EASL 2012: New HCV Drug Induces Rapid, Durable Drops in Viral Load

From Medscape Medical News

Daniel M. Keller, PhD

April 30, 2012 (Barcelona, Spain) — In 3 phase 2 trials of GS-7977, there was a concordance between the sustained virologic response (SVR) 4 weeks after the end of therapy (SVR4) and SVRs at 12 and 24 weeks after therapy (SVR12 and SVR24) in treatment-naive patients infected with hepatitis C virus (HCV) genotypes 1, 2, or 3.

No patient relapsed after posttreatment week 12, and 99% of patients with SVR4 for whom posttreatment week 12 data were available achieved SVR12, Eric Lawitz, MD, from Alamo Medical Research in San Antonio, Texas, reported here at the International Liver Congress 2012.

GS-7977 (formerly PSI-7977) is a specific nucleotide analogue inhibitor of HCV NS5B RNA polymerase and is taken orally once daily. Previous reports have shown that it has broad antiviral activity against HCV genotypes 1, 2, and 3, with or without interferon, in treatment-naive patients, and has a high barrier to the development of viral resistance.

The aim of the study was to evaluate concordance between SVR4 and SVR12 or SVR24 among treatment-naive patients taking GS-7977 400 mg daily in the PROTON (n = 144), ELECTRON (n = 120), and ATOMIC (n = 332) phase 2 clinical trials. The trial protocols differed somewhat, but in general were various combinations and durations of GS-7977, pegylated interferon (Peg-IFN), and ribavirin.

In the PROTON and ATOMIC trials, depending on viral genotype, patients received GS-7977 plus Peg-IFN/ribavirin for 12 weeks followed by Peg-IFN for 12 weeks, Peg-IFN/ribavirin alone for 48 weeks, GS-7977 plus Peg-IFN/ribavirin for 12 or 24 weeks, GS-7977 plus PegIFN/ribavirin for 12 weeks followed by 12 weeks of GS-7977 alone or by GS-7977 plus ribavirin.

In the ELECTRON trial, some patients with genotypes 2 or 3 virus received similar combinations but only out to 12 weeks. Other patients with genotypes 1, 2, or 3 received GS-7977 plus ribavirin for 12 weeks.

The analysis involved only patients treated with GS-7977 400 mg in combination with interferon, ribavirin, or both for at least 4 weeks who had SVR4 plus SVR12 or SVR4 plus SVR24 data available. Of the 596 patients in the 3 studies, 259 (43%) were eligible for analysis.

At baseline in all treatment groups, mean age ranged from 43 to 52 years, and most patients were white, male, had similar body mass indices (mean, 26 to 28 kg/m²), and had interleukin-28B genotype non-CC. Mean baseline HCV RNA levels were mainly in the range of 6.3 to 6.7 log₁₀ IU/mL.

Dr. Lawitz presented results for virologic response at the end of therapy and for SVR4, SVR12, and SVR24.

"If we look at all regimens and look at the concordance between SVR4 and SVR12, we can see that 249 of the 251 [patients] were concordant between SVR4 and SVR12 — a concordance rate of 99%," he said. "If we look at concordance between SVR4 and SVR24, we can see that although the numbers are smaller, there is complete concordance — all 107 patients who had an SVR4 achieved an SVR24.... The concordance held, irrespective of the presence or absence of interferon. However, the dataset is fairly small in the noninterferon arm, limiting conclusions."

Dr. Lawitz concluded that "much of the concordance is due to the high response rates observed across all treatment groups. To date, relapse after week 4 is infrequent and was only observed in patients who received a peg-interferon-containing regimen."

Session moderator George Papatheodoridis, MD, associate professor of medicine and gastroenterology at the Medical School of Athens University, staff member at Hippokration General Hospital, in Athens, Greece, and a member of the European Association for the Study of the Liver Governing Board Scientific Committee, told Medscape Medical News that GS-7977 "is a very interesting, very promising molecule. It seems to be rather safe and very effective, even in combination with ribavirin." Dr. Papatheodoridis was not involved in any of the studies.

In terms of new drugs to treat HCV, he said, "some of the new molecules are very genotype-specific.... Most of the protease inhibitors are developed to work only for genotype 1; some of them work for genotype 2, but not 3 and 4. The nucleoside polymerase inhibitors seem to work better across almost all genotypes, so this is the only class [of drug] that is not that genotype-specific."

Dr. Papatheodoridis wondered about the use of SVR4 as a standard efficacy measure. "I don't think that SVR4 will and should be the standard for SVR," he told Medscape Medical News. "Of course, we know that the FDA and most of the physicians have now accepted SVR12. So probably...SVR12 is going to be the standard for reporting trials in the near future. Still, with all these combinations, patients should have at least 1 examination, maybe 6 months or 12 months after SVR12, so we can be sure that this SVR remains over time. I think that SVR12 is going to be the standard from now on, but the patients treated with the new regimens should be followed for a bit longer."

He admitted that SVR4 looks predictive of later sustained responses. "You expect most of the patients to relapse soon after stopping treatment [if they are going relapse]. Of course, SVR4 is reasonable; we know and we expect that it is going to be associated with SVR12 and SVR24. There is no rush to decide the SVR just 4 weeks after treatment.... We should be sure that we eradicated the virus," he cautioned.

Dr. Lawitz reports financial relationships with Abbott, Achillion Pharmaceuticals, Anadys Pharmaceuticals, Biolex Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, GlobeImmune, Idenix Pharmaceuticals, Idera Pharmaceuticals, Inhibitex Pharmaceuticals, Medarex, Medtronic, Merck, Novartis, Pharmasset, Roche, sanofi-aventis, Schering-Plough, Santaris Pharmaceuticals, Scynexis Pharmaceuticals, Tibotec, Vertex Pharmaceuticals, ViroChem Pharma, and ZymoGenetics. Dr. Papatheodoridis has disclosed no relevant financial relationships.

The International Liver Congress 2012: Abstract 7. Presented April 19, 2012.

