March 19, 2014

Ribavirin Works Against Hep E

Published: Mar 19, 2014

By Michael Smith, North American Correspondent, MedPage Today

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The antiviral drug ribavirin can clear chronic hepatitis E virus (HEV) in solid-organ transplant recipients, researchers reported.

In a retrospective case series, 3 months of the drug resulted in a sustained virologic response (SVR) in 78% of patients, according to Nassim Kamar, MD, PhD, of the Centre Hospitalier Universitaire Rangueil in Toulouse, France, and colleagues.

Retreatment of six patients who failed the therapy resulted in four achieving an SVR, Kamar and colleagues reported in the March 20 issue of the New England Journal of Medicine.

HEV infection is usually self-limiting, except in patients with a suppressed immune system, where it can evolve to chronic hepatitis and cirrhosis, Kamar and colleagues noted.

There is no established HEV treatment, they added, and simply reducing immunosuppression in transplant patients with HEV only resulted in clearance in about 30%.

To evaluate the effects of ribavirin, they examined case records for 59 solid-organ recipients in 13 French centers who were treated with ribavirin alone between Sept. 10, 2009, and June 27, 2012.

Ribavirin is a general antiviral that inhibits replication of many RNA and DNA viruses. It has long been used to treat hepatitis C, along with pegylated interferon-alfa and now several direct-acting anti-HCV agents.

In the transplant case series, Kamar and colleagues reported, 37 patients got a kidney, 10 got livers, five got hearts, five got a kidney-pancreas transplant, and two got lungs.

Physicians started ribavirin a median of 9 months after HEV was diagnosed, and it was delivered at a median dose of 600 mg daily, equivalent to 8.1 mg/kg of body weight.

Patients got the drug for a median of 3 months (with a range from 1 to 18 months), but 66% got it for 3 months or less, the researchers reported.

One patient who started ribavirin was lost to follow-up after a month of treatment, and another was withdrawn for psychiatric reasons, Kamar and colleagues reported.

Among the remaining 57 patients, 56 had no detectable virus 3 months after the end of their therapy and, of those, 10 had a recurrence of HEV viremia.

Overall, a sustained virologic response -- defined for this study as no detectable viral RNA 6 months after the end of treatment -- was observed in 46 of the 59 patients, or 78%.

At the most recent follow-up -- a median of 25 months after the end of therapy -- the 46 patients were still free of the virus, Kamar and colleagues noted.

Of the 10 patients with relapse, six were retreated with ribavirin and four achieved an SVR.

Analysis found that a higher lymphocyte count when ribavirin therapy was initiated was the only factor associated with a greater likelihood of SVR, the researchers reported.

The main side effect of the drug was anemia, which necessitated a dose reduction in 29% of patients, erythropoietin in 54%, and blood transfusions in 12%, they found.

Kamar and colleagues cautioned that the study was retrospective and had only a small number of patients. In addition, care was clinically driven so that ribavirin dosing, duration, and monitoring varied from patient to patient. Drug levels were not measured.

Primary source: New England Journal of Medicine
Source reference: Kamar N, et al "Ribavirin for chronic hepatitis E virus infection in transplant recipients" NEJM 2014; 370: 1111-20.

Source

Gilead's HCV Challengers Near The Starting Gate

By AMY REEVES, INVESTOR'S BUSINESS DAILY
Posted 05:28 PM ET

Though still in the early days since its Dec. 6 approval, Gilead Sciences' hepatitis C drug Sovaldi may be enjoying one of the most massive drug launches of all time. Current consensus calls for sales of $4.6 billion this year — and the whisper numbers are running even higher.

This doesn't surprise Wall Street, as Sovaldi provides a faster, safer and stronger alternative to a punishing yearlong regimen of interferon. But as analysts obsessively watch the weekly prescription numbers grow, they're also eyeing data from Sovaldi's potential challengers in a market that's estimated at $20 billion a year and growing.

