Sofosbuvir Works for Patients Who Cannot Take Peginterferon

Published in Journal Watch Gastroenterology May 24, 2013

Two phase III studies confirm the efficacy of a sofosbuvir and ribavirin therapy in patients with HCV genotype 2 or 3 infection for whom peginterferon is not an option.

In patients infected with hepatitis C virus (HCV) genotype 2 or 3, treatment with peginterferon plus ribavirin has a sustained virologic response (SVR) of 70% to 85%. However, adverse effects of peginterferon are a barrier to treatment for many patients. Now, two industry-funded, phase III trials have evaluated the efficacy of sofosbuvir (400 mg daily) plus ribavirin (1000 mg–1200 mg daily) in these patients.

In a blinded, placebo-controlled trial, investigators randomized 280 patients for whom peginterferon therapy was not an option (e.g., adverse effects, contraindications for interferons, and patient refusal) to receive sofosbuvir/ribavirin or matching placebo for 12 weeks. In a blinded, active-control trial, researchers randomized 202 patients with prior nonresponse to peginterferon therapy to receive 12 or 16 weeks of sofosbuvir/ribavirin. The primary endpoint in both studies was SVR at 12 weeks after therapy ended.

In patients for whom peginterferon therapy was not an option, SVR was 78% for treatment with sofosbuvir/ribavirin compared with 0% for placebo (P<0.001). In previously treated patients, SVR was 50% for 12 weeks of therapy versus 73% for 16 weeks (P<0.001). SVR rates were lower for patients with genotype 3 versus genotype 2 in both treatment-naive patients (61% vs. 93%) and treatment-experienced patients who received therapy for 12 weeks (30% vs. 86%) or 16 weeks (62% vs. 94%).

SVR rates were lower in patients with cirrhosis than without, both in treatment-naive patients (overall, 61% vs. 81%; genotype 3 vs. 2, 21% vs. 94%) and treatment-experienced patients (overall, 66% vs. 76%; genotype 3 vs. 2 in 16-week group, 61% vs. 78%). In both studies, investigators found no evidence of resistance development, and discontinuation rates were low (1%–2%).

Comment: Oral sofosbuvir plus ribavirin is effective in patients with HCV genotypes 2 or 3 for whom peginterferon-based therapy is not an option or was previously ineffective. Of note, these sustained virologic response rates for sofosbuvir plus ribavirin are comparable to or higher than those previously reported for therapy with peginterferon plus ribavirin in this population.

— Atif Zaman, MD, MPH

Citation(s):

Jacobson IM et al. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med 2013 May 16; 368:1867. (http://dx.doi.org/10.1056/NEJMoa1214854)

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Australia's PBAC recommends use of XIFAXAN 550 mg for hepatic encephalopathy

Published on May 24, 2013 at 7:23 AM

Norgine today announced that the Australian assessment body the Pharmaceutical Benefits Advisory Committee (PBAC) has recommended the use of XIFAXAN 550 mg in the prevention of the recurrence of hepatic encephalopathy (HE) where other treatments have failed or are contraindicated; a potentially life-threatening neuropsychiatric condition associated with liver disease.

XIFAXAN 550 mg is the only treatment that has demonstrated a reduction in the recurrence of episodes of overt HE and hospitalisation due to HE compared with placebo in a 6-month randomised, double blind, placebo-controlled study in which ~91% patients were taking concomitant lactulose in both arms, in patients who were in remission from HE, resulting from chronic liver disease.

The PBAC announced its final decision as follows:

The PBAC recommended listing of rifaximin on the basis of high clinical need, improved clinical benefit over the existing treatments and acceptable cost effectiveness.

On the basis of the information available to it at the April 2013 meeting, the PBAC considered that there was no longer a requirement for a managed entry scheme approach.

This outcome represents the first acceptance for use made by a health technology assessment (HTA) process for XIFAXAN 550 mg in their healthcare system based on cost effectiveness review. Norgine and Alfa Wassermann are working closely with other HTA bodies across Europe including the National Institute for Health and Care Excellence (NICE) and The Scottish Medicines Consortium (SMC) to ensure patients have appropriate access to this important medicine. The review processes are currently underway and Norgine expects these bodies to make their decision in the second half of 2013.

'It's critical that we deliver medicines that treat serious conditions and improve quality-of-life as well as alleviate the cost burden on healthcare systems caused by hospital admissions," said Peter Martin , Norgine Chief Operating Officer.

"XIFAXAN 550 mg provides healthcare professionals with a world-leading treatment option for patients with hepatic encephalopathy, which is a recognised growing problem that may lead to premature death," added Peter Martin .

Norgine currently holds marketing rights for XIFAXAN 550 in: Australia, Belgium, Denmark, Egypt, Finland, France, Germany, Ireland, Luxembourg, the Netherlands, New Zealand, Norway, Switzerland, Sweden and the UK.

In Europe, XIFAXAN® 550 mg /TARGAXAN® 550 mg is already available in Denmark, Germany and in the UK for healthcare professionals to prescribe in accordance with local guidance.

SOURCE Norgine

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Marijuana tied to better blood sugar control

By Genevra Pittman

NEW YORK | Thu May 23, 2013 3:44pm EDT

NEW YORK (Reuters Health) - People who had used marijuana in the past month had smaller waists and lower levels of insulin resistance - a diabetes precursor - than those who never tried the drug, in a new study.

The findings, based on surveys and blood tests of about 4,700 U.S. adults, aren't enough to prove marijuana keeps users thin or wards off disease. And among current pot smokers, higher amounts of marijuana use weren't linked to any added health benefits, researchers reported in The American Journal of Medicine.

"These are preliminary findings," said Dr. Murray Mittleman, who worked on the study at Beth Israel Deaconess Medical Center in Boston.

"It looks like there may be some favorable effects on blood sugar control, however a lot more needs to be done to have definitive answers on the risks and potential benefits of marijuana usage."

Although pot smoking is a well-known cause of "the munchies," some previous studies have found marijuana users tend to weigh less than other people, and one suggested they have a lower rate of diabetes. Trials in mice and rats hint that cannabis and cannabinoid receptors may influence metabolism.

The new study used data from a national health survey conducted in 2005-2010. Researchers asked people about drug and alcohol use, as well as other aspects of their health and lifestyle, and measured their insulin and blood sugar levels.

Just under 2,000 participants said they had used marijuana at some point, but not recently. Another 600 or so were current users - meaning they had smoked or otherwise consumed the drug in the past month.

Compared to people who had never used pot, current smokers had smaller waists: 36.9 inches versus 38.3 inches, on average. Current users also had a lower body mass index - a ratio of weight to height - than never-users.

When other health and lifestyle measures were taken into account, recent pot use was linked to 17 percent lower insulin resistance, indicating better blood sugar control, and slightly higher HDL ("good") cholesterol levels.

However, there was no difference in blood pressure or blood fats based on marijuana use, Mittleman's team found.

A CAUSAL LINK?

Mittleman said that in his mind, it's still "preliminary" to say marijuana is likely to be responsible for any diabetes-related health benefits.

"It's possible that people who choose to smoke marijuana have other characteristics that differ (from non-marijuana smokers)," and those characteristics are what ultimately affect blood sugar and waist size, he told Reuters Health.

Dr. Stephen Sidney from the Kaiser Permanente Division of Research in Oakland, California, said he wonders if cigarette smoking may partially explain the association. Marijuana users are also more likely to smoke tobacco, he told Reuters Health.

"People who use tobacco oftentimes tend to be thinner," said Sidney, who has studied marijuana use and weight but didn't participate in the new study. "So I really wonder about that."

Another limitation with this and other studies, Sidney and Mittleman agreed, is that all of the data were collected at the same time, so it's unclear whether marijuana smoking or changes in waist size and blood sugar came first.

"The question is, is the marijuana leading to the lower rate (of diabetes) or do they have something in common?" said Dr. Theodore Friedman, who has studied that issue at Charles R. Drew University of Medicine and Science in Los Angeles.

He and his colleagues think the link is probably causal. "But it's really hard to prove that," Friedman, who also wasn't involved in the new research, told Reuters Health.

One possibility is that the anti-inflammatory properties of marijuana help ward off diabetes, he said. But he agreed that more research is needed to draw out that link.

"I want to make it clear - I'm not advocating marijuana use to prevent diabetes," Friedman said. "It's only an association."

SOURCE: bit.ly/10Ty3La The American Journal of Medicine, online May 16, 2013.

