HCV Next: The Challenge Of Treating Genotype 3

HCV Next

Good morning folks, in case you missed it the following articles appeared in the September 2014 print edition of HCV Next published online at Healio.

"HCV Next" offers information on a range of topics, which include diagnosis, new combination therapies, side effects, drug/drug interaction, guidelines, fatty liver disease and more.

COVER STORY

The Challenge of Genotype 3
For many clinicians, genotype 3 now presents the greatest challenge in the treatment and management of patients with hepatitis C virus.

In a recent paper published in the Journal of Viral Hepatology, HCV Next Editorial Board member Nezam H. Afdhal, MD, and Elliot B. Tapper, MD, from Beth Israel Deaconess Medical Center, called genotype 3 “potentially the most difficult-to-treat genotype and an area of intense research for new drug development.”

EDITORIAL

HCV Next Now Delivered Monthly
This has been a landmark year for the care of patients with hepatitis C virus. The development of new drugs is rapidly changing the treatment landscape and important news is released almost daily about different regimens and combinations, improved protocols and screening processes, and more.

FEATURE
A Goal to Improve the Continuum of HCV Care
New treatment options and mandated screening of baby boomers should translate into a flood of new patients with hepatitis C virus entering the health care system, but adoption of new guidelines is often slow in health care. With a goal of achieving sustained virologic response in as many people living with hepatitis C virus as possible, the clinical community faces the challenge of identifying and keeping them engaged in the health care system, from initial visits through the cure of infection.

THE BIG PICTURE
HCV: A Systemic Disease with Extrahepatic Features
Hepatitis C virus infection is known to be associated with chronic hepatitis, cirrhosis and hepatocellular carcinoma. However, HCV can have serious consequences for other organ systems as well. Extrahepatic HCV-associated disorders include cardiovascular, central nervous system, dermatological, endocrine, renal and rheumatologic diseases.

Ira M. Jacobson, MD
HCV RX
Challenges with Pharmacotherapy of HCV/HIV Coinfection
Hepatitis C virus infection is common among individuals already infected with HIV, affecting about one-third of patients. Experts anticipate this number may increase given the shared risk factors for acquisition of both infections. In fact, a proportional rise in the sexual transmission of HCV has been observed since antiretroviral therapy (ART) became widely available in the mid-1990s, possibly reflecting longer duration and improved quality of life, and perhaps a perception of fewer risks associated with unprotected sexual intercourse while receiving treatment for HIV. However, blood exposure remains the most efficient mode of infection, which explains the very high incidence, more than 90%, of HCV coinfection and injection drug use in the HIV-positive population.

TREND WATCH
Gaps in HCV Care Identified in US

First All-Oral Interferon- and Ribavirin-Free HCV Therapy Approved in Japan
Bristol-Myers Squibb announced in July that the Japanese Ministry of Health, Labor and Welfare approved daclatasvir, a potent, pan-genotypic NS5A replication complex inhibitor, and asunaprevir, an NS3/4A protease inhibitor, for patients with hepatitis C virus.

The Daklinza and Sunvepra Dual Regimen is Japan’s first all-oral, interferon- and ribavirin-free treatment option for patients with HCV genotype 1 infection, including those with compensated cirrhosis, according to a press release.

Grant Aids Researchers Studying Patients Cured of HCV
Doctors from the Perelman School of Medicine at University of Pennsylvania and Massachusetts General Hospital will co-direct a $12 million grant to study patients who have been effectively cured of hepatitis C virus infection.

FDA: New HCV Therapies Create Better Alternatives for Patients
IN THE JOURNALS

Therapeutic advances in the treatment of hepatitis C virus infection have greatly increased a patient’s chance for a cure and at a faster rate, according to a consumer update from the FDA.

Genotype 1 Most Prevalent Worldwide
Hepatitis C virus genotype 1 is the most prevalent genotype and accounts for 83.4 million infections, or 46.2% of all cases, worldwide, according to a study published in Hepatology.

MK-5172 with PEG-IFN/Ribavirin, Effective, Safe
The protease inhibitor MK-5172 in combination with pegylated interferon and ribavirin was safe and effective for the treatment of patients with hepatitis C virus without cirrhosis.

