HIV No Bar to HCV Therapy With New Agents

Published: Mar 4, 2014

By Michael Smith, North American Correspondent, MedPage Today

BOSTON -- New drugs for hepatitis C mean HIV co-infection is no longer a barrier to successful HCV treatment, researchers said here.

Three studies using different medications in co-infected patients all found cure rates similar to the same drugs in people who had only HCV, according to Douglas Dieterich, MD, of Mount Sinai Hospital in New York City.

"All of these drugs work remarkably well in co-infection," Dieterich told reporters at the annual Conference on Retroviruses and Opportunistic Infections.

Dieterich presented some details of phase III studies of faldaprevir, an investigational HCV protease inhibitor used with pegylated interferon-alfa and ribavirin; simeprevir (Olysio), a protease inhibitor approved for use with interferon and ribavirin; and sofosbuvir, an HCV NS5B inhibitor used with ribavirin.

All three medications are "direct-acting agents" -- they target aspects of viral replication, in contrast to interferon, which boosts the patient's immune system, and ribavirin, which is a general antiviral drug.

In all three studies, Dieterich said, the rate of cure was "exactly the same in co-infected patients as they are in mono-infected patients." A cure in the context of HCV is a sustained virologic response (SVR) -- defined as undetectable viral RNA at some prespecified point after ending therapy, usually 12 or 24 weeks.

The results of the trials are "good news" but not entirely surprising, commented Jean-Michel Pawlotsky, MD, PhD, of Henri Mondor University Hospital in Créteil, France, who moderated a press conference at which some details were presented.

Investigators had been seeing similar results with the first approved direct-acting agents, the protease inhibitors telaprevir (Incivek) and boceprevir (Victrelis), Pawlotsky told MedPage Today.

But treatment just with peginterferon and ribavirin -- for years the only available HCV therapy -- was more difficult for people who also had HIV. "The main difference was due to interferon," Pawlotsky said. "These patients were not responding well to interferon."

One implication, he said, is that in the future, separate trials in co-infected patients might not be needed in order to get approval for new direct-acting agents.

"A trial in mono-infected patients might lead to approval for co-infected patients as well," he said.

Dieterich said the so-called STARTVerso4 was intended to test the efficacy and safety of two different doses of faldaprevir, in combination with peginterferon and ribavirin, in 308 patients with genotype 1 of HCV.

Almost all the patients -- 96% -- were also on highly active antiretroviral therapy for HIV.

The overall SVR rate 12 weeks after the end of treatment (SVR₁₂), he said, was 72% and did not differ significantly between the two doses; phase III results in mono-infected patients were about 80%.

The simeprevir trial (dubbed Study C212) was also investigating the safety and efficacy of the drug among 108 HIV patients with genotype 1 HCV. The drug is approved for mono-infected patients.

In the trials used to support approval, the SVR rates were about 80% in treatment-naive and previously treated but relapsed patients, although they were lower -- 53% to 65% -- among patients who responded either partly or not at all to therapy with peginterferon and ribavirin.

In the co-infected cohort, Dieterich said, the SVR₁₂ rate was 74%. Interestingly, a mutation that usually predicts poor response to interferon -- the Q80K polymorphism -- had no effect, he said, although its presence made a significant difference among mono-infected patients.

In both studies, the drugs were well-tolerated, he said, and the safety profile was similar to what has been seen in mono-infected patients, with most of the adverse events related to interferon.

The final study, dubbed PHOTON-1, looked at sofosbuvir and ribavirin in 223 co-infected patients with several HCV genotypes and differing treatment status.

But overall, he said, SVR12 rates ranged from 70% to 90%, depending on genotype, and in most cases were "exactly the same as in mono-infected patients." SVR₂₄ rates did not change, except for one patient with genotype 1 who appeared to be re-infected after achieving SVR₁₂.

The regimen, he noted, is the first interferon-free regimen to be tested in HIV/HCV co-infected patients.

The regimen was well-tolerated, he said, with only a handful of patients stopping treatment owing to adverse events.

Source

SVR12 results from a phase IIa study evaluating Simeprevir and Daclatasvir in Hepatitis C patients of genotype 1 have been presented at CROI 2014

Stockholm, Sweden — Medivir AB (OMX: MVIR) today announced that study results from a phase IIa trial evaluating simeprevir, a once-daily protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB, in combination with daclatasvir, an investigational once-daily NS5A inhibitor developed by Bristol-Myers Squibb (NYSE: BMY), with and without ribavirin, in patients with hepatitis C (HCV) genotype 1 infection, have been presented at the 21th Conference on Retroviruses and Opportunistic Infections (CROI) on March 4th in Boston, USA. The study was conducted by Bristol-Myers Squibb.

Data from the study demonstrate that sustained virologic response 12 weeks after the end of treatment (SVR12) was reached in 75 to 85 percent of treatment-naïve patients and 65 to 95 percent of prior null responders with HCV genotype 1b after 12 or 24 weeks of treatment.

“We are pleased to report on the successfully completed exploratory phase IIa clinical trial of simeprevir and daclatasvir. The results are promising, but further studies would be required in order to fully assess the potential of the simeprevir/daclatasvir combination.” says Charlotte Edenius, EVP Development, Medivir AB.

Study Design
In this phase IIa open-label study, HCV genotype 1b treatment-naive patients (N=104) and prior null responders (N=43) were randomly assigned (1:1) to receive daclatasvir 30mg QD + simeprevir 150mg QD with or without ribavirin. Two treatment durations were evaluated: patients who completed 12 weeks treatment were re-randomized (1:1) to stop at Week 12 orcontinue treatment through Week 24.

In an exploratory evaluation of HCV genotype 1a patients, treatment naive (N=12) and prior null responder patients (N=9) received daclatasvir + simeprevir + ribavirin for 24 weeks.

Summary – Efficacy
In treatment-naïve HCV genotype 1b patients SVR12 was achieved by 75% (38/51) and 85% (45/53) when treated with simeprevir and daclatasvir, with or without ribavirin, respectively. In HCV genotype 1b prior null responders SVR12 was achieved by 95% (19/20) and 65% (15/23) with or without ribavirin, respectively. Estimated SVR12 rates in HCV genotype 1b patients (adjusted for pre-Week 12 discontinuations) were similar after 12 or 24 weeks of treatment in naive patients but higher after 12 than 24 weeks in prior null responders.

In treatment-naïve HCV genotype 1a patients 67% (8/12) achieved SVR12. All HCV genotype 1a prior null responders were offered pegylated interferon alfa-2a in addition to ribavirin + daclatasvir + simeprevir as rescue therapy due to frequent on-treatment breakthroughs and were counted as treatment failures.

Overall, patients were 92% white, 49% male, 21% cirrhotic, and 76% IL28B non-CC genotype and were well-balanced across treatment groups.

Summary - Safety
The all-oral combination of daclatasvir plus simeprevir, with and without ribavirin, was generally well tolerated. There were two treatment-related serious adverse events (neurotoxicity, liver disorder) and one on-treatment death (unrelated trauma-associated intracranial hematoma). Three patients experienced treatment-related adverse events leading to discontinuation. Seventeen patients experienced grade 3/4 total bilirubin elevations without concurrent transaminase elevations, mostly in patients receiving ribavirin (14/17), consistent with ribavirin-induced hemolysis and known effects of simeprevir on bilirubin transporters.

For more information please contact:
Rein Piir, EVP Corporate Affairs & IR, mobile: +46 708 537 292

Medivir is required under the Securities Markets Act to make the information in this press release public. The information was submitted for publication at 18.15 CET on 4 March 2014.

About Simeprevir
Simeprevir is an NS3/4A protease inhibitor jointly developed by Medivir and Janssen R&D Ireland for the treatment of chronic hepatitis C infection in combination with other antivirals in hepatitis C genotype 1 and 4 infected patients with compensated liver disease, including cirrhosis.

Simeprevir was approved for the treatment of genotype 1 hepatitis C in September 2013 in Japan and in the USA and Canada in November. A Marketing Authorisation Application was submitted to the European Medicines Agency (EMA) in April 2013 by Janssen-Cilag International NV seeking approval of simeprevir for the treatment of genotype 1 and and genotype 4 chronic hepatitis C. To date, more than 3,700 patients have been treated with simeprevir in clinical trials.

About Daclatasvir
Daclatasvir is an investigational NS5A replication complex inhibitor that has been studied in more than 5,500 patients to date as a foundational agent for multiple direct-acting antiviral-based combination therapies and is currently in phase III development. Daclatasvir has shown antiviral potency and pan-genotypic activity across hepatitis C genotypes in vitro. Daclatasvir has a drug-drug interaction profile that supports its continued study in a variety of hepatitis C combination regimens. Daclatasvir-based regimens are currently under review by regulatory authorities in Japan and Europe.

