ABBV/ENTA’s Global Phase-3 HCV Program

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DewDiligence
Monday, 11/18/13 06:19:26 PM

Re: DewDiligence post# 169165

[Updated for release of top-line data from SAPHIRE-1.]

ABBV/ENTA have 9 global phase-3 trials testing an all-oral regimen in HCV genotype-1a/1b : 6 trials that comprise the initial NDA/MAA submissions in 2Q14, and 3 trials for subsequent use. Full details of the 6 trials comprising the initial NDA/MAA will be presented at the EASL conference in Apr 2014.

All 9 of these global phase-3 trials include the 3-DAA combination of the protease inhibitor, ABT-450/r (licensed by ABBV from ENTA); the NS5A inhibitor, ABT-267 (from ABBV’s pipeline); and the non-nucleoside polymerase inhibitor, ABT-333 (from ABBV’s pipeline). Some of these trials also include ribavirin in one or both trial arms.

(ABBV/ENTA are testing the 2-DAA regimen of ABT-450/r + ABT-267 in a phase-3 trial for genotype-1b patients in Japan [#msg-91870291] and in various phase-2 trials globally.)

Six phase-3 trials comprising initial NDA/MAA submissions:

SAPPHIRE-1—treatment-naïve GT1a/1b w/o cirrhosis; ABT-450/r + ABT-267 + ABT-333 + ribavirin for 12w vs. identical regimen delayed by 12 weeks of placebo use;631 patients (68% GT1a, 32% GT1b); top-line results were released on 11/18/13 and discussed in #msg-94169219:
http://www.clinicaltrials.gov/ct2/show/NCT01716585

SAPPHIRE-2—(see #msg-91739317 for discussion)—treatment-experienced GT1a/1b w/o cirrhosis; ABT-450/r + ABT-267 + ABT-333 + ribavirin for 12w vs. identical regimen delayed by 12 weeks of placebo use; 400 patients; expected completion Nov 2013:
http://www.clinicaltrials.gov/ct2/show/NCT01715415

PEARL-2—treatment-experienced GT1b w/o cirrhosis; ABT-450/r + ABT-267 + ABT-333 ± ribavirin for 12w; 210 patients; expected completion Mar 2014:
http://www.clinicaltrials.gov/ct2/show/NCT01674725

PEARL-3—treatment-naïve GT1b w/o cirrhosis; ABT-450/r + ABT-267 + ABT-333±ribavirin for 12w; 400 patients; expected completion Dec 2013:
http://www.clinicaltrials.gov/ct2/show/NCT01767116

PEARL-4—treatment-naïve GT1a w/o cirrhosis; ABT-450/r + ABT-267 + ABT-333±ribavirin for 12w; 300 patients; expected completion Dec 2013:
http://www.clinicaltrials.gov/ct2/show/NCT01833533

TURQUOISE-2—DAA-naïve GT1a/1b with cirrhosis; ABT-450/r + ABT-267 + ABT333 + ribavirin for 12w vs. identical regimen for 24w; 380 patients; expected completion Jan 2014:
http://www.clinicaltrials.gov/ct2/show/NCT01704755

Three phase-3 trials not part of initial NDA/MAA submissions:

TURQUOISE-1—DAA-naïve GT1a/1b with HIV co-infection; ABT-450/r + ABT-267 + ABT333 + ribavirin for 12w vs. identical regimen for 24w; 300 patients; expected completion Dec 2014:
http://clinicaltrials.gov/ct2/show/NCT01939197

MALACHITE-1—5-arm trial including 3 DAA arms and 2 control arms—treatment-naïve GT1a/1b; ABT-450/r + ABT-267 + ABT-333 + ribavirin for 12w vs. Incivek + peg-IFN + ribavirin for 12w plus an additional 12w or 36w of peg-IFN/ribavirin on a response-guided basis; separate DAA and control arms for GT1a and GT1b; additional DAA arm for GT1b without ribavirin; 314 patients; expected completion Jul 2015:
http://www.clinicaltrials.gov/ct2/show/NCT01854697
(Note: This is essentially a phase-4 trial.)

MALACHITE-2—treatment-experienced GT1a/1b; ABT-450/r + ABT-267 + ABT-333 + ribavirin for 12w: vs. Incivek + peg-IFN + ribavirin for 12w plus an additional 12w or 36w of peg-IFN/ribavirin on a response-guided basis; 150 patients; expected completion Jul 2015:
http://www.clinicaltrials.gov/ct2/show/NCT01854528
(Note: This is essentially a phase-4 trial.)

Triple-positive tumor markers predict recurrence and survival in early-stage hepatocellular carcinoma

Hepatology Research

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Original Article

Shigeki Nakagawa¹, Toru Beppu^1,2,  Hirohisa Okabe¹, Keita Sakamoto¹,  Hideyuki Kuroki¹, Kosuke Mima¹,  Hidetoshi Nitta¹, Katsunori Imai¹,  Hiromitsu Hayashi¹, Yasuo Sakamoto^1,2,  Daisuke Hashimoto¹, Akira Chikamoto¹,  Takatoshi Ishiko¹, Masayuki Watanabe¹,  Hideo Baba^1,*

DOI: 10.1111/hepr.12277

This article is protected by copyright. All rights reserved.This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi:10.1111/hepr.12277

Publication History
Accepted manuscript online: 19 NOV 2013 03:37AM EST
Manuscript Accepted: 11 NOV 2013

Keywords: alpha-Fetoprotein;  DCP;  Hepatocellular Carcinoma;  PIVKA-Ⅱ; prognosis

Abstract

Aim

Hepatectomy is feasible for patients with HCC with good hepatic function who meet the Milan criteria. Several studies have indicated that tumor markers of HCC, AFP, AFP-L3%, and PIVKAII were good predictors of malignant potential. It is important to identify highly malignant cases of HCC, and the aim of this study was to clarify the impact of triple positive tumor markers as the prognostic factors for early-stage HCC within the Milan criteria.

