Geneva, Switzerland, May 22, 2014 —Today, four years after introducing its first viral hepatitis resolution, the World Health Assembly (WHA)—the decision-making body of the World Health Organization (WHO)—passed the Hepatitis Resolution, which commits the WHO and United Nations (UN) member states to urgent action to address the global hepatitis pandemic, including that of hepatitis C virus (HCV).

Globally, an estimated 185 million people have been infected with HCV. Since 2010, more than a million of them have died from HCV-related liver disease, although hepatitis C is treatable and curable. Since 2010, 9–12 million people have become infected with hepatitis C, although it is preventable. In addition, in an increasing number of countries, liver disease caused by HCV has become the leading cause of non-AIDS-related death in people coinfected with HIV/HCV.

The resolution comes at a critical moment, as new drugs to treat HCV are hepatitis C virus (HCV) entering the market. These new drugs, called direct-acting antivirals (DAAs), demonstrate cure rates of more than 90 percent in clinical trials and provide radically simpler treatment. DAAs offer the unprecedented promise of global HCV eradication, especially in low- and middle-income countries (LMICs), where 85 percent of people with HCV live.
 
Yet, in high-income countries, a 12-week combination regimen of DAA treatment can cost US$140,000, although it costs less than US$250 to produce.[1] During the resolution proceedings, dozens of countries, including Malaysia, Ukraine, South Africa, Venezuela, and France remarked on the prohibitive cost of new HCV treatments.

The World Trade Organization’s Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) provides LMICs with certain legal flexibilities. The Hepatitis Resolution supports LMICs’ use of these flexibilities to produce or import generic versions of DAAs and other medications if companies refuse to offer them at affordable prices. Brazil, the sponsor of the resolution, which was unanimously voted in, stated during the vote that governments, “should use TRIPs flexibilities whenever needed” in order to gain access to safe, effective, quality generics.
 
The WHO must vocally and unequivocally support countries’ use of compulsory licenses, parallel importation, and other TRIPs flexibilities to facilitate universal access to lifesaving treatment and to stop the 500,000 annual deaths related to HCV.

The inclusion of harm reduction—an evidence-based approach to reducing transmission of bloodborne viruses and mortality among people who inject drugs (PWID)— is retained in this resolution as a key recommendation, despite early opposition by some countries. During the vote, a number of governments, including Indonesia, Iran, Russia, and Canada spoke out on the need to address PWID as a key population. Now the WHO must prioritize providing technical assistance to UN member states to dramatically scale up needle and syringe programs, opioid substitution therapy, access to HCV treatment, and decriminalization of PWID and harm reduction for this critically important population, 67 percent of whom are HCV-infected. Most new infections occur among PWID, yet access to sterile injection equipment and other HCV prevention tools is staggeringly inadequate, reaching only a tiny percentage of those who need it. This egregious public health failure allows the epidemic to continue spreading.
 
The Hepatitis Resolution challenges WHO Director–General Margaret Chan and her agency to mobilize global political will and resources to effectively address viral hepatitis, and to help UN member states develop the technical capacity to implement prevention, treatment, and care plans. Without a massive resource investment from donors and UN member states to support a global plan, millions will continue to become infected and die.

Contacts:
Ms. Chloé Forette, Médecins du Monde, +33-609-537-369  (France)
Ms. Karyn Kaplan, Treatment Action Group, +1-646-316-8979 (United States)
 
For further information on key issues concerning the Hepatitis Resolution at the World Health Assembly, please see: Defuse hepatitis C, the viral time bomb: Test and Treat Hepatitis C: Position Paper for the 67th World Health Assembly, May 19–24, 2014. Available at: http://www.hepcoalition.org/advocate/advocacy-tools/article/defuse-hepatitis-c-the-viral-time.

 

[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. 2014 Apr; 58(7):928–36. doi: 10.1093/cid/ciu012.

 

Research by Andrew Talal shows that people who inject drugs want to be educated about hepatitis C and are willing to be treated.

More effective, new medications for HCV infection with fewer side effects also are causing a shift in patients’ attitudes

Release Date: May 16, 2014

People who inject drugs and are enrolled in a drug treatment program are receptive to education about, and treatment for, hepatitis C virus, according to a study by researchers at several institutions, including the University at Buffalo.

That finding, published online this week in the Journal of Addiction Medicine will be welcome news to health care providers. The paper notes that injection drug use is a primary mode of infection, making for an HCV infection prevalence as high as 80 percent among people who inject drugs.