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A baby is born addicted to drugs about once an hour, study says

By Karen Kaplan, Los Angeles Times / For the Booster Shots blog

April 30, 2012, 1:47 p.m.

Here’s some depressing news to kick off your week: The proportion of pregnant women who are addicted to opiates increased nearly fivefold between 2000 and 2009. Accordingly, the proportion of babies born addicted to the drugs who experience withdrawal after birth nearly tripled during the same period.

These calculations come courtesy of researchers from the University of Michigan and the University of Pittsburgh, who reported their findings in a study published online Monday by the Journal of the American Medical Assn. After combing through hospital data compiled by the federal Agency for Healthcare Research and Quality, the team found that 3.39 out of every 1,000 babies born in an American hospital in 2009 had neonatal abstinence syndrome, up from 1.2 out of every 1,000 hospital births in 2000. That translates to 13,539 newborns in 2009 – or roughly one born per hour that year.

Neonatal abstinence syndrome, or NAS, affects babies who become addicted to drugs in utero -- especially opiates -- and go through withdrawal once they are living outside the womb. Symptoms include seizures and tremors, respiratory distress, vomiting and an inability to eat without becoming sick.

Treatments haven’t improved much in the past decade, and some babies require morphine or methadone to get over their addictions. The typical baby born with NAS winds up staying in the hospital for about 16 days before he or she can be discharged, according to the JAMA report.

The immediate cause for this spike in babies with NAS is an even larger spike in pregnant women addicted to prescription painkillers, heroin and other opiates. According to the federal data, 5.63 out of every 1,000 mothers who gave birth in a hospital in 2009 were addicted to opiates, up from 1.20 per 1,000 in 2000, the study found. Experts estimate that 60% to 80% of babies exposed to heroin or methadone in utero wind up addicted themselves.

The average cost of caring for a baby with NAS has risen from $39,400 in 2000 to $53,400 in 2009 – an increase of 35%, despite the fact that the amount of time affected infants remained in the hospital didn’t change over the decade. Adjusting for inflation, the total money spent to care for babies with neonatal abstinance syndrome jumped from $190 million to $720 million over that period. The share of the total tab picked up by Medicaid rose from 69% in 2000 to 78% in 2009, according to the JAMA study.

In an editorial that accompanies the study, two experts from Maine (which has one of the highest rates of addiction to prescription opiates) bemoan the fact that treatment for infants with NAS and their addicted mothers has improved so little in recent years.

“Novel pharmacotherapy research is needed to improve maternal opiate maintenance strategies to protect the fetus from in utero withdrawal, and to reduce the incidence and severity of NAS,” they write. As one hopeful sign, they mention recent findings that link two particular genes with the severity of withdrawal symptoms in newborns. Someday, doctors may be able to tailor their treatments for these babies by checking to see what versions of these (and perhaps other) genes they have.

You can read the study here and the editorial here.

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May Is Hepatitis Awareness Month

April 30, 2012

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; and John Ward, MD, Director, Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention

Every May, the Department of Health and Human Services (HHS), the Centers for Disease Control and Prevention (CDC), and our public health partners across the nation observe Hepatitis Awareness Month. This year, we are very pleased to be marking this observance during a time of increased awareness about and collaboration around viral hepatitis –due in large part to the work of our federal partners over the past year on the implementation of the Action Plan for the Prevention, Care and Treatment of Viral Hepatitis.

Developed by an inter-agency working group and announced last May by Dr. Howard Koh, Assistant Secretary for Health, the Action Plan details steps to increase viral hepatitis awareness and knowledge among healthcare providers and communities and strategies to improve access to quality prevention, care, and treatment services for persons living with viral hepatitis. For the past year, we have been collaborating with our colleagues across HHS, as well as from the Department of Veterans Affairs and Department of Justice’s Federal Bureau of Prisons, to pursue the strategies detailed in the Action Plan. Together, we are working to ensure that new cases of viral hepatitis are prevented and that persons who are already infected are tested, informed about their infection, and provided with counseling, care, and treatment.

Learn More About Viral Hepatitis Risks, Tests and Treatment
An estimated 3.5–5.3 million Americans are living with chronic (lifelong) hepatitis B or hepatitis C virus infection. Most of them do not know that they are infected, placing them at greater risk for severe, even fatal, complications from the disease and increasing the likelihood that they will spread the virus to others. We encourage you to use Hepatitis Awareness Month to learn more about this “silent epidemic.” One place to start learning more is CDC’s Hepatitis Awareness Month webpage. Check back over the course of the month as exciting new resources and tools are added to this page. The CDCNPIN webpage is another important resource, where federal partners working to implement the Action Plan have posted downloadable materials designed to educate the public, patients, and providers about viral hepatitis. Select “hepatitis” as your topic and add relevant keywords below, such as “testing,” “treatment,” or “Asian American,” and you will get a list of materials to read and share with others.

Inaugural Hepatitis Testing Day Coming on May 19
As called for in the Action Plan, May 19th has been designated as Hepatitis Testing Day in the United States. Coinciding with Hepatitis Awareness Month, this inaugural Hepatitis Testing Day offers an important opportunity to remind healthcare providers and educate the public about who should be tested for viral hepatitis. We’ll be sharing more about this observance in a blog post later this month. In the meantime, to learn more and start thinking about how you and your organization can participate in promoting viral hepatitis awareness and testing, visit CDC’s Hepatitis Testing Day webpage.

We hope you will join with us in promoting both important observances as a way to enhance public awareness of viral hepatitis prevention, testing, care and treatment across the United States. Won’t you please commit to learning more yourself and/or sharing information about viral hepatitis with at least two other people? They can be family, friends, co-workers or neighbors. Working together, we can end the silence around this epidemic and in so doing, make great strides in improving the health of persons who are at risk for or living with viral hepatitis.