About Medivir
Medivir is an emerging research-based pharmaceutical company focused on infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company’s key pipeline asset is simeprevir, a novel protease inhibitor for the treatment of hepatitis C that is being developed in collaboration with Janssen R&D Ireland. The company is also working with research and development in other areas, such as bone disorders and neuropathic pain. Medivir has also a broad product portfolio with prescription pharmaceuticals in the Nordics.

For more information about Medivir AB, please visit the Company’s website: www.medivir.com

Medivir is a collaborative and agile pharmaceutical company with an R&D focus on infectious diseases and a leading position in hepatitis C. We are passionate and uncompromising in our mission to develop and commercialize innovative pharmaceuticals that improve people’s lives.

Source

The face of liver disease could be your own

March 4, 2014 5:59 AM

Canadian Liver Foundation urges Canadians to 'face facts' and recognize own risk factors

TORONTO, March 4, 2014 /CNW/ - Most Canadians are oblivious to their own risks of developing liver disease. Unfortunately, this 'who me?' attitude is leading to a rise in complications and deaths due to advanced liver disease. To help change attitudes, the Canadian Liver Foundation is using Liver Health Month to urge Canadians to recognize that liver disease may have many faces - even their own or someone they love.

"If you were to ask people on the street if they thought they needed to worry about liver disease, the answer would typically be 'no'," says Gary Fagan, president of the Canadian Liver Foundation. "This is alarming because liver disease is a much bigger issue in this country than anyone realizes. Unfortunately people don't understand their own risk factors and few have ever been tested."

The Canadian Liver Foundation is launching a campaign called 'Face it' to promote the facts about liver disease and show Canadians that the 'face' of liver disease might be more familiar than they think. The 'Face It' campaign will use social media to promote liver disease facts under the hashtag #faceliverdisease and will encourage people to visit www.liver.ca/facefacts to learn how to protect themselves and their families.

Currently fatty liver disease, hepatitis B, hepatitis C, liver cancer and alcoholic liver disease are the most common forms of liver disease in Canada. According to the CLF's report, Liver Disease: A Crisis in the Making, deaths from liver disease have risen by almost 30% in a period of only eight years.

"Liver disease is often overlooked and yet every week there are children, teens and adults who are diagnosed with genetic, autoimmune, viral, toxin or obesity-related liver disease," says Mr. Fagan. "There are simple blood tests that can detect problems with the liver but we hear countless stories from people that were stunned to find out they had severe liver disease despite having few, if any, symptoms," says Mr. Fagan. "We want people to face the facts about liver disease before it's too late."

Throughout the month of March, several leading health and wellness experts -- Rose Reisman, Theresa Albert, Bryce Wylde, Stephanie Joanne and Tosca Reno -- will be lending their support to the campaign by helping to dispel the myths and offering liver health advice.

"People are always flabbergasted to learn how many different things can impact your liver health - not the least of which being what you eat," says Theresa Albert, nutritionist, author and member of the CLF's National Board. "One of the best ways to get people thinking beyond the stereotype is asking them 'have you ever'  or ' do you ever' questions about diet,  medication, body art, sex, travel and so on. Once people see how the liver plays a vital role in day-to-day life, they're a step closer to taking action to protect their liver health."

For more information on the Face It campaign and Liver Health Month activities, visit www.liver.ca/facefacts

About the Canadian Liver Foundation
Founded in 1969 by a group of doctors and business leaders concerned about the increasing incidence of liver disease, the Canadian Liver Foundation (CLF) was the first organization in the world devoted to providing support for research and education into the causes, diagnoses, prevention and treatment of all liver disease. Through its chapters across the country, the CLF strives to promote liver health, improve public awareness and understanding of liver disease, raise funds for research and provide support to individuals affected by liver disease.

SOURCE Canadian Liver Foundation

For further information:

Melanie Kearns
416-491-3353 ext. 4923
mkearns@liver.ca

Source

Estimate of US Individuals Living With Chronic Hepatitis C Virus Infection Sharply Reduced, Possibly Due to Deaths

Provided by news@JAMA

BY BRIDGET M. KUEHN on MARCH 3, 2014

A new estimate finds 500 000 fewer cases of chronic hepatitis C infection in the United States compared with previous estimates of prevalence. The authors suggest higher than expected death rates among infected individuals may be responsible. Image: Krasimira Nevenova/iStockphoto.com

The number of US individuals living with chronic hepatitis C virus (HCV) infection is about 500 000 fewer than previously estimated, according to new findings from the US Centers and Disease Control and Prevention (CDC). But despite this large change in prevalence, the new estimate still finds a substantial population of individuals with chronic HCV in the United States.

Concern about a silent epidemic of undiagnosed chronic HCV infections among the baby boom generation has prompted the CDC to urge more aggressive screening of this population. The hope was that screening could identify the infections early enough to allow treatment that can clear the virus from the body or reduce the risk of the infection progressing to liver cancer or liver disease.

The CDC’s new estimate is based on HCV testing of individuals participating in the National Health and Nutrition Examination Survey (NHANES) between 2003 and 2010. Of the roughly 30 000 tested, 273 (about 1%) tested positive for chronic HCV infection. If extrapolated to the wider US population, this would suggest that there are 2.7 million US individuals currently living with HCV compared with the 3.2 million predicted based on NHANES data from 1999 to 2002.

The reason for this apparent decrease is not clear, according to the authors. It may be a statistical glitch; the old estimate falls within the confidence interval for the analysis. Another possibility is that increased death rates among those with HCV over the past decade may have reduced the overall population living with the disorder,  said Scott D. Holmberg, MD, MPH, chief of epidemiology and surveillance for viral hepatitis at CDC and one of the study’s authors. It is unlikely to be the result of more successful treatment of HCV during the interval between the 2 estimates because only about half of HCV-infected individuals are ever tested, and many of those who are diagnosed with the infection never receive medical care for it, according to the authors.

“Whether this decline in numbers of infected people is real or not, there are still millions of people infected with hepatitis C,” said Holmberg.  “This emphasizes the urgency of getting people tested, into care and treated.”

Both the old and new estimates likely underestimate the total prevalence of chronic HCV infection in the United States. NHANES does not include homeless individuals or those in prison, who are known to have high rates of HCV infection. According to Holberg, these uncounted populations would likely raise the estimates by about 500 000.

The US Food and Drug Administration has approved 4 new medications for HCV infection in the past 3 years, and more than a dozen new drugs are under development. There has been a renewed push by the CDC and infectious disease experts to head off HCV complications by boosting treatment. New guidelines for HCV treatment were issued in January.

But the costs of HCV care may be a barrier to many patients, particularly the lower-income and marginalized populations who are disproportionately infected. (The new study found higher rates of chronic HCV infection among individuals aged 40 to 59 years, those who are black, and those with lower income and education.) The most recently approved treatment costs more than $80 000 per course, and some insurance companies do not cover these new therapies.

Source

Factors That Affect Efficacy Of Ultrasound Surveillance For Early-Stage Hepatocellular Carcinoma In Patients With Cirrhosis

Clinical Gastroenterology and Hepatology

Article in Press

Factors That Affect Efficacy Of Ultrasound Surveillance For Early-Stage Hepatocellular Carcinoma In Patients With Cirrhosis

Paolo Del Poggio, Stefano Olmi, Francesca Ciccarese, Mariella Di Marco, Gian Ludovico Rapaccini, Luisa Benvegnù, Franco Borzio,  Fabio Farinati, Marco Zoli, Edoardo Giovanni Giannini, Eugenio Caturelli, Maria Chiaramonte, Franco Trevisani, Italian Liver Cancer (ITA.LI.CA) group

Received 15 October 2013; received in revised form 11 February 2014; accepted 12 February 2014. published online 28 February 2014.
Accepted Manuscript

Abstract

Summary

Background & Aims

Ultrasound surveillance does not detect early-stage hepatocellular carcinomas (HCCs) in some patients with cirrhosis, although the reasons for this have not been well studied. We assessed the rate at which ultrasound fails to detect early-stage HCCs and factors that affect its performance.

Methods

We collected information on 1170 consecutive patients included in the Italian Liver Cancer (ITA.LI.CA ) database who had Child-Pugh A or B cirrhosis and were diagnosed with HCC during semi-annual or annual ultrasound surveillance, from January 1987 through December 2008. Etiologies included: hepatitis C virus infection (59.3%), alcohol abuse (11.3%), hepatitis B virus infection (9%), a combination of factors (15.6%), and other factors (4.7%). Surveillance was considered to be a failure when patients were diagnosed with HCC at a stage beyond the Milan criteria (1 nodule ≤5 cm or ≤3 nodules each ≤3 cm).

