November 18, 2013

Don't Crown the Hepatitis C Drug Winner Just Yet

Provided by The Motley Fool

By Brian Orelli | More Articles
November 18, 2013 | Comments (0)

Put that order for a hepatitis C crown for Gilead Sciences (NASDAQ: GILD ) on hold. Competitor AbbVie (NYSE: ABBV ) looks like it can give Gilead a run for its money.

In its first phase 3 trial, 96% of patients taking AbbVie's five-drug combo -- ABT-333, ribavirin, ABT-450, ritonavir, and ABT-267 -- were virus-free 12 weeks after finishing the medication. Essentially, the drug combination cured almost all the patients.

The trial enrolled patients infected with genotype 1 hepatitis C virus, the most common in the U.S. Within that genotype, there are two subtypes, 1a and 1b, and the drug combo did quite well on the harder-to-treat genotype 1a, scoring a cure rate of 95%.

More to come
This is just the first in a six-trial phase 3 program. AbbVie is also testing patients that already failed a previous treatment containing Roche's Pegasys or Merck's (NYSE: MRK ) Pegintron. Vertex Pharmaceuticals' (NASDAQ: VRTX ) Incivek, the first-generation oral drug that has to be combined with Pegasys, grabbed some of those treatment-experienced patients -- that's part of the reason Vertex had such a successful launch -- but there are still an awfully large number of them considering that Roche's and Merck's drugs were the only thing available for a long time and they only cured about half of the patients that took the drugs.

AbbVie is also testing a five-drug combination that skips the ribavirin. The generic drug can cause birth defects, so leaving it out would be an advantage if it doesn't lower the cure rate substantially. The company expects the trials to read out in the coming months, putting it on target to file marketing applications in the second quarter of next year.

Picking a winner
We'll have to wait for Gilead's phase 3 trials for its all-oral combination in genotype 1 patients to know which drug cures patients the best. When you're comparing the two, make sure it's an apples-to-apples comparison. Genotype, including the subtype, and whether the patient has failed a previous treatment affect how easy it is to treat patients.

Ultimately, though, the competition between AbbVie and Gilead is likely to end up being less about the cure rate than the other factors. If one combination beats the other by a couple of percentage points, I doubt that's going to sway doctors much. The difference might not even be meaningful since the breakdown of the populations in trials might be different.

With comparable efficacy, doctors' and patients' preference is likely to come down to side effects, cost, and convenience, likely in that order. So far, AbbVie's safety profile looks good; if Gilead can match it, the battle might come down to price. Part of AbbVie's regimen has to be taken twice a day while other drugs have to be taken three times a day, so AbbVie may lose on the convenience factor if it comes down to that.

The biggest winner might be Enanta Pharmaceuticals (NASDAQ: ENTA ) , which helped develop ABT-450 and is due up to $195 million in regulatory milestones, as well as double-digit royalties on sales of ABT-450. If AbbVie can make ABT-450 a blockbuster, Enanta Pharmaceuticals will benefit substantially considering it doesn't have any costs associated with the developing or selling the drug.

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OxyElite Pro Supplements Recalled

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    Following actions by the Food and Drug Administration (FDA), a Texas-based company has agreed to recalland destroy a dietary supplement linked to dozens of cases of acute liver failure and hepatitis, including one death and illnesses so severe that several patients required liver transplants.

    In addition to the recall of certain OxyElite Pro products, USPLabs assured FDA officials that it will destroy warehouse stocks of the supplement, with a retail value of about $22 million. FDA will oversee the destruction of the product.

    "As soon as we suspected a possible link between OxyElite Pro products and cases of liver failure and non-viral hepatitis in Hawaii, we warned the public and immediately launched an investigation with state officials and the Centers for Disease Control and Prevention (CDC)," said Daniel Fabricant, Ph.D., director of FDA's Division of Dietary Supplement Programs. "Our mandate to protect the public was fulfilled by ensuring the swift removal of the product from the marketplace."

    FDA used new enforcement tools provided by the FDA Food Safety Modernization Act to act quickly in the face of a potential danger to public health.

    The supplement was advertised as an aid to losing weight and building muscles. FDA warned the company on Oct. 11, 2013, that certain OxyElite Pro products and another supplement, VERSA-1, are considered adulterated because they contain a new dietary ingredient, aegeline, for which the company did not provide evidence of safety.

    While FDA's investigation is still ongoing, the agency continues to warn consumers to avoid using OxyElite Pro and VERSA-1.

    Earlier this year, a stockpile of another formulation of OxyElite Pro was destroyed after being held through an FDA administrative detention order. A stimulant included in those products, DMAA, or dimethylamylamine, can cause high blood pressure and lead to heart attacks, seizures, psychiatric disorders and death.

    After removing DMAA from its products, USPLabs substituted aegeline, among other ingredients, in certain OxyElite Pro products. Non-synthetic aegeline is an alkaloid extract from leaves of the Asian bael tree (Agele marmelos).

    "Twice in a short period, this company has added new dietary ingredients to supplements without notifying the FDA and providing a reasonable expectation of safety, as required by law," said Fabricant. "Losses to the company should also serve as a reminder that FDA's laws and regulations serve a purpose and must be followed."

    Evidence of Danger

    On Sept. 13, 2013, FDA learned of a cluster of seven Hawaii residents with acute liver failure/non-viral hepatitis.

    A joint investigation by the Hawaii Department of Health and CDC revealed that the patients all had consumed OxyElite Pro products. FDA meanwhile identified patients outside of Hawaii with similar liver dysfunction after using OxyElite Pro.

    The FDA urged the public to avoid using products labeled as OxyElite Pro or VERSA-1 while the agency investigated further.

    On Oct. 11, 2013, FDA warned the company that certain OxyElite Pro and VERSA-1 products were deemed adulterated and that failure to immediately cease distribution of both products could lead to enforcement actions. The FDA also outlined its findings of harm linked to OxyElite Pro.

    As of the end of October 2013, there were 56 cases of acute liver failure or acute hepatitis linked to OxyPro Elite, 43 of them in Hawaii. The investigation continues.