Methods

This study investigated 199 patients who underwent hepatectomy for HCC within the Milan criteria between January 2001 and May 2009. Cumulative recurrence-free survival (RFS), overall survival (OS) and clinicopathological parameters were analyzed according to the number of positive tumor markers.

Results

In patients with triple-positive tumor markers, 5-year RFS and OS was poor (17.1 and 61.4%, respectively). Multivariate analyses revealed independent risk factors for recurrence to be HCV-antibody positive (relative risk [RR] 1.65, P=0.0154), non-initial treatment for HCC (RR 1.87, P=0.0047) and triple-positive tumor markers (RR 1.68, P=0.0376), and the independent risk factors for OS were high ICGR15 value (RR 2.46, P = 0.0146), maximum tumor size (RR 2.71, P = 0.0035) and triple-positive tumor markers (RR 2.57, P = 0.0198). Pathologically invasive growth, microvascular invasion and moderate to poor differentiation were significantly related to the number of the three tumor markers.

Conclusions

Triple-positive tumor markers for early-stage HCC within the Milan criteria showed poor prognosis and malignant characteristics. These markers could be a useful predictor for the degree of malignant potential in early-stage HCC.

Source

Dr. Maggie Ham and Dr. Albert Crimaldi, Ph.D.: Understanding hepatitis

By Dr. Maggie Ham and Dr. Albert Crimaldi Ph.D./Daily News Correspondents

The MetroWest Daily News

Posted Nov 19, 2013 @ 10:00 AM

Dr. Maggie Ham and Dr. Albert Crimaldi Ph.D.

Affecting millions of Americans, hepatitis is a disease of the liver, one of the largest organs in the human body that’s responsible for critical bodily functions, such as the clotting of blood, resisting infections and clearing waste. It is a major cause of liver cancer and a leading cause of death by infection, claiming some 15,000 lives every year.

Understanding this condition requires some insight: the word hepatitis simply means an inflammation of the liver, and the disease can take various forms and result from distinctly different causes.

Hepatitis can be acute (lasting a short time) or chronic (recurring or persistent), and some acute forms can become chronic. It can be viral (caused by a virus) or non-viral (caused by a number of other factors, including genetic disorders, prescription or over-the-counter medications, alcohol, toxins or even the body’s own immune system). One form is even triggered by the buildup of fat cells in the liver. Illness from the disease can range from mild to severe. Some types require medication; some will clear the body naturally.

The viral form is widespread in the U.S. and has five strains (A, B, C, D, and E), each caused by a different virus. The most common types are A (usually caused by contaminated food or water) and B and C (spread by infected blood). According to estimates from the U.S. Centers for Disease Control (CDC), about 70,000 people become infected every year with one type of acute viral hepatitis. In addition, about 1.2 million have chronic hepatitis B, and 3.2 million have chronic hepatitis C – and most of those are unaware they have the disease.

The CDC considers "hep C" a major public health threat because so many have the disease. Estimates are that 75 percent of those infected are baby boomers (those born between 1945 and 1965), believed to have contracted the disease in the 1970s and 1980s when the rates of hepatitis C were the highest, prior to both the availability of screening tests to eliminate hepatitis C from the blood supply and the heightened public awareness of hepatitis C virus transmission through high-risk activities such as intravenous (IV) drug use. Public health officials are urging everyone in that group to get tested, as testing is the only way to discover if the virus is present. Most people who get hepatitis C – a leading cause of liver cancer and the most common reason for liver transplants - end up with a chronic form of the illness.

Source

Using Nanoparticle Tracking Analysis in Study of Liver Disease

Published on 19 November 2013

The Gores Laboratory of the Mayo Clinic in Rochester, Minnesota (US) does basic research into liver disease. One of the main research areas of interest is lipotoxicity and its role in development of nonalcoholic steatohepatitis, a common feature of metabolic syndrome or obesity.

The group has developed the hypothesis that lipotoxicity induces the release of extracellular vesicles (exosomes and microvesicles) from the liver cells. They speculate that these extracellular vesicles are involved in immune cell recruitment and activation, resulting in liver inflammation. 
Choosing NanoSight's Nanoparticle Tracking Analysis enables Dr Gores' team to precisely measure the size distribution and quantity of the extracellular vesicles in samples. This is a crucial requirement of their research. With NTA technology, they are also able to measure vesicles immediately after their isolation, which allows their use at defined concentrations in subsequent experiments the very same day. 
Prior to using the NanoSight system, the Group has used scanning electron microscopy to visualize and measure size of particles and basic absorbance to measure protein amount for inaccurate measurements of vesicle numbers. Since having NanoSight NS300 instrument, they only use NTA to measure size distribution and quantity of their vesicles. 
Speaking about the NS300, research fellow, Dr Petra Hirsova, says "There really is no comparison with other techniques; being able to see, count and measure size of the particles in real time is a huge advantage over other techniques that we have used. Compared to scanning electron microscopy, preparing the sample and obtaining the results is much easier and faster with NTA. NTA provides a much more precise assessment of extracellular vesicle amount compared to measurement of total protein of the vesicles."