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AHF: Protesters Target Hershey at May 1st Annual Meeting over Child Labor/Fair Trade Violations and AIDS Discrimination

PRESS RELEASE

April 30, 2012, 5:00 p.m. EDT

 

Groups including Global Exchange, Green America and the International Labor Rights Forum, all part of the 'Raise The Bar Campaign' to make Hershey fair trade, will join together with activists from the National Guestworker Alliance (NGA) as well as MCC Philadelphia, ACT UP Philadelphia & AHF, protesting Hershey over AIDS discrimination at the Milton Hershey School

HERSHEY, Pa., Apr 30, 2012 (BUSINESS WIRE) -- --Protest Tuesday, May 1st from 9:30am to 11:30am outside Hershey's AGM in Hershey, PA

While the Hershey Company hosts its Annual General Meeting Tuesday, May 1st, in Hershey, PA, as many as one hundred activists from Global Exchange, Green America, International Labor Rights Forum, all from the Raise The Bar Campaign to make Hershey fair trade, will join together with activists from the National Guestworker Alliance (NGA) as well as Metropolitan Community Church of Philadelphia (MCC-Philadelphia), ACT UP Philadelphia, AIDS Healthcare Foundation (AHF), protesting Hershey over an incident of AIDS discrimination at the Milton Hershey School, will descend on Hershey, PA to host a lively protest outside the company's AGM. The protest is set for Tuesday, May 1st from 9:30am to 11:30am (Eastern).

WHAT: HERSHEY PROTEST--Up to 100 protesters expected to picket Hershey's Annual General Meeting over child labor and fair trade violations as well as a the case of AIDS discrimination at the Milton Hershey School following its decision to deny admission to an HIV-positive teen

WHEN: Tuesday, May 1st 9:30am - 11:30am (EASTERN)

WHERE: The Hershey Company Hershey Park Blvd. and Park Blvd., Hershey, PA 17033 (outside of Chocolate World)

WHO: Global Exchange, Green America, International Labor Rights Forum, all from the Raise The Bar Campaign; the National Guestworker Alliance (NGA) as well as Metropolitan Community Church of Philadelphia, ACT UP Philadelphia, and AIDS Healthcare Foundation

CONTACT: Jessica Reinhart, Grassroots Community Manager, Cell: (323) 203-6146

"Hershey needs to take corporate responsibility for their practices and we are demanding Hershey executives and trustees to stop exploiting children, students and workers as well as that the Milton Hershey School--funded by Hershey--reverse its decision to deny admission to an HIV-positive teen," said Jessica Reinhart, Grassroots Community Manager for AIDS Healthcare Foundation and a leader of several protests against Hershey over its AIDS discrimination. "We are honored to join again with MCC and Act Up Philadelphia to protest Hershey's AIDS discrimination and with the groups running Raise The Bar campaign targeting Hershey over fair trade and child labor issues as well as with NGA in their quest to protect Hershey workers and create local living wage jobs at the company in dignified conditions."

Background on Hershey School AIDS Discrimination

The Milton Hershey School--a boarding school for low-income students funded by the Hershey Company--recently rejected the boy for admission citing his HIV-positive status as the reason, misguidedly calling him a "direct threat to the health and safety of others." AHF has also launched a website www.EndHIVStigma.org where the public can learn more about the case, learn the facts about HIV/AIDS and send e-letters to three Hershey Company board members who also sit on the board of the Milton Hershey School Trust, urging them to denounce the discrimination and facilitate the boy's admission into the school.

"The blatant discrimination and ignorance displayed by Hershey in this case is simply unacceptable. Ultimately, it is the Hershey Company itself, as the main funder of the school, that must answer for the decision not to admit the boy--a decision fueled by prejudice and fear," said Michael Weinstein, President of AIDS Healthcare Foundation. "If Hershey is truly a company that believes in its social responsibility creed of 'commitment to consumers, community and children,' it will denounce this illegal and repugnant discrimination and immediately facilitate the enrollment of the boy at the school."

"It's appalling that Hershey Company would sit by and let AIDS stigma dictate school policy at the Milton Hershey School," said Rev. Jeffrey Jordan, pastor of MCC-Philadelphia. "We want to see the Hershey Company use their leverage as Board members to change the policy at the school for good."

According to the Associated Press (claim:Hershey School Rejects HIV-Positive Pa. Boy)(claim:By Peter Jackson)(claim:12/1/11): "A private boarding school connected with the Hershey chocolate company says it was trying to protect other students when it denied admission to a Philadelphia-area teenager because he is HIV-positive. The AIDS Law Project of Pennsylvania filed a lawsuit on behalf of the unidentified boy in U.S. District Court in Philadelphia on Wednesday, claiming the Milton Hershey School for disadvantaged students violated the Americans with Disabilities Act. School officials acknowledged that the 13-year-old boy was denied admission because of his medical condition. They said they believed it was necessary to protect the health and safety of the 1,850 others enrolled in the residential institution, which serves children in pre-kindergarten to 12th grade and where students live in homes with 10 to 12 others."

"The ignorance displayed by the Hershey School's leadership is unacceptable and demonstrates just how much work there is still to be done to dismantle the fear and misinformation that still surrounds this disease more than 25 years after Ryan White," said Jessica Reinhart, Grassroots Community Manager for AIDS Healthcare Foundation.

Ryan White was an American teenager from Kokomo, Indiana who, in the mid-1980s, was expelled from middle school because he was HIV-positive. A lengthy legal battle with the school ensued and White became a galvanizing force in educating the country about HIV & AIDS at a time when misinformation about the disease was widespread. After his death in 1990, the U.S. Congress passed a major piece of legislation named in his honor, the Ryan White CARE Act, which provides funding for HIV/AIDS programs for low-income Americans.

AIDS Healthcare Foundation (AHF), the largest global AIDS organization, currently provides medical care and/or services to more than 166,000 individuals in 25 countries worldwide in the US, Africa, Latin America/Caribbean, the Asia/Pacific Region and Eastern Europe. www.aidshealth.org

SOURCE: AIDS Healthcare Foundation

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Digital Arts: Virtually Stitching The AIDS Memorial Quilt

(Credit: Anne Balsamo, University of Southern California)

Lori Kozlowski, Contributor

4/13/2012 @ 10:36AM

The first time one sees the AIDS Memorial Quilt, it’s the sheer size of it that is most striking. Panel after creative panel — each square with a personality and a name.