    Following the Law

    While manufacturers of dietary supplements are not required to provide proof of safety and effectiveness prior to marketing, they are required to notify the FDA of plans to include a new dietary ingredient. They are also required to submit evidence that the dietary ingredient would reasonably be expected to be safe under the conditions of use recommended or suggested in the supplement labeling. A new dietary ingredient is defined as one not marketed in the United States before Oct. 15, 1994.

    Companies are required to provide evidence of safety of the new dietary ingredient 75 days before the product goes to market. This notification was not made by USPLabs before it began using DMAA, a new dietary ingredient, in OxyElite Pro. FDA was likewise not informed when the company, no longer formulating with DMAA, began using the new dietary ingredient aegeline.

    The FDA Food Safety Modernization Act has been instrumental in FDA's enforcement actions regarding the OxyElite Pro dietary supplements.

    This article appears on FDA's Consumer Updates page, which features the latest on all FDA-regulated products.

    Nov. 18, 2013

    Source FDA

    Viral Hepatitis Policy Meets Practice at the Liver Meeting

    November 18, 2013 • 0 comments • By Ronald Valdiserri, M.D., M.P.H., Deputy Assistant Secretary for Health, Infectious Diseases, and Director, Office of HIV/AIDS and Infectious Disease Policy, U.S. Department of Health and Human Services


    Earlier this month, the “Liver Meeting” – the annual meeting of the American Association for the Study of Liver Diseases (AASLD )– took place in Washington, DC. As part of a session re-capping the major viral hepatitis highlights from the conference, I had the pleasure of sharing with several thousand scientists and healthcare professionals from around the world who specialize in liver disease, updates on federal activities aimed at ending the silent epidemic of viral hepatitis in the United States.

    The meeting featured exciting new research announcements from experts working to make progress toward expanding what we know about viral hepatitis and liver disease. Working in parallel, improved policies and clinical advances can pave the way to a future in which people are routinely screened for viral hepatitis and once identified, receive timely, high quality care and, in many instances, treatment that results in a cure.

    The conference also featured a number of presentations highlighting research, clinical practice models, and other important activities underway at federal agencies including the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), the U.S. Food and Drug Administration (FDA) and others. These included a presentation by my former colleague at the U.S. Department of Veterans Affairs (VA), Dr. Lisa Backus who presented on VA research  that supports the CDC recommendation to screen “Baby Boomers” for hepatitis C (HCV) and steps that the VA is taking to enhance their already impressive HCV screening rates. Dr. Backus and her colleagues believe that additional screening efforts could find up to an additional 51,000 veterans of the baby boomer generation who are infected with HCV and not yet diagnosed.

    This year, advances in the treatment of hepatitis C captured tremendous attention at the Liver Meeting. These advances herald a new era in which people who are chronically infected with HCV could access vastly improved and easier to take treatments. New treatments on the horizon have fewer side effects and a shorter duration of therapy and some result in cure rates of up to 90 percent – or more. But improved treatments alone cannot turn the tide of an epidemic. As my colleague, Corinna Dan, R.N., M.P.H., Viral Hepatitis Policy Advisor noted, “In order to realize the goals of the national Viral Hepatitis Action Plan, we must learn to use the improved therapies effectively and work with new partners to identify all patients who can benefit from them, especially the hundreds of thousands of individuals who are undiagnosed and therefore unaware of their infection.”

    Toward that end and guided by the Action Plan for the Prevention, Care & Treatment of Viral Hepatitis, federal partners have prioritized a number of efforts to engage greater numbers of health care providers and increase their capacity to diagnose, care for, and treat hepatitis C, hepatitis B and other forms of viral hepatitis. Among the examples I shared during my presentation at the Liver Meeting, the Centers for Disease Control and Prevention (CDC) funds a number of training initiatives:

    • Hepatitis Web Study , a free education service developed by the Seattle STD/HIV Prevention Training Center and the University of Washington which offers free continuing medical and nursing education on hepatitis A, B, and C on a state-of-the-art website. Case-based learning modules provide training on diagnosis and care for health care providers as well as training on counseling for health educators.
    • In response to the rapidly evolving HCV treatment field, the Hepatitis C Online Course  for healthcare providers currently offers four modules and soon will include two additional modules on hepatitis C treatment.
    • The CDC-funded National Hepatitis Training Institute , offered by the University of Alabama at Birmingham, provides training on hepatitis prevention, diagnosis, management, treatment, and the integration of viral hepatitis into existing activities via practice-focused distance learning programs for frontline HIV and STD prevention workers in community-based organizations and clinics.

    The Department of Veterans Affairs (VA) has long led the charge on improving care and treatment of Americans with chronic hepatitis C. The VA is the single largest provider of medical care to people living with HCV in the U.S. and is making significant contributions to increasing provider capacity through the National Hepatitis C Program. The online resources for providers include useful guidelines, best practices, clinical tools, and much more. Equally important are the resources for Veterans and the public including an introductory guide for patients, information on the importance of reducing alcohol intake, and simple handouts on how to take the current treatment.

    Non-federal partners such as AASLD, the leading organization of scientists and healthcare professionals committed to preventing and curing liver disease, and the Infectious Diseases Society of America (IDSA) , an organization of physicians, scientists, and other health care professionals dedicated to promoting health through excellence in infectious diseases research, education, prevention, and patient care, play critical roles in building health care provider capacity to diagnose and treat chronic HCV.

    Recognizing that the confluence of the rapid development of new HCV treatments along with increasing numbers of people being identified with HCV will greatly increase the need for updated expert clinical guidance, AASLD announced on World Hepatitis Day in July 2013 that they are collaborating with IDSA to develop clinical recommendations for the management of HCV. Working together, leadership from these organizations will review current treatment recommendations and use evidence-based, consensus guidance to develop updated recommendations for managing patients. These recommendations will be updated regularly and made available online. AASLD and IDSA are key partners in the national, indeed global, response to viral hepatitis.