"One of the most important findings of this work is that people who inject drugs do want to be educated about the disease and that education is associated with willingness to be treated," says senior author Andrew H. Talal, MD, professor of medicine in the Division of Gastroenterology, Hepatology and Nutrition at UB and adjunct associate professor of medicine at Weill Cornell Medical College. First author is Marija Zeremski, PhD, senior research associate in medicine at Weill Cornell Medical College and research assistant professor of medicine at UB.

Talal and colleagues previously demonstrated that treatment of addiction significantly enhances the ability of people who use drugs to complete HCV therapy.

"These new findings support the premise that addiction-treatment facilities can help provide sustained HCV treatment for this population," Talal says. "These facilities have the added advantage of being able to link HCV care to drug treatment, allowing for closer patient evaluation, which will likely lead to improved adherence to treatment regimens."

HCV infection often is asymptomatic, but 75 to 80 percent of those infected will develop chronic infection that can progress to liver cirrhosis and/or liver cancer, potentially requiring liver transplantation as a life-saving intervention. However, in order to be considered for a liver transplant, people who use drugs must remain "clean" for at least six months.

The study was based on a survey of 320 patients enrolled in a New York City-based methadone treatment program (START Treatment and Recovery Centers). Nearly half of them reported that they had tested positive for HCV infection.

Seventy-eight percent of respondents expressed willingness to participate in HCV-related education and to receive treatment for HCV. More than half of those surveyed correctly responded to at least five of seven questions assessing their knowledge about HCV.



"People who inject drugs have always wanted to be treated for hepatitis C, but there have been a variety of barriers at the patient, provider and institutional levels," says Talal. "Most importantly, there has been a lack of education about the disease, a fear of side effects of interferon, discomfort in conventional health care venues and a lack of awareness of the status of the infection."

In some cases, the percentage of HCV-infected people who use drugs that show up for HCV-related medical appointments is as low as 10 percent, according to Talal.

In the current research, patients cited fear of side effects from interferon, which remains as part of the standard treatment regimen for genotype 1 infection, as a key barrier to their willingness to accept HCV treatment. Interferon can cause multiple side effects, ranging from fatigue, fever, nausea, anorexia, muscle pain and hair loss, to insomnia, depression and irritability. In addition, interferon-based therapies are only effective in eliminating infection in half of those who take it.

"A major change in the attitudes of people who use drugs is due to knowledge about greatly improved treatment efficacy and the ability to provide HCV treatment at the same site as the substance abuse treatment," says Talal.

Talal adds that the New York State law mandating that all individuals born between 1945 and 1965 be offered HCV screening is increasing the number of people diagnosed with the infection, thereby also making them more receptive to HCV education and treatment.

This study, funded by the Viral Hepatitis Action Coalition and performed in collaboration with the Centers for Disease Control and Prevention, documents the initial phase of a project called Prevention, Evaluation and Treatment of Hepatitis C in Opiate Agonist Treatment (PET-C). Led by Talal, the project's goal is to assess how telemedicine can be used to evaluate a model of HCV treatment for people who inject drugs and are enrolled in a drug treatment program.

Talal conducts research on HCV in UB's Clinical and Translational Research Center and he sees patients as a physician with UBMD, the practice plan of the UB School of Medicine and Biomedical Sciences. He previously served on the advisory board for Abbott Molecular, received support from Gilead Sciences and disclosed a prior relationship with Vertex Pharmaceuticals, all of which helped sponsor the study.

Media Contact Information 
Ellen Goldbaum Senior Editor, Medicine 
Tel: 716-645-4605 
goldbaum@buffalo.edu 
Twitter: @egoldbaum

- See more at: http://hepatitiscresearchandnewsupdates.blogspot.com/2014/05/methadone-programs-can-be-key-in.html#sthash.bL3uMQpw.dpuf

 

Walter Bianco has had hepatitis C for decades. He's known about it for 20 years. And now he's reaching the end of the road.

"The liver is at the stage next to becoming cirrhotic," the 65-year-old Arizona man says.

That means he's approaching the end stage of hep C infection. Cirrhosis is a precursor of liver failure, which requires a transplant. And it can lead to liver cancer.

More and more baby boomers like Walter Bianco are approaching this stage of chronic hep C infection. Researchers estimate that 3 to 5 million Americans have the insidious virus.

 

Alexandra Olgin

Many, like Bianco, got it from injecting illegal drugs in their youth. (He says he's been drug- and alcohol-free for 32 years.) Some got it from transfusions before 1992, a period when blood wasn't screened for the virus. Some got infected from sharing razors or toothbrushes. From contaminated needles used for tattoos or hospital equipment. Some from sexual transmission.

Whatever the source of infection, Bianco's ominous situation is increasingly common.