In its 25-year history, more than 91,000 names have been added.

What began in 1987 as a simple folk art installation to remember those who had died from AIDS, grew into the largest public art display of its kind.

Now, the quilt is being digitized. Images of the quilt panels have been virtually stitched together and displayed on Microsoft Surface – a 60-inch wide interactive table. Viewers can scroll through the large touchscreen tablet and see the quilt in its entirety.

Anne Balsamo, Professor of Interactive Media and Communication and a senior research fellow at the University of Southern California’s Annenberg Innovation Lab, led the project.

“The idea is that you use the table not as a substitute for looking at the textile panels. You still look at the physical panels — they’re richer than any digital experience. But what our table will allow you to do is search for a particular one. And also get a sense of the scale,” she said.

The table browser will allow viewers to see the entire 1.3 million square feet of the quilt, or zoom in and get metadata about a single person’s panel. The effort will also offer the opportunity for the public to add their own reflections.

The first version of the table will be on display at the Smithsonian Folklife Festival, June 27 – July 8.

On July 20, sections of the physical quilt will be laid out on the National Mall. (At this point, the quilt is so large that the whole thing can not fit on the Mall). When the quilt is displayed, four interactive tables will be placed around the Mall for viewers to use.

Balsamo is also building a mobile application that will offer a map to locate any panel and digital memorial pages, so people can leave messages. “If you walk by a panel that really moves you, you can type in the panel number, go to the digital memorial page, and leave a remembrance,” she said.

“We want to give people a way to get into the stories of the quilt.”

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Management of Anemia in Patients Receiving Protease Inhibitors

Gastroenterology & Hepatology Volume 8, Issue 4 April 2012

Stephen A. Harrison, MD, LTC, MC
Chief of Hepatology
Brooke Army Medical Center
Clinical Associate Professor of Medicine
University of Texas Health Science Center at San Antonio
San Antonio, Texas

G&H How frequently does anemia occur in patients who are receiving protease inhibitor– based therapy?

SAH Anemia occurs frequently in these patients—certainly more frequently than it does in patients receiving only pegylated interferon and ribavirin. In a pooled analysis of the clinical safety data from trials of telaprevir (Incivek, Vertex), hemoglobin values less than 10 g/dL were found to occur in approximately 36% of patients receiving telaprevir-based triple therapy. More severe anemia, defined as hemoglobin values less than 8.5 g/dL, was observed in about 14% of patients. Among patients treated with pegylated interferon and ribavirin alone, only 17% had hemoglobin values less than 10 g/dL, and 5% had hemoglobin values less than 8.5 g/dL.

Similar rates of anemia were seen in trials of boceprevir (Victrelis, Merck). Pooled data from SPRINT-1 and SPRINT-2 showed that approximately 49% of patients had hemoglobin values less than 10 g/dL, and approximately 6% of patients had hemoglobin values less than 8.5 g/dL. Similar rates of anemia were observed in RESPOND-2, a trial that evaluated boceprevir-based triple therapy in interferon-experienced patients: Approximately 49% of these patients had hemoglobin values less than 10 g/dL, and approximately 10% of patients had hemoglobin values less than 8.5 g/dL. Among patients in the control group, who were treated with pegylated interferon and ribavirin alone, approximately 30% of patients showed a hemoglobin value less than 10 g/dL, and only approximately 3% of patients had a hemoglobin value less than 8.5 g/dL. Overall, there is a significantly higher rate of clinically significant anemia when therapy includes either boceprevir or telaprevir compared to treatment with pegylated interferon and ribavirin alone.

G&H Are rates of anemia similar between these 2 protease inhibitors?

SAH Yes, rates of anemia seem to be fairly similar with both telaprevir and boceprevir. While the pooled registration data suggest that telaprevir has higher rates of grade 3/4 anemia (hemoglobin levels <8.5 g/dL; 14% with telaprevir vs 6–10% with boceprevir), the boceprevir studies allowed the use of erythropoietin at the investigator’s discretion. While prospective, randomized, head-to-head trials assessing both frequency and severity of anemia are lacking, interim data from an ongoing French study (presented as an abstract at HepDART 2011) found on preliminary analysis that moderate, grade 2 anemia (hemoglobin level of 8–10 g/dL) occurred in 33% of telaprevir-treated patients and 31% of boceprevir-treated patients. Grade 3/4 anemia (hemoglobin level <8 g/dL) occurred in 13% of telaprevirtreated patients and 6% of boceprevir-treated patients. The transfusion rate was 18% for telaprevir-treated patients and 6% for boceprevir-treated patients. Overall, these findings correlate with clinicians’ anecdotal clinical experience, which shows significant anemia with both drugs.

G&H How frequently does anemia lead to either dose reduction or discontinuation of therapy?

SAH Dose reductions occur roughly twice as often when a protease inhibitor is added to the treatment regimen. According to the registration trial data, dose reductions occur in approximately 26% of patients treated with boceprevir.

Similarly, data from the telaprevir registration trials show that dose reductions occur in approximately 32% of patients. In terms of treatment discontinuation, data show that boceprevir-based therapy is discontinued in approximately 1% of patients, and telaprevir-based therapy is discontinued in 3–4% of patients. Again, both drugs show roughly similar rates of dose reductions and discontinuation.

G&H What are the clinical consequences of anemia?

SAH The presence of anemia does not negatively impact sustained virologic response (SVR) rates. However, it is well known that quality of life is certainly affected, which can lead to potential compliance or adherence issues. Recent data with the protease inhibitors suggest that clinicians can dose-reduce ribavirin fairly significantly in the setting of anemia and still achieve high SVR rates. Treatment discontinuation obviously has a more significant effect on clinical outcomes, but discontinuation is rare. Nonetheless, more data are needed to clearly show how quickly ribavirin dose reductions can occur (before virus negativity) and how long ribavirin can be stopped without affecting overall SVR rates. In the meantime, I advocate dose reduction instead of drug discontinuation for anemia, especially given that clinicians can probably get by with lower doses of ribavirin in the era of direct-acting antiviral drugs than they could when treating patients with pegylated interferon and ribavirin alone. If clinicians must discontinue ribavirin, they should do so for a short period of time (2–3 days) and then restart ribavirin at a lower dose.