Results

Ultrasound surveillance failed to detect HCC in 34.3 % of patients and more often in the annual program than in the semiannual one. (41.3% vs 32.2 % ; P<0.01). Nearly half of surveillance failures were associated with at least one indicator of aggressive HCC (levels of AFP >1000 ng/ml, infiltrating tumors, or vascular invasion and metastases). Semi-annual surveillance, female sex, Child-Pugh class A, and AFP levels ≤ 200 ng/ml were independently associated with successful ultrasound screening for HCC.

Conclusion

Based on analysis of surveillance for HCC in patients with cirrhosis , the efficacy of ultrasound-based screening is acceptable. Ultrasound is least effective in identifying aggressive HCC, and at surveillance intervals >6 months.

Key Words: liver cancer, early detection, fibrosis, survival

List Of Abbreviations: HCC, hepatocellular carcinoma, AFP, alpha-fetoprotein

Source

Liver metabolism study could help patients awaiting transplants

Provided by Rice University News & Media

Jade Boyd – March 3, 2014

Metabolic profiling of liver cells suggests new treatments for cirrhosis patients

In a new study that could help doctors extend the lives of patients awaiting liver transplants, a Rice University-led team of researchers examined the metabolic breakdown that takes place in liver cells during late-stage cirrhosis and found clues that suggest new treatments to delay liver failure.

More than 17,000 Americans are awaiting a liver transplant, and of those, about 1,500 will die this year while still waiting, according to the American Liver Foundation. The new research, which appeared online Feb. 27 in the Journal of Hepatology, suggests new treatments that could keep some of those patients alive long enough to receive a transplant. The research was conducted by a team from Rice University, the University of Pittsburgh, Children’s Hospital of Pittsburgh, the University of Nebraska Medical Center and the University of Texas MD Anderson Cancer Center.

“There’s an old saying that ‘the beginning of health is to know the disease,’” said lead researcher Deepak Nagrath of Rice. “There’s never been a clear understanding of what causes liver cells to stop working during the final stages of cirrhosis. Our goal was to probe the metabolic processes inside liver cells in this stage of the disease to better understand what causes them to fail.”

Liver disease is a growing problem worldwide, especially in countries where fatty diets and obesity are also problems. According to the American Liver Foundation, one in 10 Americans suffers from liver disease and as many as one in four Americans is at risk, including many who suffer from “nonalcoholic fatty liver disease,” a buildup of extra fat in the organ.

Nagrath, the director of Rice’s Laboratory for Systems Biology of Human Diseases, said his group wanted to examine the role that energy metabolism played in the breakdown of hepatocyte function during cirrhosis. To do that, the group needed to examine the biochemistry of liver cells at various stages during the disease.

The first stage of liver disease, called “steatosis,” is marked by the fat buildup. The next stage is fibrosis, when fibers start getting deposited. This leads to damage of the liver cells, or hepatocytes, which leads to the final stage, cirrhosis.

Nagrath said the studywas made possible by a unique animal model for cirrhosis that was developed by Ira Fox and Alejandro Soto-Gutierrez at the University of Pittsburgh’s McGowan Institute for Regenerative Medicine.

“Most models cannot mimic what actually occurs in humans, but this one, which uses rats, captures all of the features, particularly the pathological features, that occur in humans,” he said.

Using hepatocyte samples collected at Pittsburgh, Nagrath’s lab conducted a detailed search for chemical and genetic clues about hepatocyte metabolism. In particular, they focused on how the cells were producing adenosine triphosphate, or ATP, the “molecular unit of currency” that all living cells use to transport chemical energy.

In healthy hepatocytes, most ATP is produced in the mitochondria, via a process known as “oxidative phosphorylation.” Nagrath said previous studies had shown that a second form of ATP production — a process known as “glycolysis” — was also activated in diseased liver cells.

“Mitochondrial production of ATP is more efficient than glycolysis, but in times of stress, when the cells needs extra energy to repair themselves or respond to a crisis, they can employ both processes at the same time,” said Nagrath, assistant professor of chemical and biomolecular engineering and of bioengineering. “It’s also well-known that some forms of cancer rely almost exclusively on the glycolytic pathway, so people tend to associate glycolysis with an unhealthy or diseased state.”

In their study, Nagrath and colleagues found that the story of ATP production in liver cells was considerably more complex than previously understood.

“It’s well-known that energy production from the mitochondrial pathway goes down during cirrhosis, and many people had assumed that this was the primary driver of metabolic failure,” he said. “While we did find that mitochondrial production decreased, it was not down-regulated enough to say that it was a complete failure. It didn’t change that much. Glycolysis, on the other hand, changed a great deal.”

The study showed that in the middle stage of cirrhosis, liver cells up-regulate the glycolytic pathway to produce more energy in response to the disease. Combined with the reduced but still significant production from the mitochondrial pathway, the glycolytic input results in a large net gain in metabolic output. In the final stage of the disease, the cells are unable to sustain their glycolytic output, and net ATP production falls.

“When that happens, and the cells are no longer able to use glycolysis to maintain energy, liver failure occurs,” Nagrath said.

The researchers confirmed the clinical relevance of the findings by comparing the gene expression patterns in the rodents with the genetic profiles of 216 human patients who have cirrhosis.

Nagrath said the findings are important because there are drugs that clinicians can use to target the glucose pathway. These could potentially be used to boost glycolytic energy production and keep patients alive longer.

“This would not represent a cure for liver disease,” he said. “It would only apply to patients in the final stage of liver disease, but if such treatments did prove effective, they could extend the lives of some patients who are awaiting transplants.”

The National Institutes of Health and Rice University funded the research. Study co-authors include lead author Taichiro Nishikawa, Han Bing and Fox at Children’s Hospital of Pittsburgh; Nadège Bellance, Aaron Damm and Nagrath at Rice; Vasudha Sehgal, Tyler Moss and Prahlad Ram at MD Anderson; Kan Handa, Mladen Yovchev, Michael Oertel and Soto-Gutierrez at the University of Pittsburgh; and Zhen Zhu and Iraklis Pipinos at the University of Nebraska Medical Center.

Source

Hepatitis C Cases Fall 165% in U.S., CDC Survey Finds

Provided by Bloomberg News

By Drew Armstrong Mar 3, 2014 5:05 PM ET

The number of Americans with hepatitis C fell 16 percent to 2.7 million over almost a decade, a government survey found, just as new, more effective treatments for the chronic liver disease reach the market.

The survey by the Centers for Disease Control and Prevention covers data gathered from 2003 to 2010. It updates information gathered in 1999 to 2002 that counted 3.2 million people as being infected. Hepatitis C can be symptomless for years before it begins to scar the liver, leading to cancer, organ failure and, eventually, a transplant.

New drugs such as Gilead Science Inc. (GILD)’s Sovaldi, which costs $84,000 for 12 weeks of treatment, are coming to market as more effective cures that are easier for patients to take with fewer side effects. The profile of U.S. patients with the disease may be a barrier to use, according to the study published today in the Annals of Internal Medicine.

“Our study and others have found that persons with chronic hepatitis C virus infection are frequently poor and less educated, factors that could pose barriers to the receipt of these costly novel hepatitis C virus treatments,” the study’s authors said.

The researchers looked at 20,042 patients’ blood samples to test hepatitis C rates, and found that 1 percent of those tested were infected. Neither new data nor the previous study include people in prison, where hepatitis C rates are higher, or the homeless.

Trend Decreasing

Today’s study put the range of those infected with the virus in the U.S. at 2.2 million to 3.2 million, compared with 2.7 million to 3.9 million in the earlier survey. “The trend is that there’s a decrease in the number of people living with hepatitis C,” John Ward, the CDC’s director of the division of viral hepatitis, said in a a telephone interview.

The CDC, based in Atlanta, currently recommends screening for everyone in the U.S. born from 1945 to 1965. The virus is transmitted by blood and wasn’t tested for until 1992. Patients can be infected from blood transfusions as well as through intravenous drug use.

While the number of patients dying from the disease is decreasing, the total number of those with hepatitis C, the rate of new cases is increasing as younger people -- mostly intravenous drug uses -- become infected, he said.

Infection rates were highest among 40- to 59-year-old black men. Those with the virus were more likely not to have completed education past high school, and to have incomes less than $23,000. They were also more likely to be intravenous drug users or have had more than 10 sexual partners, the study found.