Source

The Media Needs to Stop Stigmatizing Our Best Weapon Against Heroin Addiction

NOVEMBER 19, 2013

BY ALEC MACGILLIS @AlecMacGillis

Earlier this year, I followed Senator Joe Manchin to town hall meetings with constituents in southern West Virginia to see how voters were reacting to his role in pushing for expanded background checks for gun purchases. What I found, on the whole, was that voters weren’t that exercised about guns. What they wanted to talk about most of all was painkiller drug abuse, which has been wreaking havoc in Appalachia and many other parts of the country (prescription drug abuse is up 36 percent since 2002, according to the federal government, afflicting some 2.5 million Americans) and leading to a rise in heroin usage (doubling over the decade to more than 450,000 users) as authorities try to restrict access to prescription pills. One of the primary concerns the constituents raised with Manchin was the lack of options for opiate addicts seeking treatment. For one thing, they said, local residents had to drive a long ways to get access to buprenorphine.

Haven’t heard of buprenorphine? That means you’re happily sheltered from the hellscape of opiate addiction. But the drug, which goes by the commercial name Suboxone, has emerged over the past decade as the biggest development on the drug treatment front. Made by the British consumer goods company Reckitt Benckiser and approved by the FDA in 2002, the drug has proven remarkably effective as a “maintenance therapy” for opiate addicts. It allays cravings for painkillers or heroin while, crucially, being harder to get a high off of than methadone. That means it can be prescribed for use at home, with no need for traveling daily to a clinic, as addicts must do to legally obtain methadone.

Buprenorphine—bupe for short—has proven so successful at allowing opiate addicts to feel normal and go about their lives that advocates hail it as something of a wonder drug. And the benefits multiply—less painkiller and heroin abuse means less HIV transmission, less hepatitis C, and, yes, fewer fatal overdoses. Check out the recent trends in buprenorphine use and heroin overdoses in Baltimore, which has embraced bupe as a weapon against its deeply entrenched heroin problem. No, correlation does not equal causation—for one thing, Baltimore was over the same period also expanding the use of naloxone, medication used by drug users and EMTs to reverse overdoses as they’re occurring. Still, it’s hard not to draw certain conclusions from these lines displayed in a recent article in the American Journal of Public Health, which echo the plunge in overdoses in France, an early adopter of buprenorphine.

So what’s not to like? Why are we not shipping us much buprenorphine as possible into small towns in Maine and eastern Oregon and eastern Kentucky and all the other places reporting surges in abuse of painkillers and now, increasingly, heroin? Well, partly because bupe has gotten stuck with its own stigma—not as strong as methadone's, but damaging nonetheless. My old newspaper, the Baltimore Sun, ran a very critical series on the drug shortly after I left the paper. My current employer, theNew Republic, chimed in not long ago with a piece about the troubles that the country of Georgia has had with a more powerful form of the drug called Subutex. And now, in by far the biggest p.r. blow of all, comes a massive two-day series in the New York Times that casts bupe in a deeply ambivalent light.

The reporter, Deborah Sontag, is to be commended for deep reporting on a realm of American life that is far too easily overlooked. She takes pains to present the complex picture that has emerged since the drug’s debut, with many accounts of opiate addicts who—using their real names, in a sign of remarkable candor—credit bupe with saving their lives, alongside accounts of the complications that have arisen with the spread of the drug, including Reckitt Benckiser’s questionable efforts to keep the market all for itself. But for all of the granular reporting, the overall tone and framing of the pieces is bluntly ominous: “Addiction Treatment With a Dark Side: In Demand in Clinics and on the Street, ‘Bupe’ Can Be a Savior or a Menace” was the headline of the first article; “At Clinics, Troubled Lives and Turbulent Care” was the headline of the second one.

The dark cast of the series, running in the nation’s paper of record, is surely going to make it even harder for buprenorphine to gain acceptance from doctors, regulators and the friends and families of addicts. “If you’re somebody that doesn’t like it already, it’s not going to make you like it. And if you do like it, you may have doubts now,” said Dr. Sharon Stancliff, medical director of the Harm Reduction Coalition in New York and a strong advocate of buprenorphine treatment. “Policy makers will say we need more restrictions, when the science says we need fewer restrictions.”

And that could well only exacerbate the complications described by the article, because so many of those problems grow out of the restrictions on addicts’ access to the drug. When the drug was approved, it came with strict limits—doctors needed to attend lengthy training sessions, they could prescribe to no more than 30 patients at a time, and they needed to provide counseling. The 30-person threshold was later raised to 100, but advocates say that it is still far too hard for many addicts to find prescriptions, not least because the regulations forbid prescriptions by physicians' assistants and nurse practitioners, who are the primary health care providers in many rural areas.

With so many physicians not wanting to go through the hassles of being approved to prescribe the drug—and the attendant hyper-scrutiny from the Drug Enforcement Agency—addicts have increasingly had to turn to the doctors who are less shy about milking the drug for its commercial potential. And not surprisingly, the lack of ready access to buprenorphine has resulted in some addicts buying and selling it on the street, a fact that both the Sun and Times series dwell on considerably.

But this street-selling is not necessarily as foreboding as it’s made to sound. Of course addicts are looking to get their hands on bupe by whatever means they can—it staves off the horror of opiate withdrawal and makes them feel normal. Yes, some addicts go to great lengths to abuse the drug to try to get a high off of it despite its pharmacological limitations, by injecting it or mixing it with other drugs. But this needs to be kept in perspective, too. The Times cites data showing 402 fatal overdoses linked to buprenorphine in the United States reported to the F.D.A. from spring 2003 through September. As the article notes, this pales in comparison with the 2,826 attributed to methadone over roughly the same period and the more than 19,000 fatal overdoses from opioids overall in 2010 alone.

The fact is, there is no silver bullet for the country’s growing opiate addiction problem. And any approach is going to seem tainted, to bourgeois eyes, by the inherently chaotic and desperate nature of the milieu in which opiate addiction is rooted (though not confined to—painkiller abuse has been on the rise in tony suburbs, too). It would be deeply unfortunate if fraught portrayals in the media with decidedly oversimplified, alarmist headlines had the side effect of dulling one of the best tools we have in this fight.