Bristol-Myers Squibb's (BMY) daclatasvir grabbed headlines last April when a phase two trial combining it with Sovaldi scored a 100% cure rate.

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But Gilead (GILD) elected not to pursue the combo further. Instead, it's studying Sovaldi in combination with its similar drug ledipasvir, so that it can co-formulate the two into a single pill and not share the market.

Bristol, however, filed in the European Union for approval of daclatasvir "for use in combination with other agents, including sofosbuvir" (the generic name for Sovaldi), and was granted accelerated review there in early January. The firm plans to submit a similar filing to the Food and Drug Administration soon.

Sovaldi Sets New Standard

In October, Bristol filed to approve a combo of daclatasvir with another of its drugs, asunaprevir, in Japan, which has an unusually high rate of hepatitis C virus (HCV) infection due to a formerly tainted blood supply.

Douglas Manion, Bristol's vice president of development, virology and Japan, says that the dual regimen scored good results, but its 24-week duration is looking like yesterday's news now that Sovaldi has set a 12-week standard. He hopes that will be resolved by a triple therapy involving daclatasvir, asunaprevir and a drug dubbed BMS-791325, co-formulated into one pill to be taken twice a day, now in phase three testing.

Ultimately, however, he does not expect a single regimen to conquer the others because not all patients are the same.

Treating Toughest Patients

"Daclatasvir has been studied with so many different drugs, it's used in all genotypes (of the hepatitis C virus) and all patient populations — especially the toughest-to-treat populations," Manion said. "These are going to be liver-transplant patients, genotype 3 patients, patients with cirrhosis, and ultimately patients with decompensation."

Decompensated cirrhosis, the worst form of liver damage that can result from HCV, usually results in liver transplant or death.

The decompensated group was one population not included in AbbVie's (ABBV) six phase three trials of its "3D" regimen combining three antiviral agents. AbbVie also stuck to the most common genotype, genotype 1. It did very well in the trials, with cure rates ranging from 90% to 100%. The company plans to file in the U.S. during the second quarter and hit the market late this year.

In one respect it will have nearly caught up with Gilead, because current FDA guidelines on Sovaldi recommend that it be used with interferon in genotype 1, unless the patient can't tolerate interferon. Gilead is banking on its sofosbuvir-ledipasvir combo to be its first official interferon-free genotype 1 treatment — also expected to launch later this year after a Feb. 10 filing.

Barry Bernstein, AbbVie's vice president of infectious disease development, touted 3D's strong safety profile and the fact that it cured upward of 92% of patients with compensated cirrhosis.

"We believe that the regimens will provide an option for any genotype 1-infected patient," Bernstein told IBD.

AbbVie, Bristol-Myers and Gilead are all expected to report final study details at the International Liver Congress, meeting in London April 9-13. Company officials are keeping mum on which studies will be presented, but abstracts will go online March 24. (Late-breaking abstracts, which appear right before the conference, often have the hottest data.)

Next-Generation Regimes

Further down the road, even more drugs are on the way.

AbbVie and partner Enanta Pharmaceuticals (ENTA) are already working on a next-generation regime that will treat more genotypes and also be simpler to take. (A common criticism of the 3D is that it's more complicated than Gilead's promised pill-a-day routine.)

Earlier this month, Merck (MRK) also reported very strong phase two results for its two-drug combo for genotype 1 patients, some of whom were co-infected with HIV. Johnson & Johnson (JNJ) last October acquired three HCV drugs from GlaxoSmithKline (GSK), which it hopes to combine with its already approved Olysio into an all-oral regimen.

Sovaldi, meanwhile, has lately been under pressure both for its $1,000-a-pill price tag and concerns about sustainability — after all, one outcome of finding a curative drug is that the patient population eventually shrinks.

Still, Morningstar analyst Damien Conover says Gilead has a first-mover advantage and such strong trial data that it likely will be the biggest player for the indefinite future.

"I think we'll have Gilead representing 50% of the hep C market," he told IBD. "AbbVie will take the lion's share of what's remaining."