Gilead, AbbVie

Drugs for the disease are being developed by Gilead, AbbVie Inc., Bristol-Myers Squibb Co. (BMY), Johnson & Johnson (JNJ) and Merck & Co. Gilead’s Sovaldi was approved last year. The new therapies are taken as pills and replace injections.

Because the disease is symptomless early on, patients may not seek treatments because they don’t know they have the virus, researchers said.

“All available current information indicates that no more than one half of persons with chronic HCV infection have been tested for anti-HCV; many who are anti-HCV–positive do not receive medical care,” the researchers said in the study.

To contact the reporter on this story: Drew Armstrong in New York atdarmstrong17@bloomberg.net

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net

Source

Alsop See: HCV Prevalence Down Slightly

HCV Prevalence Down Slightly

Infectious Disease

Published: Mar 3, 2014

By Michael Smith, North American Correspondent, MedPage Today

About 2.7 million people in the U.S., roughly 1.0% of the population, have chronic hepatitis C (HCV), according to new CDC prevalence estimates for the period from 2003 through 2010.

That appears to be down from the previous estimate of 3.2 million for the period 1999 through 2002, or about 1.3% of the population, according to Scott Holmberg, MD, and colleagues at the agency.

But the 95% confidence intervals of the estimates overlap, so that the prevalence might not have changed significantly, the researchers cautioned in the March 4 issue of Annals of Internal Medicine.

On the other hand, Holmberg and colleagues noted, the figure of 1.0% is likely an under-estimate because the data -- from the regular National Health and Nutrition Examination Surveys (NHANES) -- do not include the homeless and those behind bars.

Those groups, the researchers said, are "probably at higher risk for HCV infection."

The report comes as the annual Conference on Retroviruses and Opportunistic Infections opens in Boston, where data are expected on new therapies for HCV.

The NHANES is a nationally representative household survey of about 5,000 participants a year that includes interviews, physical exams, and testing of biological samples, including blood.

For the 2003-2010 and 1999-2003 analyses, investigators tested serum samples from participants 6 and older for antibody to HCV, an indication of current or previous infection. If the samples were positive or indeterminate, they were tested for HCV RNA, which indicates current chronic infection.

Of the 30,074 participants analyzed, 273 tested positive for HCV RNA; extrapolating that to the general population suggested a prevalence of 1.0% or 2.7 million people, Holmberg and colleagues reported.

Breaking the analysis down by age suggested that an estimated 2.68 million of those chronically infected were 20 or older, the researchers reported, and most of them were so-called baby boomers -- born between 1945 and 1965.

In that age group, the estimated prevalence of chronic HCV infection was 2.6%, corresponding to 2.16 million people, Holmberg and colleagues reported.

Put another way, they noted, the prevalence among those born between 1945 and 1965 is six times greater than that among other adults, and represents 81% of all those chronically infected with HCV, they estimated.

Analysis of demographic factors suggested that, compared with people who had never been infected with HCV, those who had ever been infected were more likely to be 40 to 59, male, and non-Hispanic black.

They were also more likely to have a high school education or less and to have a lower family income.

The analysis also showed that illicit drug use (including injection drugs) and receipt of a blood transfusion before 1992 were significantly associated with chronic HCV infection.

But, Holmberg and colleagues noted, 49% of people with HCV infection did not report either risk factor, suggesting that risk-based screening is likely to miss a large proportion of people with the virus.

To such screening, the CDC has recommended adding a one-time HCV test for all baby boomers, hoping to identify some 800,000 people currently not aware of their infection.

Primary source: Annals of Internal Medicine
Source reference: Denniston M, et al "Chronic hepatitis C virus infection in the United States, National and Nutrition Examination Survey 2003 to 2010" Ann Intern Med 2014; 160(5).

Source

AbbVie to Present Late-brealer Pearl-III Study in Patients with Chronic Hepatitis C at CROI 2014

-- SVR(12) RATES OF 99 PERCENT WITH AND WITHOUT RIBAVIRIN WERE ACHIEVED IN GENOTYPE 1B PATIENTS NEW TO TREATMENT

-- RESPONSE RATES IN PEARL-III WERE ALSO HIGH IN SPECIFIC PATIENT CHARACTERISTICS, SUCH AS GENDER, RACE AND GENETICS

Mar 3, 2014

BOSTON, March 3, 2014 /PRNewswire/ -- The first detailed results from AbbVie's (NYSE: ABBV) pivotal phase III study, PEARL-III, were presented today as part of the 21st Conference on Retroviruses and Opportunistic Infections (CROI) press conference and will also be presented as a late-breaker at the conference on March 4. PEARL-III evaluated the efficacy and safety of 12 weeks of treatment with AbbVie's investigational therapy with or without ribavirin (RBV) in non-cirrhotic, adult patients with chronic genotype 1b (GT1b) hepatitis C virus (HCV) infection who were new to treatment.

The PEARL-III study met its primary and secondary endpoints. In the 419-patient study, sustained virologic response rates 12 weeks post-treatment (SVR₁₂) of 99.5 and 99.0 percent were achieved with the AbbVie regimen with and without RBV, respectively. There were no study drug discontinuations due to adverse events.

"Results from PEARL-III are encouraging, as they demonstrate AbbVie's regimen can achieve high rates of SVR, with and without ribavirin across several patient characteristics in those with genotype 1b chronic hepatitis C infection," said Peter Ferenci, M.D., professor of Gastroenterology and Hepatology, Medical University of Vienna.

PEARL-III enrolled patients across different demographics and characteristics. Response rates in patients with certain characteristics (male gender, Black race and IL28B non-CC genotypes) were examined, as these patient populations have historically been associated with having a decreased response to treatment. High response rates were observed across all patients in the study, including those with these characteristics.

"We are excited about the strong PEARL-III results which demonstrate the AbbVie regimen achieved high SVR rates with no discontinuations due to adverse events in patients new to treatment with genotype 1b infection," said Scott Brun, M.D., vice president, pharmaceutical development, AbbVie. "Additionally, with these data, we continue to be on track to begin major regulatory submissions in the second quarter of 2014. AbbVie will continue to disclose additional detailed phase III study results at future scientific congresses and in publications."

About Study M13-961 (PEARL-III)
PEARL-III is a global, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 12 weeks of treatment with AbbVie's regimen with and without RBV in non-cirrhotic, GT1b HCV-infected, treatment-naive adult patients.

The study population consisted of 419 GT1b treatment-naive patients with no evidence of liver cirrhosis: 209 patients randomized to the regimen without RBV for 12 weeks, and 210 patients randomized to the regimen with RBV for 12 weeks. Following 12 weeks of treatment, 99.0 percent receiving the regimen without RBV (n=207/209) and 99.5 percent receiving the regimen with RBV (n=209/210) achieved SVR₁₂. Patients in the treatment arm without RBV received placebo in substitution for RBV.

Patients with different demographics and characteristics were enrolled in the study, including gender, race (Black vs. non-Black), Hispanic/Latino ethnicity, age, geographic region, body mass index (BMI), liver fibrosis stage, IL28B genotype and viral load.

Across treatment arms in PEARL-III, there were no documented relapses within 12 weeks post-treatment. No on-treatment virologic failures occurred in the treatment arm without RBV and a single virologic failure occurred in the treatment arm with RBV. While all patients in the study completed therapy, two patients in the arm without RBV were lost to follow-up and therefore were considered treatment failures.

The most commonly reported adverse events (>10 percent for either arm) were headache, fatigue, pruritus, nausea and asthenia, with pruritus and nausea occurring at a statistically higher rate in the treatment arm with RBV compared to the arm without RBV. Anemia occurred more commonly among patients in the RBV-containing arm with clinically significant anemia requiring RBV dose reductions occurring in 9 percent of these patients. 

Additional information about AbbVie's phase III studies can be found on www.clinicaltrials.gov.

About AbbVie's Investigational HCV Regimen
The AbbVie investigational regimen consists of the fixed-dose combination of ABT-450/ritonavir (150/100mg) co-formulated with ABT-267 (25mg), dosed once daily, and ABT-333 (250mg) with or without RBV (weight-based), dosed twice daily. The combination of three different mechanisms of action interrupts the HCV replication process with the goal of optimizing SVR rates across different patient populations.

AbbVie's HCV Development Program
The AbbVie HCV clinical development program is intended to advance scientific knowledge and clinical care by investigating an interferon-free, all-oral regimen with and without RBV with the goal of producing high SVR rates in as many patients as possible, including those that typically do not respond well to treatment, such as previous non-responders to interferon-based therapy or patients with advanced liver fibrosis or cirrhosis.

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

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

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

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

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

See approved product labels for more information.