    Terrie Lenhart-Jenson: My Personal HCV Story

    picture002 (2) - Copy

    HCV bio Nov. 2013

    Sharing my story about Hepatitis C and getting rid of the stigma attached to the illness has been my goal since I was diagnosed in April 2006 with Hepatitis C, genotype 4. I found out I was infected from my regular annual blood work that showed a high liver panel, so I was tested and found to be positive.

    I believe I contracted the virus by a massive transfusion I received in 1963 after being hit by a car the day before my 2nd birthday. In MN where this occurred, there is a genotype 4 population. Ironically, the accident ruptured my liver and spleen, of which the latter was removed. Even though how I caught it really doesn't matter, I tell people that part so they are aware that this insidious virus has the capacity to stay dormant and hidden for a very long time.

    I'm currently stage 1, no grade, and use herbal therapy to support my immune system which keeps my numbers under control.

    I have one son and by the grace of God, he tested negative. It would have devastated me if he had tested positive. I have had to come to grips with the knowledge that due to stupid choices and general life events, I have passed this scourge on to others. Not knowing you carry a pathogen allows one to take risks or handle wounds very differently than those who know.

    When I was diagnosed, I cried a lot. My son had just begun college and my husband and I had just begun building a house. I was afraid of missing seeing my son succeed with his education or being able to live in our new house. I was given a fabulous book about Herbs and Hepatitis C, that put me on the road to learning about alternative ways to fight the virus. I began taking Milk Thistle right away and gradually added more as I learned more.

    I had lost a dear friend to HCV about six months before my diagnoses, so I was rightfully scared. Unfortunately, six months after learning I had this, I lost another friend. He was diagnosed just before I was, but his treatment took a huge toll and the damage was just too far gone. Seeing him jaundiced and bloated with ascites was overwhelming. I was so afraid of treatment by then that I decided then and there that I would not undergo the currently available treatment and would wait, if I could, for something better.

    I really haven't seriously considered treatment since that decision. I have had some mild depression and my Dr. thinks I'm fine for now and can wait for something better. My blood work has remained in the normal range since right after my diagnoses. My viral load is just over a mill., so it's not been a big concern either. I was told if I chose to treat, it would be treated the same as 1a, but with lower odds. Egypt has had some good treating results since genotype 4 is their primary type, but the U.S. isn't using the same for us since we're on the rarer side.

    I have worked as a substitute teacher for many years at the Jr high and high school level in our small town and have been very open about my status. I talk to the kids about choices they make and explain all the risk factors. I want to arm them. I will be talking to a class about HCV next week since they have been studying infectious diseases. I also work in our town's government, so I'm sort of high profile, but am very vocal about DE-stigmatizing this virus. I'm all about education and healthy choices. I'm so open about my status that I have a tattoo on my left wrist of the Caduceus with a dragon in place of one of the snakes and HCV + under it. It's my medical alert. It opens up dialog and leads to educational opportunities.

    New Phase II Data from All-Oral Regimens --- AASLD 2013

    Provided by NATAP

    Reported by Jules Levin
    AASLD 2013 Nov 1-4 Wash DC

    Fred Poordad, MD
    VP, Academic and Clinical Affairs
    The Texas Liver Institute
    Professor of Medicine
    University of Texas Health Science Center
    San Antonio, Texas

    Dr Poordad noted this presentation did not include all the regimens in phase 2 & not all of them presented at this AASLD because of time constants of his time allotted for this talk.. there are additional regimens which I reported in the NATAP coverage, including these 2 noteworthy studies in African-Americans and HIV/HCV coinfected using IFN-free regimens:

    AASLD: Combination Oral, Ribavirin Free, Antiviral Therapy to Optimize Treatment Outcomes for Hepatitis C Treatment Naïve Patients: Interim Results from the NIAID SYNERGY Trial (6 & 12 weeks therapy) - (11/06/13)

    AASLD: All-Oral Therapy With Sofosbuvir Plus Ribavirin For the Treatment of HCV Genotype 1, 2, and 3 Infection in Patients Co-infected With HIV (PHOTON-1) - (11/06/13)

    64rd Annual Meeting of the American Association for the Study of Liver Diseases Washington, DC Nov 1-5 2013




    from Jules: As Dr Poordad made reference to - Previous negative predictive factors did not affect SVR rates here. Even in this null responder population responses were the same: male vs female, 1a vs 1b, high baseline viral load vs low baseline viral load, F0-1 vs F2-3 but this analysis did not include cirrhotics (we will look to phase 3 for that), and CC vs non-CC.



    AASLD: Interferon- and Ribavirin-free Regimen of ABT-450/r + ABT-267 in HCV Genotype 1b-infected Treatment-naïve Patients and Prior Null Responders - (11/04/13)


    - (11/05/13)


    - (11/06/13)







    Dr Poordad commented regarding the far left bar that the cirrhotic treat-exp GT3 still had only 60% SVR rates suggesting that perhaps prior experience with Peg/Rbv may have for some reason disadvantaged this patient group. (from Jules: this has been a theme mentioned by several researchers at several recent conferences which of course is interesting & perhaps true but I don't think there i s any evidence of this theory).


    BUT IN THIS STUDY the same group of Treatment-Exp recd 12 weeks of Peg/rbv + Sofosbuvir with a 83% SVR rate, Dr Poordad said this suggests this might be the best treatment for GT3 treat-exp cirrhotics.


    from Jules: 2 relapsers & 2 lost to discontinuations in the GT3 group, I think 1 relapser & 1 discontinuation in the 10/12 in the GT3 cirrhotic group, and the same in the non-cirrhotic group.