Source

Hepatitis C genotype 1 virus with low viral load and rapid virologic response to peginterferon/ribavirin obviates a protease inhibitor

Hepatology

Early View (Online Version of Record published before inclusion in an issue)

Viral Hepatitis

Brian L. Pearlman^1,2,3,4,*, Carole Ehleben²

Article first published online: 18 NOV 2013

DOI: 10.1002/hep.26624

Copyright © 2013 by the American Association for the Study of Liver Diseases

Potential conflict of interest: Dr. Pearlman has been on the speaker's bureau for Merck; C.E. has no conflicts of interest.

Abstract

The new standard of care for treatment-naïve patients with hepatitis C virus (HCV) genotype 1 includes triple therapy with peginterferon, ribavirin, and a protease inhibitor. However, patients who achieve a rapid virologic response after 4 weeks of peginterferon and ribavirin therapy are likely to achieve a sustained virologic response (SVR), and we hypothesized that protease inhibitor therapy may be unnecessary in these patients. Treatment-naïve, noncirrhosis patients infected with genotype-1 HCV and a low viral load at baseline were considered for inclusion (n = 233). After 4 weeks of lead-in therapy with peginterferon α-2b and ribavirin, 101 patients (48%) had a rapid virologic response (defined as undetectable levels of hepatitis C virus RNA at 4 weeks) and were eligible to participate. Patients were randomized 1:1 to 20 weeks of additional therapy with peginterferon α-2b and ribavirin (double therapy) or to 24 weeks of peginterferon α-2b, ribavirin, and boceprevir (triple therapy). There was no significant difference in rates of SVR-12 in patients treated with double versus triple therapy. This similarity persisted regardless of viral subtype (genotype 1a or 1b), interleukin (IL)−28b genotype (CC or non-CC), or ethnicity (African American versus non-Hispanic white). Conclusion: Protease inhibitor therapy could be obviated in genotype 1-infected treatment-naïve patients with low viral load at baseline who achieve undetectable viremia after 4 weeks of peginterferon/ribavirin.(Hepatology 2013)

Source

¿Para qué sirven las regiones no codificantes de los genomas de los virus RNA? Revisión sobre dominios funcionales del RNA viral.

Original Translation

Los virus RNA muestran una gran capacidad para evolucionar y adaptarse a nuevos ambientes, lo que les permite variar de hospedador o incrementar su resistencia a los tratamientos antivirales. Esto convierte la infección por determinados patógenos, como la causada por el virus de la hepatitis C (VHC), en un problema de salud pública. El genoma de los virus RNA contiene la información genética que da lugar a las proteínas virales. También actúa como molde durante la replicación para producir numerosas copias de sí mismo. Además el RNA genómico codifica otra información representada por dominios estructurales que desempeñan funciones imprescindibles para el virus. En este proceso, la introducción de mutaciones por la RNA-polimerasa viral genera un amplio espectro de mutantes que contribuye de manera efectiva a la proliferación del virus y amplía las posibles variantes virales capaces de evadir la respuesta inmunológica del individuo infectado. Todo ello debe de hacerse sin comprometer las funciones esenciales codificadas en el genoma viral. Para ello, los virus han desarrollado un sistema de almacenamiento de la información adicional al código genético universal. Este sistema está compuesto por elementos de estructura compleja que se conservan entre distintas variantes virales, denominados dominios funcionales de RNA. En este sentido, el VHC puede ser considerado el prototipo en las investigaciones que se están llevando a cabo en la materia. Los dominios funcionales pueden interaccionar con otros dominios localizados en regiones distantes del RNA viral o con proteínas bien del virus o bien de la célula infectada para dirigir y regular las distintas etapas del ciclo viral. Por tanto, el ser funcionalmente esenciales les convierte en excelentes dianas para el desarrollo de nuevos fármacos que permitan disminuir la carga viral de forma eficaz. El trabajo presentado resume los datos de los que se disponen en la actualidad sobre los dominios funcionales en genomas virales RNA y revisa los logros conseguidos en el desarrollo de nuevos antivirales dirigidos frente a estas dianas, prestando especial atención a aquellos diseñados frente al VHC.

Unmasking the information encoded as structural motifs of viral RNA genomes: a potential antiviral target. Cristina Romero-López and Alfredo Berzal-Herranz. Rev. Med. Virol., 2013; 23: 340–354.

---

Translation

Monday, November 18, 2013

What are the noncoding regions of the genomes of RNA viruses? Review of functional domains of viral RNA.

RNA viruses show a great ability to evolve and adapt to new environments, allowing them to vary or increase host resistance to antiviral treatments. This makes the infection by certain pathogens, such as that caused by the hepatitis C virus (HCV) in a public health problem.The RNA genome of the virus contains the genetic information leading to viral proteins. It also acts as a template during replication to produce many copies of itself. Furthermore, the genomic RNA encodes other information represented by structural domains serving essential for virus. In this process, the introduction of mutations in the viral RNA polymerase generates a broad spectrum of mutants which effectively contributes to the spread of the virus and potential viral variants extends able to evade the immune response of the infected individual. All this must be done without compromising the essential functions encoded in the viral genome. For this reason, viruses have developed a system for storing additional information to the universal genetic code. This system consists of a complex structure elements that are conserved among different viral variants, termed RNA functional domains. In this regard, HCV can be considered the prototype research being carried out in the field. Functional domains can interact with other domains located in remote regions of the viral RNA or proteins either virus or infected cell to direct and regulate the viral cycle stages. Therefore, the essential be functionally makes them excellent targets for the development of new drugs that may decrease the viral load effectively. The present work summarizes the data that is currently available on the functional domains in RNA viral genomes and reviews the achievements in the development of new antiviral drugs directed against these targets, with special attention to those designed against HCV.