About AbbVie
AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories.  The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases.  AbbVie employs approximately 25,000 people worldwide and markets medicines in more than 170 countries.  For further information on the company and its people, portfolio and commitments, please visit www.abbvie.com.  Follow @abbvie on Twitter or view careers on our Facebook or LinkedIn page.

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

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

SOURCE AbbVie

For further information: Media: Elizabeth Hoff, +1 (847) 935-4236, elizabeth.hoff@abbvie.com, or Javier Boix, +1 (847) 937-6113, javier.boix@abbvie.com; Investor Relations: Elizabeth Shea, +1 (847) 935-2211, elizabeth.shea@abbvie.com

Source

Vitamin D Could Impact On Hepatitis Cure Rates

Feb 27 2014 05:07 AM

A team of researchers from Dundee University, key Scottish Hepatitis services and Hepatitis Scotland is to test speculation as to whether Vitamin D can enhance Hepatitis C cure rates when used in combination with currently available treatment therapies.

New Hepatitis C treatments will soon be available but are likely to be very expensive. With approximately 150 million people chronically infected with Hepatitis C worldwide, and 38,000 in Scotland alone, cost factors are likely to play a significant part in future treatment decisions. The research team will use evidence from previous small trials as a basis for a new investigation which will provide firm evidence to confirm the impact that Vitamin D might have on cure rates.

Hepatitis Scotland’s Lead Officer, Leon Wylie said, “This study could have significant impact on the future of Hepatitis C treatment, both here and internationally. If this study replicates other findings then a very cheap and safe method of increasing treatment success rates could be available, at a cost of pennies a day. When we first saw the early research it seemed very exciting and I am extremely pleased that our partnership working has helped achieve the start of this research. “

Dr John Dillon, Dundee University Clinical Reader, NHS Tayside Consultant Hepatologist and co-Chair of the National Hepatitis C Clinicians group, said, “This trial shows Scotland working together to discover new ways of helping cure patients affected by hepatitis C, here in Scotland and across the world. It further establishes Scotland’s reputation as a world-leading centre for research into Hepatitis C.”

The trial has been funded as a pilot through the Chief Scientist’s Office and depending on its success may be expanded to cover a much larger number of patients. Merck Serono KgAA have supplied the high concentration Vitamin D supplements at no charge.

Source

Pharma Refuses to Ensure Access to Lifesaving Hepatitis C Treatment at Global Meeting

FOR IMMEDIATE RELEASE

February 28, 2014 - Bangkok

Contacts:

Mr. Shiba Phurailatpam, Asia Pacific Network of People Living with HIV/AIDS (APN+), +66-86-600-0738 (Thailand)
Ms. Karyn Kaplan, Treatment Action Group, +1-646-316-8979 (U.S.)
Ms. Chloé Forette, Médecins du Monde, +33-609-537-369  (France)

Bangkok, Thailand, February 28, 2014 —Thirty-eight activists from 22 countries joined forces at the first-ever Hepatitis C Virus (HCV) World Community Advisory Board (CAB) to demand equitable access to treatment for hepatitis C virus (HCV) from six multinational pharmaceutical companies. Yet AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Merck, and Roche refused to provide a plan for equitable access to treatment for HCV, a curable infection that kills over 350,000 people each year.

AIDS activists, including people living with HIV, people living with HCV, people who inject drugs (PWID), and their allies, are fighting for access to a new generation of HCV drugs—called direct-acting antivirals (DAAs). These drugs offer the potential to eradicate HCV; they have cured up to 100 percent of people in clinical trials.

All of the companies refused to commit to price reductions that would allow affordable access for low- and middle-income countries (LMICs), home to more than 85 percent of the 185 million people living with HCV. Even Roche and Merck, producers of older, soon-to-be-obsolete HCV drugs, refused to lower prices to affordable levels.

In high-income countries, DAA treatment costs US$140,000, although DAAs are cheap to produce. According to an analysis by academic experts, it costs less than US$250 for a 12-week DAA regimen.[1] “This level of greed is inexcusable, and keeps the cure out of reach for almost everyone who needs these drugs,”says Shiba Phurailatpam, regional coordinator of the Asia Pacific Network of People Living with HIV/AIDS (APN+).

“Most people cannot afford HCV treatment—nor can their governments,” explains Paata Sabelashvili of the Georgian Harm Reduction Network. “My government, like others in the Eastern European region, is launching a national treatment program, but astronomically high prices will limit it. How can governments and donors effectively address HCV if Pharma refuses to drop drug prices?”

The strategies currently employed by these pharmaceutical companies, that include delayed drug registration, voluntary licensing, and patient assistance programs, are less likely to facilitate better access in LMICs. “Governments should use every means available to them, including compulsory licenses, to protect public health and expand access to DAAs, even where they are patented,”said Lorena Di Giano, general coordinator of the Red Latinoamericana por el Acceso a Medicamentos (RedLAM).

We are deeply committed to strategies that allow generic production of DAAs. Access to affordable generic drugs brought down HIV drug prices from US$10,000 to under US$100, savingmillions of lives. People living with HCV deserve access to treatment; they should not become hostages to Pharma greed.

Contacts:

Mr. Shiba Phurailatpam, Asia Pacific Network of People Living with HIV/AIDS (APN+), +66-86-600-0738 (Thailand)
Ms. Karyn Kaplan, Treatment Action Group, +1-646-316-8979 (U.S.)
Ms. Chloé Forette, Médecins du Monde, +33-609-537-369  (France)

1^st HCV World CAB Participant List

East and Southeast Asia

Jirasak Sripramong, Thai AIDS Treatment Action Group (TTAG), Thailand

Dr. Kieu Thi Mai Huong, SCDI, Vietnam

Dr. Lisa Peiching Huang, Médecins du Monde, Vietnam

Edo Agustian, PKNI, Indonesia

Aditya Wardhana, IAC, Indonesia

Do Dang Dong, VNP+, Vietnam

Zhang Bo, Yunnan IDA, China

Thomas Cai, AIDS Care China

Odilon Couzin, Hong Kong

Shiba Phurailatpam, Thailand

Giten Khwairakpam, Thailand

Kajal Bhardwaj, India

Paul Cawthorne, Médecins Sans Frontières (MSF), Thailand

Dr. Gonzague Jourdain, Thailand

Eastern Europe/Central Asia   

Paata Sabelashvili, Georgian Harm Reduction Network, Georgia

Sergey Golovin, ITPC-Russia

Ludmila Maistat, The HIV/AIDS Alliance-Ukraine

U.S./Europe         

Karyn Kaplan, Treatment Action Group, United States

Tracy Swan, Treatment Action Group, United States

Khalil Elouardighi, Coalition Plus, France

Noah Metheny, Global Forum on MSM & HIV, United States

Camila Picchio, Treatment Action Group, United States

Simon Collins, HIV i-Base, United Kingdom

Chloé Forette, Médecins du Monde, France

Pauline Londeix, Act Up-Basel/ITPC, France

Jude Byrne, International Network of People Who Use Drugs (INPUD), United Kingdom

Jorrit Kabel, AIDS Fonds, The Netherlands

Els Torreele, Open Society Foundations, United States

Azzi Momenghalibaf, Open Society Foundations, United States

Tahir Amin, I-MAK, United States

Priti Radhakrishnan, I-MAK, United States

Africa

Abshiro Halake, Kenya Red Cross Society

Ed Ngoksin, Global Network of PLWHA (GNP+), South Africa      

Middle East/North Africa   

Heba Wanis, Egyptian Initiative for Personal Rights

Dr. Mustapha Sodqi, ALCS (Association de Lutte Contre le Sida), Morocco

Othman Mellouk, ITPC-MENA, Morocco

Islands

Nudhar Bundhoo, Prévention Information et Lutte contre le Sida (PILS), Mauritius

Latin America                            

Lorena Di Giano, Red Latinoamericana por el Acceso a Medicamentos – RedLAM, Argentina

---

[1] Hill A, Khoo S, Fortunak J, Simmons B, Ford N. Minimum Costs for Producing Hepatitis C Direct-Acting Antivirals for Use in Large-Scale Treatment Access Programs in Developing Countries. Clin Infect Dis. 2014 Feb 13.

Source

Could new hepatitis C drugs bust state budgets?

Michael Ollove, Pew/Stateline staff writer12:24 p.m. EST March 3, 2014

Two new drugs have been approved to help millions of Americans who suffer from hepatitis C, but both are extremely expensive.(Photo: USA TODAY photo)

Two new medications to treat the deadly epidemic of hepatitis C promise millions of Americans a better chance of a cure, shorter periods of treatment and fewer side effects than older drugs. They also threaten to bust state budgets and raise private insurance rates.