Source

Promacta (eltrombopag) tablets

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)

February 2014

Summary View1

BOXED WARNING
 
WARNING: RISK FOR HEPATIC DECOMPENSATION IN PATIENTS WITH CHRONIC HEPATITIS C
  • In patients with chronic hepatitis C, PROMACTA® in combination with interferon and ribavirin may increase the risk of hepatic decompensation [see Warnings and Precautions (5.1)].
WARNINGS AND PRECAUTIONS
 
5.1 Hepatic Decompensation in Patients With Chronic Hepatitis C
  • Moved from 5.2 to 5.1 and revised to include the risk of hepatic decompensation.…In patients with chronic hepatitis C, PROMACTA in combination with interferon and ribavirin may increase the risk of hepatic decompensation. In two controlled clinical trials in patients with chronic hepatitis C and thrombocytopenia, ascites and encephalopathy occurred more frequently on the arm receiving PROMACTA plus antivirals treatment (7%) than the placebo plus antivirals arm (4%). Patients with low albumin levels (<3.5 g/dL) or Model for End-Stage Liver Disease (MELD) score =10 at baseline had a greater risk for hepatic decompensation on the arm receiving PROMACTA plus antivirals 124 treatment. Discontinue PROMACTA if antiviral therapy is discontinued.
5.2 Hepatotoxicity
  • Moved from 5.1 to 5.2 and revised…PROMACTA can cause liver enzyme elevations [see Adverse Reactions (6.1)]. Measure serum ALT, AST, and bilirubin prior to initiation of PROMACTA, every 2 weeks during the dose adjustment phase, and monthly following establishment of a stable dose. PROMACTA inhibits UGT1A1 and OATP1B1, which may lead to indirect hyperbilirubinemia….
5.3 Bone Marrow Reticulin Formulation …section removed.
 
5.5 Laboratory Monitoring…section removed.
 
ADVERSE REACTIONS
  • Hepatic Decompensation in Patients With Chronic Hepatitis C [see Warnings and Precautions (5.1)]
6.1 Clinical Trials Experience
  • Clinical Trial data added
17 PATIENT COUNSELING INFORMATION
  • confusion
  • swelling of the stomach area (abdomen)
MEDICATION GUIDE

What is the most important information I should know about PROMACTA?

  • Liver problems. If you have chronic hepatitis C virus, and take PROMACTA with interferon and ribavirin treatment, PROMACTA may increase your risk of liver problems.

“What is the most important information I should know about PROMACTA?”

  • Bone marow changes…section deleted.
  • Abnorman liver functions…section added.

Source FDA

SLACK Incorporated launches HCV Next

March 18, 2014

THOROFARE, N.J. — SLACK Incorporated, publisher of Infectious Disease News, has launched HCV Next, the first multidisciplinary publication exclusively focused on hepatitis C.

Published six times annually, HCV Next will reach more than 10,000 physicians who actively diagnose and treat hepatitis C virus.

Continue reading article here …..


2014_01_January

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The following articles appeared in the print edition of HCV NEXT.

Cover Stories

Editorial

Trend Watch

Pediatric HCV

Feature

HCV Rx

Patient Profile

The Take Home

5 Questions

Source

Provided by Phys.org

March 19th, 2014

University of Birmingham researchers are to lead a worldwide collaboration of scientists looking at the possibility of transplanting stem cells from one person to another to reduce inflammation in the liver.

Prof Philip Newsome and Dr Gideon Hirschfield, from the University's School of Immunity and Infection, will lead the €5.4 million Mesenchymal stem cells (MSC) to Reduce Liver Inflammation (MERLIN) programme which will include the first clinical trial of mesenchymal stem cells in liver disease in the UK.

The EU-funded programme will study how mesenchymal stem cells can reduce inflammation in the liver of people suffering from primary sclerosing cholangitis (PSC), a disease which causes inflammation and thickening of the bile ducts, build-up of bile in the liver and life-threatening liver disease.