Unmasking the information encoded as structural motifs of viral RNA genomes: a potential antiviral target. Cristina Romero-Lopez and Alfredo Berzal-Herranz. Rev. Med Virol., 2013, 23: 340 - 354.

Source

Indonesia’s Hidden Hepatitis C Time Bomb

By Claudia Stoicescu on 12:20 am September 10, 2013.
Category Featured, Health, News
Tags: antivirals, hepatitis C

A nurse loads a syringe with a vaccine against hepatitis B. No vaccine exists yet for hepatitis C, with which 28 million Indonesians are infected. (AFP Photo/Robyn Beck)

Aris was diagnosed with hepatitis C in 2001. For the previous four years, he had injected heroin daily. Sometimes he shared needles, syringes and other injecting equipment with friends, unaware that this practice can easily transmit blood-borne viruses like hepatitis B and C, and HIV, the virus that can lead to acquired immune deficiency syndrome (AIDS).

“I didn’t know anything about safe injecting and harm reduction,” he said. “I was offered to be tested for HIV by a health worker, and thought, ‘It wouldn’t hurt to find out about hepatitis C, too.’ I tested positive for both.”

Indonesia has one of the highest rates of viral hepatitis in Southeast Asia. Aris is one of 28 million people in the country living with the hepatitis C virus. Of these 28 million, half could potentially progress to chronic liver disease, and over a third to liver fibrosis and liver failure or cancer. Hepatitis and other liver-related disease is a leading cause of death among Indonesians.

According to the Health Ministry, more than 7 million people across 21 provinces — or more than 2 percent of the country’s population — had hepatitis C as of 2007. People who inject drugs and live with HIV carry an especially heavy disease burden. Anecdotally, it’s estimated that over two-thirds of Indonesian drug injectors have hepatitis C, with about 60 percent to 90 percent of these also living with HIV. Co-infection with HIV more than triples the risk for liver disease, liver failure, and liver-related death from hepatitis C.

Two years after his double diagnosis, Aris started taking antiretroviral treatment (ARV) to manage his HIV infection.

“By that point I was so weak that I had to resort to bed rest every few days,” he recalls. “I didn’t find out until years later that my HIV infection was worsening my liver disease. At the time, I lived in Salatiga, a small town in Central Java, where access to information about hepatitis and co-infection was very limited.”

Curable

Hepatitis C is preventable, treatable and curable. Effective, evidence-based strategies for preventing hepatitis C transmission among drug injectors include a combination of long-term, consistent provision of harm-reduction services like needle syringe exchange programs and opioid substitution treatment, and antiviral treatment for those who already have the virus.

First-line recommended treatment consists of pegylated interferon alfa and ribavirin, both of which are included in the World Health Organization’s so-called complementary Model Essential Medicines List, an internationally recognizable set of safe, cost-effective medicines to guide countries in treating critical health needs.

“In Indonesia, these proven strategies are not implemented at the level or quality needed to have a significant impact on the explosive HIV epidemic,” says Suhendro Sugiharto, program manager at the Indonesian Drug Users’ Network (PKNI).

Research conducted by PKNI earlier this year among 240 members of the drug-using community across eight cities in Indonesia revealed that in contrast to government reports that existing harm reduction services reached nearly two-thirds of people who inject drugs, close to half of service beneficiaries reported never receiving any information on hepatitis C testing and treatment.

Twelve years after his diagnosis, Aris still hasn’t accessed antiviral treatment. In order to determine what treatment course and duration are most appropriate, he is required to undergo a series of diagnostic tests that, combined, cost up to Rp 6.5 million ($580) — almost three times the average monthly salary in Indonesia. Depending on which genotype he is infected with — there are six genotypes of the hepatitis C virus, each of which may respond differently to treatment — he could face costs up to Rp 144 million for treatment alone.

“I got the basic liver function tests because those are the cheapest. But the rest are too expensive for me,” Aris admits. “Although part of my stomach is permanently swelled up and increasingly painful by the day, I only take traditional herbal medicine. Even if I could cover the diagnostic tests and the huge cost of treatment, I am worried about the side effects and the interactions it might have with my ARV treatment.”

Limited reach

Hepatitis C treatment in several Southeast Asian countries, including in Indonesia, is licensed to pharmaceutical companies Roche and Merck.

On July 28, a group of 16 international and regional advocates, including PKNI, sent a joint, open letter to Roche and Merck to demand lower prices for peginterferon alfa in Asia. In his reply, Roche chief executive Severin Schwan acknowledged the role of treatment access in hepatitis care but stayed clear of mentioning price reductions as an option for facilitating such access. The groups are due to meet with the pharmaceutical company in the near future.

Officially, the Indonesian government publicly funds treatment for hepatitis C under a number of insurance schemes, including Askes, which covers health costs including treatment for hepatitis C for government employees, Jamsostek, which acts as social insurance for employers that choose to register with the scheme, and Jamkesmas, Indonesia’s health waivers for low-income individuals.

But the reach of existing insurance and support schemes is extremely limited. A majority of people either don’t know these subsidies exist or don’t qualify for them.

Speaking on Sunday at Aksi Hepatitis, an event held at Monas commemorating World Hepatitis Day, Indonesia’s Minister of Health Nafsiah Mboi announced that hepatitis C treatment will be covered by National Health Insurance beginning in 2014, in accordance with the 2004 National Social Security Law.

“This is an important step forward,” says the PKNI’s Suhendro. “But we need to make sure that such schemes facilitate treatment access for the most vulnerable among us, and that they do so with minimal bureaucracy attached. Hepatitis C among our community is a ticking time bomb,” he adds.