Patients with HIV, HCV Showed Spontaneous HCV Clearance during ART
Three patients with hepatitis C virus and HIV coinfection spontaneously became negative for HCV RNA while undergoing antiretroviral therapy, and all had the IL28B CC genotype, researchers in Sweden reported.

PHOTON-1: Sofosbuvir, Ribavirin Combo Yielded High SVR in Coinfected Patients
A majority of treatment-experienced and treatment-naive patients with hepatitis C virus and HIV coinfection achieved sustained virologic response after treatment with combination sofosbuvir and ribavirin, according to results from the PHOTON-1 study published in JAMA.

Study Predicts HCV Will Become Rare Disease by 2036
Effective drugs and screening could make hepatitis C virus a rare disease in the United States by 2036.

5 QUESTIONS

A Conversation with Camilla S. Graham, MD, MPH

In this issue, HCV Next asks five questions of Camilla S. Graham, MD, MPH, assistant professor of medicine at Beth Israel Deaconess Medical Center and Harvard Medical School.

Weekend Reading - Prioritizing Patients for HCV Therapy: The Case for Treating Before Advanced Disease

Hello everyone, enjoying this lovely weekend? Today, Nana will be taking in a movie with my short people, we are going to see "The Boxtrolls" can't wait, or can I?

Anyway, our friends at Clinical Care Options (CCO) have released slides from their recent satellite symposium in San Francisco, with expert commentary on the use of direct-acting antiviral HCV therapy in liver transplantation patients.

Click here to begin.

Redefining Best Practices in HCV Management in the Transplant Setting
In this downloadable slideset, Norah Terrault, MD, MPH, leads a review of a series of cases with Jean C. Emond, MD, and Paul Y. Kwo, MD, evaluating the optimal use of available HCV therapies in the pretransplantation and posttransplantation patients.

Key Challenges in HCV Management in the Transplant Setting
In this downloadable slideset, Jean C. Edmond, MD, offers insight into managing HCV in pretransplant and posttransplant patients.

Interferon-Free HCV Therapy in the Transplant Setting
In this downloadable slideset, Paul Y. Kwo, MD, reviews current and forthcoming options for interferon-free treatment of pretransplantation and posttransplantation patients with HCV.

Prioritizing Patients for HCV Therapy: The Case for Treating Before Advanced Disease
In addition, Nancy Reau, MD., offers commentary on the cost of treating HCV, why patients may wait to start therapy, and liver-related effects (extrahepatic manifestations) seen in certain individuals living with this sometimes life threatening disease. See the article provided below.

A quick free registration is required to view links provided in the article, and to download slides.

Of Interest:

Over at NATAP, Mr. Jules Levin has provided slides from the AASLD/EASL Special Conference, which took place in NY this month. On the topic of extrahepatic manifestations in relation to HCV therapy, I thought this was of interest;

Most patients with HCV-associated lymphoma present with mild liver disease at cancer diagnosis: A call to revise indications for HCV treatment

Check it out, here. View all reports from the conference, here.

Prioritizing Patients for HCV Therapy: The Case for Treating Before Advanced Disease 

by Nancy Reau, MD

Chronic hepatitis C virus (HCV) infection is clearly associated with significant liver-related morbidity and mortality, but HCV infection can also cause life-threatening effects outside of the liver, such as vasculitis, renal failure, and malignancies. Those infected with HCV have higher all-cause mortality rates, including higher mortality from cerebrovascular and kidney diseases. The risk for insulin resistance is also increased, and in those with established diabetes, HCV infection increases the risk of cardiovascular and renal events. 

Fortunately, HCV is curable, and cure decreases the risk for liver-related mortality, liver cancer, and insulin resistance and lowers all-cause mortality. So why would any patient choose not to receive therapy?

Past Reasons for Treatment Deferral
Traditionally, HCV treatment has involved undesired adverse effects that, at the least, can affect quality of life—for some, significantly so. Many individuals have deferred therapy, choosing to live with a disease that can be deadly but is often asymptomatic or minimally symptomatic for many years.

However, current HCV therapy includes well-tolerated, highly efficacious, all-oral options. Treatment duration is rarely longer than 12 weeks and expected cure rates exceed 90% for most patients. Given these vast improvements in treatment options, why do we continue to see delays in therapy initiation?