    AASLD: Sofosbuvir in Combination With PegIFN and Ribavirin for 12 Weeks Provides High SVR Rates in HCV-Infected Genotype 2 or 3 Treatment- Experienced Patients with and without Compensated Cirrhosis: Results from the LONESTAR-2 Study




    AASLD: High Efficacy and Safety of the All-Oral Combination Regimen, MK-5172 / MK-8742 ± RBV for 12 Weeks in HCV Genotype 1 Infected Patients: The C-WORTHY Study - (11/05/13)

    AASLD: Efficacy and Safety of an Interferon-Free Regimen of MK-5172 + Ribavirin for 12 Weeks or 24 Weeks in Treatment-Naive, Noncirrhotic Subjects With HCV GT1 Infection: The C-SPIRIT Study - (11/04/13)



    from jules: As noted by Dr Poordad in the LONESTAR study addressing duration of therapy, the number of patients is small but 8 weeks and 12 weeks with SOFosbuvir+Ledipasvir+Rbv in treat-naive non-cirrhotics yielded the same SVR rate but 6 weeks with this regimen was not as good. In the LONESTAR Study which you can see by clicking the link just below HCV protease inhibitor failures recd the same regimen for 12 weeks with & without Rbv & 50% were cirrhotic & this yielded 21/21 achieving SVR12 with Rbv & 18/19 without Rbv achieved SVR12.

    AASLD: Sofosbuvir and Ledipasvir Fixed-Dose Combination with and without Ribavirin in Treatment-Naïve and Previously Treated Patients with Genotype 1 Hepatitis C: The LONESTAR Study


    HCV Oral Combo Nearly Perfect

    Infectious Disease

    Published: Nov 18, 2013

    By Michael Smith, North American Correspondent, MedPage Today

    A four-drug oral regimen for hepatitis C (HCV) achieved near-perfect cure rates in a large clinical trial, according to the company developing the drugs.

    First results from the phase III SAPPHIRE-1 study show that 96% of treated patients had undetectable virus 12 weeks after the end of therapy, according to a release from AbbVie, of North Chicago, Ill.

    That endpoint -- a virologic response sustained for 12 weeks after stopping treatment , or SVR12 -- is regarded as a cure, since few patients relapse after that point.

    While the company released some details, results of the 631-patient study have not yet been presented at scientific meetings or in peer-reviewed journals.

    The SAPPHIRE-1 study is one of six phase III trials evaluating three so-called direct-acting agents being developed by AbbVie -- ABT-333, a non-nucleoside polymerase inhibitor; ABT-450/r, an HCV NS3/4A protease inhibitor boosted with the protease inhibitor ritonavir (Norvir); and ABT-267, which blocks the viral nonstructural protein NS5A.

    The latter two drugs were given in a fixed-dose combination.

    All patients in the treatment arm were also given ribavirin, an oral medication that, withpegylated interferon, forms the backbone of standard therapy. But interferon, which is given by injection and has severe side effects, was not used, the company said.

    The goal of much recent investigation has been to develop all-oral regimens that do not include either ribavirin or interferon, and several of the other phase III trials directed by AbbVie are testing only the company's three direct-acting agents.

    Study participants had genotype 1 HCV, the most prevalent form of the virus, and no evidence of liver cirrhosis; 473 patients were randomly assigned to the treatment arm for 12 weeks and the remaining 158 got placebos.

    After the initial 12-week period, placebo patients were switched to open-label treatment with the four drugs for another 12 weeks. The company did not report outcomes for that treatment period.

    Among the 473 patients in the treatment arm, 455 reached an SVR12 in an intent-to-treat analysis where patients with missing data were considered failures.

    There was a slight difference in outcomes based on genotype 1 subtype, the company release said: 148 of the 151 patients with genotype 1b achieved SVR12 compared with 307 of the 322 with genotype 1a, or 98% versus 95%.

    The company said the most commonly reported adverse events were fatigue, headache, and nausea; the proportion of patients stopping the trial because of adverse events was 0.6% in each arm.

    Among patients in the active arm, the combined rate of virologic relapse (after treatment and before 12 weeks) or breakthrough (during therapy) was 1.7%.


    Also See: Abbvie Releases First of Six Phase III Results From Investigational All-Oral, Interferon-Free, 12-Week Regimen, Showing 96% SVR12 In Genotype 1 Hepatitis C Patients New To Therapy

    "Compassionate Use": DGVS welcomes award of hepatitis C drug to seriously ill

    Original Article

    Medizin - Kommunikation Medizinkommunikation

    Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften

      Berlin – Die Europäische Arzneimittelbehörde EMA empfiehlt, den noch nicht zugelassenen Wirkstoff „Sofosbuvir“ für Patienten vor und nach Lebertransplantationen in einem so genannten „Compassionate Use“-Programm zu ermöglichen. Das Programm – wörtlich übersetzt bedeutet es „Anwendung aus Mitgefühl“ – soll schwerstkranken Patienten, für die keine anderen Therapieoptionen zur Verfügung stehen, ein wirksames Heilmittel frühzeitig zugänglich machen. Die Deutsche Gesellschaft für Verdauungs- und Stoffwechselkrankheiten (DGVS) begrüßt die Entscheidung und setzt sich für eine kontrollierte Umsetzung des Programms in Deutschland ein.