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Spring Bank Pharmaceuticals Initiates a Phase I Clinical Trial for SB 9200 in HCV-infected Patients

MILFORD, Mass., May 23, 2013 /PRNewswire/ -- Spring Bank Pharmaceuticals, Inc., a biopharmaceutical company developing innovative medicines for the treatment of viral infections, today announced that it has initiated dosing in a Phase I study of SB 9200, its investigational, once daily, oral therapy for the treatment of HCV infection. This study will be conducted in healthy, HCV-infected patients and is designed to assess both the safety and antiviral efficacy of SB 9200. SB 9200 is a first-in-class drug for the treatment of chronic HCV infections and is based on the Company's proprietary Small Molecule Nucleic Acid Hybrid (SMNH) technology platform. It has a unique mechanism of antiviral action involving the selective activation of the host-immune response in HCV-infected cells.

"The initiation of this clinical trial is an important milestone for our Company," said Doug Jensen , Spring Bank 's CEO. "This trial should not only give us proof of concept in HCV, but also will facilitate the advancement of our technology in other viral diseases such as HBV and RSV." SB 9200 is the first of a potentially important new class of drug based on Spring Bank 's proprietary "SMNH" technology platform. The Phase I clinical trial has been designed to provide a significant amount of data related not only to safety of SB 9200 but also the antiviral activity against multiple HCV genotypes.

"Unlike other classes of drugs for HCV infection that act directly on the virus, SB 9200 targets host cytosolic sensor proteins, RIG-I and NOD2," states Dr. Kris Iyer , CSO and Co-founder of Spring Bank . "This leads to the selective activation of the host immune response in the presence of viral infection." By way of its novel mechanism of action, SB 9200 is ideally suited for combination with other classes of HCV antivirals, including direct-acting antiviral agents (DAA) currently in clinical development. In preclinical studies, SB 9200 has shown synergistic antiviral activity when combined with other anti-HCV compounds and has demonstrated an excellent safety profile. In in vitro studies, the compound has demonstrated potent antiviral activity against multiple HCV genotypes 1a, 1b and 3. Thus, this novel mechanism of action is suggestive of pan-genotypic activity and potentially a high barrier to resistance. Moreover, this novel mechanism of action suggests it could have pan-genotypic activity and potentially a high barrier to resistance. These attributes could lead to the use of SB 9200 as part of an Interferon-free, all-oral regimen for HCV therapy.

The Phase I trial is currently being conducted in Australia with plans to expand into clinical sites in New Zealand. The trial is being conducted in two parts. Part A is a single ascending dose of SB 9200 to evaluate the safety and tolerability of a single oral dose of SB 9200, with 8 treatment naive Genotype 1 patients being enrolled into four sequential cohorts of 2 patients each with increasing doses ranging from 100-800mg. Part B of the study is a randomized, double blind, placebo-controlled multiple ascending dose escalation of once daily doses of SB 9200 once a day for 7-14 days. Part B will enroll approximately 40 HCV patients with 5 dosing cohorts, randomized 6:2 active versus placebo. The final dosing cohort will be in Genotype 2/3 patients to demonstrate pan-genotypic activity. The primary endpoint for both parts of the trial is safety. Secondary objectives include an analysis of dose versus viral load reduction, liver function, safety labs, host immune expression, as well as characterization of plasma and urine pharmacokinetics and assessment of pharmacodynamic activity.

About Spring Bank Pharmaceuticals

Spring Bank Pharmaceuticals is engaged in the discovery and development of an entirely new class of pharmaceuticals based on the Company's proprietary SMNH, "Small Molecule Nucleic Hybrid" technology program. The company's lead compound, SB 9200, is a potential breakthrough drug for the treatment of HCV and HBV. The Company also has preclinical programs for the development of immune-modulating therapies against Respiratory Syncytial Virus (RSV) infections, a Broad-Spectrum Antiviral, and a SMNH based therapy to treat Chronic Obstructive Pulmonary Disease (COPD). For more information please visit our website: www.springbankpharm.com

Contact: Douglas Jensen (508) 473-5993 Ext.105

SOURCE Spring Bank Pharmaceuticals, Inc.

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Hepatitis C treatment challenged by rising costs

Provided by Healio

May 23, 2013

The total spending trend for hepatitis C-related medications rose 33.7% in 2012 compared with 2011, according to a recent Express Scripts report. The increase is primarily due to new medications on the market, experts said. In a field where the medications did not change for about a decade, major cost increases associated with changes in hepatitis C-related treatments are challenging patients and clinicians but also showing promise for better cure rates.

Incidence rate for hepatitis C

The incidence rate for hepatitis C has remained generally unchanged in recent years, clinicians note.

“The incidence of hepatitis C has not really spiked in the last couple years,” Andrew J. Muir, MD, director of hepatology at Duke University, told Healio.com. “Awareness on the part of clinician providers as well as the patients themselves has led to more people being in our clinics and to more overall awareness of hepatitis C.”

Muir said most patients he sees were infected years ago and are just now presenting with complications from advanced hepatitis C.

“We are seeing increased rates of cirrhosis and liver transplants and liver cancer all related to hepatitis C. But, new cases of hepatitis C are somewhat reduced compared with 20 years ago,” Muir said.

Bruce R. Bacon, MD, James F. King MD Endowed Chair in Gastroenterology, professor of internal medicine, Saint Louis University School of Medicine, is seeing similar patterns in his practice.

“The incidence rate has not changed,” he told Healio.com. “What has changed is that there is a little bit of increased awareness, so a few more people are being diagnosed.”

Jumps in treatment costs

Researchers of the Express Scripts report credited the rise in the total spending trend for hepatitis C-related medications to the release of two protease inhibitor (PI) drugs that help treat genotype 1 hepatitis C. Incivek (telaprevir, Vertex Pharmaceuticals) and Victrelis (boceprevir, Merck) were released in May 2011, and experts agree these drugs have helped to drive treatment cost increases.

“Overwhelmingly, what has made the difference … is the increased cost for new treatments,” Bacon said. “We used the same treatment of pegylated interferon-alfa and ribavirin since 2001 to 2011. So, for 10 years the treatment regimen that we used didn’t change.”

With the availability of Incivek and Victrelis, patient options and costs changed. According to the Express Scripts report, 4 months after market availability for the two new drugs, more than 46% of patients treated for hepatitis C had been prescribed one of the new PIs.

“In 2011, for most patients of hepatitis C, when the two new drugs telaprevir and boceprevir were added to the current regimen of pegylated interferon-alfa and ribavirin, there was a substantial increase in cost,” Muir said.

The total spending trend for hepatitis C-related medications had the largest increase — 194.8%, or more than 10 times the total trend for any other specialty therapy class — in 2011 compared with 2010 among drugs for all observed major illnesses, according to the Express Scripts report. In 2011, the average cost for a hepatitis C prescription was estimated at $3,370, compared with $1,389 in 2010, the report said.

Along with the prescription costs, the current regimen, even with telaprevir or boceprevir, requires frequent lab tests, close monitoring and follow-up clinician visits, which drive up overall costs, Muir said.

More predicted cost jumps

Spending for hepatitis C-related medications will continue to grow, the report researchers predicted. As new treatments and screening guidelines are introduced, spending is estimated to grow by 32.3% in 2013 and 56.3% in 2014. Experts note, however, the cost of new treatments is not yet apparent.

“The hepatitis C treatment field is evolving,” Muir said. “There are a number of medications that are in phase 3 trials that are hopefully going to be approved in a couple of years.”

Some of those medications are initially going to be administered with peginterferon-alfa and ribavirin and some without interferon. The cost of those new drugs is unclear, according to Muir.

Better cure rates with increased costs

Clinicians are seeing better cure rates with telaprevir and boceprevir and hope for fewer side effects with new interferon-free treatments that are currently being studied. Side effects associated with interferon therapy include fatigue, anemia, depression, rash and flu-like symptoms.

Within the next 18 to 24 months, Muir anticipates that most Americans will be eligible for an interferon-free regimen that produces a greater response rate and “much better side effect profile.”

“Between 2001 and 2011, when we didn’t have telaprevir and boceprevir for genotype 1 patients, who are the most common in the United States — about 70% to 75% of all patients — we could only cure about 40% of those patients,” Bacon said. “Now with telaprevir and boceprevir we can cure between 70% and 75% of those patients. With newer agents that are in the pipe for another year or two, we are going to be able to cure 90% to 100% of these patients.

“So with the increase in costs with telaprevir and boceprevir, we are getting results. We are getting better cure rates. And, with the next round of treatments in the next couple of years, we are going to get even better cure rates. It is going to cost a little bit more, but fortunately it is going to be associated with fewer side effects.”

Financial burden

The promise of better cure rates and fewer side effects has prompted some patients to elect to wait for interferon-free medications.

