Abbvie Demonstrates 96 Percent SVR(12) in its Phase III Study of Treatment-experienced Patients with Genotype 1 Hepatitis C

-RESULTS FURTHER CONFIRM PHASE II STUDIES, WITH CONSISTENT VIROLOGIC RESPONSE AND TOLERABILITY PROFILE-

- SAPPHIRE-II IS THE SECOND OF SIX PHASE III TRIALS STUDYING THE INVESTIGATIONAL 3D REGIMEN-

- FUTURE DATA ANTICIPATED FROM ABBVIE'S CLINICAL TRIALS EXAMINES 3D REGIMEN WITH AND WITHOUT RIBAVIRIN, AS WELL AS TREATMENT OF HEPATITIS C IN PATIENTS WITH CIRRHOSIS-

Dec 10, 2013

NORTH CHICAGO, Ill., Dec. 10, 2013 /PRNewswire/ -- AbbVie (NYSE: ABBV) released phase III results for the investigational three direct-acting-antiviral (3D) regimen plus ribavirin in patients with chronic, genotype 1 (GT1) hepatitis C virus (HCV) infection. In the 394-patient SAPPHIRE-II study, 96 percent of patients who previously failed pegylated interferon and ribavirin treatment, including approximately 49 percent of who were prior null responders, achieved sustained virologic response at 12 weeks (SVR₁₂) with the regimen. The majority of patients were GT1a, considered a difficult-to-treat subtype, and the SVR₁₂ rates of GT1a and GT1b were 96 percent and 97 percent, respectively. Virologic relapse or breakthrough was noted in 2 percent of patients receiving the 3D regimen plus ribavirin. In addition, the discontinuation rate due to adverse events was 1 percent.

Globally, approximately 160 million people are chronically infected with hepatitis C[1]. AbbVie's multinational HCV program is the largest all-oral, interferon-free clinical program in GT1 patients being conducted to date[2]. GT1 (with subtypes 1a and 1b) is the most prevalent genotype worldwide, with a higher prevalence of 1a in the U.S. and 1b in Europe.

"SAPPHIRE-II demonstrates that treatment-experienced genotype 1 HCV patients achieved high rates of virologic response with AbbVie's interferon-free, all-oral 3D regimen plus ribavirin," said Scott Brun, M.D., vice president, pharmaceutical development, AbbVie. "Completion of the two placebo-controlled SAPPHIRE studies is an important step in AbbVie's HCV clinical development program.  We look forward to the results of studies looking at AbbVie's 3D regimen with and without ribavirin in different patients, as well as data from our dedicated study in patients with cirrhosis."

About Study M13-098 (SAPPHIRE-II)

Following SAPPHIRE-I, SAPPHIRE-II is the second placebo-controlled trial and the second of six phase III trials supporting AbbVie's investigational 3D regimen for the treatment of GT1 hepatitis C patients. AbbVie will disclose detailed SAPPHIRE-II results at future scientific congresses and in publications.

SAPPHIRE-II is a global, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 12 weeks of treatment with ABT-333 (250mg), ribavirin (weight-based), both dosed twice daily, and the fixed-dose combination of ABT-450/ritonavir (150/100mg) co-formulated with ABT-267 (25mg) and dosed once daily in non-cirrhotic, GT1a and GT1b HCV-infected, treatment-experienced adult patients who previously failed treatment with pegylated interferon and ribavirin.

The study population consisted of 394 GT1 treatment-experienced patients with no evidence of liver cirrhosis with 297 patients randomized to the 3D regimen plus ribavirin for 12 weeks, and 97 patients randomized to placebo for the initial 12 weeks. Patients initially randomized to placebo for the first 12 weeks then received open-label treatment with the 3D regimen plus ribavirin for 12 weeks. In the study, 49 percent of patients were prior null responders to pegylated interferon and ribavirin, generally considered among the most difficult to treat successfully.

Following 12 weeks of treatment with AbbVie's 3D regimen plus ribavirin, 96 percent (n=286/297) of patients achieved SVR₁₂ based on intent-to-treat analysis where patients with missing values for any reason were considered treatment failures. The SVR₁₂ rates in GT1a and GT1b patients were 96 percent (166/173) and 97 percent (119/123), respectively. One subject had HCV genotype 1 and achieved SVR₁₂, but was unable to be subgenotyped.

The most commonly reported adverse events in both the 3D and placebo arms were headache, fatigue and nausea. Discontinuations due to adverse events were reported in three (1 percent) patients receiving the 3D regimen and no patients receiving placebo. Virologic relapse or breakthrough was noted in 2 percent of patients receiving the 3D regimen plus ribavirin.  