      Hepatitis C-Infektionen gehören zu den häufigsten Gründen für Lebertransplantationen. „Besteht zum Zeitpunkt einer Lebertransplantation eine Infektion mit einem Hepatitis C-Virus ist die Wahrscheinlichkeit, dass auch die neu transplantierte Leber infiziert wird, sehr hoch“, erklärt Professor Dr. med. Peter Galle, Direktor der I. Medizinischen Klinik und Poliklinik an der Universitätsmedizin Mainz und Vorstandsmitglied der DGVS. Gerade für diese Patientengruppe fehlten jedoch häufig wirksame und verträgliche Medikamente, um die Infektion zu bekämpfen.
      In ersten Studien, die wie üblich vom Hersteller finanziert wurden, hatte sich der neue Wirkstoff Sofosbuvir – verabreicht in Kombination mit dem herkömmlichen Medikament Ribavirin – als äußerst wirksam erwiesen. So zeigten etwa die Ergebnisse der „FUSION“- Studie, dass Patienten, die sich mit den Hepatitis C-Viren der Genotypen 2 und 3 infiziert hatten, zu 94 Prozent (Genotyp 2) und 62 Prozent (Genotyp 3) geheilt werden konnten, wenn sie über 16 Wochen hinweg die Kombinationstherapie erhielten. Die Patienten galten zuvor als austherapiert. „Das Medikament greift direkt in den viralen Vermehrungszyklus ein und stoppt die Bildung neuer Viren in der Leber“, erklärt Galle. Andere Studienergebnisse weisen zudem darauf hin, dass das Medikament auch Neu-Infektionen transplantierter Lebern verhindern kann.
      Bis zur endgültigen Zulassung gilt Sofosbuvir als Prüfpräparat, dessen Sicherheit und Wirksamkeit nicht endgültig bewiesen ist. Experte Peter Galle geht jedoch davon aus, dass die Zulassung in Kürze bevorsteht. Die Entscheidung in den USA durch die Food and Drug Administration (FDA) werde bereits im Dezember 2013 erwartet.
      Hält der Wirkstoff was er verspricht, verbessert dies die Prognosen für Hepatitis C-Patienten erheblich, so Galle. Erst vor zwei Jahren sorgte die Zulassung der beiden Wirkstoffe „Telaprevir“ und „Boceprevir“ dafür, dass die Heilungschancen vieler Hepatitis C-Patienten deutlich stiegen. „Allerdings sind diese Wirkstoffe auf Infektionen mit dem Hepatitis-Virus der Genotyp 1-Variante beschränkt“, so Galle. Sofosbuvir hingegen komme auch bei Infektionen mit den anderen Hepatitis C-Genotypen 2 bis 6 in Betracht.
      Schätzungsweise eine halbe Million Menschen sind in Deutschland mit Hepatitis C-Viren infiziert – viele ohne es zu wissen. Denn die Infektion verursacht oft über Jahrzehnte keine Beschwerden, bis am Ende die Leber schwer geschädigt ist. Jeder Dritte der jahrelang Infizierten entwickelt eine Leberzirrhose, die mit einem deutlich erhöhten Risiko für Leberkrebs einhergeht. Um möglichst frühzeitig Leberschäden vermeiden zu können, fordert die DGVS, dass Leberwerte in Screening-Untersuchungen – wie den Check up 35 – mit aufgenommen werden.
      Die Deutsche Gesellschaft für Verdauungs- und Stoffwechselkrankheiten (DGVS) wurde 1913 als wissenschaftliche Fachgesellschaft zur Erforschung der Verdauungsorgane gegründet. Heute vereint sie mehr als 5000 Ärzte und Wissenschaftler aus der Gastroenterologie unter einem Dach. Die DGVS fördert sehr erfolgreich wissenschaftliche Projekte und Studien, veranstaltet Kongresse und Fortbildungen und unterstützt aktiv den wissenschaftlichen Nachwuchs. Ein besonderes Anliegen ist der DGVS die Entwicklung von Standards und Behandlungsleitlinien für die Diagnostik und Therapie von Erkrankungen der Verdauungsorgane – zum Wohle des Patienten.

      Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. Jacobson et al.; N Engl J Med. 2013 May 16;368(20):1867–77.

      Kontakt für Journalisten:
      DGVS Pressestelle
      Anna Julia Voormann
      Irina Lorenz-Meyer
      Postfach 30 11 20
      70451 Stuttgart
      Berliner Büro im Langenbeck Virchow-Haus:
      Luisenstraße 59
      10117 Berlin
      Tel.: 0711 8931-552/-642
      Fax: 0711 8931-167

      Weitere Informationen:

      Merkmale dieser Pressemitteilung:
      Forschungs- / Wissenstransfer


      18/11/2013 13:00

      Medicine - Communication Communication Medical

      Association of the Scientific Medical Societies in Germany

        Berlin - The European Medicines Agency EMA recommends that the drug not yet approved "Sofosbuvir" for patients before and after liver transplantation possible in a so-called "compassionate use" program. The program - literally translated, it means "application of compassion" - intended to make seriously ill patients for whom no other treatment options are available, an effective cure for early access. The German Society for Digestive and Metabolic Diseases (DGVS) welcomes the decision and is working for a managed implementation of the program in Germany.

        Hepatitis C infections are the most common reasons for liver transplants. "If at the time of liver transplantation, infection with a hepatitis C virus is the probability that the newly transplanted liver is infected, very high," says Professor Dr. Peter Galle, director of the First Medical Clinic at the Mainz University Medical Center and a board member of the DGVS. However, just for this group of patients were missing often effective and safe drugs to fight the infection. Preliminary investigations which were, as usual, funded by the manufacturer, the new drug Sofosbuvir had - given in combination with the conventional drug ribavirin - proved highly effective . Thus, the results showed about the "FUSION" - study that patients who had been infected with the hepatitis C virus genotypes 2 and 3 to 94 percent (genotype 2) and 62 percent (genotype 3) could be cured if they received the combination therapy over 16 weeks. The patients were previously regarded as untreatable. "The drug acts directly in the viral replication cycle and stops the formation of new viruses in the liver," says Galle. Other study results also suggest that the drug may also prevent re-infection of transplanted livers. Pending final approval Sofosbuvir is considered investigational, its safety and effectiveness has not been definitively proven.Expert Peter Galle, however, assumes that the approval shortly to come. The decision in the United States by the Food and Drug Administration (FDA) was expected in December 2013. Keeps the drug what it promises, it greatly improved the outlook for hepatitis C patients, as bile. Only two years ago, the authorization of both agents "Telaprevir" and "Boceprevir" made ​​sure that the chances of recovery of many hepatitis C patients clearly increased. "However, these drugs are limited to infection with the hepatitis virus of genotype 1 variant" as bile. Sofosbuvir however'm also in infections with other hepatitis C genotypes 2 to 6 into account. estimated half a million people in Germany are infected with hepatitis C virus - many without knowing it. Because the infection often causes no symptoms for decades, until the end of the liver is severely damaged. One in three of the years those infected develop cirrhosis, which is associated with a significantly increased risk of liver cancer. Order as early as possible to avoid liver damage, urges the DGVS that liver function tests in screening tests - such as the check-up 35 -. Be included The German Society for Digestive and Metabolic Diseases (DGVS) was founded in 1913 as a scientific society for the study of digestive organs . Today, it brings together more than 5,000 physicians and scientists from the gastroenterology under one roof. The DGVS promotes very successful scientific projects and studies, organizes conferences and training courses, and actively support young scientists. A particular concern is the DGVS the development of standards and treatment guidelines for the diagnosis and treatment of diseases of the digestive organs - for the benefit of the patient. literature: Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. Jacobson et al, N Engl J Med 2013 May 16; 368 (20) :1867-77.. Contact for Journalists: DGVS Press Office Anna Julia Voormann Irina Lorenz-Meyer Postfach 30 11 20 70451 Stuttgart Berlin office in the Langenbeck Virchow House: Luis Street 59 10117 Berlin Tel: 0711 8931-552/-642 Fax: 8931-167 0711