The Impact of Access on Treatment Rates
The answer is access. Namely, access to insurance coverage of these new drugs is a limiting step in initiating treatment for many patients. Current all-oral options cost in excess of $100,000 in the United States. In my practice, it is not rare for individuals seeking approval from their insurance companies to be denied coverage, unless they have well-established advanced disease. It is undeniable that those with advanced disease urgently need treatment. However, eradicating disease when fibrosis is already advanced is not preventive care, as cure at this stage does not eliminate all risk of future complications. Despite successful therapy, patients with cirrhosis will require long-term monitoring for liver cancer and manifestations of decompensated cirrhosis. This subset of patients is still the most likely to use future healthcare resources, especially those who are unlucky enough to develop hepatocellular carcinoma despite cure of their HCV. The cost of liver transplantation is estimated at $500,000 without considering the associated costs of subsequent lifelong immune suppression. Local-regional cancer management is expensive, and studies have confirmed that those with cirrhosis, especially decompensated cirrhosis, require more hospitalizations.

Costs Associated With Treatment Deferral
Deferral of therapy may increase risk to those not considered to be a priority. For instance, HCV treatment could prevent the onset of diabetes, improve glycemic control, and prevent diabetes-associated complications. Similar to cardiovascular prevention, HCV eradication should be an important aspect to risk reduction. In addition, once extrahepatic manifestations of HCV occur, such as vasculitis, they do not always improve with elimination of the virus.

Studies also suggest that healthcare utilization may not be solely linked to disease stage and that patients in earlier stages of disease still use resources in terms of disease management and monitoring. Deferral of therapy may also mean deferral of costs. Notably, between 2001-2010, inpatient care for those infected with HCV cost $15 billion; 71% of admissions involved patients born in the CDC-identified birth cohort (individuals born between 1945-1965).

The Impact of Reduced Access on Patients
Limited access to therapy is frustrating for patients, who face being told that there is a curative therapy but access to treatment cannot be gained until severe consequences develop that are preventable but possibly not reversible. Ideal timing of therapy is nebulous but certainly occurs before significant fibrosis or debilitating extrahepatic manifestations emerge.

Your Thoughts?
I want to hear from you on this issue. How do you believe access to HCV therapy should be managed, and how are you managing it in your practice? I encourage readers throughout the world to share your insights and challenges in the comments section below. 

Topics: HCV - Treatment

If you haven't read this article; New Hepatitis C Drugs and Faulty Journalism, by Lucinda K. Porter, RN., I hope you consider taking the time to review it.

See you all soon.

Tina

CHMP Adopts Positive Opinion for Gilead's Harvoni® (Ledipasvir/Sofosbuvir) for the Treatment of Chronic Hepatitis C Infection in Adults

European CHMP Adopts Positive Opinion for Gilead's Harvoni® (Ledipasvir/Sofosbuvir) for the Treatment of Chronic Hepatitis C Infection in Adults

Date(s): 26-Sep-2014 7:18 AM

FOSTER CITY, Calif.--(BUSINESS WIRE)--Sep. 26, 2014-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency, has adopted a positive opinion on the company's Marketing Authorization Application (MAA) for Harvoni®, an investigational once-daily tablet combining the NS5A inhibitor ledipasvir (LDV) 90 mg and the nucleotide analog polymerase inhibitor sofosbuvir (SOF) 400 mg, for the treatment of chronic hepatitis C virus (HCV) infection in adults.

The CHMP opinion was adopted following an accelerated review procedure, which is reserved for medicinal products that are expected to be of major public health interest. The CHMP's recommendation will now be reviewed by the European Commission, which has the authority to approve medicines for use in the 28 countries of the European Union.

The CHMP positive opinion for Harvoni is supported by data from three Phase 3 studies (ION-1, ION-2 and ION-3). These studies evaluated 8, 12 or 24 weeks of treatment with Harvoni, with or without ribavirin, among nearly 2,000 genotype 1 HCV patients with compensated liver disease. These studies included cirrhotic and non-cirrhotic patients who were new to HCV treatment and those who had failed prior therapy with an interferon-based regimen, including regimens containing an HCV protease inhibitor. The positive opinion was also supported by preliminary data from the SOLAR-1 trial in decompensated cirrhotic and pre- and post-transplant patients, the ELECTRON-2 trial in genotype 3 patients and phase 2 studies in genotype 4 patients.