"There isn't a day that goes by where I don't have a story very similar to Mr. Bianco's," says Dr. Hugo Vargas of Mayo Clinic in Scottsdale, Ariz., Bianco's liver specialist.

Vargas has been trying for two years to stave off the deadly complications of Bianco's infection. So far, nothing has worked.

But there's a very good chance that Bianco can be cured of his hep C. Potent new drugs can clear the virus from his body for good.

"People are ecstatic," Vargas says. "It really is amazing to be seeing what's happening."

These new drugs are curing more than 90 percent of patients – virtually 100 percent in somerecent studies. Just a few years ago, cure rates were 50 percent or less.

But there's a big problem: The cost.



Shots - Health News

$1,000 Pill For Hepatitis C Spurs Debate Over Drug Prices

One of the new drugs, called sofosbuvir (brand name Sovaldi) costs $1,000 per pill.

Vargas says Sovaldi combined with another new drug calledsimeprevir (Olysio) is highly effective in patients like Bianco.

And the new drugs are easy to take. Bianco says the older drugs caused horrible side effects. "Just terrible itching, terrible headaches, nausea," he says.

But Medicare won't pay for the drugs that Vargas says Bianco needs.

Medicare officials wouldn't comment on coverage of new hep C drugs. A spokesman says the federal program turns such decisions over to private insurers that administer its drug plan.

One of those private insurers has twice rejected Vargas's prescription because the Food and Drug Administration hasn't approved use of the two drugs in combination. (Last week Olysio's maker, asked the FDA for approval of the regimen.)

Together the two drugs would cost around $150,000 – far more than Bianco can afford.

"It is a lot of money, and there are a lot of hep C sufferers out there," Bianco says. "I think Medicare's probably thinking. 'If we can hold off for a year or two, some of these following drugs will be cheaper.' "

“If he were my father I would want Mr. Bianco to be treated now — not in a year, not in a year and a half.

- Dr. Hugo Vargas

But Vargas says Bianco, like many others with end-stage liver disease, may not have that long to wait.

"If he were my father," the Mayo specialist says, "I would want Mr. Bianco to be treated now – not in a year, not in a year and a half."

Update 3:05 pm: A spokesman for the Centers for Medicare and Medicaid called NPR to report that the agency is "looking into" Walter Bianco's case. "The policy is trying to catch up with reality," the CMS spokesman said, asking not to be identified by name. "It has been a slow process. We want to try to be helpful as much as we can to get beneficiaries the drugs that they need."

It's not yet clear how insurers and government programs will cope with the problem. The Department of Veterans Affairs and expert panels recently recommended reserving the new drug regimens for patients awaiting liver transplants and others with the most advanced liver disease.

But consumer advocates cringe at the idea that patients may have to wait for a cure until their livers have suffered irreversible damage. For one thing, once a patient has cirrhosis he will have to be monitored for liver cancer every six months for the rest of his life.



Shots - Health News

Costly Hepatitis C Pill Shreds Drug Industry Sales Record

"If I had a chronic infectious disease that could lead to advanced liver disease and complications, I'd want to be treated," says Ryan Clary of the National Viral Hepatitis Roundtable, an advocacy group. "The news is the cure is here. We need to get people into treatment."

But those asked to pay the bill for treatment are expressing alarm at the hundreds of billions of dollars that hep C drugs could cost them. Olysio costs around $66,000 per patient for a 12-week course of treatment. Sovaldi costs $84,000.

"People were very shocked by the price, because it hit a psychological barrier in terms of. 'This is too expensive,'" says Dr. Camilla Graham of Beth Israel Deaconess Hospital in Boston. She recently was turned down in her request to prescribe the two drugs for a Medicare patient.

But Graham says the cost per patient for hep C drugs is not unique.

"We have a lot of drugs where we spend in that $80,000 to $100,000 range –- and the outcome is not cure," Graham says, alluding to specialty drugs for rheumatoid arthritis, multiple sclerosis and cancer.

The cost problem with hep C drugs is that millions of people will need them in the near future, especially as federally recommended screening programs to detect infected people ramp up.

Graham says many of these patients can't wait long for their chance at a cure.

"Hepatitis C is a ticking time bomb," she says. "We have a very limited amount of time to get in here and alter the course of the disease for a good number of people."