Continue to die

Indonesia does not conduct routine surveillance for hepatitis C, and that makes it challenging to assess the true scale of the crisis. It was not until 2011 that the Health Ministry established a national program focused on viral hepatitis, under the Sub-Directorate for Gastrointestinal Infections and Diarrheal Diseases.

“We are currently preparing an action plan for hepatitis control to be implemented between 2015 and 2019, as well as national guidelines for management of hepatitis C,” said Naning Nugrahini, who heads the sub-directorate. “We also plan to strengthen data collection and surveillance among most affected populations.”

A policy briefing launched on Sunday by the PKNI to coincide with Aksi Hepatitis demands that the government scales up its commitment to hepatitis by joining affected communities in negotiating price reductions with pharmaceuticals.

“I want treatment,” Aris says. “My dream is to see hepatitis C medication produced locally and affordably. Until pharmaceutical companies drop their patents, people will continue to die.”

Claudia Stoicescu is a doctoral researcher investigating sexual and drug injecting risk behaviors

among women who inject drugs in Indonesia. She is based in Jakarta.
Source

The new epidemic - hepatitis C and HIV coinfection

Positive Living 2013 September

Positive Living article • Graham Stocks

Photo: KNICKOHR

New cases of hepatitis C (HCV) are still being seen largely amongst people who inject drugs (PWID). However, in recent years it has become more recognised that HCV is also passed on sexually and that a disproportionate number of people living with HIV (PLHIV) are also living with HCV.

Between 2004 and 2008, the Australian Trial in Acute Hepatitis C (ATAHC) 1 found that around 30% of those who had recently acquired HCV were also HIV positive, and that 15% of those new HCV infections were attributed to male-to-male sexual activity 2.

In Australia, around 13% of PLHIV are also living with HCV. This estimate is similar in the USA 3, while in Europe up to 25% of PLHIV also have hepatitis C 4.

Globally, the figures vary widely across different geographic regions. Researchers taking a mobile medical clinic across the American urban northeast discovered this recently. Within this population, they found that 33% of those diagnosed with HIV between 2003 and 2011 also had hepatitis C 5 and that gay and other MSM were over three times more likely to have both infections compared to heterosexuals. In some areas of Eastern Europe and Central Asia (former states of the USSR) the rates of coinfection are higher still.

In her IAS 2013 plenary lecture, Karine Lacombe from the Université Pierre et Marie Curie in Paris, claimed that HIV/HCV coinfection constitutes a new epidemic, and provided an overview of the harmful and synergistic effects of having both.

Put simply, having both viruses complicates your clinical care considerably. The combination increases the chance of liver fibrosis and impairs Natural Killer (NK) cell anti-fibrotic activity. End-stage liver disease is the highest cause of death in people who are living bi-virally.

But it’s not all bad news. Treating HIV can restore your anti-HCV T-cell response (a good reason to initiate it early), and unlike HIV, HCV is a curable disease because it doesn't integrate into the host genome, so there are no archived mutations.

Plus, when you add the new first generation direct-acting antivirals, protease inhibitors boceprevir and telaprevir, to standard treatment peginterferon and ribavirin it can shorten treatment time and you’ve got a better chance of curing the HCV.

Results of trials with second generation protease inhibitors are also very encouraging. Both naive patients and relapsers showed an 80% sustained virological response with simeprevir and almost 90% early virological response with faldaprevir.

Treating people with HCV to reduce new transmissions is a real possibility in the near future, however this is a monumental task as globally around 185 million people are living with the virus.

A range of newer drugs are also in the pipeline, and hopefully some of these will be eventually licensed for use.

Treating and clearing HCV infection still results in a health burden, as there is an increased risk of liver cancer, specifically hepatocellular carcinoma. So, ongoing care and monitoring of liver health is essential 6.

Go to an excellent presentation for which both the webcast and presentation slides are available.

Another presentation on HCV and HIV coinfection amongst gay and MSM was delivered by Thomas Martin on behalf of a team from Chelsea and Westminster Hospital in London.

He began with a fairly gloomy overview. Having both infections reduces spontaneous clearance rates of HCV (PLHIV account for only 20% of all cases)7. HCV RNA set points tend to be higher which increases the chance of transmission8. Having both also increases the chance of progressing to cirrhosis faster. And while treatments are improving, there is still a reduced success rate among PLHIV.

Liver disease is a major non-AIDS cause of death among PLHIV, accounting for 9% of all deaths in the largely treated D:A:D Cohort (2009 to 2011) 9. Viral hepatitis infection (mainly HCV) was the main contributor to these deaths.

Sexual transmission of HCV in HIV positive gay men in Western Europe, North America and Australia has been occurring since the mid 1990s. But it has been increasing, rising steeply from 2005, and currently up to 5% of positive gay may become infected annually 10

The opposite is the case for PWID. A recent analysis of the needle and syringe program (NSP) in Australia revealed that between 1995 and 2010 the number of new cases of HCV in people using NSPs had halved 11.

Some risk factors which have been identified for HCV transmission include ulcerating genital infections, unprotected anal intercourse and activities such as use of sex toys, group sex, fisting and recreational drug use.

A major German study recently confirmed that blood (even in imperceptible amounts) is the critical medium of transmission, noting that HCV remains transmissible at room temperature for the order of 16 hours 12.

A UK study specifically addressed HCV reinfection rates in 191 coinfected gay men who had either been successfully treated for acute or chronic HCV or who had spontaneously cleared their HCV. Overall 23% of these gay men were reinfected within two years, and were treated a second time. Of the 24 who cleared their HCV a second time, 8 (33%) were reinfected again. This represents a very high risk of ongoing reinfection in gay men with HIV who are diagnosed with HCV infection.
Treatment was generally successful for those who were reinfected, with sustained virological response (SVR) of 73% for HCV genotype 1 and 4 and 100% for genotypes 2 and 3. Standard treatment (pegIFN/RBV) was used for all patients in these clinics.