Approximately nine million people in Europe are infected with the hepatitis C virus, a major cause of liver cancer and liver transplantation. Genotype 1 is the most prevalent form of HCV in Europe, and accounts for 60 percent of infections worldwide. This is followed by genotypes 2 and 3, while genotypes 4-6 are more prevalent in Asia and Africa.

Sofosbuvir as a single agent was granted marketing authorization in the European Union on January 16, 2014 under the trade name Sovaldi®. Sovaldi is also approved for use in the United States, Canada, Australia, New Zealand, Egypt, Switzerland and Turkey.

Harvoni is an investigational product and its safety and efficacy have not been established in the European Union.

About Gilead Sciences

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

Forward-Looking Statement

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the risk that the MAA may not be approved by the European Commission, and marketing approval, if granted, may have significant limitations on its use. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead's Quarterly Report on Form 10-Q for the quarter ended June 30, 2014, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

Sovaldi and Harvoni are registered trademarks of Gilead Sciences, Inc., or its related companies

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


Source: Gilead Sciences, Inc.

Gilead Sciences, Inc.
Patrick O'Brien, +1 650-522-1936 (Investors)
Cara Miller, +1 650-522-1616 (Media, U.S.)
Arran Attridge, +44 208 587 2477 (Media, EU)

Ledipasvir/Sofosbuvir - Gilead Submits NDA to Japan’s PMDA

Gilead Submits New Drug Application to Japan’s Pharmaceutical and Medical Devices Agency for Fixed-Dose Combination of Ledipasvir/Sofosbuvir for Chronic Hepatitis C Genotype 1 Infection

FOSTER CITY, Calif., Sep 24, 2014 (BUSINESS WIRE) -- Gilead Sciences, Inc. GILD, -1.26% today announced that the company has submitted a New Drug Application (NDA) to Japan’s Pharmaceutical and Medical Devices Agency (PMDA) for approval of an investigational once-daily fixed-dose combination of the NS5A inhibitor ledipasvir (LDV) 90 mg and the nucleotide analog polymerase inhibitor sofosbuvir (SOF) 400 mg for the treatment of chronic genotype 1 hepatitis C virus (HCV) infection in adults. The data submitted in the NDA, which include a Japanese Phase 3 study showing 100 percent SVR12 rates, support the use of LDV/SOF for 12 weeks in treatment-naïve and treatment-experienced patients with chronic genotype 1 HCV infection, including those with cirrhosis. Patients who achieve SVR12 are cured of HCV infection. If approved, LDV/SOF would simplify HCV treatment for genotype 1 patients in Japan to one daily tablet, eliminating the need for interferon and ribavirin (RBV).

Primarily due to HCV, Japan has one of the highest rates of liver cancer of any industrialized country. Of the more than one million people in Japan chronically infected with HCV, 70-80 percent are infected with the genotype 1 strain of the virus.

The NDA is based on data from a Phase 3 clinical trial conducted in Japan (GS-US-337-0113) among 341 treatment-naïve and treatment-experienced genotype 1 patients. In the study, 100 percent (n=83/83) of treatment-naïve and 100 percent (n=88/88) of treatment-experienced patients receiving 12 weeks of LDV/SOF without RBV achieved SVR12. Adverse events observed with LDV/SOF without RBV were generally mild and included nasopharyngitis (28 percent), headache (6 percent) and malaise (5 percent).

The NDA is also supported by SVR12 results from three Phase 3 studies (ION-1, ION-2 and ION-3) evaluating eight, 12 or 24 weeks of LDV/SOF among genotype 1 HCV patients. Trial participants included patients from the United States, Europe and Puerto Rico who were treatment-naïve or who had failed previous treatment, including protease inhibitor-based regimens, and also included patients with compensated cirrhosis. Trial participants in the ribavirin-free arms (n=863) achieved SVR12 rates of 94 to 99 percent.

LDV/SOF is currently under regulatory review in the United States and European Union.

On June 27, 2014 Gilead submitted an NDA to Japan’s PMDA for SOF as a single agent in combination with RBV for the treatment of genotype 2 HCV infection. SOF as a single agent has been approved by regulatory authorities in the United States, European Union, Australia and Canada under the tradename Sovaldi®.