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

AbbVie's HCV Development Program

The clinical program supporting our 3D regimen includes more than 2,300 GT1 patients in more than 25 countries around the world. The AbbVie HCV clinical development program is intended to advance scientific knowledge and clinical care by investigating an interferon-free, all-oral 3D regimen with or without ribavirin 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. Results from the remaining four studies in AbbVie's phase III program will be available in the coming months, supporting regulatory submissions starting in the second quarter of 2014.

Overview of AbbVie's phase III clinical program is as follows:

Overview of AbbVie's phase III clinical program is as follows:

Study	Patients (N)	Treatment Regimen	Treatment Duration
SAPPHIRE-I	GT1, treatment-naive (631)	ABT-450/rb +ABT-267c ABT-333 Ribavirin	12 weeks
		Placebo	12 weeks, then active treatment for 12 weeks
SAPPHIRE-II	GT1, treatment-experienced (394)	ABT-450/r +ABT-267 ABT-333 Ribavirin	12 weeks
		Placebo	12 weeks, then active treatment for 12 weeks
PEARL-II	GT1b, treatment-experienced (210 a)	ABT-450/r +ABT-267 ABT-333 Ribavirin	12 weeks
		ABT-450/r +ABT-267 ABT-333	12 weeks
PEARL-III	GT1b, treatment-naive (400 a)	ABT-450/r +ABT-267 ABT-333 Ribavirin	12 weeks
		ABT-450/r +ABT-267 ABT-333 Placebo	12 weeks
PEARL-IV	GT1a, treatment-naive (300 a)	ABT-450/r +ABT-267 ABT-333 Ribavirin	12 weeks
		ABT-450/r +ABT-267 ABT-333 Placebo	12 weeks
TURQUOISE-II	GT1, treatment-naive and treatment-experienced (with compensated cirrhosis) (380 a)	ABT-450/r +ABT-267 ABT-333 Ribavirin	12 weeks
		ABT-450/r +ABT-267 ABT-333 Ribavirin	24 weeks

^a projected study population

^b ABT-450/ritonavir

^c ABT-267 is co-formulated with ABT-450/r, administered as two pills once daily

The 3D regimen consists of boosted protease inhibitor ABT-450/ritonavir, NS5A inhibitor ABT-267, and non-nucleoside polymerase inhibitor ABT-333. The combination of three different mechanisms of action interrupts the HCV replication process with the goal of optimizing SVR rates across different patient populations. In May of 2013, AbbVie's investigational 3D regimen with and without ribavirin for HCV GT1 was designated as a Breakthrough Therapy by the U.S. Food and Drug Administration (FDA).

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, automimmune hepatitis, hemoglobinopathies, or in combination with peginterferon alfa-2a in HIV/HCV co-infected patients with cirrhosis and Child-Pugh score ≥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. 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. In 2013, AbbVie employs approximately 21,000 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.

[1] Lavanchy D. Evolving epidemiology of hepatitis C virus. Clin Microbiol Infect. 2011; 17(2):107-15. 

[2] Comparison based on review of data from clinicaltrials.gov for phase 3a programs of Gilead, BMS and BI as ofNovember 15, 2013

SOURCE AbbVie Inc.

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, or For Investor Relations: Elizabeth Shea, +1 (847) 935-2211, elizabeth.shea@abbvie.com

Source

Simeprevir is now available for Hepatitis C patients in Japan, USA and Canada

Stockholm, Sweden—Medivir AB (OMX: MVIR) Based on the recent approvals in Japan, Canada and USA, simeprevir is now available in all three markets. Simeprevir is administered once-daily for 12 weeks in combination with pegylated interferon and ribavirin, followed by pegylated interferon and ribavirin alone for an additional 12 or 36 weeks.

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 8.30 a.m. CET on 10 December 2013.

About Simeprevir
Simeprevir is an NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB for the treatment of chronic hepatitis C infection in combination with other antivirals in HCV genotype 1 & 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 and has now been launched in all three markets. 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 or genotype 4 chronic hepatitis C.

To date, more than 3,700 patients have been treated with simeprevir in clinical trials. Simeprevir is also being studied in several interferon-free regimens using selected combinations of direct-acting antiviral agents with different mechanisms of action.

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 health and quality of life.

Source

Diabetes Identified as Risk Factor for Liver Cancer Across Ethnic Groups

Dec. 9, 2013 — Diabetes was associated with an increased risk for developing a type of liver cancer called hepatocellular carcinoma, and this association was highest for Latinos, followed by Hawaiians, African-Americans, and Japanese-Americans, according to results presented here at the Sixth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved, held Dec. 6-9.