In addition to necessitating dose reductions or discontinuations, anemia can significantly affect patients’ quality of life in terms of fatigue, inability to go to work and/or be productive at work, and difficulty in performing activities of daily living. As a result, compliance with therapy can become an issue. Thus, the effects of anemia extend beyond the possible impact on SVR rates to include compliance and quality-of-life issues as well.

G&H Have any studies compared SVR rates in patients with and without anemia?

SAH Yes. There are 2 large studies in genotype 1 hepatitis C virus (HCV)-infected patients treated with pegylated interferon and ribavirin (IDEAL, n=3,070; CHARIOT, n=871) showing that patients who developed anemia (hemoglobin level <10 g/dL) were significantly more likely to obtain SVR than those without anemia. Post–hoc, retrospective studies with telaprevir and boceprevir have also been conducted, but to date, these results remain in abstract form. Data from the REALIZE trial and combined data from ADVANCE and ILLUMINATE (with telaprevir) demonstrate that anemia is not a significant predictor of SVR. However, a retrospective review of the SPRINT-2 and RESPOND-2 trials (with boceprevir) did find a positive association with anemia and SVR.

G&H Are there any factors that predict the likelihood of anemia in patients receiving protease inhibitor–based therapy?

SAH Patients who had significant anemia during prior treatment with pegylated interferon and ribavirin and are re-treated with boceprevir- or telaprevir-based triple therapy are likely to develop anemia again, and anemia may be more severe given the addition of the protease inhibitor. Retrospective data from the telaprevir registration trials show on multivariate analysis that older age, lower body mass index, lower baseline hemoglobin level, more advanced fibrosis, and genotype 1b HCV are all significantly associated with anemia. Retrospective data from the boceprevir registration trials show on multivariate analysis that baseline hemoglobin level, gender, age greater than 40 years, statin use, and race were associated with anemia.

G&H Can clinicians address some of these factors before starting treatment?

SAH Clinicians need to do due diligence and look at the patient’s past treatment. Was there significant anemia? Are patients starting out with lower hemoglobin levels? Are they cirrhotic? Are they older? Do they have any renal impairment issues? If any of these factors are identified ahead of time, then clinicians should be quicker to dose-reduce or add an agent like erythropoietin if hemoglobin levels begin to drop.

G&H How effective is erythropoietin for the management of anemia in patients who are receiving a protease inhibitor plus pegylated interferon and ribavirin?

SAH We lack good, clear-cut data regarding the effect of erythropoietin on SVR rates in patients treated with directacting antiviral drugs. Erythropoietin was not allowed in the telaprevir registration trials. In the boceprevir registration trials, erythropoietin was allowed at the discretion of the investigator, but these studies were not designed to evaluate the effect of erythropoietin on SVR rates. The results of a recently completed prospective trial assessing the benefits of concomitant erythropoietin use for anemia in boceprevir-based therapy are anxiously awaited.

Prior to the advent of direct-acting antiviral drugs, a prospective, randomized, placebo-controlled trial showed that the use of erythropoietin for anemia related to treatment with pegylated interferon and ribavirin resulted in maintenance of the ribavirin dose, stabilization of the hemoglobin decline, and improvement in quality of life compared to ribavirin dose reduction alone.

G&H When do you consider adding erythropoietin to a patient’s treatment regimen?

SAH This decision should be made at the discretion of the individual clinician, as there are no guidelines regarding the use of erythropoietin. If a patient experiences anemia, I personally prefer to try ribavirin dose reduction of 400–600 mg as a first-line measure, depending on the initial severity of the anemia. Then, if the hemoglobin level has not stabilized, I will add erythropoietin before further dose-reducing ribavirin or withholding ribavirin. While adding erythropoietin is not my first-line treatment for anemia, it is an option if a patient’s hemoglobin level is not stabilizing. Consideration can also be given to pegylated interferon dose reduction, as this may also help anemia. Data from the previously mentioned IDEAL trial show that with conventional pegylated interferon and ribavirin therapy, dose reductions from 1.5 mcg/kg/week to 1.0 mcg/kg/week did not adversely affect SVR.

G&H In which patients is erythropoietin contraindicated?

SAH The black box warning for erythropoietin states that this drug should not be used in patients with hemoglobin values greater than 12 g/dL. Thus, clinicians should not start erythropoietin until the patient’s hemoglobin level falls below 12 g/dL, and erythropoietin should be discontinued once the hemoglobin level rises back above 12 g/dL. Caution should be used when treating patients with endstage renal disease as well. Clinicians should also be aware of the relatively rare, but significant, complication of pure red cell aplasia that has been reported with the use of recombinant erythropoietin.

G&H What further research do you hope to see in this area over the next couple of years?

SAH Telaprevir and boceprevir, both of which are now approved by the US Food and Drug Administration, are the first direct-acting antiviral agents to come onto the market. Unfortunately, these drugs are associated with significant anemia; in general, patients who are receiving either of these drugs experience an additional hemoglobin decline of approximately 1 g/dL beyond the hemoglobin decline caused by pegylated interferon and ribavirin alone. The good news is that the second-generation direct-acting antiviral agents currently in development will probably cause less anemia than the 2 drugs that are currently available.

In addition to new drugs, we need further research regarding treatment of anemia in patients receiving telaprevir or boceprevir, including studies assessing how quickly we can dose-reduce ribavirin and by how much. The use of erythropoietin for anemia and its effect on SVR should be assessed. Finally, data suggest that polymorphisms in the inosine triphosphate pyrophosphatase (ITPA) gene may help to predict ribavirin-associated anemia during antiviral treatment, and further research is needed regarding the utility of this test. Should we be testing for this gene mutation in the same way that we now test for interleukin-28B (IL-28B) mutations prior to initiating antiviral therapy? More data are needed to determine whether this information would positively impact outcomes.