“We [Bacon and fellow hepatologists] have large backlogs of patients who are waiting for new medicines,” Bacon said. “Mostly, these are patients who have been treated before with interferon and don’t want to deal with the side effects again.”

With patients awaiting interferon-free regimens and the cost estimated to rise considerably, the cost burden on the health care system is going to go up considerably within the next 1 to 2 years, explained Bacon. These costs also may cause patients to forgo treatment altogether.

“We are seeing across the country that increasingly Americans are on high deductible health plans. Health care is becoming increasingly unaffordable,” Neel T. Shah, MD, executive director and founder of the nonprofit, Costs of Care, told Healio.com. “Traditionally, we are not trained to think about how patients will pay for care, but it is becoming increasingly important that we do that.

“There is very good evidence from other aspects of health care that when you increase the proportion that patients have to pay, they forgo treatments, even treatments that are necessary.”

“It is difficult to answer the question about costs and what it is going to be like because it is challenging for the patients to keep up,” Muir said, “and it’s actually challenging for the payers to plan on what a likely budget will be for a patient and the population with hepatitis. Because we have many patients who are uninsured or underinsured, we hope they will benefit from new health care legislation.

“This is a rapidly evolving field and people do essentially need to stay tuned. The big picture message is that hepatitis C treatment is getting better as far as better response rates and better side effect profiles in the next couple of years,” Muir said, adding that increased awareness and screening are important parts of this picture.

“If we can treat the patients before they develop advanced complications and cure them of their hepatitis C, then we can prevent them from going on to develop the complications of cirrhosis and liver cancer. The goal is to cure the disease,” Muir said.

Disclosure: Muir has received grant support from Abbott Laboratories, Achillion Pharmaceuticals, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Merck, Pfizer, and Vertex Pharmaceuticals.

Bacon has received research support from Roche/Genentech Laboratories, Bristol-Myers Squibb and Abbott Laboratories. He is a consultant, on the speakers’ bureau and has received research support from Merck. He has received research support, is a speaker on the hepatitis advisory board and on the Data and Safety Monitoring Board for Gilead Sciences. He has received research support, is a speaker and is on the hepatitis advisory board for Kadmon Pharmaceuticals; he has received research support, is an advisory board and Data and Safety Monitoring Board member, and is a speaker for Vertex Pharmaceuticals; and is a Data and Safety Monitoring Board member for ISIS Pharmaceuticals.

Shah is on the advisory board for Haymarket Media’s electronic Monthly Prescribing Reference (eMPR) and also receives funding from the ABIM Foundation.

- Suzanne Bryla Reist

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Risks small between HCV patients’ use of DAAs, neuropsychiatric events

Provided by Healio

Sockalingam S. BMC Gastroenterol. 2013;doi:10.1186/1471-230X-13-86.

May 24, 2013

The risks for neuropsychiatric adverse events among patients with hepatitis C virus being treated with direct-acting antivirals appear minimal, but the risks for drug-drug interactions are high, according to recent study results.

Researchers conducted a literature search of PubMed from 2000 to April 2013 using the search terms, “hepatitis C” and “boceprevir” or “telaprevir,” along with “mental disorders,” “psychotropic drugs” and “drug interactions.” The analysis was designed to evaluate studies on neuropsychiatric adverse effects as a result of direct-acting antivirals (DAAs) and drug-drug interactions (DDIs) involving psychotropic medications and DAAs among hepatitis C virus (HCV) patients.

For lack of published literature, researchers also included data collected from major trials for protease inhibitors telaprevir and boceprevir and their association with psychiatric adverse events. In reviewing studies that included triple therapies of pegylated interferon-alfa, ribavirin and either telaprevir or boceprevir and those without DAAs, researchers determined there were no significant differences in neuropsychiatric side effects. Events included anxiety, depression, insomnia, fatigue and irritability. Trials excluded patients with significant psychiatric illness, possibly resulting in underestimated rates for neuropsychiatric adverse events, researchers wrote.

Researchers also examined DDIs between DAAs and anticonvulsants, antipsychotics, antidepressants and benzodiazepines. Contraindications existed between DAAs and carbamazepine, triazolam, oral midazolam, pimozide and St. John’s Wort. In some cases, DDIs potentially can occur via cytochrome P450 and p-glycoprotein induction, researchers said.

“Although DAAs do not add significant neuropsychiatric risk, the potential for DDIs is high,” the researchers concluded. “Additional drug interaction studies between DAAs and commonly used psychotropic agents are urgently needed. The results of these studies will be essential to guiding clinicians presented with challenges in interpreting DDI risks related to psychiatric care in the era of HCV triple therapy.”

Disclosure: See the study for a full list of relevant disclosures.

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Rise Up to HIV Re-Launches the No Shame About Being HIV Positive Anti Stigma Campaign

The No Shame About Being HIV Positive campaign, a project of Rise Up To HIV, launched in January of 2013. This campaign quickly grew to over 400 photos accompanied by testimonials by people living with HIV and AIDS and our allies; see how you can join the campaign!

Minneapolis, MN (PRWEB) May 23, 2013

The campaign was readily featured by major HIV/AIDS social media outlets like The Body, Huffington Post, Poz Magazine, Positive Aware, Positive Lite and others.

“By showing our faces, sharing our experiences, letting people know there is nothing to be ashamed of, we affirm ourselves as human beings with dignity, and we call attention to a disease that needs not be there; says Mario Ferri long term survivor of HIV”

The campaign has served as a source of inspiration and as a launching platform for many HIV/AIDS advocates and activists all across the globe. This Summer of 2013, we are accepting photos and stories to be featured in the follow up campaign titled “The Summer of No Shame About Being HIV Positive”. Goals of the campaign are to help reduce stigma and fear, educate, and inspire others to share their experiences, strengths and hope while LIVING with HIV/AIDS. We are also interested in developing a more permanent online tribute to those who have participated and to the overall HIV/AIDS Movement (name of project TBA).

Driven by people living with HIV/AIDS and our allies in the cause the campaign is harnessing the power of social media, which allows communities of people impacted by HIV to share their stories with all of us regardless of our status. “Understanding that someone who is HIV+ is living next door, teaching our children or is our relative or partner is still difficult for some folks. Let’s work towards ending the stigma of HIV and work towards building a more cohesive world” says Kevin Maloney Founder of Rise Up To HIV and the No Shame About Being HIV Positive Campaign.

How to join the campaign:

1) E-mail your photo and story (e mail on right side of press release)

2) Or visit the page of the campaign and message the page with your photo and story http://www.facebook.com/riseuptohivandhcv

What is HIV/AIDS Related Stigma?

HIV/AIDS-related stigma refers to prejudice, negative attitudes, abuse and maltreatment directed at people living with HIV and AIDS. The consequences of stigma are wide-ranging: being shunned by family, peers and the wider community; poor treatment in health care and education settings; erosion of rights; psychological damage; and has an overall negative effect on the success of HIV testing and treatment.

##############################################################################

Rise Up To HIV is a volunteer grassroots movement blazing a trail in social media with it's commitment to highlighting relevant news stories and showcasing individuals impacted by HIV/AIDS in communities across the globe.

Mission
To educate, inspire, empower, advocate, network and partake in social change through unilateral and collaborative social media efforts of organizations, PLWHA, and our supporters with diverse backgrounds from all over the world.

Vision
To create positive change for individuals, families and communities through an army of compassionate individuals and organizations with a goal of reducing stigma as we march towards the cure for HIV/AIDS.

About the Founder:
Visit http://www.riseuptohiv.org/about-the-founder/.

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Delayed versus immediate treatment for patients with acute hepatitis C: a randomised controlled non-inferiority trial

The Lancet Infectious Diseases, Volume 13, Issue 6, Pages 497 - 506, June 2013

doi:10.1016/S1473-3099(13)70059-8 Cite or Link Using DOI

This article can be found in the following collections: Global Health; Public Health; Nutrition & Metabolism (Undernutrition); Paediatrics (Paediatrics-other)

Published Online: 22 March 2013

Katja Deterding MD a b, Norbert Grüner MD a e, Peter Buggisch MD a g, Johannes Wiegand MD a f, Prof Peter R Galle MD a h, Prof Ulrich Spengler MD a i, Holger Hinrichsen MD a j, Prof Thomas Berg MD a f k, Andrej Potthoff MD a b, Prof Nisar Malek MD a l, Anika Großhennig PhD c, Prof Armin Koch PhD c, Prof Helmut Diepolder MD a e, Stefan Lüth MD a g, Sandra Feyerabend MD a, Prof Maria Christina Jung MD a e, Magdalena Rogalska-Taranta PhD a d, Verena Schlaphoff PhD a d, Markus Cornberg MD a b, Prof Michael P Manns MD a b , Prof Heiner Wedemeyer MD a b , for The Hep-Net Acute HCV-III Study Group

Summary

Background

Early treatment of acute hepatitis C virus (HCV) infection with interferon alfa monotherapy is very effective, with cure rates of greater than 85%. However, spontaneous clearance of HCV occurs in 10—50% of cases. We aimed to assess an alternative treatment strategy of delayed antiviral therapy in patients who do not eliminate the virus spontaneously compared with immediate treatment.