Spontaneous clearance of HCV reinfection was 20% which is consistent with primary (first) HCV infection clearance. The study also demonstrated weak evidence for any protective immunity after spontaneous clearance.

Go to this stimulating and informative presentation for which the abstract and selected presentation slides are available. (see also 13).

This study confirms findings from previous smaller studies in two large HIV clinics in Amsterdam which found that overall 33% of positive gay men who cleared their HCV became reinfected 14.

The authors recommend PLHIV who have previously cleared their HCV to ensure that subsequent reinfection is detected and treated early. The British HIV Association (BHIVA) guidelines for the management of hepatitis virus and HIV coinfections issued earlier this year recommend HCV antibody testing every 3-6 months for gay men who remain at risk following clearance of an initial HCV infection. The current (2010) In Australia, the Sexually Transmissible Infections In Gay Men Action Group STIGMA Guidelines recommend annual HCV testing for HIV positive MSM, recognising that HCV may be acquired during sex.

These presentations add further to growing evidence base that HCV may be acquired sexually and that for PLHIV the course of HCV disease and its treatment may be more complicated. A number of PLWH organisation have information about reducing the risk of acquiring HCV through sex for HIV+ve gay men, go to just one  recent resource.

1.Dore GJ et al. for Australian Trial In Acute Hepatitis C Study Group. Effective treatment of injecting drug users with recently acquired hepatitis C virus infection. Gastroenterology. 2010 Jan;138(1):123-35.e1-2. doi: 10.1053/j.gastro.2009.09.019.

2.Grebely J et al for ATAHC Study Group. Hepatitis C virus reinfection and superinfection among treated and untreated participants with recent infection. Hepatology. 2012 Apr;55(4):1058-69. doi: 10.1002/hep.24754.

3.Spradling PR et al for HIV Outpatient Study Investigators. Trends in hepatitis C virus infection among patients in the HIV Outpatient Study, 1996-2007. J Acquir Immune Defic Syndr. 2010 Mar;53(3):388-96.

4.Lacombe K, Rockstroh J. HIV and viral hepatitis coinfections: advances and challenges. Gut. 2012 May;61 Suppl 1:i47-58. doi: 10.1136/gutjnl-2012-302062.

5.Morano JP, Gibson BA, Altice FL. The burgeoning HIV/HCV syndemic in the urban Northeast: HCV, HIV, and HIV/HCV coinfection in an urban setting. PLoS One. 2013 May 14;8(5):e64321. doi: 10.1371/journal.pone.0064321.

6.Taylor LE, Swan T, Mayer KH. HIV coinfection with hepatitis C virus: evolving epidemiology and treatment paradigms. Clin Infect Dis. 2012 Jul;55 Suppl 1:S33-42. doi: 10.1093/cid/cis367 http://cid.oxfordjournals.org/content/55/suppl_1/S33.full.pdf+html

7.Webster DP, Wojcikiewicz T, Keller M, Castelnovo D, Mistry H, Gilleece Y, Tibble J, Fisher M. Spontaneous clearance and treatment of acute hepatitis C infection in HIV-positive men with 48 weeks of interferon-alpha and ribavirin. Int J STD AIDS. 2013 Mar 20. doi: 10.1177/0956462412472317

8.Sherman KE et al. Viral kinetics in hepatitis C or hepatitis C/human immunodeficiency virus-infected patients. Gastroenterology. 2005 Feb;128(2):313-27

9.Weber R, Smith C, D:A:D Study Group. Trends over time in underlying causes of death in the D:A:D study from 1999 to 2011. Program and abstracts of the XIX International AIDS Conference; July 22-27, 2012; Washington, DC. Abstract THAB0304

10.van der Helm JJ, Prins M, del Amo J, Bucher HC, Chêne G, Dorrucci M, Gill J, Hamouda O, Sannes M, Porter K, Geskus RB; CASCADE Collaboration. The hepatitis C epidemic among HIV-positive MSM: incidence estimates from 1990 to 2007. AIDS. 2011 May 15;25(8):1083-91. doi: 10.1097/QAD.0b013e3283471cce.

11.Iversen J, Wand H, Topp L, Kaldor J, Maher L. Reduction in HCV incidence among injection drug users attending needle and syringe programs in Australia: a linkage study. Am J Public Health. 2013 Aug;103(8):1436-44. doi: 10.2105/AJPH.2012.301206.

12.Schmidt AJ et al. Trouble with bleeding: risk factors for acute hepatitis C among HIV-positive gay men from Germany--a case-control study. PLoS One. 2011 Mar 8;6(3):e17781. doi: 10.1371/journal.pone.0017781.

13.Martin TC, Martin NK, Hickman M, Vickerman P, Page EE, Everett R, Gazzard BG, Nelson M. HCV reinfection incidence and treatment outcome among HIV-positive MSM in London. AIDS. 2013 Jun 3. doi: 10.1097/QAD.0b013e32836381cc.

14.Lambers FA et al for MOSAIC (MSM Observational Study of Acute Infection with hepatitis C) study group. Alarming incidence of hepatitis C virus re-infection after treatment of sexually acquired acute hepatitis C virus infection in HIV-infected MSM. AIDS. 2011 Nov 13;25(17):F21-7. doi: 10.1097/QAD.0b013e32834bac44.