G&H How might such information help clinicians prevent treatment-induced anemia?

SAH If I had information suggesting that a patient was at increased risk for anemia, then I would probably check for anemia more frequently at the start of therapy. My preferred strategy—especially in patients who I feel are at risk for developing anemia—is to obtain complete blood counts at Week 1 and Week 2. If these tests show that the patient is doing well, then I may wait until Week 4 before performing follow-up testing. However, if testing at Week 1 and Week 2 shows that the patient’s hemoglobin level has dropped significantly, then I would adjust the ribavirin dose and obtain another complete blood count at Week 3. The key for treating anemia in the setting of HCV therapy is to address anemia very quickly, because it is much harder to bring hemoglobin levels back up after they have declined than it is to mitigate the rate of decline.

The opinion or assertions contained herein are the private views of the author and are not to be construed as official or reflecting the view of the US Department of the Army or the US Department of Defense.

Suggested Reading

Alavian SM, Tabatabaei SV, Behnava B. Impact of erythropoietin on sustained virological response to peginterferon and ribavirin therapy for HCV infection: a systematic review and meta-analysis. J Viral Hepat. 2012;19:88-93.

Mac Nicholas R, Norris S. Review article: optimizing SVR and management of the haematological side effects of peginterferon/ribavirin antiviral therapy for HCV—the role of epoetin, G-CSF and novel agents. Aliment Pharmacol Ther. 2010;31:929-937.

Nishimura T, Osaki R, Shioya M, et al. Polymorphism of the inosine triphosphate pyrophosphatase gene predicts ribavirin-induced anemia in chronic hepatitis C patients. Mol Med Report. 2012;5:517-520.

Jacobson IM, McHutchison JG, Dusheiko G, et al; ADVANCE Study Team. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011;364:2405-2416.

Zeuzem S, Andreone P, Pol S, et al; REALIZE Study Team. Telaprevir for retreatment of HCV infection. N Engl J Med. 2011;364:2417-2428.

Poordad F, McCone J Jr, Bacon BR, et al; SPRINT-2 Investigators. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011;364:1195-1206.

Bacon BR, Gordon SC, Lawitz E, et al; HCV RESPOND-2 Investigators. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med. 2011;364:1207-1217.

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Life expectancy for HIV patients improving

[Date: 2012-04-30]

Life expectancy for HIV patients treated with antiretroviral drugs, now considered common course in treating the virus, can expect to live considerably longer lives, new research from the United Kingdom shows. This study was funded in part by the EUROCOORD ('European network of HIV/AIDS cohort studies to coordinate at European and international level clinical research on HIV/AIDS') project, which is backed with EUR 12 million under the Health Theme of the EU's Seventh Framework Programme (FP7). EUROCOORD brings together a number of other networks, all of which have played a central role in developing our understanding, progression and treatment of HIV.

The efforts of healthcare professionals treating HIV patients are bearing fruit. In this latest study, a British team of researchers was able to discern that HIV patients aged 20, who started antiretroviral treatments 16 years ago, could expect to live to an average age of 50. Life expectancy, however, jumps to 66 for subjects in the same group who began their treatment just 4 years ago. The sample was made up of 17 661 adults aged 20 and over who had HIV and had started antiretroviral treatment in the United Kingdom between 1996 and 2008.

The study also discovered that HIV patients had a lower life expectancy when they began their antiretroviral treatment later in life. It should be noted that the average life expectancy of a person with HIV being treated with antiretrovirals was still shorter than that of a similarly aged person in the general population.

HIV is a pressing matter in Europe; it is currently estimated that more than 1.5 million Europeans are infected with HIV. In 2007, it was estimated that 100 000 people were newly infected with the disease, but the outcome for HIV patients has dramatically improved in countries where patients have access to combination antiretroviral therapy (cART). Healthcare professionals stress, however, that cART is not a cure for HIV and once a patient begins treatment, they must continue it for life.

The researchers stressed that the projected life expectancies will need to be confirmed by longer term follow-up. Their study they did not include other external factors that could influence results, such as lifestyle factors, which could lead to increased death from non-HIV causes. With those caveats in mind, the researchers said they feel confident in concluding that improvements in antiretroviral treatment are responsible for at least some of this improvement.

Overall, these results are encouraging and emphasise the improvements in treatments seen in recent years. However, the life expectancies among people with HIV are still projected to be lower than people among the general population. The researchers also excluded patients whose records were not 100% complete and were missing important information, including age, sex or ethnicity. Also excluded from the sample base were patients who, it was assumed, had contracted HIV through injecting drug use; the reason behind this exclusion is that they are reported to have a worse outlook than other groups.

For more information, please visit:
EUROCOORD:
http://www.eurocoord.net/

Related stories: 34095

Category: Project results
Data Source Provider: EUROCOORD
Document Reference: Based on information from the Queensferry Gazette.
Subject Index: Coordination, Cooperation; Life Sciences; Medicine, Health; Scientific Research

RCN: 34568

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Media Advisory - Interview Local Nurses Dedicated to the Hepatitis C Community: National Nursing Week - May 7 to 13, 2012

PRESS RELEASE

April 30, 2012, 7:00 a.m. EDT

TORONTO, April 30, 2012 /PRNewswire via COMTEX/ -- During National Nursing Week, Canadians will recognize and celebrate the important contributions nurses make daily to patient care in Canada. The role nurses play in the prevention and management of chronic hepatitis C, a potentially life-threatening virus, provides a powerful example of their impact as supporter, educator and counsellor.

Canadians living with chronic hepatitis C often fear the judgment of others because the virus infecting them is often associated with injection drug use. The reality is that people can contract the virus through a number of different ways including, body piercings, tattoos, blood transfusions or personal care items (razors).

Members of the Canadian Association of Hepatology Nurses (CAHN) build trusted relationships with patients by not focusing on how the hepatitis C virus was contracted, but rather on providing care and support that is beneficial, respectful and can lead to a cure.