Methods

In our open-label phase 3 non-inferiority trial, we enrolled adults (≥18 years) with acute hepatitis C but no HIV or hepatitis B co-infection at 72 centres in Germany. We randomly allocated patients with symptomatic acute hepatitis C (1:1) to receive immediate pegylated interferon alfa-2b treatment for 24 weeks or delayed treatment with pegylated interferon alfa-2b plus ribavirin (for 24 weeks) starting 12 weeks after randomisation if HCV RNA remained positive. We used a computer-generated randomisation sequence and block sizes of eight, stratified by bilirubin concentration. We assigned all asymptomatic patients to immediate treatment with pegylated interferon alfa-2b for 24 weeks. The primary endpoint was sustained HCV RNA negativity in all randomly allocated participants who completed screening (intention-to-treat analysis), with a non-inferiority margin of 10%. For the primary analysis, we calculated the virological response of patients in the immediate and delayed treatment groups and an absolute risk difference stratified by bilirubin status. The trial was stopped early on advice from the study advisory committee because of slow recruitment of participants. This study is registered, number ISRCTN88729946.

Findings

Between April, 2004, and February, 2010, we recruited 107 symptomatic and 25 asymptomatic patients. 37 (67%) of 55 symptomatic patients randomly allocated to receive immediate treatment and 28 (54%) of 52 symptomatic patients randomly allocated to receive delayed treatment had a sustained virological response (difference 13·7%, 95% CI −4·6 to 32·0; p=0·071). 18 (72%) of 25 asymptomatic patients had a sustained virological response. 22 (42%) of 52 symptomatic patients allocated to receive delayed treatment did not complete follow-up compared with 20 (25%) of 80 symptomatic or asymptomatic patients assigned immediate treatment (p=0·037). 11 symptomatic patients (21%) assigned delayed treatment had spontaneous HCV clearance. 14 patients who received delayed pegylated interferon alfa-2b plus ribavirin treatment and completed follow-up achieved sustained virological response.

Interpretation

Delayed treatment is effective although not of equal efficacy to immediate treatment; coupled with the rate of spontaneous clearance it can reduce unnecessary treatment in closely monitored populations. Immediate treatment seems preferable in populations where loss to follow-up is great.

Funding

German Network of Competence on Viral Hepatitis (HepNet, funded by the German Federal Ministry of Education and Research, grants 01KI0102, 01KI0401, and 01KI0601), MSD, Schering-Plough.

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Adverse Events Common With Triple Therapy in HCV Cirrhosis

Reuters Health Information

May 22, 2013

By David Douglas

NEW YORK (Reuters Health) May 22 - In cirrhotic patients, triple-therapy against hepatitis C virus (HCV) produces a high virological response rate, but at the cost of a high rate of serious adverse events, French researchers say.

In the French CUPIC cohort, four in ten cirrhotic patients on triple therapy with pegylated interferon and ribavirin plus boceprevir or telaprevir suffered a serious complication (death, severe infection, or hepatic decompensation).

This cohort, Dr. Christophe Hézode told Reuters Health by email, consisted of "HCV genotype 1 treatment-experienced patients with compensated cirrhosis."

In a May 13th online paper in The Journal of Hepatology, Dr. Hézode of Universite Paris-Est, Creteil and colleagues say phase III trials have yielded similar results in treatment-experienced cirrhotics and non-cirrhotics, but patients were highly selected.

To evaluate the effect in "real-world" patients, the team analyzed 497 patients who reached at least week 16 in a 48-week triple therapy early access program. All had previously received interferon.

Forty percent (199 patients) had serious adverse events, with 58 patients stopping their treatment as a result. Refractory anemia was also common. Six patients died and another 32 (6.4%) had severe infection or hepatic decompensation or another serious event.

Death or severe complications were related to platelet counts at or below 100,000/mm3 (odds ratio 3.11) and albumin <35 g/dL (OR 6.33).

In patients with both of these risk factors, who accounted for 7.9% of the cohort, the rate of severe complications was 44.1%, "suggesting that they should not be treated with the triple therapy." In the remaining 92.1%, the risk was at or below 7.1%.

In an intention-to-treat analysis in the 292 patients treated with the telaprevir combination, HCV RNA was undetectable in 78.8% at week 12 and 67.1% at week 16. In the 205 given boceprevir, the corresponding proportions were 54.6% and 58.0%.

Although the safety profile of triple therapy is poor in a real-life setting, the approach "was associated with high rates of on-treatment virological response," the authors report.

Overall, they say "Serum albumin level and platelet count should be evaluated to determine the risk/benefit ratio of triple therapy in cirrhotic patients and to decide treatment."

"Patients combining a platelet count of less 100,000 /mm3 and serum albumin below 35 g/L should not be treated with a triple combination," Dr. Hézode stressed.

"The other patients," the team concludes, "could be treated cautiously and carefully monitored."

Commenting on the findings by email, Dr. Savino Bruno of A. O. Fatebenefratelli e Oftalmico, Milan, Italy told Reuters Health that "risk overcame benefit" in a number of patients. However, "a more reliable on-treatment stopping rule... may maximize benefit and minimize risk."

Other research on the CUPIC cohort that was recently presented at the 48th annual meeting of European Association for the Study of the Liver, sheds more light on a related strategy. In that study, by investigators including Dr. Hézode found that independently of cirrhosis severity, baseline concentration of apolipoprotein H was associated with early virological response.

SOURCE: http://bit.ly/14S1CwV

J Hepatol 2013.

Source

Significant Progress in the Treatment of Hepatitis C

By: Badar Muneer, MD
Wednesday, May 22, 2013

Hepatitis C (HCV) is a common cause of liver disease and cirrhosis in the United States. It is the most common indication for liver transplantation, and the cause of more than 50% of hepatocellular carcinoma in the U.S.

Most patients with HCV are asymptomatic, and are thus not tested. Diagnosing and treating patients at earlier stages of HCV would be beneficial, and could prevent the development of cirrhosis and its associated complications. The Centers for Disease Control and Prevention (CDC) estimates that without diagnosis and treatment, about 1.7 million HCV patients will develop cirrhosis, more than 400,000 will develop hepatocellular carcinoma, and almost 1 million will die from HCV-related complications. Another benefit of early diagnosis is that patients with less fibrosis respond better to HCV therapy.

Testing everyone born between 1945 and 1965 would find an estimated 800,000 undiagnosed HCV cases.

The CDC now recommends one-time HCV antibody testing for all individuals born between 1945 and 1965, also known as “Baby Boomers.” The prevalence of HCV antibody in this group is five times higher than people born before or after. In fact, 75% of adults with HCV were born in these years. Testing everyone born between 1945 through 1965 would find an estimated 800,000 undiagnosed HCV cases.

The standard of care for the treatment of HCV had been combination therapy with pegylated interferon and ribavirin. This therapy had suboptimal sustained virologic response (SVR or cure) rates. In 2011, the Food and Drug Administration approved the first generation of direct-acting antiviral agents (DAAs) for the treatment of genotype 1 HCV. These protease inhibitors (Boceprevir and Telaprevir) in combination with pegylated interferon and ribavirin significantly increased the SVR rates to 68-75% in treatment-naïve white patients, 52-63% in treatment-naïve black patients, and 29-83% in treatment-experienced patients. In addition, these regimens allowed shortening therapy in certain subgroups of patients to only 24 weeks (compared to the standard 48 weeks).

However, there are still many limitations and challenges with Telaprevir and Boceprevir. The discontinuation rate due to severe adverse events is about 10-12%, and even higher in cirrhotic patients (20-25%). Anemia is a major side effect with both Telaprevir and Boceprevir. More than 40% of patients develop anemia requiring dose adjustment of ribavirin with or without the use of erythropoietin. Skin rash is also common with Telaprevir and about 10% of patients stop treatment due to severe skin rash. These side effects are more common in patients with cirrhosis. Drug-drug interactions are also major problems with Telaprevir and Boceprevir. In addition, DAAs are not yet approved for HCV patients co-infected with HIV or hepatitis B, post-liver transplant patients, or patients infected with non-genotype 1 HCV.