The new hepatitis C medications present a dilemma for Medicaid and other insurers, who must balance the cost against the huge number of people who could benefit from the treatment. A course of treatment costs between $84,000 and $168,000 -- or $1,000 to $2,000 per pill.

More people now die of hepatitis C than HIV/AIDS, according to the U.S. Centers for Disease Control and Prevention (CDC).The infectious disease can lead to scarring of the liver, cirrhosis, liver cancer, liver failure and death. For some sufferers, the only option for survival is a liver transplant.

The new drugs — simeprevir (sold as Olysio by Janssen Therapeutics, a division of Johnson & Johnson) and sofosbuvir (marketed as Sovaldi by Gilead Sciences) — could stamp out the disease, which afflicts an estimated 3.2 million to 5.2 million Americans. In clinical trials, the new drugs, which have already reached the market, have reached cure rates as high as 95%. Patients take them by pill, usually every day for 12 weeks, and they have mild side effects.

Until now, the drug of choice for treating hepatitis C was interferon. But patients typically must be injected with interferon for nearly a year, and it can have severe side effects including flu-like symptoms, fatigue, anemia, and depression. It also isn't all that effective, with a 45% cure rate for those with hepatitis C, genotype 1, the most common strain.

The Food and Drug Administration (FDA) approved the two medications late last year, after states had already completed their Medicaid budgets. It was no secret that the drugs were coming—patients were eagerly awaiting their approval. It wasn't clear, however, just how expensive they would be. By comparison, treatment with interferon or other drugs costs $15,000 to $20,000. Many patients have declined those treatments in anticipation of simeprevir and sofosbuvir hitting the market.

"I don't recall any other situation in which we've had very effective, very expensive drugs come out for an important condition with such a large patient population potentially eligible for treatment," said Steven Pearson, president of the Institute for Clinical & Economic Review. ICER is convening the California Technology Assessment Forum of scholars, policymakers and insurers later this month in San Francisco to consider the clinical and policy ramifications of the new hepatitis C drugs.

The potential cost of treating even a fraction of those with the disease is nothing short of astronomical.

ICER's preliminary study estimates that in California alone, treating just half of all those with chronic hepatitis C with the new medications would cost an additional $18 billion this year, compared to what is being spent now. Because the prevalence of hepatitis C is about two times higher among Medicaid beneficiaries than the general population, a disproportionate share of the financial burden of these drugs could fall on the states and the federal government, which jointly finance Medicaid.

"If you do back-of-the envelope calculations, it's clear budgets couldn't take on the potential of every eligible patient," said Pearson.

One of the drugmakers, Janssen, defended the pricetag. "We think the price reflects the value that Olysio brings to patients, medical providers and health care systems," spokesman Craig Stoltz said.

More specialty meds coming

Matt Salo, executive director of the National Association of State Medicaid Directors, said it's likely the new hepatitis C medications will be part of a new wave of extremely expensive, complex, and finely tuned "specialty" medications that will create continuing dilemmas for the health care system.

"I don't know that public policy has yet come up with how we are going to deal with this," Salo said. "If a cure comes out for lupus and it costs $300,000 a year, at what point do we say, 'We can't do this for everybody?' Those are big policy questions we're going to have to start to grapple with."

In the case of the new hepatitis C medications, the grappling starts in earnest at ICER's San Francisco conference. The group may issue recommendations on which privately insured and Medicaid patients should be approved for the new medications first. For example, it could advise that only those patients showing signs of cirrhosis should receive the new drugs, and that the remainder could use the old medications or wait for the next generation of hepatitis C drugs to reach the market, presumably at lower cost.

If there is rationing of the new drugs, it won't be an easy sell to patients, many of whom have lived with liver disease for years and some of whom could not tolerate the old treatments.

"Are you going to say to patients, 'We understand you have a viral infection and there's a cure, but because you are in a mild stage, we don't think you need treatment now?'" said Mark Sulkowski, an infectious disease specialist and professor of medicine at Johns Hopkins School of Medicine.

The high cost of the drugs also raises concerns over how they will be dispensed. Does it make sense to hand over to patients a bottle of pills worth at least $84,000? Will there be a black market for the drugs? And what happens if a patient stops taking the medications before the end of treatment? Should they get to resume another full course of treatment?

Hepatitis C on the rise

No one yet knows how strong demand for the new drugs will actually be. But the number of eligible patients could soar. Asymptomatic until advanced stages, hepatitis C can go undetected for years, often decades, and it is estimated that least half of the people with the disease do not know they have it. Today, it is often spread by blood-to-blood contact associated with intravenous drug use. But in the past, people often contracted it through blood transfusions and transplants.

Last year, the CDC and the U.S. Preventive Services Task Force both came out with a new recommendation that all baby boomers – everyone born between 1945 and 1965 — be screened for hepatitis C. For unknown reasons, researchers have found a greater prevalence of hepatitis C in that population than others. Additional screening will only increase demand for treatment.

State Medicaid agencies are just now beginning to react to the implications of the two new medicines. The majority of Medicaid beneficiaries are in managed care plans, but those managed care plans set their capitation rates (the amount Medicaid pays managed care plans per patient in a year) for 2014 before the FDA approval of simeprevir and sofosbuvir. Now, some of those plans are asking their state Medicaid agencies for a carve-out or "pass-through" for these drugs, meaning that the Medicaid agencies would bear the costs of those drugs above the capitations. The states could also try to negotiate with the manufacturers for a better price.

"This is going to fall on taxpayers because we think it will fall disproportionally on those in Medicaid," said J. Mario Molina, chief executive of Molina Healthcare Inc., a Medicaid managed care plan with 2.1 million beneficiaries in California.The potential costs of these drugs could overwhelm the Medicaid agencies, forcing them to turn to their legislatures for additional money.

Mike Wofford, chief of pharmacy policy with the California Department of Health Care Services, said it is possible his agency would have to ask the legislature for help. "If a budget breaker comes along we have to figure out how to pay for it," he said. But he also noted that it's too soon to know if events are heading in that direction because of uncertainty over demand. Already, though, California Medicaid is requiring that patients obtain prior authorization if they want the new hepatitis C drugs.

Private insurers also are grappling with the implications of the new drugs. Susan Pisano, a spokesperson for America's Health Insurance Plans, said "There's always the potential that a high level of new costs to the system can have an impact on premiums."

Drug companies currently are free to set prices based on market demand, but Pisano suggested that drug pricing deserves more scrutiny, particularly since more specialty drugs are in the pipeline, including new treatments for hepatitis C. "Heretofore there's been great focus on insurance but little focus on what the pharmaceutical companies are charging," she said.

Gilead Sciences, maker of Solvaldi, said the drug represents a significant advance over other treatments. Spokeswoman Michele Rest said Medicaid agencies are eligible for "deep discounts."

The two drugmakers are not likely to have the market to themselves for long. A new generation of hepatitis C drugs is expected to win approval later this year. That increased competition could drive down prices. Or, if the drugs are deemed even more effective, it could lead to more sticker shock.

Stateline is a nonpartisan, nonprofit news service of the Pew Charitable Trusts that provides daily reporting and analysis on trends in state policy.

Source

There’s a Life-Saving Hepatitis C Drug. But You May Not Be Able To Afford It.

Provided by Kaiser Health News

By Julie Appleby
KHN Staff Writer
Mar 03, 2014

This KHN story was produced in collaboration with The Daily Beast

There's a new drug regimen being touted as a potential cure for a dangerous liver virus that causes hepatitis C.  But it costs $84,000 -- or $1,000 a pill. And that price tag is prompting outrage from some consumers and a scramble by insurers to figure out which patients should get the drug —and who pays for it.

Called Sovaldi, the drug is made by California-based Gilead Sciences Inc. and is the latest in handful of new treatments for hepatitis C, a chronic infection that afflicts at least 3 million Americans and is a leading cause of liver failure. It was approved by the U.S. Food & Drug Administration in December.

"Everyone is still scrambling to figure out how to handle this," said J. Mario Molina, president and CEO of Molina Healthcare, one of the nation's largest Medicaid managed care companies, which is seeking emergency guidelines from the 11 states in which it operates.  "It's far superior to anything we've had to treat hepatitis C.  The problem is it's extraordinarily expensive."

Medicaid programs may be particularly hard hit because they are likely to cover a higher proportion of patients with the virus and cannot raise premiums like commercial insurers, Molina said. Medicaid managed care firms like his are paid a set amount per member per month by the state to cover all their medical costs.