If that doesn't happen, a lot of them will suffer liver failure and liver cancer. And that will cost a lot more to treat in the long run.

by RICHARD KNOX May 12, 2014 3:25 AM ET

Hepatology March 1 2014
Andrew Aronsohn,1,2 Nancy Reau,1 and Donald Jensen1

The next generation of direct-acting antiviral agents (DAAs) will change the landscape of hepatitis C virus (HCV) therapy. Approval of complimentary oral agents will also introduce new opportunities for off-label treatment. Off-label therapy in HCV will include (1) combinations of approved drugs, used for the approved indication in an unapproved combination, such as combining two DAAs in an interferon (IFN)-sparing regimen, and (2) combinations of approved drugs used in an unapproved combination for an unapproved indication, such as using two available DAAs to treat patients post-LT (liver transplantation). Both providers and patients might find off-label combinations attractive; however, there may be limited data to support safety and efficacy. These treatment choices may also go against the recommendations published in therapeutic guidelines.

This article will address anticipated issues regarding off-label use of HCV medications, including the role of the U.S. Food and Drug Administration (FDA), consumer pressure, medical society guidelines, and third-party payers. Off-label issues specific to the United States will be described; however, many concepts, such as uncertainties of cost, label regulation, and reimbursement, can be applied to health care systems globally.

The FDA

Regulation of Off-Label Use

The FDA regulates market entry for all new prescription drugs in the United States. Once approved, physicians are not bound to prescribe according to the label-in many cases, off-label prescriptions may be part of best practice or standard of care. Off-label prescribing is legal and has been shown to occur in over one fifth of office-based prescriptions.[1] Upcoming generations of DAAs represent robust therapeutic innovation, which will likely outpace the breadth and capacity of the FDA-approved label. Prescribing already approved agents in an off-label combination may be desired to improve efficacy. In addition, safety may also be improved using these combinations by potentially eliminating drugs with toxicity, such as IFN. FDA approval for these combinations would require a new and unique application for the combined regimen, which would be costly and would require partnership between separate manufacturers. As a result, although the FDA will not regulate a provider's ability to prescribe off-label HCV treatment as they see fit, appropriate applications of use may be ambiguous because they will ultimately be based on a combination of opinion and potentially limited available data.

Defining the Need for Off-Label Combinations

Over 185 million people are infected with HCV worldwide.[2] It has surpassed human immunodeficiency virus (HIV) as a cause for mortality and has been linked to higher all-cause mortality and diminished quality of life.[3, 4] Despite data showing that sustained viral response (SVR) reduces mortality, relatively few patients have undergone successful treatment.[5] Historically, suboptimal efficacy and toxicity of IFN-based therapy has limited therapeutic options for many; however, opportunity is on the horizon. Multiple agents are in the late stages of development. These drugs will target various aspects of the HCV life cycle, making combinations of these agents a natural strategy to more effectively treat HCV and eliminate intolerable side effects or adverse events. Data involving various combinations of DAAs, often from different manufacturers, is rapidly becoming available; however, many of these studies are performed as proof of concept and are unlikely to progress to FDA-approved combinations. Combining DAAs based on these data in an off-label manner may be an attractive option for patients unwilling to undergo IFN-based therapy in addition to patients with comorbidites that have previously disqualified candidacy for standard-of-care therapy. This strategy is not without risk. Insurers may be unwilling to pay for off-label therapy,[6] and these combinations may have inadequate supporting safety and efficacy data.

Recent Centers for Disease Control and Prevention and U.S. Preventive Services Task Force guidelines to screen all patients born between 1945 and 1965 will help identify many patients who have been infected for decades and are at risk for developing complications of chronic liver disease. Although most of these patients are candidates for standard-of-care therapy, with anticipated rates of SVR reaching 75%,[7, 8] many patients and providers have chosen to defer therapy in anticipation for IFN-free regimens. Deferring therapy comes with risk, which includes progression of disease, change in health status, which may make future treatment impossible, possibility of infecting others, and change in patient insurance status, making therapy unaffordable. Although FDA-approved IFN combinations will likely be available in upcoming years, patients and providers may begin to feel restless, deferring therapy, and opt for a readily available off-label IFN-free combination. This patient population will likely represent a Òshort-termÓ utilization of off-label DAA combinations, which will diminish as IFN-free regimens come to market.

Alternatively, there are many subsets of individuals with HCV that that are in need of DAA-based treatment, but will be excluded from upcoming FDA labels because of limitations in supporting data. These patients include those with decompensated cirrhosis, first-generation protease inhibitor failures, chronic kidney disease, pediatric populations, HIV coinfection, and post-LT. Because many of these populations represent relatively small numbers of patients with HCV, it may be difficult to accumulate requisite data and possibly cost prohibitive for manufacturers to apply for FDA approval. These patients may represent Òlonger-termÓ utilization of off-label treatment.

Is There Precedent for Off-Label Use of Therapy?