The most exciting research ongoing for HCV is the use of interferon-free (and often, ribavirin-free) regimens. The goal of such therapies will be simpler and more effective treatment options for HCV. These will have higher SVR rates, less side effects, purely oral regimens, shorter duration, and will be effective against all HCV genotypes. Currently, there are a multitude of such phase 2 and phase 3 trials being performed. The preliminary data has been excellent with SVR rates as high as 100% with treatment durations as short as 12 weeks.

In summary, significant progress has been made in the treatment of HCV. Although somewhat limited by toxicity and the continued need for interferon, the currently-approved medications are able to cure a majority of patients with HCV. However, in the next 2-5 years, we will likely reach a point of being able to cure almost all patients with shorter, interferon-free, well-tolerated regime.

Dr. Badar Muneer is a transplant hepatologist at University Hospitals Digestive Health Institute and an instructor at Case Western Reserve University School of Medicine. For more information, visit www.uhhospitals.org/transplant.

Source: MD News June/July 2013, Northeastern Ohio/Western PA Edition

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Spleen stiffness predicted risk for large, bleeding esophageal varices in cirrhotic patients

Provided by Healio

Sharma P. Am J Gastroenterol. 2013;doi:10.1038/ajg.2013.119.

May 23, 2013

Measuring spleen stiffness in patients with cirrhosis was an effective, noninvasive method of predicting and differentiating large and small esophageal varices and determining those at risk for bleeding, according to recent study results.

Using transient elastography (FibroScan), researchers measured spleen stiffness (SS) and liver stiffness (LS) in 200 consecutive patients with cirrhosis between September 2011 and March 2012. Other measurements conducted in some of the cohort included hepatic venous pressure gradient (HVPG), upper gastrointestinal endoscopy, LS-spleen diameter to platelet ratio score (LSPS) and platelet count to spleen diameter ratio (PSR).

Among 174 evaluable patients who met inclusion criteria and had valid LS and SS measurements, 124 (71%) had esophageal varices (EV). Seventy-eight patients had large EV (more than 5 mm); 46 had small varices (less than 5 mm). Patients with EV displayed a significant difference in median SS (54 kPa compared with 32 kPa), LS (51.4 kPa vs. 23.9 kPa), LSPS (6.1 vs. 2.5) and PSR (812 vs. 1,165) compared with patients without EV (P=.001 for all differences).

Although LS could not be used to differentiate between large and small varices (53 kPa vs. 45.3 kPa; P=.57), SS was greater and indicative of patients with large varices (56 kPa vs. 49 kPa; P=.001) compared with small varices. Patients who had variceal bleed (n=46) also had greater SS than nonbleeder (n=78) patients (58 kPa vs. 50.2 kPa; P=.001).

Among only patients who submitted to HVPG (n=52), a significant correlation was observed with SS (P=.001) and LSPS (P=.01), but not LS (P=.207).

“Given the need to screen patients with cirrhosis, noninvasive tests, such as SS, may help to identify patients at risk of having EVs, particularly large, and those at risk of bleeding,” the researchers concluded. “Spleen stiffness, along with liver stiffness measurement, could select patients with cirrhosis, who should undergo upper gastrointestinal endoscopy to decrease burden upon endoscopy units.”

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The Majority of Physicians that Treat Hepatitis C Virus (HCV) Have Begun "Warehousing" and Preparing Their HCV Patients for the Next Generation of HCV Treatments

Sixty Percent of Surveyed Physicians Agree That They Are Beginning To Warehouse HCV Patients Until New Interferon-Free Regimens Are Available, According to a Recently Published BioTrends Report

EXTON, Pa., May 23, 2013 /PRNewswire/ -- BioTrends Research Group, one of the world's leading research and advisory firms for specialized biopharmaceutical issues, finds that, unaided, one in five surveyed gastroenterologists, hepatologists, and infectious disease specialists reported that in the past six months, they have begun warehousing patients (e.g., intentionally delaying treatment) in anticipation of the next generation of HCV treatments—notably more physicians than six months ago, when only 6 percent reported that they had begun warehousing patients.

(Logo: http://photos.prnewswire.com/prnh/20130103/MM36805LOGO )

Furthermore, only one in five physicians agrees that they are satisfied with currently available treatment options, underscoring the high unmet need for alternatives to treat chronic HCV infections. The trending analyses of physician-reported anticipated prescribing in TreatmentTrends^®: Hepatitis C Virus (US), Wave 1 also finds that, for the first time in a year, surveyed physicians are expecting to treat a greater proportion of their genotype 1 (3 percent) and 2/3 (3 percent) patients in the next six months with regimens that are not currently available. Unaided responses from most physicians who expect to be using other treatments suggest they are expecting products in development, potentially interferon-free regimens, to be available for use in the next six months.

In aided physician responses, Gilead's sofosbuvir and Janssen/Medivir's simeprevir garnered the highest degree of familiarity for use in HCV treatment, followed closely by Bristol-Myers Squibb's daclatasvir and asunaprevir. Additionally, 20 percent of the surveyed physicians believe that Gilead's sofosbuvir is the most promising product in development, primarily due to its favorable tolerability, oral dosing, pan-genotypic activity, and its possibility to be utilized as an interferon-free regimen.

"The protease inhibitors, Vertex's Incivek and Merck's Victrelis, were very important advances in the management of HCV infections," said BioTrends Research Group Associate Director, Lynn Price . "However, there is still a clear unmet need for alternative HCV therapies and the recent NDA filings for simeprevir and sofosbuvir have physicians hopeful for new treatment options that are highly efficacious and more tolerable than the currently available protease inhibitors."

TreatmentTrends^®: Hepatitis C Virus (US), Wave 1 is a report that covers the use of agents for the treatment of HCV infections. This bi-annual study focuses on current and future use of leading HCV treatment regimens, patient market share, perceived strengths and weaknesses of the key brands, barriers to broader usage, sales force performance, and perceived value of manufacturers' patient assistance programs. In addition, this report assesses potential impact of regimens in development, including Abbott's ABT-267, ABT-333, and ABT-450, Boehringer Ingelheim's BI-207127 and faldaprevir, Bristol-Myers Squibb's asunaprevir and daclatasvir, Janssen's simeprevir, and Gilead's sofosbuvir and ledipasvir. In the current wave of research, BioTrends surveyed 101 U.S. gastroenterologists, hepatologists, and infectious disease specialists in March 2013.

About BioTrends Research Group
BioTrends Research Group provides syndicated and custom primary market research to pharmaceutical manufacturers competing in clinically evolving, specialty pharmaceutical markets. For information on BioTrends publications and research capabilities, please contact us at www.bio-trends.com. BioTrends is a Decision Resources Group company.

About Decision Resources Group
Decision Resources Group is a cohesive portfolio of companies that offers best-in-class, high-value information and insights on important sectors of the healthcare industry. Clients rely on this analysis and data to make informed decisions. Please visit Decision Resources Group at www.DecisionResourcesGroup.com.

All company, brand, or product names contained in this document may be trademarks of their respective holders.

For more information, contact:

Decision Resources Group
Christopher Comfort
781-993-2597
ccomfort@dresources.com

SOURCE BioTrends Research Group

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Assessment of motivating factors associated with the initiation and completion of treatment for chronic hepatitis C virus (HCV) infection

Published on: 2013-05-23

Infection with hepatitis C virus (HCV) is associated with high morbidity and increased mortality but many patients avoid initiation of treatment or report challenges with treatment completion. The study objective was to identify motivators and barriers for treatment initiation and completion in a community sample of HCV-infected patients in the United States.

Methods: Survey methods were employed to identify factors reported by patients as important in their decision to start or complete HCV treatment.

Study participants included 120 HCV-infected individuals: 30 had previously completed treatment with pegylated interferon/ribavirin (PR), 30 had discontinued PR, 30 were treated with PR at the time of the survey, and 30 were treatment-naive. Telephone interviews occurred between May and August of 2011 and employed a standardized guide.

Participants assigned factors a rating from 1 (not at all important) to 5 (extremely important). Trained researchers coded and analyzed interview transcripts.

Results: Of 33 factors, expected health problems from not treating HCV infection was reported as most encouraging for treatment initiation and completion, while treatment side effects was most discouraging.

Sixty-nine percent of participants reported that the ability to obtain information during treatment on the likelihood of treatment success (i.e ., results of viral load testing) would motivate them to initiate therapy. Median preferred timing for learning about test results was 5 weeks (range: 1--23 weeks). Conclusion: Understanding challenges and expectations from patients is important in identifying opportunities for education to optimize patient adherence to their HCV treatment regimen.