"People with diabetes have a two- to threefold higher risk for hepatocellular carcinoma compared with those without diabetes," said V. Wendy Setiawan, Ph.D., assistant professor in the Department of Preventive Medicine at Keck School of Medicine of the University of Southern California. "We also found that the interethnic differences in the prevalence of diabetes were consistent with the pattern of hepatocellular carcinoma incidence observed across ethnicities: Ethnic groups with a high prevalence of diabetes also have high hepatocellular carcinoma rates, and those with a lower prevalence of diabetes have lower hepatocellular carcinoma rates."

The number of new cases of hepatocellular carcinoma in the United States tripled in the past three decades, with Latinos and African-Americans experiencing the largest increase in incidence. Prior research has suggested that diabetes may be a risk factor for hepatocellular carcinoma, and its increasing incidence may be contributing to the rising rate of hepatocellular carcinoma.

"People with diabetes should be aware that their condition is associated with a higher risk of developing hepatocellular carcinoma," Setiawan said. "Maintaining a healthy weight, managing their diabetes, preventing and treating hepatitis infection, and limiting alcohol and tobacco use should be in their priority to-do list."

In addition, Setiawan said that public health efforts encouraging obesity/diabetes prevention and effective diabetes management should be directed at high-risk populations.

Setiawan and colleagues examined if the association between diabetes and hepatocellular carcinoma differed by race/ethnic group. They analyzed data from more than 150,000 people enrolled in the Multiethnic Cohort Study between 1993 and 1996. During the study follow-up period of about 15 years, 506 cases of hepatocellular carcinoma were reported: 59 cases in non-Hispanic whites, 81 in African-Americans, 33 in Hawaiians, 158 in Japanese-Americans, and 175 in Latinos.

Compared with non-Hispanic whites, Latinos had 2.77 times the risk for being diagnosed with hepatocellular carcinoma, the highest risk identified. Native Hawaiians had 2.48 times the risk; African-Americans, 2.16; and Japanese-Americans, 2.07.

The prevalence of diabetes was consistent with that of hepatocellular carcinoma. Sixteen percent of Hawaiians, 15 percent of Latinos and African-Americans, 10 percent of Japanese-Americans, and 6 percent of non-Hispanic whites had diabetes. Compared with those without diabetes, Latinos with diabetes had 3.3-fold higher risk for hepatocellular carcinoma; Hawaiians, 2.33-fold higher risk; Japanese-Americans, 2.02-fold higher risk; African-Americans, 2.02-fold higher risk; and non-Hispanic whites had 2.17-fold higher risk.

Hepatocellular carcinoma was attributed to diabetes in 26 percent of cases in Latinos, 20 percent of Hawaiians, 13 percent of African-Americans, 12 percent of Japanese-Americans, and 6 percent of non-Hispanic whites, the researchers estimated. According to Setiawan, eliminating diabetes could potentially reduce hepatocellular carcinoma incidence in all racial/ethnic groups, with the largest potential reduction possible in Latinos.

Story Source:

The above story is based on materials provided by American Association for Cancer Research (AACR).

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

A Better Treatment for Hepatitis C

Provided by The New Yorker

DECEMBER 9, 2013

POSTED BY CELINE GOUNDER

Two years ago, the pharmaceutical company Gilead Sciences paid eleven billion dollars for Pharmasset, a small biotechnology firm based in New Jersey. Pharmasset did not have a single major drug on the market, but the company had developed a drug called sofosbuvir, which promised to do for hepatitis C what protease inhibitors did for H.I.V. in the mid-nineties: transform a hard-to-treat illness into an easily managed disease. The Food and Drug Administration officially approved sofosbuvir, also known by the brand name Sovaldi, last week, six years after it was first synthesized. It is now all but guaranteed to become a blockbuster drug and generate billions of dollars in sales for Gilead.

Hepatitis C, the target of sofosbuvir, is behind what the magazine’s Jerome Groopman described as a “shadow epidemic” of liver disease and cancer: rates of liver cancer are increasing faster than rates for any other type of cancer in the United States. Hepatitis C, which inflames and scars the liver, is thought to account for half of this rise. Worse, up to three quarters of the three million Americans who are infected with hepatitis C are not aware of it. By the time they become symptomatic, they may have been infected for decades. All the while, the hepatitis-C virus has been silently doing its terrible work. About a third of the six thousand Americans who get liver transplants each year now do so as a result of hepatitis C, as the late Lou Reed did.