The Human Immunodeficiency Virus Paradigm

Acquired immune deficiency syndrome (AIDS) was identified in 1981; however, zidovudine was not available until 1987. Between 1987 and 2008, 25 anti-HIV (human immunodeficiency virus) compounds were licensed for use. Similar to HCV, these agents directly target various aspects of the HIV life cycle. As single agents were approved, there was pressure by clinicians and advocates to find off-label combinations that would prevent emergence of viral resistance. By 1996, combination regimens were widely accepted, although the first regimen, Combivir (zidovudine and lamivudine), was not FDA approved until September 26, 1997.[9] The turning point in therapeutics began in 1996, when data presented at the 11th International Conference on AIDS in Vancouver, British Columbia, Canada, represented HIV as a highly efficient virus, producing 10 billion virions per day. Several key publications followed, illustrating the substantial benefit of three agent-based highly active antiretroviral therapies.[10] Although multiagent therapy was quickly incorporated into clinical practice and eventually established as the standard of care, this principle was first supported by expert opinion and guidelines-not necessarily the package insert. In most instances, payers reimbursed these off-label combinations and the Ryan White Comprehensive AIDS Resources Emergency (CARE) Act provided support. A loud and vocal advocacy campaign provided the necessary impetus for this outcome.

Experience With Hepatitis B

Before the approval of entecavir and tenofovir for hepatitis B virus (HBV), the combination of adefovir and lamivudine was used to control HBV resistant to monotherapy, as well as to prevent the development of resistance in those considered at high risk. Tenofovir, commercially available as an approved drug for HIV, was used off label in the management of hepatitis B well before the FDA approved the drug for this indication. Truvada (tenofovir in combination with emtracitabine) continues to be used off label in the management of HBV. Clinical guidelines advocate for off-label combinations of these medications to manage resistant HBV.[11]

HCV Therapy May Be Different

Although there is precedent for off-label therapy in many diseases, HCV has unique considerations. First, unlike HIV, in patients without advanced fibrosis there is often no urgency to initiate therapy. Progression to clinically significant disease in HCV often takes decades, and patients and providers may be less willing to take on the risk of off-label treatment when an approved regimen is only months to years away. Second, for many patients, the current standard-of-care HCV treatment is safe and offers high rates of SVR. Alternatively, drug-resistant HBV, HIV, and many cancers may have limited, if any, FDA-approved treatments, making an off-label therapy the only option. Finally, there is not the same intensity of HCV advocacy as there had been for HIV, a pivotal factor in swaying third-party reimbursement.

Practical Considerations in Off-Label Use of DAAs

How Much Supporting Data Will Be Required?

Off-label use of upcoming DAAs will certainly occur; however, the degree of utilization will rely on availability of safety and efficacy data. One emerging source of data may come from prospective observational studies, such as HCV TARGET and CUPIC. These multicenter studies enroll large numbers of patients undergoing HCV therapy and have the potential to capture vast amounts of off-label therapeutic data. If a high level of evidence from observational studies or well-controlled clinical trials is available, it is possible that off-label combinations may be advocated by authoritative guidelines from well-respected academic associations. More likely, especially in understudied populations, robust data will not be available. In these cases, providers and patients will have to determine their minimal threshold of safety and efficacy data to initiate off-label therapy without the assistance of guidelines or a package insert. Treatment based on limited data will require extensive communication and understanding of therapeutic options between the patient and provider.

What Will Be the Role of Industry and How Will It Be Regulated?

Although prescribing practices are unregulated, industry promotion of off-label use is highly restricted. Pharmaceutical companies are required to submit final promotional materials to the FDA for review at the time of public dissemination. Off-label promotion in these materials is strictly prohibited and is subject to FDA regulatory action. In contrast, the FDA has taken a more lenient position on activities that fall under the safe harbor of Òscientific exchangeÓ of information. Recent guidelines allow for industry dissemination of scientific literature of non-FDA-approved drug use, provided it is in an unabridged form, published in a peer-reviewed journal, and accompanied by a clear statement that indicates the study involves off-label use of a given therapy.[12] Another potential outlet for marketing will be industry-sponsored continuing medical education activities, which may include nonpromotional discussion of off-label use of a therapy. Both of these practices are already highly utilized in the HCV therapy market and will likely increase in volume as new agents prepare to come to market and are approved. Providers who treat HCV will encounter vast amounts of data presented in these formats that are unregulated by the FDA and will be required to critically evaluate the quality and utility of these data before integrating it into clinical practice.