Author: Lauren FusfeldJyoti AggarwalCarly DougherMontserrat Vera-LlonchStephen BubbMrudula DonepudiThomas F Goss
Credits/Source: BMC Infectious Diseases 2013, 13:234

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AASLD members at forefront to raise awareness of hepatitis B and C

Published on May 23, 2013 at 2:26 AM

Viral hepatitis is an asymptomatic disease affecting more than 5.3 million Americans. More than 75 percent of those with hepatitis C are unaware they have the virus.

Hepatitis B and C Testing and Awareness Day in the U.S. House of Representatives will take place at 10:00 am - 2:00 pm in the Rayburn Foyer of the Rayburn House Office Building in Washington, D.C.

The American Association for the Study of Liver Diseases (AASLD) is pleased to participate with the Congressional Hepatitis Caucus, the National Viral Hepatitis Roundtable, the Community Education Group, Hepatitis B Initiative of Washington DC, Caring Ambassadors Program, the National Alliance of State and Territorial AIDS Directors, the Association of Chinese American Physicians, and private industry to provide testing for hepatitis B and C.

In May 2011, the United States Department of Health and Human Services (HHS) released "Combating the Silent Epidemic of Viral Hepatitis: Action Plan for the Prevention, Care & Treatment of Viral Hepatitis." The plan runs through 2013, and AASLD -- the leading organization of scientists and healthcare professionals committed to preventing and curing liver disease -- welcomes the HHS announcement that it intends to update and renew the plan for 2014-2016.

Access to care and support of liver disease research are at the center of AASLD's advocacy efforts and Hepatitis Awareness Month and hepatitis testing events are necessary to make Americans aware that they can now be tested and treated for hepatitis C.

Research in the area of hepatitis C has led to FDA approval of two direct acting antiviral drugs for the treatment of hepatitis C, and numerous other direct acting antiviral drugs are in the development pipeline. AASLD looks forward to -- and its members work diligently to realize -- the day when an all-oral, interferon-free, shortened treatment can be used to eradicate the virus from patients with hepatitis C.

As research in hepatitis C continues, the fight against hepatitis B does so too, and AASLD members are at the forefront of these battles. We are proud to partner with the Centers for Disease Control and Prevention and others at HHS wherever there is an opportunity to raise awareness of both hepatitis B and C.

• May is Hepatitis Awareness Month.
• May 2013 is the second anniversary of the National Viral Hepatitis Action Plan.
• May 19, 2013, was the second annual Hepatitis Testing Day.
• May 23, 2013, is Hepatitis B and C Testing and Awareness Day in the U.S. House of Representatives.

SOURCE American Association for the Study of Liver Diseases

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FDA Rethinking Personalized Drug Trials

By David Pittman, Washington Correspondent, MedPage Today

Published: May 22, 2013

WASHINGTON -- The FDA will need to "turn the clinical trial paradigm on its head" in order to allow more specifically targeted, personalized drug therapies to get on the market faster, a top agency official said Tuesday.

"We are going to have to change the way drugs are developed. Period," said Janet Woodcock, MD, head of the FDA's Center for Drug Evaluation and Research.

Answering every question needed from regulators about targeted therapies -- such as who should receive the drug, at what dose, and with what expected side effects -- won't be possible in a traditional clinical trial, she explained at a luncheon hosted by the Personalized Medicine Coalition, a group of insurers, drugmakers and patient communities here whose goal is to "promote the understanding and adoption of personalized medicine concepts, services and products to benefit patients and the health system," according to its website.

Instead of embarking on traditional clinical trials, drugmakers and clinical investigators need to work in different ways to select patients for what will inevitably be smaller trials, she said.

"Ever smaller subsets of patients are being identified, and we're really going to have to put our heads together and figure out how do you study these small subsets of diseases," Woodcock said in a 45-minute speech on the FDA's efforts to advance the field. "What types of trials and development programs do you do? And when does a subset get so small that you're not going to be able to do a randomized trial?"

Advances in genomics has allowed drugmakers to develop not just a new breast cancer treatment, for example, but one that targets a specific genotype of that cancer like HER2, as was done with trastuzumab (Herceptin).

Anywhere from an eighth to half of companies' drug pipelines are targeted therapies, Woodcock said. About a third of new entities approved by the FDA last year had some type of genotyped biomarker in its marketing application.

Developments in cancer drugs, infectious diseases, and genetic disorders have led the way on such personalized therapies.

But in order to develop trials to test these drugs, the FDA and drug developers need a "new definition of clinical trials" that recognizes therapies will be targeted at subsets of conventionally defined diseases, Woodcock said.

Rather than doing a single trial in all patients with a particular disease, developers need to stratify patients into needed subsets based on certain biomarkers, she continued. Only then will trials be able to test the safety and effectiveness of their drug candidates.

The way trials were developed in the past should not influence or govern the way things are done in the future, Woodcock said.

For decades, the agency has requested two randomized, controlled, non-inferiority trials. But those may not be possible with the small number of patients possible in trials.

In order to identify these subset of patients -- which may be very few in number -- drugmakers may have to work together or work with third parties like patient advocacy groups to identify them, the FDA drug center head said.

"We haven't seen a lot of this so far," Woodcock said. "We're hoping that independent groups set up these trial networks and standing trials, so that then companies are comfortable coming together through a third party to do development of their drugs."

The personalized cystic fibrosis drug ivacaftor (Kalydeco), which treats the disease arising from the G551D-CFTR mutation, was developed through such a patient group network, Woodcock said.

But there are other challenges the agency and developers must tackle too.

Such targeted therapies have had difficulty receiving insurance coverage, in part because of their price. Woodcock noted this trend has slowed development of diagnostics that accompany such products.

Therefore, targeted therapies need to slow or stop chronic diseases and not just show a positive short-term benefit to silence critics. "If we can cure Hepatitis C, there's not going to be a peep from anybody because the cost effectiveness of that will be absolutely clear," she said. "Same with cancer."

The FDA is also thinking about how to translate prescribing information to providers, who want simple, easy-to-understand instructions.

"They want directions. They don't want education. They don't want to be taught genetics," Woodcock said. "They want [to know] 'what do I do. please tell me.' "

Therefore, diagnostics that accompany drugs and information in labeling needs to be detailed and accurate but also easily understood.

That path ahead won't be easy and will require a grand change in the way clinical trials are thought about by drug regulators and developers. "We're going into uncharted waters here," Woodcock said. "I think it's going to be a big challenge for everyone."

Source

Hepatitis C: A 21st Century Success Story (Op-Ed)

Credit: Dreamstime

Dr. David Bernstein, North Shore-LIJ Health System

Date: 22 May 2013 Time: 03:38 PM ET

Dr. David Bernstein is chief of the Division of Hepatology / Center for Liver Disease at the North Shore-LIJ Health System, and a professor of medicine at Hofstra North Shore-LIJ School of Medicine. He contributed this article to LiveScience's Expert Voices: Op-Ed & Insights.

Hepatitis C has been called a silent epidemic: As the most common blood-borne viral infection in the country, it affects more than 7 million Americans — yet, most don't know they have it. But the condition can lead to the development of cirrhosis and liver cancer, and is the leading indication for liver transplantation in the United States.

Baby boomers have the highest rate of hepatitis C infection, so the Centers for Disease Control and Prevention (CDC) recently recommended that all people born between 1945 and 1965 get tested at least once for it. People with other risk factors for hepatitis C (e.g., previous intravenous drug users, previous cocaine users, recipients of blood transfusions before 1992, and people with tattoos and body piercings in places other than the ears) should also get tested, regardless of age.

Once hepatitis C is diagnosed, it is curable, unlike other common blood-borne viruses , such as hepatitis B and HIV. Advances in hepatitis C therapies have been rapid. The first therapy for hepatitis C infection consisted of interferon injections alone, with a cure rate of less than 10 percent. In the mid-1990s, a pill called ribavirin was added to injectable interferon, and cure rates increased to about 40 percent. For more than 10 years, once-weekly injectable interferon plus oral ribavirin for a course of 24 to 48 weeks was the standard treatment method.

The high prevalence of hepatitis C has led to a considerable effort to improve cure rates with newer therapies. The first step was to understand the mechanism of hepatitis C viral replication. After researchers determined the disease's molecular structure, they identified the two main classes of enzymes involved in hepatitis C replication: protease and polymerase inhibitors. As a result of that research, direct-acting medications were manufactured to inhibit those enzymes — thus preventing replication and promoting higher cure rates.