The consortium will study how the actions of mesenchymal stem cells, which are found throughout the body including in teeth and bone marrow, can be improved and prolonged for greater clinical benefit. The consortium, which will work on this programme over the next 4 years, includes partners from the UK, Ireland, Italy, the Netherlands and the United States.

Prof Newsome said: "Gaining experience of improving the manufacture of mesenchymal stem cells and using them in this clinical trial will address a huge unmet need for treatment of PSC, which is currently incurable. It will also open up extensive opportunities for their use in other common inflammatory conditions such as rheumatoid arthritis and kidney disease."

"This will complement our other ongoing studies of cell therapy, consolidating Birmingham's position as a world-leading centre for cutting-edge clinical trials of novel therapies."

Provided by University of Birmingham

This Phys.org Science News Wire page contains a press release issued by an organization mentioned above and is provided to you “as is” with little or no review from Phys.Org staff.

Source

Hepatitis C Treatment Viable in Primary Care

Medscape Medical News

Fran Lowry
March 18, 2014

Hepatitis C infection is typically treated by gastroenterologists and hepatologists, but primary care physicians can feel confident that they too can treat this illness — especially if they have the right interdisciplinary team to help, say clinicians wanting to expand care.

"We found that in our urban primary care practice, hepatitis C treatment was feasible; we achieved good treatment initiation and response rates," said Keith Sigal, MD, from the Mount Sinai School of Medicine in New York City. "Plus, we achieved these results in the era of the first generation of direct-acting antiviral medications and in a very vulnerable population," he told Medscape Medical News.

The treatment of hepatitis C infection "tends to be difficult," Dr. Sigal said. "At the time we were doing this study, the shortest treatment course was about 6 months and involved weekly injections of interferon and then a lot of pills. The reason it had been handled by specialists is because there are a lot of complexities regarding the decision-making process to put people on treatment, and the monitoring can be intense as well," he explained.

Dr. Sigal described the experience of his primary care practice, which has been serving very vulnerable patients since 2003, at the International Conference on Viral Hepatitis 2014 in New York City.

"We're at Mount Sinai, which is at the intersection of the Upper East Side and Harlem. There is a pretty significant burden of hepatitis C in our community, and we recognized that people were not getting evaluated and treated," he said. "The protocol that we've developed over the years takes a lot of the complexity out of the treatment process. We feel it is a program that anyone could potentially do."

The primary care clinic is composed of physicians, nurse practitioners, and patient navigators.

“This is a treatment that can be delivered in primary care, but the system does require a bit of extra help.”

"We rely heavily on patient navigators, who act as case managers and help guide the patients through their complex evaluation and treatment," Dr. Sigel noted. "This is a treatment that can be delivered in primary care, but the system does require a bit of extra help."

Dr. Sigal presented data on 125 patients with genotype 1 hepatitis C virus infection who were treated at the clinic from August 2011 to April 2013.

Of these patients, 39 (31%) were started on triple therapy (weekly injections of pegylated interferon plus ribavirin, with either telaprevir or boceprevir).

"Traditionally, initiation rates of treatment have been very low, ranging from 10% to 40%; our number is actually at the high end," he noted. "It's especially gratifying because our patient population had a very significant burden of mental illness and pretty significant drug-abuse histories."

Patients who started treatment were younger than those who did not, but the demographic characteristics and severity of liver fibrosis were similar in the 2 groups.

Also, patients who were treated and achieved sustained viral suppression at 4, 12, or 24 weeks were less likely to have a history of major depression or substance abuse than patients who did not achieve viral suppression.

Post-treatment viral suppression was achieved by 16 patients (45%), although 2 (6%) relapsed, and viral breakthrough was achieved by 6 (16%).

The treatment regimen was toxic and this caused 9 (25%) patients to stop treatment early. Additionally, 3 (8%) patients were nonadherent.

"With the rapid advances in hepatitis C therapy and the availability of potent, relatively nontoxic, and increasingly shorter durations of therapy, it is essential that we make these treatments sourceable by those in need," said Mark Nelson, MD, from Chelsea and Westminster Hospital in London, United Kingdom.

