduced risk of cholecystectomy (RR 0.20, 95% CI 0.07-0.53).

    Weight loss was equal among groups in all of the ursodeoxycholic acid trials. Among those who received bariatric surgery as their weight-loss intervention, type of surgery did not affect ursodeoxycholic acid-related outcomes, nor did dosage of ursodeoxycholic acid. Quality of life was not assessed in these studies.

    In studies comparing high- versus low-fat diets, no patients in the high-fat groups developed gallstones, compared with 45% of control patients. There was no significant difference in weight lost. Quality of life was not assessed. Bile lithogenicity did not differ significantly between the two studies.

    There were no adverse events reported with the high- versus low-fat diet studies.

    Few serious events were reported related to ursodeoxycholic acid consumption; gastrointestinal-related complaints were the most common adverse events.

    The authors noted that the small number of identified trials and low sample sizes in each trial limited their study. In addition, high risk of attrition bias may have also limited outcomes. The research was limited by an inability to perform a meta-analysis of other interventions that reduce cholesterol precipitation in bile.

    Primary source: Clinical Gastroenterology and Hepatology
    Source reference: Lammert F, et al "Ursodeoxycholic acid and high-fat diets prevent gallbladder stones during weight loss: a meta-analysis of randomized controlled trials" Clin Gastroenterol Hepatol 2013; DOI: 10.1016/j.cgh.2013.11.031.