If left untreated, hepatitis C causes liver damage over the course of decades. The U.S. Preventive Services Task Force recommends that all baby boomers be tested for the blood-borne virus, which often goes undiagnosed because it produces few symptoms. It is spread mainly by intravenous drug use, but many people were unknowingly infected by poorly sterilized medical equipment and blood transfusions before widespread screening of the blood supply began in 1992.  Some may also been infected through tattoos and piercings with contaminated needles.

Big Gains Over Current Drugs

With a success rate of better than 90 percent, Sovaldi is seen as a vast improvement over older treatments, some of which helped only half of patients. Those older drugs cost about $25,000 per treatment, while some newer products approved in 2011 have prices closer to Sovaldi, but have more side effects or are more complex to administer.

A typical course of treatment with Sovaldi goes 12 weeks and costs $84,000, but some patients may need to take the drug for twice as long. Guidelines also suggest that for some patients, Sovaldi be used with other drugs, such as interferon and ribavirin, adding to the cost.

Molina said he has asked state Medicaid directors for guidance on how to proceed with its 2.1 million beneficiaries. In the meantime, he said his firm will not cover the drug, which he says could add $300 million to $400 million to its costs this year.  He wants states to cover the drug outside its contracts with his company because the costs were not built into rates negotiated for this year.

"Whether we pay for it or the state pays for it, it will be a huge expense,” he said. “California spends $3,500 per person a year in the Medicaid program. You could cover an awful lot of people for $84,000."

A Molina spokeswoman said the company is not required to cover the drug since it was approved after its managed care contracts were negotiated. “In the meantime, we are continuing to cover the same medically necessary hepatitis C treatments that were available prior to December 2013,” said the spokeswoman, Sunny Yu.

In traditional Medicaid, states must cover FDA-approved drugs marketed by companies that have negotiated rebates with the federal Medicaid drug rebate program. Gilead participates in that program, a spokeswoman said.

But states have flexibility to manage their Medicaid drug costs by using preferred drug lists and requiring prior authorizations for some treatments. In addition, enrollees covered under the health law’s expanded Medicaid program may have access to a narrower selection of drugs in some cases, depending on how the state has set up its program.

Limiting How Many Are Eligible

Private insurers, meanwhile, are developing their own criteria for which patients are eligible for the drug, said Steven Pearson, who is organizing a public forum in San Francisco on March 10 to help patients, doctors, insurers and policymakers compare Sovaldi’s cost and effectiveness with other treatments.

Some insurers are limiting it to patients who have tried the older drugs, but failed to get satisfactory results. Others will provide it to those in the middle stages of liver damage, but not to those who show little or no signs of damage, said Pearson, who heads the Institute for Clinical and Economic Review, a nonprofit organization that helps groups evaluate the effectiveness of different medical interventions.

A report prepared for the San Francisco forum estimates that if every patient in California with advanced liver damage were treated, the cost would be $6.3 billion.

Gilead says its price is justified because of the drug’s effectiveness. Those who take it can head off chronic problems, such as liver disease or the need for an eventual liver transplant.

“Gilead believes that the price of Sovaldi is fair based on the value it represents to a larger number of patients, including many of those with no current options,” said Michele Rest, a company spokeswoman. “The cost of the entire … regimen of 12 weeks of Sovaldi with interferon and ribavirin is consistent with and, in many cases, actually less than the cost of the previous … regimens – with shorter duration of therapy, increased tolerability, and higher efficacy. “

She said the company has financial aid programs to assist patients who are uninsured, underinsured or who need assistance to help pay for the medicine, but declined to say how many were enrolled.

‘What Is The Proper Cost?’

In 2011, Gilead paid $11 billion to buy Pharmasset, the company that developed the drug, while it was still in final stage testing. Analysts have estimated that the drug will reap billions in annual sales.

Molina says Gilead is entitled to a return, but questions whether taxpayers should be paying so much of its acquisition costs.

"It is estimated that half the patients who get this will be covered by government programs," Molina said. "If they overpaid for the company they acquired, why should the government have to bail them out?"

Similar questions are being raised by the AIDS Healthcare Foundation, a Los Angeles-based advocacy and health care group, which is urging state Medicaid directors to bargain hard for rebates on the drug’s cost.

“The pricing of Sovaldi is being driven by Gilead's desire to recoup its investment in Pharmasset, and assumes it can accomplish this by charging Medicaid and other taxpayer-funded programs whatever it wants," President Michael Weinstein wrote in letters to state Medicaid directors.

Medicaid managed care nonprofit CareSource, headquartered in Dayton, Ohio, says it is already covering the drug, mainly for members who have had bad reactions to the older treatments.

"It's a great medication for the members, but we are concerned about the cost," said Chief Medical Officer Craig Thiele.

While there was some discussion about waiting to see if other drugs to treat hepatits C might be approved, Thiele said CareSource didn't want to delay.

He noted that the questions raised by Sovaldi may apply to many new pharmaceuticals, including potential hepatitis C treatments.

"What concerns me is this may be a trend, a wave of expensive medications," he said.

Matt Salo, executive director of the National Association of Medicaid Directors, said many state officials share those concerns.

"The broader question is what is the proper cost of life-saving pharmaceuticals?" he said. "This is not an isolated incident ... this is a trend that is going to get worse before it gets better."

Source

Costly hepatitis drug Sovaldi rattles industry

Provided by The Washington Post

By Sandhya Somashekhar, Saturday, March 1, 2:32 PM

When the Food and Drug Administration approved a medication called Sovaldi in December, it was hailed as a breakthrough in the fight against hepatitis C, a blood-borne disease that affects 3.2 million Americans and kills more people in the U.S. annually than AIDS.

Then California-based Gilead Sciences, the manufacturer, announced the price: $84,000 for a 12-week course, more than what many cancer treatments cost in a year.

The hefty price tag has rattled patient advocacy groups and insurance companies, who say most costly new treatments coming on the market are targeted for a smaller patient population. Putting such a premium on a drug that could help so many will be crushing, they say.

At least one prescription drug plan is encouraging doctors to delay prescribing Sovaldi for patients who can wait. One insurer has said it risks bankruptcy if it’s required to cover the drug for everyone who needs it this year. Advocates say Gilead has taken corporate greed to new levels.

The drug has also prompted a new round of hand-wringing over a larger issue: the escalating cost of specialty drugs, which are designed to treat chronic illnesses such as rheumatoid arthritis and multiple sclerosis and sometimes require special handling.

While these therapies are delivering body blows to some of the world’s most pernicious diseases, they also are testing the limits of what society is willing to pay for sought-after treatments or cures.

“The advancements that are coming in medicine are going to be stunning and amazing, both in terms of the kinds of things we can treat that we never could and what their cost is going to be,” said Matt Salo, executive director of the National Association of Medicaid Directors. “We’re going to need to think as a country about how do we value health and health care.”

In the past, treating hepatitis C was not always successful and involved lengthy treatment with injectable drugs that had significant side effects. By contrast, Sovaldi promises to cure nearly all sufferers with a once-daily pill that has far fewer side effects.

The Centers for Disease Control and Prevention has called hepatitis C an undeclared public-health crisis, affecting as much as 2 percent of the adult U.S. population and killing 1,500 Americans a year. It is caused by a virus and is typically transmitted through blood contact, such as dirty syringes.

Many people contracted the disease through blood transfusions before routine testing of donated blood for hepatitis C began in 1992.

The disease can go undetected for years and can eventually lead to cancer or cirrhosis of the liver. It is particularly prevalent among baby boomers. Federal health authorities recommend that everyone born between 1945 and 1965 be tested for the disease.

Ronni Marks, 60, of New York City contracted the disease from one of the many blood transfusions she underwent since childhood. After two unsuccessful treatments in the past that caused debilitating side effects, she began a course of Sovaldi and two other drugs this year.

“Hopefully these are the wonder drugs they say they are,” she said.

When a friend asked Marks for a photo of the slim, yellow pill — a single dose costs $1,000 — she snapped a picture of it on a blue background. “She said that it looked like it was taken on a Tiffany’s box,” Marks said. “I joked that it should have been, considering the price.”

In a statement to The Washington Post, Gilead said the price is fair because it is a significant improvement from previous treatments and it is not more expensive than the old treatment. It said it has had a good response from insurance companies agreeing to cover the drug. Gilead added that it offers a generous assistance program to help low-income people get the drug at a low cost.

The fact that Sovaldi actually cures hepatitis C gives it an advantage over other types of therapies, allowing the company to price it higher, said Kenneth Kaitin, director of the Tufts Center for the Study of Drug Development, an independent nonprofit research group at Tufts University.

“It is legitimately a big deal,” he said.

He noted that several other companies also are developing therapies for hepatitis C and that Gilead wants to lock in an aggressive price before it faces tougher competition.