        Cannabis Science, Inc. (CBIS) Featured in A&U Magazine Regarding Potential Utility of Cannabinoids to Address Emerging Crisis of HIV Drug Resistance


        Nov. 18, 2013, 11:52 a.m. EST


        COLORADO SPRINGS, Colo., Nov. 18, 2013 /PRNewswire via COMTEX/ -- (nasdaq otc:CBIS) Cannabis Science, Inc., a U.S. Company specializing in cannabis formulation-based drug development, highlights two articles validating Cannabis Science's research premise addressing the utility of cannabinoid-mediated viral suppression of HIV's replication cycle: an independent article in the July 2013 issue of A&U magazine, entitled "CB Breaker: Cannabinoids May Be Effective In Treating HIV, Not Just Relieving the Symptoms" and an article in the September 2013 issue of POZ, entitled "Pot - the Next HIV drug?" The A&U article features Cannabis Science's CS-TATI-I clinical research program developing a cannabinoid-based HIV Tat inhibitor to interfere with the transactivation of Kaposi's sarcoma herpesvirus (KSHV), the cause of Kaposi's sarcoma (KS). KS is a devastating cancer that remains a significant threat to human health throughout Africa, other resource-poor regions contending with the AIDS crisis and related oncological complications, while also increasing in long term survivors of anti-retroviral therapy.

        The article in A&U, authored by Jeannie Wraight, Editor-in-Chief of HIV HAVEN and Contributing Writer for A&U, reviewed data generated via NIH grants from Yuri Persidsky, MD, PhD, Chairman, Department of Pathology and Laboratory Medicine, Temple University, published in the Journal of Leukocyte Biology that indicates anti-inflammatory activity of cannabinoids correlating with a decreased level of HIV in macrophages that directly causes a decrease in HIV replication. The article also covered data generated by Mt. Sinai School of Medicine, also funded by the NIH in 2012, which demonstrates the utility of cannabinoids to suppress HIV infection by blocking signaling between HIV and CXCR4, a critical receptor required by HIV to infect T cells. Data in a 2011 article from the Journal of Neuroimmune Pharmacology found that cannabinoids inhibit HIV Tat, an essential gene necessary for viral replication.

        "The fact that patient communities are following relevant cannabis and cannabinoid-based research highlights the need for these therapies to receive appropriate public facilitation in order to address the current disparities facing drug-resistant treatment-experienced and newly infected non-responding HIV patients. The HIV community has a long history of advocating for new potential therapies and support further efforts to accelerate the commercial development of CS-TATI-I," said Dr. Dorothy Bray, CEO of Cannabis Science.

        Dr. Robert Melamede, President of Cannabis Science, noted, "This article appeared immediately following the release of new data on HIV and Kaposi's sarcoma presented at IAS 2013 and the STI & AIDS World Congress 2013. The growing volume of studies demonstrating the effect of cannabinoids on HIV and other diseases is reaching a tipping point as Cannabis Science is aggressively moving through the preclinical development process."

        POZ magazine, the leading national HIV publication, reported in the September 2013 issue on a series of recent peer-reviewed publications demonstrating the antiviral effect of cannabinoids on HIV, further demonstrating the validity of Cannabis Science's therapeutic approach of cannabinoid-based antiviral therapy. POZ magazine ( has provided essential clinical information to HIV patients around the world since 1994. An award-winning print and online publication, POZ is identified by its readers as their most trusted source of information about HIV.

        "Acknowledgement from POZ and A&U is a historically essential aspect for advancing new discoveries into the clinic. The current momentum of interest by HIV community-based publications on this important research will help ensure that legislators and key opinion leaders in scientific research prioritize support for further clinical investigations that will advance cannabinoid research into publicly supported therapeutic settings," noted Dr. Melamede.

        At the recent 7th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2013, that took place in Kuala Lumpur, Malaysia, critical data on how cannabinoids suppress HIV replication was presented by researchers at Temple University, entitled "Targeted transcriptomic analysis reveals cellular factors responsible for the suppressive effect of cannabinoids on HIV-1 replication". The authors developed a transcription-based approach to examine the mechanisms of how cannabinoids appeared to be able to suppress HIV. The study identified specific host factors and cellular pathways associated with cannabinoid signalling and HIV replication and initial characterization of cannabinoid-mediated viral suppression. This research will contribute to the overall knowledge of the effects of cannabinoids on HIV and help enable cannabinoid-based therapies to be developed.

        In the past six months, Cannabis Science established corporate operations in Amsterdam, The Netherlands in initial efforts, among others, to establish collaborations with the Amsterdam Innovation Motor, Amsterdam BioMed Cluster, Amsterdam Life Sciences Fund, I amstarter program and the University of Amsterdam in the development of CS-TATI-I.

        About A&U MagazineFounded in 1991, A&U Magazine ( is a publication focused on the current course of the AIDS crisis and responses to the AIDS pandemic including nutrition, treatment, and innovative therapies.

        About the 7th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2013)IAS 2013 ( is the world's largest open scientific gathering on HIV/AIDS and took place from June 30-July 3, 2013 in Kuala Lumpur, Malaysia. Organized by the International AIDS Society (IAS) and held every two years, the conference attracts over 5,000 of the world's leading scientists, clinicians, policy makers and community leaders to learn about the latest developments in HIV-related research and clinical competency and collaborate on translating the latest scientific advances to the global response to HIV/AIDS. The IAS is the world's leading association of HIV professionals that provides critical platforms for presenting new research, promoting dialogue, education and best practices and advocating for an evidence-based and the continuous improvement of the global response to HIV.