Source

VIH/VHC En Prison, L’urgence (HIV/HCV In Prisons, Emergency)

Original Translation

VIH/VHC EN PRISON, L’URGENCE

Depuis les années 90, les associations de lutte contre le sida  dénoncent la situation sanitaire catastrophique des prisons françaises. L'étude PREVACAR (estimation de la prévalence virale et de l'offre de soins en milieu carcéral) publiée par l’InVS (Institut national de Veille Sanitaire) vient, une nouvelle fois, confirmer les constats et les cris d'alarme des acteurs de terrains. Le TRT-5 monte au front dans un communiqué (6 novembre). Le voici.

"Dans les prisons françaises, la prévalence du VIH est de 2 % : c’est 10 fois celle de la population générale. La  prévalence du VHC de 4,8 % c’est 6 fois celle la population générale. L'étude demande un dépistage et une prise en charge de ces pathologies infectieuses pour en limiter la transmission et améliorer le pronostic des patients. L'an dernier, l'étude PRI2DE (accès aux mesures de prévention et réduction des risques infectieux en milieu pénitentiaire) confirmait l'existence de pratiques à risques liées à l'injection de drogues par voie intraveineuse.

Trente ans après le début de l'épidémie du VIH, nous sommes toujours dans l’attente de mesures urgentes de réduction des risques et de l’application de la loi du 18 janvier 1994 sur l'égalité de la prise en charge sanitaire entre le milieu libre et le milieu carcéral.

Les ministres de la Justice et de la Santé ont initié en début d’année des groupes de travail paritaires, l’un sur la suspension de peine, le second sur la prévention et la réduction des risques en milieu carcéral. Le groupe prévention et réduction des risques infectieux a récemment transmis ses recommandations aux ministères concernés, proposant de débuter une expérimentation de programmes d’échanges de seringues.

Notre collectif participe à ces études et travaux et considère qu'il n'existe aucune justification fondée pour continuer à priver les personnes détenues d'un égal accès aux soins et aux mesures de prévention. La mise en place de programmes d'échanges de seringues expérimentaux constituerait une formidable avancée. Des programmes d'échanges de seringues en milieu carcéral ont été expérimentés depuis plus de 20 ans dans de nombreux pays et ont montré l'efficacité d'une approche combinée de traitements de substitution aux opiacés, de programme d’échange de seringues et d’éducation par les pairs. Ces dispositifs n'ont pas entraîné de recrudescence de la toxicomanie, ni provoqué d’incidents de sécurité liés à la détention de seringues. Au vu de cette nouvelle enquête et des conclusions des derniers travaux d’experts, nous demandons un engagement ferme et immédiat du gouvernement pour la mise en place de programmes d'échanges de seringues expérimentaux en prison."

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Translation

HIV / HCV IN PRISONS, EMERGENCY

Since the 90s, associations fighting against AIDS denounce catastrophic health situation of French prisons. The PREVACAR study (estimation of viral prevalence and health care provision in prisons) published by InVS (Institut National de Veille Sanitaire) has, once again, confirm the findings and alarm cries of actors land. The TRT-5 goes to the front in a statement (November 6). Here it is.

"In French prisons, HIV prevalence is 2%, it is 10 times that of the general population prevalence of HCV is 4.8% 6 times that in the general population The study requires.. detection and treatment of these infectious diseases to reduce transmission and improve the prognosis of patients. Last year, the PRI2DE (access to prevention and reduction of risk of infection in prison) study confirmed the existence of risk practices related to injection drug intravenously.

Thirty years after the beginning of the HIV epidemic, we are still waiting for urgent measures to reduce risks and the application of the law of 18 January 1994 on the equality of health care between free environment and prisons.

Ministers of Justice and of Health have initiated earlier this year of joint working groups, one on the suspended sentence, the second on the prevention and reduction of risks in prisons. The prevention and reduction of risk of infection group has recently submitted its recommendations to the ministries concerned, proposing to start an experiment of needle exchange programs.

Our group is involved in these studies and work and considers that there is no justification for continuing basis to deprive detainees of equal access to care and prevention. The establishment of experimental needle exchange programs would be a huge step forward. Of needle exchange programs in prisons have been tested for over 20 years in many countries and have shown the effectiveness of a combined approach to treatment of opiate substitution of needle exchange program and peer education. These devices have not resulted in increase of drug or caused by security incidents related to the detention of syringes. In light of this new investigation and the findings of recent work of experts, we require a firm and immediate government commitment to the development of experimental needle exchange programs in prison. "

Source

TRAINING MANUAL FOR TREATMENT ADVOCATES: Hepatitis C Virus and Coinfection with HIV

Provided by Treatment Action Group (TAG)

DOWNLOAD:

The Manual as PDF (1.2MB)

Sections are available as PDF slides here.

November 2013

By Karyn Kaplan and Tracy Swan

The purpose of this manual is to provide information for you and your community. This information can be used to advocate for access to prevention and diagnosis of, and care and treatment for, hepatitis C virus (HCV).

The information here is written by and for people who are not medical specialists. We are treatment activists who learned about hepatitis C because it was a problem for people in our communities. We designed it to help you understand basic information about hepatitis C and coinfection with HIV: how it is transmitted, how to prevent hepatitis C, how a person can find out if he or she has hepatitis C, what happens to both HIV-negative and HIV-positive people who have hepatitis C, information used for making treatment decisions, and treatment options.

This manual is organized into short sections, and each section can be shared with a small group of people in less than one hour.

There are discussion points and action steps at the end of each section. The discussion points are intended to start conversations about the key issues raised in each section. The action steps are intended to start conversations about how to translate the key issues into advocacy in the community and to allow participants to find solutions together.

All of the sections are available as PDF slides here.

Source

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

Consumer Updates by E-mail

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On this page:

• Evidence of Danger
• Following the Law

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.

Source

Terrie Lenhart-Jenson: My Personal HCV Story

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

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