Still, the price has provoked an outcry from the insurance industry, as well as from state Medicaid directors who say taxpayers will have to shoulder much of the cost of the drug because many with hepatitis C get their health care from the government through Medicare, Medicaid and the prison system.

Molina Healthcare, a company that operates Medicaid ­managed-care plans for 11 states, has told state officials it cannot bear the cost of covering the drug. The company, which gets a flat fee from states for each Medicaid recipient, negotiated its 2014 rates before the FDA approved Sovaldi. It is asking states to pay for the drug separately and is deciding whether to cover the drug at all.

“We can’t absorb this kind of a hit,” said chief executive J. Mario Molina.“It would cause us and other health plans to potentially become insolvent.”

Express Scripts, the nation’s largest prescription drug benefit manager, has said it is encouraging some doctors in its networks to delay prescribing Sovaldi for hepatitis C patients who can safely wait. It is the first time the company, which helps employers keep down the prescription drug costs for their employee health plans, has asked doctors to avoid a drug because of the cost.

The company hopes that when rival hepatitis C drugs hit the market, the increased competition will drive down costs.

“We have a public health crisis that’s been identified in hepatitis C. We now have a drug that is wonderful in its promise,” said Karen Ignagni, president of America’s Health Insurance Plans. “But the pricing of this drug for a public health crisis doesn’t match the situation.”

Lena H. Sun contributed to this story.

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Does the Latest HCV Breakthrough Therapy Spell Trouble for Gilead Sciences, Inc.?

Provided by The Motley Fool

By Cory Renauer | More Articles
February 26, 2014 | Comments (9)

Gilead Sciences (NASDAQ: GILD ) was the first to submit its highly anticipated hepatitis C virus (HCV) combination therapy to the FDA. Recently, Bristol-Myers Squibb (NYSE: BMY ) earned a Breakthrough Therapy designation for its dual regimen, likely to compete with Gilead's. AbbVie (NYSE: ABBV ) , and Merck (NYSE: MRK ) are also developing combination HCV treatments of their own, both with breakthrough designations.

Gilead's combo carries an enormous price tag, but America's largest pharmacy benefit manager Express Scripts (NASDAQ: ESRX ) has voiced its intent to curtail the pharmaceutical industry's pricing power. Here's a look at the competing therapies, and the expedited regulatory pathway that could result in several of them reaching the market at roughly the same time.

About the Breakthrough Therapy designation
The FDA has implemented expedited pathways in the past, but I don't think any has been as well defined as the Breakthrough Therapy designation. Implemented in 2012, the designation is reserved for targeted therapies that hit significant efficacy marks in early or mid-stage clinical trials. The nature of the condition must also be serious enough that patients are clearly willing to trade safety for speed, like HCV.

Without an expedited pathway, HCV therapies would likely need to provide data on the percent of patients surviving for several years after dosing. With the designation the FDA will work with the drug makers to define acceptable, shorter-term endpoints that should warrant approval. Of course, early approvals remain contingent on longer safety trials also designed in partnership with the agency. In the meantime, patients with unmet needs gain access to lifesaving new treatments.

Clash of the combos
From Gilead's perspective, the designation can erode the lead its HCV therapy had on its competitors. Gilead's Sovaldi as a single agent may have beat competitors to the US market in December last year, and last month in the EU, but it's the combination therapies that seem to have doctors warehousing patients by the thousands.

Fellow Foolish author Brian Orelli raised an important point recently. As a single agent, Sovaldi pills must be taken with pegylated interferon injections to be effective for genotype 1 (GT1) patients. Interferon injections produce very uncomfortable side effects. Sovaldi's first year on the market flying solo may be one of the most successful launches ever, but there are potentially millions of HCV patients that can wait for interferon and ribavirin free combination therapies. And that's where the trouble lies for Gilead in the years ahead.

In order to see a return on the $11 billion spent acquiring Sovaldi, Gilead has priced the single-agent therapy at $84,000 for a 12 week regimen in the US. If Express Scripts, America's largest pharmacy benefit manager, has its way, the combo will be far less expensive. During an interview with Bloomberg late last year, Express Scripts' Chief Medical Officer Steven Miller said his company would, "identify which drugs can be pitted against each other and make some really tough formulary decisions." Others may compete with Gilead on price, and the HCV combo field is getting more crowded each month.

A Breakthrough Therapy breakdown
AbbVie, Merck, and Bristol-Myers all have Breakthrough Therapy designated, HCV combinations in development. In a recent post I highlighted some data that makes AbbVie's and Merck's cocktails seem just as effective as Gilead's combination pill.

Since then Gilead has filed a New Drug Application with the FDA for the once-daily fixed-dose combination of ledipasvir and sofosbuvir for the treatment of GT1 HCV. On February 24, the FDA granted a Breakthrough Therapy designation to Bristol-Myers' daclatasvir and asunaprevir combination therapy for genotype 1b HCV patients. This is the second Breakthrough designation granted to Bristol-Myers' HCV combos.

While AbbVie and Gilead are widely expected to compete in order to remain on the Express Scripts formulary, Bristol-Myers' two drug combo was designated for the GT1b indication. Generally GT1b is more prevalent in Europe, so Gilead and AbbVie might not be competing with Bristol-Myers for a place on the Express Scripts formulary. At least not for a majority of GT1 patients.

Merck's two-pill HCV combination received its breakthrough designation last October for GT1 HCV. The company has remained quiet about the combo since reporting interim data at the American Association for the Study of Liver Diseases Meeting last November. During the latest earnings call, Merck's management mentioned its HCV program only in passing. The company's R&D head, Roger Perlmutter responsed to a direct question regarding the regimen by stating that data so far was not yet ideal. I'll keep my eyes open for more from the company. For now it doesn't seem that Merck is willing to enter the ring with AbbVie, Gilead, and Bristol-Myers just yet.

Final take
There may be three other HCV combination therapies in development with breakthrough designations, but for now it seems Gilead needs to concern itself with just one, AbbVie's. We can nitpick over the data, but the opinion that matters is that of major payers, like Express Scripts.

The late stage data from AbbVie and Gilead are outstanding, and Merck doesn't seem like it's willing to compete with them. If Bristol-Myers' combo's designation will only support an early approval for GT1b patients specifically, that should leave the majority of the US market to Gilead, and AbbVie. So far, it seems the only clear winner from that fight will be the payers.

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Cory Renauer has no position in any stocks mentioned. The Motley Fool recommends Express Scripts and Gilead Sciences. The Motley Fool owns shares of Express Scripts. Try any of our Foolish newsletter services free for 30 days. We Fools may not all hold the same opinions, but we all believe that considering a diverse range of insights makes us better investors. The Motley Fool has a disclosure policy.

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New Therapies and Screening for Hepatitis C Are Changing Treatment Landscape

Provided by PharmTech

Feb 27, 2014

The American Journal of Managed Care (AJMC) recently convened an expert panel that analyzed the implications of recommendations by the US Preventive Services Task Force that all Americans born between 1946 and 1964 be screened for the hepatitis C virus (HCV). Widespread screening, along with new therapies that move patients from a chronic condition to a cure, is changing the landscape in treatment of hepatitis C, said the AJMC panel, according to a press release.

An estimated 3.2 million people have HCV, but the vast majority are unaware they have it, the AJMC noted in the press release. HCV gained steam in the early 1980s, before blood products were routinely screened for its presence. Screening people for HCV would allow candidates for treatment to rid themselves of the disease early, before complications become difficult and expensive to treat. Targeting the baby-boomer generation before most of them retire would allow those found to be carrying the virus to obtain treatment under commercial insurers, rather than Medicare. The cost of treatment to cure HCV, which may be possible in 90 to 94% of cases with new therapies, must be weighed against the cost of caring for what was once an expensive, long-term chronic condition, noted one of the panelists.

New therapies are available, with others in development. FDA recently granted breakthrough therapy designation to Bristol Myers-Squibb’s (BMS) investigational DCV Dual Regimen (daclatasvir and asunaprevir) for use as a combination therapy in the treatment of genotype 1b chronic hepatitis C infection, BMS announced in a press release. The designation is based on data from the company’s ongoing Phase III clinical trial program evaluating the all-oral combination regimen of DCV, an investigational NS5A replication complex inhibitor, and ASV, an investigational NS3 protease inhibitor, without ribavirin. BMS also recently announced that the European Medicines Agency validated the company’s marketing authorization application for the use of daclatasvir for the treatment of adults with HCV with compensated liver disease, including genotypes 1, 2, 3, and 4. The application seeks the approval of daclatasvir for use in combination with other agents for the treatment of chronic hepatitis C and will be reviewed under an accelerated regulatory review.

Source: American Journal of Managed Care

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