"Primary care — properly educated and supported — will need to be an important player in this aim," he told Medscape Medical News.

This study was funded by the New York State AIDS Institute of the New York State Department of Health and the RobinHood Foundation. Dr. Sigal has disclosed no relevant financial relationships. Dr. Nelson reports financial relationships with Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Merck Sharpe & Dohme, Roche Laboratories, ViiV Healthcare, and Boehringer Ingelheim,

International Conference on Viral Hepatitis (ICVH) 2014: Abstract 62. Presented March 17, 2014.

Source

Sovaldi-Based Regimens Will Capture More than Half of the Genotype 1 Treatment Share In the Next Six Months, According to Findings from Decision Resources Group

BURLINGTON, Mass., March 19, 2014 /PRNewswire/ -- Decision Resources Group finds that, for the treatment of hepatitis C virus (HCV) infections, regimens containing Gilead's Sovaldi account for approximately 30 percent of the patient treatment share across key genotypes at one month after launch. Regimens containing Janssen's Olysio capture less than 10 percent of the genotype 1 patient treatment share two months following its launch. Surveyed HCV specialists are also expecting to further increase their uptake of Sovaldi among their genotype 1, 2 and 3 patients, with Sovaldi regimens accounting for the majority of the patient treatment share, while the genotype 1 treatment share for Olysio is expected to be nearly 20 percent in the next six months. Additionally, survey data show that gains for Sovaldi and Olysio are at the expense of Vertex's Incivek and Merck's Victrelis – a finding underscored by interviewed specialists indicating discontinuing future use of first-generation protease inhibitors.

Other key findings from the report entitled LaunchTrends: Sovaldi and Olysio US Wave 1:

  • Sovaldi and Olysio combination: Over 10 percent of surveyed HCV specialists reported prescribing the off-label Sovaldi and Olysio combination regimen.
  • Olysio non-prescribers: Nearly 10 percent of surveyed Olysio non-prescribers do not plan to ever prescribe Olysio, while none of the surveyed specialists indicated they would not prescribe Sovaldi.
  • Patient warehousing: Surveyed specialists reported increases in both the number of HCV patients under their care and number of patients on active treatment, suggestive of de-warehousing of patients for new regimens.
  • Patient influence on uptake: HCV specialists reported recently receiving general inquires and/or prescription requests for Olysio and Sovaldi; prescribers were more likely to report receiving patient requests for the new agents as opposed to non-prescribers, suggestive of possible patient influence on uptake.

Comments from Decision Resources Group Director Brenda Perez-Cheeks, Ph.D.:

  • "Although Olysio performs well in our benchmarking analysis when compared with the launches of Incivek and Victrelis, its launch has been largely overshadowed by the market entry of Sovaldi, a drug with key advantages over Olysio. Sovaldi prevails in every key metric evaluated in this study, including frequency of sales representative contact. Olysio is going to face an uphill battle in capturing market share in the genotype 1 space. Marketing efforts and message targeting of HCV specialists is an area where Janssen will have to be competitive with Gilead in order to promote Olysio' s uptake in this key market segment."
  • "Cost is the leading prescribing barrier for both Olysio and Sovaldi. Although most surveyed prescribers did not indicate major payer obstacles, many non-prescribers reported experiencing reimbursement obstacles, suggesting that reimbursement is a barrier to prescribing. With the impending availability of several safe and highly efficacious all-oral interferon-free regimens, especially for genotype 1 infections, cost will emerge as an important differentiator, and follow-on therapies will have to offer competitive pricing to penetrate this highly dynamic space."

About Decision Resources Group
Decision Resources Group offers best-in-class, high-value information and insights on critical issues within the healthcare industry. Clients rely on this analysis and data to make informed decisions. Find out more at www.DecisionResourcesGroup.com.