Reimbursement of Off-Label Therapy

Opportunities for off-label HCV treatment with newer DAAs will only be realized if payers reimburse drug costs. Because most health plans rarely publicize policy regarding off-label reimbursement, there tends to be heterogeneity among plans with regard to reimbursement procedures. In general, the likelihood of reimbursement can be thought of as a continuum in which FDA-approved use has the highest probability of reimbursement; mention of an off-label use in society guidelines, compendia, or peer-reviewed literature are less likely to be reimbursed, and expert opinions of off-label use, including data presented in non-peer-reviewed abstract form being least likely to be reimbursed. This continuum is affected by both cost of drug and availability of therapeutic alternatives. In 2009, 34 third-party payers representing approximately one quarter of Medicare and Medicaid beneficiaries nationwide were surveyed regarding practices in off-label reimbursement.[13] Approximately 25% of these payers refused payment for off-label therapy of any kind. Of those who did reimburse off-label therapy, data sources that were felt to be Òvery importantÓ in determining eligibility for reimbursement included peer-reviewed literature (74%), clinical practice guidelines (53%), and cost-effectiveness data (21%). In instances where off-label reimbursement was allowed, restrictions of use were reported to be imposed 85% of the time. Examples of restrictions included requirement for previous authorization, step therapy (i.e., failing less costly treatment first), and quantity limits.

Off-label uses of therapies supported by high-quality evidence and seen as standard of care are more likely to be reimbursed by payers. The competitive development of HCV therapy is unique and may uncover exceptions to this rule. First, the rapid progress of the HCV therapeutic pipeline combined with the chronic nature of HCV and a highly effective standard-of-care therapy may deincentivize payers to reimburse off-label treatment when similar FDA-approved therapeutic regimens are projected to be only months away. For example, payers may be reluctant to allow for payment for both simeprevir and sofosbuvir based on the COSMOS trial when IFN-free regimens, offering similar safety and efficacy data, are under consideration for FDA approval in the near future.[14]In addition, as newer agents continue to minimize toxicity and optimize efficacy, payers will be less likely to reimburse potentially costly off-label regimens that offer only incremental benefits of efficacy, safety, or duration of therapy. Finally, because price will be independently negotiated on a per-drug basis, mixing different agents may skew cost/efficacy ratios and threaten to increase financial burden to payers.

Off-label HCV therapy will offer a unique opportunity for providers to use innovative combinations of drugs to treat patients in need; however, this treatment will come at a cost. To mitigate this cost, we can expect increasing payer requirements to justify off-label use. Ironically, third-party payers may become a de facto regulatory body by making decisions on which off-label regimens will be allowed.

Summary

The availability of new DAAs will provide unprecedented opportunities for off-label HCV therapies in many patients. These patients will include those who are unwilling to take, or intolerant of, IFN and those in need of HCV therapy with no other treatment options. For many, this will ultimately be tempered by FDA-approved all-oral options, but until that time, patients, prescribers, and payers will struggle in an environment where more questions exist than answers. There are no rules, and thus there will be little consistency. Historical precedent only serves as proof of concept. Hepatitis C therapy is not offered under the Ryan White CARE Act rules, and as a consequence, HCV treatment will certainly become polarized. No standard for the minimal amount of safety and efficacy data exists, and in many cases, providers will make treatment decisions without the support of the FDA or treatment guidelines. Patient communication, critical evaluation of available evidence, and meticulous management of off-label treatment recipients will be of paramount importance as we enter into the next era of on- and off-label DAA therapy.

Posted: 04 May 2014 02:02 PM PDT

Originally published in The Washington Post

By Julie Appleby, Published: May 2

Simple math shows the challenge facing U.S. taxpayers, patients and insurers following the launch late last year of two expensive new drugs to treat hepatitis C.

If all 3 million people estimated to be infected with the virus in the United States were treated with the drugs, at an average cost of $100,000 per person, the amount spent for all prescription drugs in the country would double, from about $300 billion in a year to more than $600 billion.

That prospect has inspired an unusually blunt public debate: Should such treatments — one drug costs $1,000 a pill — be limited to the sickest patients, or should the drugs be immediately available to everyone? And should those in taxpayer-funded programs have the same access?

“These are, at their core, ethical fights,” said Arthur Caplan, director of the bioethics division at New York University Langone Medical Center.

The issues are especially contentious because the drugs, Sovaldi by Gilead Sciences and Olysio by Janssen Therapeutics, are an advance in treatment and offer a cure for many people; they are not just medicines that ease symptoms or extend life.

“The more definitive the cure, the closer we are to asking, ‘What’s the value of a human life?’ ” said Tony Keck, director of Medicaid in South Carolina, where the treatments are covered case by case.