In May 2011, the U.S. Food and Drug Administration approved the first new hepatitis C therapies in a decade. Two new oral agents — boceprevir and telaprevir, from the class of drugs called protease inhibitors — were approved for use in combination with pegylated interferon and ribavirin. These new, triple-therapy regimens have seen cure rates as high as 70 to 75 percent. Therapy lasts from 24 to 48 weeks. Boceprevir and telaprevir are both taken three times a day for a time period ranging from three months to 44 weeks, depending on clinical circumstance for each patient.

The new protease inhibitors increased efficacy — and side effects . Telaprevir is associated with a rash that generally appears in the first four to eight weeks of therapy, as well as anal pain that can manifest at any time during treatment. Most patients are easily treated with topical creams and antihistamine pills. Boceprevir is associated with a bad taste in the mouth in almost all patients — though this is more of an annoyance than a problem. Most patients barely notice it. Both telaprevir and boceprevir are associated with the development of significant anemia, which can limit their use. The anemia can lead to fatigue and may require the use of growth factors — compounds that affect cell growth, maturity and differentiation — to alleviate symptoms.

Since the approval of boceprevir and telaprevir, drug development has been progressing rapidly. Many studies are evaluating the use of second-generation protease inhibitors, polymerase inhibitors and NS5A inhibitors in various combinations to treat all different types of patients with hepatitis C. In addition to new agents, shorter durations of therapy (eight or 12 weeks) and interferon-free, all-oral regimens are in development.

It is highly probable that an all-oral regimen for the treatment of hepatitis C genotype 2 and 3 will become available late this year or in early 2014, with similar efficacy as that of interferon-based therapies, but with fewer side effects and a shorter course. It is also likely that a new, second-generation protease inhibitor — simeprevir — and a first-in-class oral nucleotide analogue polymerase inhibitor — sofosbuvir — will be approved in early 2014.

Both of those new agents are given once daily and will be approved for use in hepatitis C genotype 1 in combination with interferon and ribavirin. The treatment duration for the new simeprevir-containing regimen will likely be 24 to 48 weeks, while the regimen with sofosbuvir will likely last 12 weeks. Neither of those new agents have any significant side effects, and cure rates should be higher than currently approved triple therapies.

After simeprevir and sofosbuvir are approved, many even newer agents are likely to come to market. It seems clear that all-oral therapy for the treatment of genotype 1 should be available sometime in 2015 or 2016. Compared to current regimens, all of the newer therapies offer higher cure rates, shorter duration of therapy and fewer side effects. A lot of work is underway to determine the best possible therapy for specific groups of patients. For example, specific regimens will likely be developed for each genotype, for patients with cirrhosis, for patients with kidney disease and for those who have had a kidney transplant.

With any luck, in the next decade, medical science should be able to treat and cure more than 90 percent of hepatitis C patients. The greater challenge is identifying patients — because most remain undiagnosed — and educating medical providers about the new therapies. Hopefully, the CDC screening guidelines will help. In addition to their other advantages, the newer therapeutic regimens may prevent the development of cirrhosis, liver cancer and the need for liver transplantation. The treatment and cure of hepatitis C will be one of the 21st century's major medical success stories.

Bernstein's disclosures are as follows:

Clinical-trial sponsors: Abbott, BMS, Gilead, Janssen, Vertex, Merck, Genentech

Consultant/speaker bureau: Abbott, Gilead, Janssen, Vertex, Merck

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Frederick A. Nunes, MD, on trial results for difficult-to-treat patients with HCV

Provided by Healio

May 22, 2013

ORLANDO, Fla. — Frederick A. Nunes, MD, associate professor of medicine, at Penn Health Systems, discusses his presentation, “Interferon‐free Regimens of ABT‐450/r, ABT‐267, ABT‐333, and Ribavirin Achieve High Sustained Virologic Response 4 Weeks Post‐Treatment (SVR4) Rates in Patients With Chronic HCV Genotype 1 Regardless of Race, Ethnicity, or Other Baseline Characteristics” during Digestive Disease Week 2013.

Among HCV patients who are difficult to treat, including African-Americans, those with high BMI and insulin resistance, achieved a very high sustained response using three direct-acting antivirals and ribavirin, Nunes says.

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P. Patrick Basu, MD, comments on RESTRAINT C trial results

Provided by Healio

May 22, 2013

ORLANDO, Fla. — P. Patrick Basu, MD, assistant clinical professor of medicine at Columbia University College of Physicians and Surgeons; division chief, department of gastroenterology and GI endoscopy at North Shore University Hospital in Forest Hills, N.Y., discusses his presentation “Romiplostim’s Effect to Optimize SVR With Telaprevir, Ribavirin, and PEG Interferon-Alfa 2A in Thrombocytopenic Cirrhotics With Chronic Hepatitis C. A Placebo Controlled Prospective Clinical Trial: RESTRAINT C Trial.”

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Mindie H. Nguyen, MD, comments on demographics among hepatitis C patients

Provided by Healio

Added 2013-05-21

Mindie H. Nguyen, MD, MAS, associate professor of medicine at Stanford University School of Medicine. Discussing her poster Sa1069: High Prevalence of Hepatitis C Virus Infection (HCV) in Asian Americans in a Community Primary Care Clinic, during DDW 2013 in Orlando, Fla.

Mindie Nguyen, MD, on HCV demographics

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Eric J. Lawitz, MD, reviews COSMOS trial with HCV genotype 1 patients

Provided by Healio

May 22, 2013

ORLANDO, Fla. — Eric J. Lawitz, MD, of the Texas Liver Institute at the University of Texas, San Antonio, discusses his late-breaking poster “SVR Results of a Once Daily Regimen of Simeprevir (Tmc435) Plus Sofosbuvir (Gs-7977) With or Without Ribavirin (RBV) in HCV GT 1 Null Responders” at Digestive Disease Week 2013....

He reports encouraging results for SVR among patients who underwent a 12-week regimen of simeprevir and sofosbuvir and were previously null responders to peginterferon and ribavirin.

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Andrew Muir, MD, analyzes recent hepatitis C clinical trial results

Provided by Healio

May 22, 2013

ORLANDO, Fla. — Andrew Muir, MD, clinical director, hepatology at Duke University Medical Center, offers an update on the most current hepatitis C research that was presented at Digestive Disease Week 2013.

With many new drugs coming forward, Muir said he provides his patients with time frames on the availability of these medications, including the much-anticipated interferon-free regimens. By understanding the regimens, a patient’s liver disease and what’s right for them, he says individualizing plans allows clinicians to better guide patients on timelines and expectations.

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European Medicines Agency Validates Gilead’s Marketing Application for Sofosbuvir for the Treatment of Hepatitis C

-- Once-Daily Sofosbuvir will Receive an Accelerated Assessment by EMA;

Designation Granted to New Medicines of Major Public Health Interest --

FOSTER CITY, Calif.--(BUSINESS WIRE)--May. 21, 2013-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the company’s Marketing Authorisation Application (MAA) for sofosbuvir, a once-daily oral nucleotide analogue inhibitor for the treatment of chronic hepatitis C virus (HCV) infection, which was submitted to the European Medicines Agency (EMA) on April 17, 2013, has been fully validated and is now under assessment. The data submitted in this MAA support the use of sofosbuvir and ribavirin (RBV) as an all-oral therapy for patients with genotype 2 and 3 HCV infection, and for sofosbuvir in combination with RBV and pegylated interferon (peg-IFN) for treatment-naïve patients with genotype 1, 4, 5 and 6 HCV infection.

Chronic HCV is a major cause of liver cancer and liver transplantation in Europe and around the world. The current standard of care for HCV involves 24-48 weeks of therapy with RBV and peg-IFN, which has to be injected and is associated with significant side effects.

“The clinical and economic burden of untreated HCV is substantial and growing rapidly. An estimated five million Europeans are living with hepatitis C, the majority of whom have not yet been diagnosed or are not in care. In addition, many are not suited to receive the current treatment regimens,” said John C. Martin, PhD, Chairman and Chief Executive Officer of Gilead Sciences. “If approved, sofosbuvir has the potential to improve cure rates, while reducing the duration of HCV therapy and reducing or eliminating the need for interferon injections.”

The MAA for sofosbuvir is supported primarily by data from four Phase 3 studies, NEUTRINO, FISSION, POSITRON and FUSION, in which 12 or 16 weeks of sofosbuvir-based therapy was found to be superior or non-inferior to currently available treatment options or historical controls, based on the proportion of patients who had a sustained virologic response (HCV undetectable) 12 weeks after completing therapy (SVR12).