LDV/SOF and SOF are investigational products in Japan and their safety and efficacy have not yet been established.

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

Forward-Looking Statement
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the possibility of unfavorable results from additional clinical trials involving SOF or the LDV/SOF fixed-dose combination. Further, the PMDA and regulatory authorities in the United States and the European Union may not approve the LDV/SOF fixed-dose combination and the PMDA may not approve SOF as a standalone agent in Japan, and any marketing approvals, if granted, may have significant limitations on their use. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2014, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

U.S. full prescribing information for Sovaldi is available at www.gilead.com.

Sovaldi is a registered trademark of Gilead Sciences, Inc.

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

Liver injury from herbals and dietary supplements may be rising in some parts of US

Liver injury from herbals and dietary supplements may be rising in some parts of US

Last Updated: 2014-09-22

By Will Boggs MD

NEW YORK (Reuters Health) - Liver injury from herbal medicines and dietary supplements appears to be on the rise in some parts of the country, according to data from the U.S. Drug-Induced Liver Injury Network (DILIN).

"More research is needed to identify more accurately what supplements, or ingredients thereof, cause liver injury and why," Dr. Victor J. Navarro from Einstein Medical Center in Philadelphia told Reuters Health by email. "Also, regulators must take note that current regulation of dietary supplements leans more toward protection of the manufacturer than the consumer."

About half of the U.S. adult population say they use herbals and dietary supplements, and there have been recent cases of life-threatening hepatotoxicity associated with the use of at least one of them (OxyElite Pro).

Dr. Navarro and colleagues examined the burden and characteristics of liver damage attributed to these products in the DILIN and compared the injuries with those caused by conventional medications. They excluded all cases related to acetaminophen, which account for the vast majority of medication-induced liver injuries.

The researchers defined liver injury as jaundice or coagulopathy in the presence of liver enzyme abnormalities or elevations of ALT or AST above five times the upper limit of normal or elevations of alkaline phosphatase above two times the upper limit of normal on two consecutive measurements at least 24 hours apart.

As for causality, medications were considered individually, whereas all herbals and dietary supplements taken by any patient were grouped together and adjudicated as a single agent, even if several were taken concurrently.

Ultimately, the analysis included 839 patients whose "definite," "very likely," or "probable" liver injuries were reported in the 10 years between 2004 and 2013. Most of these injuries (85%) were attributed to medications, and the rest were chalked up to herbals or dietary supplements.

The researchers divided those taking herbals and supplements into two groups based on whether they took the substances for bodybuilding purposes (45/130) or not (85/130).

During the first two years, cases attributed to herbals and dietary supplements accounted for 7% (eight cases) of the non-acetaminophen liver injuries. By the end of the study period, they accounted for 20% (63 cases in three years).

Liver transplantation was required more commonly in the nonbodybuilding supplements group (13%, 12 cases) than in the medications group (3%, 21 cases).

Based on the DILIN severity score, people taking herbals and dietary supplements had more severe cases than did those on conventional medications, the researchers report in Hepatology, online August 25.

The 130 patients in the herbals and dietary supplements group reported taking a total of 217 products, with only a minority of those products having a single ingredient and with 10% (bodybuilding) to 13% (nonbodybuilding) of the products containing more than 20 ingredients.

"Contrary to widespread belief, this study demonstrates that herbals and dietary supplement products are not always safe," the researchers conclude. "Indeed, our data suggest that, relative to conventional medication-induced hepatotoxicity, liver injury from herbal and dietary supplements not only occurs, but also may be increasing in frequency over time in the populations surrounding the DILIN centers and, probably, in the United States as a whole."

"The DILIN is not a population-based study, and although there was an increasing proportion of disease attributable to herbals and dietary supplements during the study, it cannot be concluded that the problem is actually on the rise in the United States," they add.

"Ask patients if they use supplements and always suspect them to be a cause for any unusual presentation, liver disease or otherwise," Dr. Navarro concluded.

How can patients protect themselves from supplement-related liver injury? "First, discuss their use with a qualified physician who understands their specific medical history and has knowledge of their other medications," Dr. Navarro suggested. "Second, if they choose to use supplements, they should stay within the labeled recommendations. Last, they should report any new symptoms to their doctor."