This is not an isolated predicament. Specialty drugs account for less than 1 percent of all prescriptions but more than a quarter of spending. Other high-cost specialty medicines in the pipeline include treatments for high cholesterol and diabetes, which affect tens of millions of people.

“This is the tip of the iceberg,” said Steven Pearson, president of the nonprofit Institute for Clinical and Economic Review. “We have about a year or two as a country to sort this out” before more specialty drugs hit the market.

For now, the question is how broadly public and private insurers will make the hepatitis drugs available. As they finalize their guidelines, many are looking to recommendations from expert groups.

A panel from the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America called the drugs an advance and said they should be the preferred treatments for most of those infected with the virus.

“We just put down the best regimen for the individual,” said Gary Davis, a hepatitis expert and panel co-chairman. “We recognize cost issues are really important, but we are clinicians, not the people who should be addressing that.”

But in April, a panel for the Department of Veterans Affairs offered a different take, suggesting that doctors should use the drugs mostly for patients with advanced liver disease, including those awaiting transplants. The VA panel said most patients at early stages of the disease should consider waiting for drugs now in development that may prove superior. Analysts expect those drugs to be available within a year or two.

Sovaldi and Olysio “should be used because they have a high clinical benefit, but not everyone needs to be treated immediately,” said Rena Fox, a VA panelist and professor of medicine at the University of California at San Francisco.

Prioritizing treatment for those with advanced liver disease was also suggested by the California Technology Assessment Forum, a panel sponsored by the Blue Shield of California Foundation that advises insurers, providers and patients.

They noted that drugs expected out this fall may prove superior because they will not require the use of interferon, a drug that can have debilitating side effects.

Even so, Ryan Clary, executive director of the National Viral Hepatitis Roundtable, a patient group, lambastes such limits as “absolutely, rationing.” His group, which receives funding from the drug industry, wants the treatments to be broadly available. “There are plenty of reasons a person with hepatitis C would like to have the virus out of their body,” he said. “To say, ‘We want you to hold off until you start to get sick,’ is really problematic.”

The hepatitis drugs are not the most expensive drugs on the market, but their cost is of concern because of the large number of people infected with the virus.

Sovaldi costs $84,000 for a 12-week treatment, although some patients will need to take the drugs for 24 weeks. Olysio is about $66,000 for a 12-week treatment but is approved for fewer types of patients. Other drugs must often be used with the two new products, adding to the cost.

In the United States, drugmakers set prices based on development costs, as well as on what the market will bear, with companies demanding higher returns for products that have little or no competition. Until they lose patent protection, brand-name drugs in the United States often are able to garner the highest prices in the world. Prices generally fall sharply once generic rivals hit the market.

The drugmakers defend the pricing, saying the drugs are curative and can prevent the need for other costly care, such as liver transplants. “Gilead believes the price of Sovaldi is fair based on the value it represents to a larger number of patients,” Gilead spokeswoman Michele Rest said.

Demand has been strong. On April 22, Gilead reported that Sovaldi sales hit $2.3 billion in the first quarter, a record-breaking launch for a drug.

Insurers and consumer advocates hope increased competition will result in lower prices for the next round of hepatitis C drugs, but that is by no means guaranteed.

Because hepatitis C produces few symptoms in the beginning, most people do not even know they have it. Thus, fewer than 20 percent of those estimated to have the virus have sought treatment with the older regimens.

More patients are expected to be diagnosed, however, as health officials urge baby boomers to get tested. The blood-borne virus is spread mainly by intravenous drug use, although many people were unknowingly infected by poorly sterilized medical equipment and blood transfusions before widespread screening of the blood supply began in 1992.

Policymakers say the cost of treating even half of those infected could raise premiums for everyone with private insurance.

In an earnings call last month, UnitedHealthcare, one of the nation’s largest insurers, said it spent $100 million on hepatitis C treatments in the first quarter of the year, far more than it had expected.

Like many private insurers, United covers the drug broadly, following medical societies’ recommendations, although some of its plans may charge patients higher co-payments for the drugs.

Because many of those infected are low-income, in prison or aging baby boomers, the spending could fall hardest on taxpayer-funded health programs such as Medicaid and Medicare.

This “has the potential to throw a wrench into short-term state budgets,” said Matt Salo, head of the National Association of Medicaid Directors.

Medicaid programs, for the most part, are still setting coverage rules. In Texas and elsewhere, Medicaid will not cover the drugs until guidance comes through.

Other states have completed initial reviews. Florida, for example, placed Sovaldi on its preferred drug list, while Pennsylvania officials will seek public comment on draft rules requiring patients to show some liver damage, get a prescription from a specialist and have their treatment overseen by a case manager to qualify.