The road to a cure is a difficult journey for patients living with chronic hepatitis C. While treatments can be very successful at getting rid of the virus, the stigma associated with the disease often requires patients to struggle through chemotherapy-like side effects in isolation.

CAHN wants to shatter the stigma for those people living with chronic hepatitis C by helping Canadians recognize that anyone, including someone they know and love, could be living with this virus. Stigma must not be a barrier to detection and treatment.

This National Nursing Week, celebrate the leadership provided by CAHN nurses in the prevention and management of chronic hepatitis C.

What: Interview opportunities with nurses and individuals living with chronic hepatitis C willing to share their stories Who: Cheryl Dale, President of the Canadian Association of Hepatology Nurses, CAHN members and individuals living with chronic hepatitis C Where: The following communities across Canada: Ontario (Toronto, Oakville, Mississauga, Guelph, Hamilton, Kitchener-Waterloo, Newmarket, Sutton, Sudbury, North Bay, and London), Quebec (Montreal), British Columbia (Vancouver, Kelowna, and Nanaimo), Alberta (Edmonton), Nova Scotia (Halifax), and Saskatchewan (Prince Albert) When: National Nursing Week (May 7-13, 2012)

SOURCE Canadian Association of Hepatology Nurses

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First full HCV infection model

doi:10.1038/nindia.2012.63; Published online 30 April 2012

Researchers have created what they claim to be the first mathematical model of the full course of infection of hepatitis C virus (HCV). This fully describes the impact of its viral and immune processes on the progression of hepatocellular carcinoma (HCC), the cancer it causes¹.

Most available mathematical models describe the short term dynamics of HCV after the antiviral therapy is given to patients. The new model, however, is based on the premise that long term conditions such as HCC are random and driven by cell-mediated immune response. The researchers have modelled the risk of cancer and the dynamics of HCV over the course of its infection.

The researchers have found approximately 9% prevalence of HCC in individuals after 40 years, a figure consistent with estimates in available literature. They also found that higher viral infection potential led to a greater likelihood of developing HCC but did not determine the speed with which it arose.

"This 'infectivity' drives the level of immune response, the amount of hepatocyte proliferation, and the risk of a mutational event," they say.

In their simulations, the probability of developing HCC increased with duration of infection at the rate of 2.4 incident cases per thousand HCV-infected person years. This indicated that the sooner viral replication can be suppressed through antiviral therapy, the greater the chance of forestalling HCC.

References

Chakrabarty, S. P.et al. Modelling hepatitis C virus infection and the development of hepatocellular carcinoma. J. Theor. Biol. 305, 24-29 (2012)

Source

Non-Interferon-Based Combination Therapy Offers High Response Rates for Hepatitis C Patients

By Chris Berrie

BARCELONA, Spain -- April 25, 2012 -- Combining ABT-450 with ritonavir
(ABT-450/r) plus ABT-333 plus ribavirin (RBV) is well tolerated, provides high
sustained virological response (SVR) in treatment-naïve patients infected with
hepatitis C virus (HCV) genotype 1, and shows relatively high SVR in previous
interferon-based nonresponders, researchers said here at the 47th Annual
Meeting of the European Association for the Study of the Liver (EASL).

At present, there are no treatment options for HCV-infected patients who are
ineligible or intolerant to the interferons.

“This is the first study combining ABT-450 with ABT-333 with ribavirin without
interferon in genotype 1 patients who were either treatment-naïve or previous
treatment failures,” stated Fred Poordad, MD, Chief of Hepatology and Liver
Transplantation at the Comprehensive Transplant Center of Cedars-Sinai Medical
Center, Los Angeles, California, presenting this open-label study here on April
21.

The study design included 3 arms, the first 2 of which treated naïve patients
with chronic HCV genotype 1 infection using ABT-333 400 mg twice daily plus RBV
1,000-1,200 mg once daily plus ABT-450/r either 250/100 mg once daily (arm 1; n
= 19) or 150/100 mg once daily (arm 2; n = 14). The third treatment arm was
similar to arm 2, but treated prior partial or null responders to previous
pegylated interferon plus RBV treatments (arm 3; n = 17).

The treatments were for 12 weeks, with 48 weeks follow-up.

These patients were mainly male, with a mean age of just over 50 years, and
were largely HCV genotype 1a. For IL28B genotype, 52.6% were CC in arm A and
35.7% in arm B, with no IL28B CC in arm 3.

The primary endpoint was extended rapid virological response (eRVR) based on
HCV RNA lower than the limit of detection from treatment weeks 4 to 12. As the
intent-to-treat analysis, these reached 90%, 79% and 59% in arms 1, 2, and 3,
respectively.

Similarly, for SVRs at weeks 4 (SVR4) and 12 (SVR12), high levels of response
were achieved for arms 1 (95%, 93%, respectively) and 2 (95%, 93%). These SVR4
and SVR12 responses were also relatively high for the previous nonresponding
patients in arm 3 (47%, 47%).

Comparisons across IL28B CT versus TT showed no differences in SVR12 either for
treatment-naïve patients, as arms 1 plus 2 (100% vs 100%) or for previous
nonresponders (50% vs 40%).

Based on clonal sequencing, Dr. Poordad highlighted the resistant variants at
baseline and at virologic failure in the previous nonresponders of arm 3. “It
is important to note that patients who had virologic failure developed
resistance variants to both the protease inhibitor as well as the polymerase
inhibitor,” he noted.

In the safety analysis, there were no deaths or serious adverse events
throughout, with only 1 adverse event leading to premature discontinuation, in
arm 1. Four patients showed adverse events assessed as severe, without
requiring study-drug interruption or discontinuation: hyperbilirubinaemia,
fatigue, pain, and vomiting.

The treatment-emergent adverse events and the laboratory abnormalities noted
were largely the same type and levels across the 3 treatment arms. Dr. Poordad
also noted that the transient asymptomatic elevation of indirect bilirubin that
was seen is consistent with the known effect of ABT-450 on the bilirubin
transporter OATO1B1.