Dr. Rolf Teschke from Goethe University Frankfurt/Main in Germany, who studies medication-related liver toxicity, said most herbals and dietary supplements carry some risk of liver toxicity.

The risk is small but unpredictable, he told Reuters Health by email, and may be related to genetic susceptibility.

"Physicians often are confronted with patients who have increased liver values of primarily unknown etiology," Dr. Teschke said. "Apart from questioning regarding synthetic drugs as possible cause, the use of herbals and dietary supplements should be excluded by thorough investigation and repetitive questionings, since they are considered as natural and thereby perceived erroneously as safe."

He also criticized DILIN's causality assessments for not being quantitative.

"Other experts in the field worldwide prefer the use of the scale of CIOMS (Council for International Organizations of Medical Sciences), which is liver specific, structured, and quantitative based on specific items which are individually scored by -3 to +3 points, while the sum of the individual scores provides the respective causality grading," Dr. Teschke said. "The CIOMS scale can easily be applied already at the bedside of the patient, with results quickly available without the time-consuming expert-based procedure."

"Herbal and dietary supplements commonly are mixtures of multiple ingredients which prevent a clear causality assessment to one single ingredient," Dr. Teschke said. "The DILIN method is not prepared assessing various comedicated compounds, as opposed to the CIOMS scale, which facilitates such assessment."

SOURCE: http://bit.ly/XNJwxK

Hepatology 2014.

Treatment of Hepatitis C Virus Infection: Is It Time for the Internist to Take the Reins?"

Ideas and Opinions | 16 September 2014, Ann Intern Med.
Source - NATAP
 
Shyam Kottilil, MD, PhD; Mary Wright, MD, MPH; Michael A. Polis, MD, MPH; and Henry Masur, MD
 
For the first time since the identification of hepatitis C virus (HCV) in 1988, communitywide eradication of HCV infection seems possible. With the U.S. Food and Drug Administration's approval in late 2013 of simeprevir and sofosbuvir, 2 direct-acting oral anti-HCV drugs, the time has come to launch major initiatives to reduce the effect of this infection on individuals and on our communities. Who should lead the charge to initiate and manage treatment: subspecialists, internists, or both?
 
Globally, 230 million persons are infected with HCV, including 2.7 to 3.9 million persons in the United States (1-2). Spontaneous resolution occurs in only 20% of HCV-infected individuals, and many chronically infected persons progress to cirrhosis (20% over 25 years) and develop hepatocellular carcinoma (20% of cirrhotic patients). Over the past 2 decades, HCV infection was treated first with parenteral interferon-α alone, then with pegylated interferon-α plus oral ribavirin, and more recently with oral boceprevir or telaprevir added to pegylated interferon plus ribavirin. Although each successive regimen incrementally reduced long-term complications of HCV infection, the regimens were lengthy (24 to 48 weeks), were only modestly effective, and were poorly tolerated (often because of depression and anemia and leukopenia). Thus, fewer than 10% of eligible patients have received treatment (3-4).
 
In addition to simeprevir and sofosbuvir, many direct-acting oral anti-HCV drugs are in late development stages. Direct-acting regimens without interferon and ribavirin, administered for only 6 to 12 weeks, have yielded response rates greater than 90% with excellent tolerability and safety (5-7). These results are stunning triumphs for translational medicine if further trials confirm and extend these findings, although much remains to be learned about specific host, viral, and drug factors that influence treatment outcomes. The Infectious Diseases Society of America and the American Association for the Study of Liver Diseases have jointly released recent dynamic online clinical guidance for providers that accommodates rapid updates ( www.hcvguidelines.org).
 
Internists have long played a unique and critical role on the forefront of HCV infection care by counseling, testing, and identifying patients with this disease. However, for treatment, most patients have been referred to hepatologists. If a cure for and communitywide eradication of HCV infection become realistic goals, will there be enough subspecialists to treat all infected patients? Is subspecialty expertise necessary for managing all HCV-infected patients?
 
Overseeing treatment of HCV infection in 2 to 4 million persons in the United States would probably overwhelm the country's 1800 hepatologists. Even if all 7000 practicing infectious disease subspecialists in the United States focused on this disease, it would not be sufficient. The subspecialist workforce would be overtaxed even if the 2 to 4 million persons eligible for treatment were prioritized to begin therapy over 5 to 10 years.
 