Review of the MAA will be conducted under the centralized licensing procedure, which, when finalized, provides one marketing authorization in all 27 member states of the European Union (EU). EMA has accepted Gilead’s request for accelerated assessment for sofosbuvir, a designation that is granted to new medicines of major public health interest. Although accelerated assessment could shorten EMA’s review time of sofosbuvir by approximately two months, it does not guarantee a positive opinion from the EMA’s Committee for Medicinal Products for Human Use (CHMP) or final approval by the European Commission. If approved, sofosbuvir could be available for marketing in the EU in the first half of 2014. Gilead submitted a U.S. regulatory application for sofosbuvir in April 2013.

Sofosbuvir is an investigational product and its safety and efficacy have not yet been established.

About Gilead Sciences

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Asia Pacific.

Forward-Looking Statement

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the risk that EMA, the U.S. Food and Drug Administration and other regulatory agencies may not approve sofosbuvir, and that any marketing approvals, if granted, may have significant limitations on its use. Further, additional studies of sofosbuvir, including in combination with other products, may produce unfavorable results. In addition, even if approved, Gilead may not be able to successfully commercialize sofosbuvir, and may make a strategic decision to discontinue its development if, for example, the market for the product fails to materialize as expected. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead's Quarterly Report on Form 10-Q for the quarter ended March 31, 2013, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

For more information on Gilead Sciences, please visit the company's website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

Source: Gilead Sciences, Inc.

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

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Integrating mental health care into HIV care

Public release date: 21-May-2013

Contact: Fiona Godwin
fgodwin@plos.org
01-223-442-834
Public Library of Science

The integration of mental health interventions into HIV prevention and treatment platforms can reduce the opportunity costs of care and improve treatment outcomes, argues a new Policy Forum article published in this week's PLOS Medicine. Syvia Kaaya from the School of Medicine at the Muhimbili University of Health and Allied Sciences in Dar es Salaam, Tanzania and her international colleagues say that effective interventions exist for recognition and treatment of co-morbid mental disorders and can be implemented successfully by trained non- specialized providers in HIV care.

The authors say that interventions delivered by "task-sharing" would require "supportive supervision, monitoring, and feedback to inform quality improvement in comprehensive HIV/AIDS services providing mental health care" and that "multidisciplinary collaboration, coordination, and communication on common concerns are imperative for HIV services that integrate mental health care."

"Clinical depression, alcohol abuse, and HIV-associated neurocognitive disorders (HAND) are prevalent in people living with HIV and have negative consequences for HIV treatment outcomes," say the authors.

The five articles providing a global perspective on integrating mental health will be published weekly in PLOS Medicine beginning 30 April 2013.

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Funding: LW's participation was supported in part by NIMH P20 MH086048. The sponsors had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: SM provides consultancy services at Mildmay Center (Uganda) for HIV care and for the Peter C Alderman Foundation (PCAF) for the care of Psycho-trauma victims. All other authors have declared that no competing interests exist.

Citation: Kaaya S, Eustache E, Lapidos-Salaiz I, Musisi S, Psaros C, et al. (2013) Grand Challenges: Improving HIV Treatment Outcomes by Integrating Interventions for Co-Morbid Mental Illness. PLoS Med 10(5): e1001447.doi:10.1371/journal.pmed.1001447

IN YOUR COVERAGE PLEASE USE THIS URL TO PROVIDE ACCESS TO THE FREELY AVAILABLE PAPER:

http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001447

Contact:

Sylvia Kaaya
Muhimbili University of Health and Allied Sciences,
Psychiatry
TANZANIA, UNITED REPUBLIC OF
skaaya@gmail.com

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No postings yet for HIV-positive Marines, sailors since policy change

By Matthew M. Burke

Stars and Stripes

Published: May 22, 2013

SASEBO NAVAL BASE, Japan — More than nine months have passed since the Navy decided to open up overseas and large-ship platform assignments to HIV-positive sailors and Marines, but not a single sailor has gotten such a posting.

The Navy’s Personnel Command is grappling with how to implement the instruction, which also covers blood-borne pathogens like hepatitis B and C.

Secretary of the Navy Ray Mabus handed down the policy in August 2012.

Personnel Command officials declined to comment on when the policy would actually take effect. Instructions can take time to implement, Personnel Command spokesman Lt. Cmdr. Rob Lyon told Stars and Stripes in an email.

“Navy Personnel Command recently completed a review of SECNAVINST 5300.30E, dealing with blood-borne pathogens, to ensure sailors affected will have the greatest opportunity to be successful, and any concerns by their receiving commands will be addressed,” Lyon said. “We will more than likely have more to discuss once the Milpersman article (implementation guidance) has been chopped by all parties.”

The policy effectively opened the assignments to HIV-positive sailors and Marines who are stable and have undetectable viral loads, which translates into minimal medical complications, Bureau of Medicine and Surgery spokeswoman Shoshona Pilip-Florea told Stars and Stripes in December.

The change was made possible because of medical advances that allow someone who contracts the Human Immunodeficiency Virus to live 20-30 years without adverse health effects with as little as one pill per day.

The implementation guidance gives medical personnel, detailers and receiving commanders a veto power for each request “based on the medical risks and needs of the Navy,” depending on whether the command in question could “support care,” Pilip-Florea said.Prospective recruits are still precluded from joining the services if they have the virus.

“The policy change better aligns the treatment of HIV with how other chronic illnesses are managed by Navy Medicine,” Pilip-Florea said. “In the case of HIV-positive servicemembers, these personnel and the services have put a lot of time and effort into their careers, and there is no medical reason for them not to be able to continue serving with pride.”

Pilip-Florea said the biggest change from the previous policy for HIV-positive sailors and Marines comes in added flexibility to case management. Those servicemembers would no longer be bound to stateside medical facilities and rules that dictated the frequency of clinical evaluations.

“The frequency of clinical evaluations for HIV-infected military personnel shall be determined by the member’s health status and by nationally accepted guidelines,” the instruction reads. “On a case-by-case basis, follow-up HIV evaluations may be performed at smaller naval medical treatment facilities with the results of those appointments being reported for tracking purposes.”

Pilip-Florea said Navy Medicine does not track cost data for specific conditions or long-term chronic illnesses so treatment costs — stateside versus overseas — are not known.

The Navy policy is unique, officials from the other service branches said.

The Army prohibits HIV-positive soldiers from being deployed or assigned overseas, according to Col. Andrew Wiesen, Western Region Medical Center’s chief of preventive medicine and the Army Surgeon General’s preventive medicine consultant. Any soldier found to be HIV positive while overseas will be reassigned stateside.

There are numerous reasons for the Army’s policy, including host-nation restrictions, the incompatibility of medical treatment and supply of medications with deployment, and protection of the blood supply, Wiesen said. Soldiers are often asked to donate blood in emergencies, and testing is not always reliable or complete in a deployed setting.

The Air Force also limits HIV-positive airmen to stateside assignments, according to spokeswoman Donna Tinsley. However, active-duty airmen can apply for a waiver if the receiving unit can provide the needed care.

“Essentially if the OCONUS (outside the continental United States) base is in need of the position and willing to take on the member and can provide adequate care, then it’s more likely to get accepted,” she said.

However, waivers are frowned upon, Air Force officials said. HIV-positive airmen are prohibited from donating blood.

“A major concern regarding deployment would be blood donation,” Air Force Capt. Candice Ismirle said. “Refusal to do so in cases of mass casualties, etc., will cause other members to question why and may make it difficult for the patient to keep their diagnosis confidential. Also, if there was pressure to donate blood and the patient did so, there could be HIV transmission in the deployed setting.”

Ismirle said all deploying airmen must be free of medical conditions that require special appliances, frequent treatment or follow-up by medical specialists or sub-specialists. The virus is disqualifying and requires a waiver to remain on flying status.

The Navy addressed the issue as HIV rates have risen steadily over much of the U.S. military in recent years. The Navy began testing for HIV antibodies in 1985.

The Navy found 128 HIV-positive sailors in 1992 and 315 in 2012, including 250 on active duty, Pilip-Florea said.

The Marine Corps had 90 HIV-positive Marines in 2012 — 71 on active duty — and the Air Force had 210 on active duty, officials said.

The Army could not provide up-to-date figures due to a transition between who keeps the figures, spokeswoman Margaret Tippy said. However, in 2008 there were more diagnoses than in any year since 1995, according to an Armed Forces Health Surveillance Center report from August.

Rates have remained high, the report said. In 2012, there were 333 active-duty HIV-positive soldiers.

OutServe, an association of active LGBT military personnel, declined to comment when reached by Stars and Stripes on Monday. The group applauded the effort when it was announced last year.

For more information, see the Secretary of the Navy instruction at http://doni.daps.dla.mil/Directives/05000%20General%20Management%20Security%20and%20Safety%20Services/05-300%20Manpower%20Personnel%20Support/5300.30E.pdf.

burke.matt@stripes.com

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