        About the Amsterdam Innovation MotorThe Amsterdam Innovation Motor (AIM,, associated with the Amsterdam Economic Board focuses on creating partnerships for innovative entrepreneurship and facilitating the translation of knowledge and applications in life science research supported by measurable economic activities to create bridges in early and mid stage life science companies. AIM has received support from the Knowledge Exploration Subsidy Program (SKE) of Technopartner (Ministry of Economic Affairs), providing life science entrepreneurs with assistance to further stimulate the Dutch economic position in the global life science arena. The Amsterdam BioMed Cluster is one of the leading biotechnology hubs in the world.

        About Cannabis Science, Inc.Cannabis Science, Inc. takes advantage of its unique understanding of metabolic processes to provide novel treatment approaches to a number of illnesses for which current treatments and understanding remain unsatisfactory. Cannabinoids have an extensive history dating back thousands of years, and currently there are a growing number of peer-reviewed scientific publications that document the underlying biochemical pathways that cannabinoids modulate. The Company works with leading experts in drug development, medicinal characterization, and clinical research to develop, produce, and commercialize novel therapeutic approaches for the treatment for illnesses caused by infections as well as for age-related illness. Our initial focus is on skin cancers and HIV related cancers such as Kaposi's sarcoma.

        Forward Looking StatementsThis Press Release includes forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Act of 1934. A statement containing works such as "anticipate," "seek," intend," "believe," "estimate," "expect," "project," "plan," or similar phrases may be deemed "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Some or all of the events or results anticipated by these forward-looking statements may not occur. Factors that could cause or contribute to such differences include the future U.S. and global economies, the impact of competition, and the Company's reliance on existing regulations regarding the use and development of cannabis-based drugs. Cannabis Science, Inc. does not undertake any duty nor does it intend to update the results of these forward-looking statements.

        Cannabis Science, Inc. Dr. Dorothy Bray, CEO & Director

        Investment InquiriesRobert Kanerkane@cannabisscience.com561.420.4824

        SOURCE Cannabis Science, Inc.

        Copyright (C) 2013 PR Newswire. All rights reserved


        Interpreting ABBV/ENTA’s SAPHIRE-1 results

        Written by DewDiligence on Invertors Hub Boards

        Re: Interpreting ABBV/ENTA’s SAPHIRE-1 results

        98% SVR12 in GT1b and 95% SVR12 in GT1a—both on an ITT basis—are excellent efficacy results, of course. However, SAPHIRE-1 (and the yet-to-report SAPHIRE-2) are primarily safety studies, as noted in #msg-91739317.

        How did the 3-DAA+ribavirin arm perform in SAPHIRE-1 relative to the placebo arm onsafety? From today’s PR:


        The most commonly reported adverse events in the 3D and placebo arms, respectively, were fatigue, headache and nausea. Discontinuations due to adverse events were reported in 0.6 percent of patients receiving the 3D regimen and0.6 percent of patients receiving placebo.

        In other words, there were no excess dropouts in the treatment arm relative to the placebo arm, which is as good an outcome as one could hope for (pending the detaileddata on AEs to be presented at a medical conference).

        All told, SAPHIRE-1 looks like an excellent start to ABBV/ENTA’s array of six phase-3 trials for the initial NDA submission in 2Q14. The five other phase-3 trials to support the initial NDA are SAPHIRE-2, PEARL-2/3/4, and TURQUOISE-2, as detailed in #msg-93647264.

        Background on SAPHIRE-1: The “placebo” arm in SAPHIRE-1 was actually a delayed treatment arm insofar as patients received the same regimen as the treatment arm, but the start of treatment was delayed by 12 weeks in order to make a safety comparison between the arms. HCV progresses much too slowly for a 12-week delay to affect the efficacy results in the delayed-treatment arm (which have yet to be reported).


        Also See: Abbvie Releases First of Six Phase III Results From Investigational All-Oral, Interferon-Free, 12-Week Regimen, Showing 96% SVR12 In Genotype 1 Hepatitis C Patients New To Therapy

        Abbvie Releases First of Six Phase III Results From Investigational All-Oral, Interferon-Free, 12-Week Regimen, Showing 96% SVR12 In Genotype 1 Hepatitis C Patients New To Therapy





        Nov 18, 2013

        NORTH CHICAGO, Ill., Nov. 18, 2013 /PRNewswire/ -- AbbVie (NYSE: ABBV) released the first phase III results for the investigational three direct-acting-antiviral (3D) regimen plus ribavirin in patients chronically infected with genotype 1 (GT1) hepatitis C virus (HCV). In the 631-patient SAPPHIRE-I study, patients new to therapy receiving 12 weeks of AbbVie's 3D regimen achieved a sustained virologic response at 12 weeks post-treatment (SVR12) of 96 percent. The majority of patients were GT1a, considered the more difficult-to-treat subtype, and the SVR12rates of GT1a and GT1b were 95 percent and 98 percent, respectively. The rate of virologic relapse or breakthrough was low, occurring in 1.7 percent of patients receiving the 3D regimen. In addition, discontinuation rates due to adverse events were low, and of an equal percentage (0.6 percent) in both active and placebo groups.

        AbbVie's multinational HCV program is the largest all-oral, interferon-free clinical program in GT1 patients being conducted to date. GT1 (with subtypes 1a and 1b) is the most prevalent genotype worldwide, with a higher prevalence of 1a in the U.S. and 1b in Europe. SAPPHIRE-I is the first of six phase III trials supporting AbbVie's investigational 3D regimen for the treatment of GT1 hepatitis C patients.