As treatment of HCV infection becomes more straightforward and does not require invasive diagnostic tests, such as liver biopsy, internists can and should take a more active role in treating most patients except those with advanced cirrhosis. Subspecialty referral should be unnecessary for many HCV-infected persons, especially those without advanced fibrosis, severe extrahepatic manifestations of HCV infection, or substantial comorbid conditions.
 
Once criteria are developed for subspecialist referral and prioritization of treatment, internists should be able to quickly develop the expertise to screen for relevant HCV-drug-resistance mutations, assess stage of liver disease, and determine which patients require subspecialist care and which patients with uncomplicated HCV infection they can treat using breakthrough drugs. Thus, internists should be leaders in this unprecedented opportunity to cure this chronic and morbid viral disease.
 
Internists, subspecialists, and public health authorities will need to work together to address barriers to adherence-as well as such issues as emergence of viral resistance-and the effect of reinfection, cost, and access (8). Finding funds to launch and operationalize widespread testing programs, persuade asymptomatic persons to be tested, link infected individuals to stable medical care, provide psychosocial support to patients with special needs, and persuade patients to receive therapy for an infection that often remains completely asymptomatic will pose considerable challenges.
 
We can learn from our 25 years of experience with HIV and AIDS. Our successes in reducing the effect of this infection in the United States have had some notable victories, but far more success is needed in important areas. Only 25% of HIV-infected patients are receiving stable care and have suppressed viral loads (9), which is sobering.
 
However, the HIV and HCV infection epidemics have some prominent differences. HIV requires lifelong therapy. In contrast, the ability to cure a life-threatening HCV infection with only 6 to 12 weeks of therapy is likely to make programmatic successes far easier in this condition than in HIV and AIDS. Internists must be leaders in educating all stakeholders about these opportunities and in transition ensuring the from patient identification to patient cure and community eradication (7).
 
Even if testing and linkage to care were readily available for all infected persons, the cost of acquisition for the new direct-acting oral anti-HCV drugs is sobering. The current market price for 1 recommended regimen, simeprevir plus sofosbuvir for 12 weeks, is $150 000 (10). Whether this price is cost-effective, let alone affordable or reasonable, requires careful analysis.
 
Patients with early disease could be counseled and monitored for years instead of being treated immediately. However, although market competition may decrease drug acquisition costs and multidrug combination regimens may allow progressively shorter regimens, it will be important to identify patients who need treatment sooner rather than later and thus those for whom current drug costs are warranted.
 
Treatment of HCV infection has entered a new era in which the cure of individual patients is eminently feasible and communitywide eradication is conceivable. A robust debate is accelerating about whom and when to treat and what fraction of our resources should be devoted to HCV infection. As advocates for their patients and communities, internists must have a strong voice in this debate to assure that those patients in imminent danger of HCV infection-related illness can access these promising drugs. The time for internists to embrace delivering therapeutic interventions for HCV infection in their practices is now.

Australia: Government refuses subsidy for hepatitis C medication, Sovaldi

Government refuses subsidy for hepatitis C medication, Sovaldi

MORE than 630 Aussies are dying from liver failure caused by hepatitis C each year but a government committee has rejected an $84,000 treatment that could cure them.

And it’s possible the residents of Fiji could access the breakthrough drug before Australian patients.

Breakthrough drug Sovaldi could see the scourge of hepatitis C - currently afflicting 230,000 Australians - eventually wiped out because it cures the disease and prevents it from being passed on.

Around a third of those on the nation’s liver transplant waiting list have hepatitis C and the treatment would free up those organs for others.

However, the Government’s Pharmaceutical Benefits Advisory Committee has rejected the medicine for subsidy because it says it too expensive and “would have a high financial impact on the health budget”.

A new treatment for hepatitis C - which does not have to be used in conjunction with the side-effect-prone interferon treatment - is likely to be available soon.

The PBAC says “patients are most likely waiting for the availability of interferon-free regiments”.

The medicine, which retails for $1000 per pill in the United States, is expected to be offered cheaper to Australia but the size of the population that needs to be treated makes it expensive.

It could cost close between $1.3 billion and $2 billion just to treat the people who already have the disease.

Gilead, the pharmaceutical company that makes the drug, is poised to allow licences for cheaper generic versions of the medicine for use in India and Fiji where they can’t afford the price being asked in the developed world.