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

For more information, contact:
Decision Resources Group
Christopher Comfort
781-993-2597
ccomfort@dresourcesgroup.com

Logo - http://photos.prnewswire.com/prnh/20130103/MM36768LOGO

SOURCE Decision Resources Group

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Social Workers to Play Role in Improving Hep C Treatment

Medscape Medical News

Fran Lowry
March 19, 2014

Adding a social worker to the hepatitis C healthcare team might be the last thing on a clinic or hospital administrator's mind, but it shouldn't be, say experts looking for ways to expand care. They suggest the benefits can be substantial, at minimal cost.

"Social workers bring unique skills and knowledge to the interdisciplinary team treating hepatitis C patients, making the team more effective," said Catherine Amory, MSW, LCSW, from the Mount Sinai Medical Center in New York City.

They have engagement skills to help get hepatitis C patients into care and understand the value of fostering a good relationship with the treating physician and members of the healthcare team, especially in high-risk marginalized populations. This can help them build a sense of community between the patient and the team, she told Medscape Medical News.

Amory described the role social workers play on the interdisciplinary hepatitis C treatment team here at the International Conference on Viral Hepatitis 2014 in New York City.

Her talk was selected as 1 of 2 top-rated abstracts and was given at a special oral session at the conference.

People in underserved urban areas "have a significant incidence of chronic hepatitis C, but face many psychosocial barriers to appropriate care," Amory explained.

The systems management skills social workers have, such as the ability to deal with homelessness and poverty, housing and legal issues, and immigration, can help patients "surmount many of these barriers," she pointed out.

"We can help patients maneuver their world, translate between the doctor and the patient, and hopefully make their lives better and give them more stability so they can complete treatment," she said.

Tackling Psychosocial Barriers to Care

"The doctors at Mount Sinai wanted a social worker on the team because they were coming across many people who were homeless, mentally ill, actively using illegal substances, getting thrown out of their house, or all of the above," Amory explained. "Some had lost their social security disability insurance and didn't know why, some didn't have car fare to come in for their next appointment so did not take their medicine, and some had changed insurance and didn't know what to do. These are barriers that prevent the doctors from doing their job."

“The doctors at Mount Sinai wanted a social worker on the team because many people were homeless, mentally ill, and actively using illegal substances.”

The psychologist on the team was able to address mental illness issues and readiness for treatment, "but when he assessed someone who was not ready for treatment, there wasn't a lot he could do about the psychosocial issues, and he could not refer for outside mental illness or substance abuse care. I think the impetus came from our psychologist, who felt he needed his skills to be supplemented with a social worker," Amory said.

"I'm also cheaper than a psychologist," she added.

Unfortunately, lack of funding often keeps social workers off interdisciplinary hepatitis C treatment teams.

Formal study is needed to prove the cost-effectiveness of having a social worker as part of the hepatitis C healthcare team, Amory said.

Hospital administrators would be more likely to fund a social worker from the hospital budget if an increase in physician productivity and the effectiveness of treatment is proven, she said.

In addition, insurance companies might allow providers to bill directly for social work services, instead of requiring hospital administrators to cover the cost from operations budgets.

"This would make our funding sustainable, so that the administrators would not have to apply for a grant for funding every year," Amory said.

Benjamin Young, MD, vice president and chief medical officer of the International Association of Providers of AIDS Care, said he fully endorses having social workers on hepatitis C healthcare teams.

"Modern treatments promise a cure for the vast majority of infected people," he told Medscape Medical News. However, "many who are infected with hepatitis C face social and structural barriers to successful engagement in care and the prescription of medications."

The expansion of care for people infected with hepatitis C "will require the most effective use of limited human health resources," he added. "In this light, understanding the role of social workers on an interdisciplinary team for hepatitis C care is most welcomed."

Ms. Amory has disclosed no relevant financial relationships. Dr. Young reports financial relationships with Gilead Sciences, Merck, and ViiV Healthcare.

International Conference on Viral Hepatitis (ICVH) 2014: Abstract 60. Presented March 17, 2014.

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