        "SAPPHIRE-I demonstrates that patients new to therapy with genotype 1 HCV achieved high rates of virologic response with AbbVie's interferon-free, all-oral 3D regimen plus ribavirin, and the SVR rate is consistent with results from our phase II studies," said Scott Brun, M.D., vice president, pharmaceutical development, AbbVie. "SAPPHIRE-I is the first of these studies to report results, and based on the progress of our clinical program to date, we are on track for major regulatory submissions in the second quarter of 2014."

        AbbVie will disclose detailed SAPPHIRE-I results at future scientific congresses and in publications.

        About Study M11-646 (SAPPHIRE-I)
        SAPPHIRE-I is a global, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 12 weeks of treatment with ABT-333 (250mg), ribavirin (weight-based), both dosed twice daily, and the fixed-dose combination of ABT-450/ritonavir (150/100mg) co-formulated with ABT-267 (25mg) and dosed once daily in non-cirrhotic, GT1a and GT1b HCV-infected, treatment-naive adult patients.

        The study population consisted of 631 GT1 treatment-naive patients with no evidence of liver cirrhosis with 473 patients randomized to the 3D regimen plus ribavirin for 12 weeks, and 158 patients randomized to placebo for the initial 12 weeks. Patients initially randomized to placebo for the first 12 weeks then received open-label treatment with the 3D regimen plus ribavirin for 12 weeks.

        Following 12 weeks of treatment with AbbVie's 3D regimen plus ribavirin, 96 percent (n=455/473) of patients achieved SVR12 based on intent-to-treat analysis where patients with missing values for any reason were considered treatment failures. In the active treatment arm, patients with GT1b infection achieved 98 percent SVR12 (148/151), while patients with GT1a achieved 95 percent SVR12 (307/322).

        The most commonly reported adverse events in the 3D and placebo arms, respectively, were fatigue, headache and nausea. Discontinuations due to adverse events were reported in 0.6 percent of patients receiving the 3D regimen and 0.6 percent of patients receiving placebo. The rate of virologic relapse or breakthrough was low, occurring in 1.7 percent of patients receiving the 3D regimen.  

        Additional information about AbbVie's phase III studies can be found on

        AbbVie's HCV Development Program
        The clinical program supporting our 3D regimen includes more than 2,300 genotype 1 patients in greater than 25 countries around the world. The AbbVie HCV clinical development program is intended to advance scientific knowledge and clinical care by investigating an interferon-free, all-oral 3D regimen with or without ribavirin with the goal of producing high SVR rates in as many patients as possible, including those that typically do not respond well to treatment, such as previous non-responders to interferon-based therapy or patients with advanced liver fibrosis or cirrhosis. Results from the remaining five studies in AbbVie's phase III program will be available in the coming months, supporting regulatory submissions starting in the second quarter of 2014.

        Overview of AbbVie's phase III clinical programs is as follows:
        Patients (N)
        Treatment Regimen
        Treatment Duration
        GT1, treatment-naive
        12 weeks
        12 weeks, then active treatment for 12 weeks
        GT1, treatment-experienced
           ABT-450/r +ABT-267
        12 weeks
        12 weeks, then active treatment for 12 weeks
        GT1b, treatment-experienced
        (210 a)
           ABT-450/r +ABT-267
        12 weeks
           ABT-450/r +ABT-267
        12 weeks
        GT1b, treatment-naive
        (400 a)
           ABT-450/r +ABT-267
        12 weeks
           ABT-450/r +ABT-267
        12 weeks
        GT1a, treatment-naive
        (300 a)
           ABT-450/r +ABT-267
        12 weeks
           ABT-450/r +ABT-267
        12 weeks
        GT1, treatment-naive and treatment-experienced (with compensated cirrhosis)
        (380 a)
           ABT-450/r +ABT-267
        12 weeks
           ABT-450/r +ABT-267
        24 weeks
        a projected study population
        b ABT-450/ritonavir
        c ABT-267 is co-formulated with ABT-450/r, administered as two pills once daily

        The 3D regimen consists of boosted protease inhibitor ABT-450/ritonavir, NS5A inhibitor ABT-267, and non-nucleoside polymerase inhibitor ABT-333. The combination of three different mechanisms of action interrupts the HCV replication process with the goal of optimizing SVR rates across different patient populations. In May of 2013, AbbVie's investigational 3D regimen with and without ribavirin for HCV GT1 was designated as a Breakthrough Therapy by the U.S. Food and Drug Administration (FDA).

        ABT-450 was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors. ABT-450 is being developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of HCV.

        Safety Information for Ribavirin and Ritonavir
        Ribavirin and ritonavir are not approved for the investigational use discussed above, and no conclusions can or should be drawn regarding the safety or efficacy of these products for this use.

        There are special safety considerations when prescribing these drugs in approved populations.

        Ritonavir must not be used with certain medications due to significant drug-drug interactions and in patients with known hypersensitivity to ritonavir or any of its excipients.

        Ribavirin monotherapy is not effective for the treatment for chronic hepatitis C virus and must not be used alone for this use. Ribavirin causes significant teratogenic effects and must not be used in women who are pregnant or breast-feeding and in men whose female partners are pregnant. Ribavirin must not be used in patients with a history of severe pre-existing cardiac disease, severe hepatic dysfunction or decompensated cirrhosis of the liver, automimmune hepatitis, hemoglobinopathies, or in combination with peginterferon alfa-2a in HIV/HCV co-infected patients with cirrhosis and Child-Pugh score >6.

        See approved product labels for more information.

        About AbbVie
        AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott. The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases. In 2013, AbbVie employs approximately 21,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit Follow@abbvie on Twitter or view careers on our Facebook or LinkedIn page.

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

        Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," in AbbVie's 2012 Annual Report on Form 10-K/A, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

        [1] Comparison based on review of data from for phase 3a programs of Gilead, BMS and BI as ofNovember 15, 2013

        [2] Lavanchy D. Evolving epidemiology of hepatitis C virus. Clin Microbiol Infect. 2011; 17(2):107-15.

        SOURCE AbbVie

        For further information: Media, Elizabeth Hoff, +1 (847) 935-4236,, or Javier Boix, +1 (847) 937-6113,; or Investor Relations, Elizabeth Shea, +1 (847) 935-2211,