“It does appear that ABT-450 with ritonavir, ABT-333 plus ribavirin for 12
weeks has the potential to achieve very high SVR in a high proportion of
patients without interferon,” he concluded.

Funding for this study was provided by Abbott.

[Presentation title: A 12-Week Interferon-Free Regimen of ABT-450/r +
ABT-333 + Ribavirin Achieved SVR12 in More Than 90% of Treatment-Naïve HCV
Genotype-1 Infected Subjects and 47% of Previous Non-responders. Abstract 1399]

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Cerus, the University Hospitals of Geneva, and the Transfusion Service of the Swiss Red Cross Intend to Collaborate on Whole Blood Pathogen Inactivation for Africa

30th of April 2012 08:30 EST

Cerus Corporation (NASDAQ:CERS), the University Hospitals of Geneva (HUG) and their Blood Transfusion Center (CTS), and the Transfusion Service of the Swiss Red Cross (Transfusion CRS Suisse or Blutspende SRK Schwietz) announced today their intent to collaborate on adapting the Cerus INTERCEPT Blood System for red cells to enable inactivation of pathogens in whole blood, specifically for the African region. While patients in developed countries receive platelet, plasma or red cell transfusions, in many African countries whole blood transfusions remain common, and require development of pathogen inactivation methods optimized for use in local blood bank facilities.

The African blood supply is challenged by both transfusion-transmitted diseases and a shortage of available units for transfusion. Pathogen inactivation can provide protection from a broad range of transfusion-transmitted diseases without further restricting the scarce supply of blood donors. The collaboration is designed to draw on the distinctive strengths of each organization to seek the funding necessary to develop a whole blood PI system that can be evaluated in clinical use in Africa.

“We believe pathogen inactivation is critical to blood safety everywhere, and we currently use the INTERCEPT system to treat all platelet units produced in Switzerland,”

said Dr. Rudolf Schwabe, chief executive officer of the Transfusion CRS Suisse. “Africa’s blood supply is at risk from many transfusion-transmitted diseases that can be prevented by use of pathogen inactivation. We see a great need in ensuring the safety and availability of blood for those patients in Africa who need it most.” 

“In countries where whole blood transfusions are used to treat acute and chronic anemia as well as post-partum hemorrhage, the opportunity to reduce the risk of bloodborne diseases fits perfectly with the aim of our university hospital policy to develop international medical cooperation, training and humanitarian health actions to improve global health,”

commented Dr. Soraya Amar-El Dusouqui, project director, CTS-HUG (University Hospitals of Geneva).

Blood safety and supply are of major health concern in Africa. Only an estimated 40 percent of the demand for transfusions is currently being supplied (Bloch et al, Transfusion Medicine Reviews, 2012 Apr;26:164-80). Obstetric hemorrhage, sickle cell disease and childhood anemia, HIV, malaria and traffic accidents are among the many indications requiring transfusion as a critical life-saving intervention.

At the same time, local blood donors frequently have significant rates of well-known transfusion-transmitted agents like HIV, HTLV, hepatitis and bacteria, as well as infections endemic to the region including malaria, dengue, Chikungunya and yellow fever.

Unlike other blood safety techniques, pathogen inactivation is able to provide protection from a broad range of viruses, bacteria and parasites from a single added safety step. Cerus’ INTERCEPT systems for platelets and plasma are already used in Europe, the Commonwealth of Independent States (CIS) and the Middle East. The INTERCEPT red cell system is anticipated to begin phase III trials in Europe later this year. To treat whole blood in Africa, a treatment system must be designed to work within the limited infrastructure of local blood banks and hospitals, as well as effectively inactivating bloodborne pathogens.

“We are honored to join HUG, CTS, and SRK in the pursuit of a pathogen inactivation system to improve blood safety in Africa where the technology can have a great impact in improving human health,“ said William ‘Obi’ Greenman, Cerus’ president and chief executive officer.

"Pathogen inactivation is being increasingly used in Europe, CIS and the Middle East, and, like our collaborators in this project, we feel an obligation to bring this technology to regions like Africa where it has the potential to transform blood safety."

ABOUT CERUS

Cerus Corporation is a biomedical products company focused on commercializing the INTERCEPT Blood System to enhance blood safety. The INTERCEPT system is designed to reduce the risk of transfusion-transmitted diseases by inactivating a broad range of pathogens such as viruses, bacteria and parasites that may be present in donated blood. The nucleic acid targeting mechanism of action enables INTERCEPT treatment to inactivate established transfusion threats, such as hepatitis B and C, HIV, West Nile virus and bacteria, and is designed to inactivate emerging pathogens such as influenza, malaria and dengue. Cerus currently markets and sells the INTERCEPT Blood System for both platelets and plasma in Europe, the Commonwealth of Independent States, the Middle East and selected countries in other regions around the world. The INTERCEPT red blood cell system is in clinical development. See http://www.cerus.com for more information.

INTERCEPT and INTERCEPT Blood System are trademarks of Cerus Corporation.

This press release contains forward-looking statements. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements, including, without limitation, statements relating to the intended collaborative activities of the parties, the potential efficacy, development and clinical evaluation of an INTERCEPT system adapted for use with whole blood and the anticipated timing of initiating Phase III INTERCEPT red blood cell studies in Europe. These forward-looking statements are based upon Cerus’ current expectations. Actual results could differ materially from these forward-looking statements as a result of certain factors, including, without limitation, risks associated with development and clinical evaluation of the INTERCEPT system for whole blood and for red blood cells, the risk that available funding may not be available to support whole blood-related activities under the proposed collaboration, risks associated with dependence on third-party potential collaborators to support whole blood-related development activities and other risks detailed in the Cerus' filings with, the Securities and Exchange Commission (SEC), including in Cerus' annual report on Form 10-K for the year ended December 31, 2011, filed with the SEC on March 5, 2012. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. Cerus does not undertake any obligation to update any forward-looking statements as a result of new information, future events, changed assumptions or otherwise.

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