The price poses a quandary. “For the price of Sovaldi for one patient, we could provide health insurance through Medicaid for [up to] 26 people for an entire year,” said J. Mario Molina, chief of Molina Healthcare, with Medicaid plans in 10 states. “No question it is a very efficacious drug. But it’s just who gets it and when.”

Molina is holding off on offering the drug in many cases while it seeks answers from state officials about whether they will cover this year’s costs, which were not built into Molina’s contracts.

Waiting is not unusual for hepatitis patients. Many delayed treatment because the options were problematic.

Older regimens were complex to administer, had to be taken for longer periods and were less effective. So there is pent-up demand for the new drugs.

But it is highly unusual to ask patients to wait for a treatment already on the market.

“When you think of diabetes, high blood pressure, cancer or other conditions, there aren’t many where there is a serious discussion of whether treatment should be given,” said David Thomas, a medical societies’ panel member and director of infectious diseases at Johns Hopkins University. “There’s no safety issue, so ‘Does it cost too much?’ is the only question left.”

He said cost questions need to be debated “with all the vested parties at the table, not just the doctor with a patient.”

Yet, doctors increasingly are asked to pay attention to cost, at the risk of a loss of trust by their patients, NYU’S Caplan said.

“That’s a shot directly across the bow of the traditional notion that my physician is my advocate, that they look out for me,” he said. “And don’t worry about the national debt or the fact that Medicare will go broke in 20 years. They worry about me.”

Goshen, NY – In observance of May’s Hepatitis Awareness Month, health officials are calling for all U.S. baby boomers – the generation born from 1945 through 1965 – to get a one-time test for the hepatitis C virus. Viral hepatitis is a leading infectious cause of death in the U.S. The Orange County Department of Health along with the US Centers for Disease Control and Prevention (CDC) will observe National Hepatitis Awareness Month this May. In addition, National Hepatitis Testing Day is observed each year on May 19.

“This is a good opportunity to create awareness in our communities about a serious health concern,” said Orange County Executive Steve Neuhaus.

Hepatitis C is a contagious liver disease that ranges in severity from a mild illness lasting a few weeks to a serious, lifelong illness that attacks the liver. It results from infection with the Hepatitis C virus (HCV), which is spread primarily through contact with the blood of an infected person. Today, most people become infected with the HCV by sharing needles or other equipment to inject drugs. Tattooing in unlicensed and unsanitary settings is also a potential source of infection. 

“It has become a serious public health problem,” said Orange County Health Commissioner Dr. Eli Avila. An estimated 3.2 million people in the United States have chronic HCV. Some scientists believe the actual number of people infected with HCV in the United States to be closer to 7 million. Unfortunately, approximately 12,000 people die every year from Hepatitis C-related liver disease.

Orange County Department of Health wants to emphasize that May 19, 2014 is the National Viral Hepatitis Testing Day. Orange County residents should visit their healthcare providers or the Orange County Department of Health’s STD clinics to be tested. Furthermore, it is a new law for physicians to offer the screening and testing to “baby-boomers” during their annual physical or office visit.               

“In New York, I had the privilege of working with the New York State Legislature to help pass the first law in the nation, which mandates healthcare facilities to offer a simple rapid screening test to this age group,” said Dr. Avila.

It is very important to screen and test for this kind of hepatitis because many who are infected with the HCV do not know that they have it until it is too late. However, unlike other viral diseases, there are actual cures for people with HCV if identified early during the disease. Presently, the cure rate is about 84% with current therapy. Dr. Avila encourages HCV screening for the following:

• All people born between 1945 and 1965
• People who currently inject drugs, injected drugs in the past, even if it was just once or occurred many years ago
• Those who have or had a sexually transmitted disease
• People who have/had multiple sexual partners
• HIV infected individuals and people with abnormal liver tests or liver disease
• Anyone who received donated blood or organs before 1992
• Individuals who have been exposed to blood on the job through a needle stick or injury with a sharp object
• Those on hemodialysis (a process that uses a man-made membrane (dialyzer) to: remove wastes, such asurea, from the blood; restore the proper balance of electrolytes in the blood; eliminate extra fluid from the body.
• Everyone that had tattoos or body piercings done in informal settings or with possibly non-sterile instruments

“It is beneficial to be proactive with your health. See your healthcare provider and get screened today,” said County Executive Neuhaus.

For more information about Hepatitis C testing, contact Orange County Department at 845-291-2330. For more information about Hepatitis C, please visit: www.cdc.gov/hepatitis/c/.