Hepatitis Australia chief executive Helen Tyrrell says “there is a likelihood that Fiji will have access to the drug before Australia”.

Professor Alex Thompson, director of gastroenterology at St Vincent’s Hospital in Melbourne says Sovaldi is a significant advance on current treatments.

“This disease could become rare or non-existent, you could be talking about eradication,” Dr Thompson said.

“This is a game changing medicine; it’s transforming health care, it’s life saving and we need to make these drugs available, there is no question,” he said.

Current treatments have cure rates of only 70-80 per cent compared to the 90 per cent cure rate for Sovaldi.

Sovaldi has a treatment time of just 12 weeks while current treatments using interferon can take up to 44 weeks.

Current treatments which include the antiviral drug interferon also have significant side effects including brain fogginess, hair loss and auto-immune problems.

Some people can’t use interferon, others stop because of the side effects and just 2,500 Australians seek treatment every year.

Liver failure caused by hepatitis C currently costs the health system $100 million a year and it will become even more expensive as people who contracted hepatitis C 30-40 years ago progress to liver failure

“If you have a cure for a condition like hepatitis C it is inhumane not to make it available,” says Helen Tyrrell.

Source

ledipasvir/sofosbuvir - Gilead Signs generic licensing agreement for hepatitis C drug

Gilead Announces Generic Licensing Agreements to Increase Access to Hepatitis C Treatments in Developing Countries

Date(s): 15-Sep-2014 6:30 AM

-- Indian companies granted license to produce generic sofosbuvir and investigational single tablet regimen of ledipasvir/sofosbuvir for treatment of chronic hepatitis C --

NEW DELHI--(BUSINESS WIRE)--Sep. 15, 2014-- Gilead Sciences, Inc. (Nasdaq:GILD) today announced that the company has signed non-exclusive licensing agreements with seven India-based generic pharmaceutical manufacturers to expand access to its chronic hepatitis C medicines in developing countries. The agreements allow the companies - Cadila Healthcare Ltd., Cipla Ltd.,Hetero Labs Ltd., Mylan Laboratories Ltd., Ranbaxy Laboratories Ltd., Sequent Scientific Ltd. andStrides Arcolab Ltd. - to manufacture sofosbuvir and the investigational single tablet regimen of ledipasvir/sofosbuvir for distribution in 91 developing countries

The countries within the agreement account for more than 100 million people living with hepatitis C, representing 54% of the total global infected population.

"Hepatitis C is a significant public health issue worldwide, and Gilead is working to make its chronic hepatitis C medicines accessible to as many patients, in as many places, as quickly as possible. In developing countries, large-volume generic manufacturing and distribution is widely regarded as a key component in expanding access to medicines. These agreements are essential to advancing the goals of our humanitarian program in these countries," commented Gregg H. Alton, Executive Vice President, Corporate and Medical Affairs, Gilead Sciences.
Under the licensing agreements, the Indian companies receive a complete technology transfer of the Gilead manufacturing process to enable them to scale up production as quickly as possible. The licensees also set their own prices for the generic product they produce, paying a royalty on sales to Gilead to support product registrations, medical education and training, safety monitoring and other essential business activities. The licenses also permit the manufacture of sofosbuvir or ledipasvir in combination with other chronic hepatitis C medicines.

Sofosbuvir was approved under the trade name Sovaldi^® by the U.S. Food and Drug Administration(FDA) in December 2013 and by the European Commission in January 2014. The FDA and theEuropean Medicines Agency are currently reviewing the company's applications for a single tablet regimen of ledipasvir/sofosbuvir; it is an investigational agent and its safety and efficacy have not been established.

For a fact sheet on the agreement, visit www.gilead.com.

Gilead's Approach to Treatment Access in Developing Countries
Gilead makes it a priority to increase access to its medicines for people who can benefit from them, regardless of where they live or their economic means. In developing countries, Gilead's treatment access strategies include tiered pricing, voluntary generic licensing (often in advance of U.S./EU regulatory approval), negotiation with national governments, regional business partnerships, product registration, medical education and partnerships with non-profit organizations. This approach has been successfully applied to Gilead's humanitarian program in HIV over the past ten years, with six million patients now receiving Gilead-based HIV medicines in developing countries.