Hepatitis C is one of a number of viruses that infect the liver. It, along with hepatitis B and D, are transmitted through sex and blood exposure. There is no vaccine for it. In 1998, the Centers for Disease Control and Prevention began recommending screenings for hepatitis C based on risk and exposure. But, because patients don’t always own up to or remember their potential exposures, and because many physicians are embarrassed to ask patients about drug use and sex, the C.D.C. now recommends that all Americans born between 1945 and 1965—the baby boomers, who make up three-quarters of those infected—also be screened. Even so, many clinicians remain reluctant to test patients, because the treatment is so difficult to endure.

The existing treatment regimen involves weekly injections of a substance called interferon combined with other drugs. Interferon is naturally produced by the body to combat viral infections; it’s what makes you feel tired, feverish, and generally miserable when you have the flu. In the treatment of hepatitis C, it boosts the immune system. But the injections have brutal side effects: reduced appetite and hair loss, and, over long periods of time, anemia, fatigue, and depression. If the side effects of interferon don’t sound bad enough, the other drugs often cause more anemia, fatigue, chills, nausea, vomiting, diarrhea, hair loss, and rash.

The months of misery do not guarantee that the patient will emerge cured, either, since some strains of hepatitis C—there are six genotypes—are more responsive to current treatment than others. Because hepatitis C and H.I.V. are transmitted similarly, patients are often infected with both, which further complicates treatment because of toxicities, drug interactions, and difficulties getting the doses right.

Sofosbuvir, on the other hand, is the first hepatitis-C treatment that does not require interferon injections, can be taken simply as a pill with other drugs—like the antiviral ribavirin—and typically works in a fraction of the time of existing treatment cycles. According to Alan Franciscus, the executive director of the Hepatitis C Support Project, a patient-advocacy group that educates patients and clinicians about hepatitis C, “Sofosbuvir has the potential to change the treatment of hepatitis C because of the ease of use—one-pill-a-day therapy, very high cure rates, shorter treatment duration, and fewer side effects.” After enduring his own year and a half of interferon treatment before finally being cured of hepatitis C, “I am a bit envious,” Franciscus admitted.

Sofosbuvir was invented by, and named after, Michael Sofia, the kind of person who daydreams about enzymes metabolizing drugs. Sofia was raised in a rowhouse on the northeastern side of Baltimore. His parents, a barber and a payroll clerk, were both children of Italian immigrants, and born within a block of each other in Baltimore’s Little Italy. Although they instilled an immigrant’s appreciation for education in their three children, who would all go on to work in science, Sofia’s reading skills were so poor as a child that in the fourth grade he was put in a remedial reading class. Sofia credits the nun who taught him with transforming into a “completely different student.”

Sofia eventually enrolled at Cornell and went on to earn his Ph.D. from the University of Illinois, before leaving academia to focus on drug development. Early in his career, at Squibb, he worked on cholesterol-lowering drugs. But he preferred working at small biotech companies, which function more like Internet startups, to Big Pharma. “You have an idea, you discuss it, you make a decision, you move forward,” Sofia explained to me. So, in 2005, Sofia took a risk and joined Pharmasset, then a minor biotech firm.

When Sofia arrived at Pharmasset, the company had already started moving away from the H.I.V.-drug development that it was initially known for, since the market had become saturated with “nucleoside” drugs that worked reliably with manageable side effects. Nucleosides are the building blocks of D.N.A. and R.N.A.; they can be chemically altered to terminate chains of genetic code early, producing something like a defective Lego that can’t be build onto, stopping the growth of the virus. Though this chemistry had been used successfully to treat H.I.V., only a few labs were trying this approach with hepatitis C. Sofia noted that one of the company’s test drugs, PSI-6130, showed activity against hepatitis C.

Sofia realized that any effective hepatitis-C drug not only needed to get into the liver, where the virus was replicating, but stay there, to avoid unintended side effects elsewhere in the body. It is relatively easy to transport a drug to the liver: when you eat or drink something, it is absorbed into the bloodstream by the stomach and intestines, and in turn flows directly to the liver, the body’s metabolic engine. The problem is that, in their active form, nucleoside drugs don’t enter liver cells. Sofia hypothesized that if he could shroud a nucleoside with an “invisibility cloak” to get it into liver cells he could then count on the liver’s enzymes to break down the cloak and activate the drug. Once the cloak has been shed, the nucleoside would be trapped inside, protecting the rest of the body from exposure. “A lot of people were telling me when I had this idea that this is never going to work,” he told me. “People have been trying to do this for a long time, this is a hopeless cause.”

Sofia explicitly engineered sofosbuvir with this and a number of other goals in mind—that the drug would be taken orally, ten times more potent than PSI-6130, and effective against all six genotypes of hepatitis C. Beginning with a modified version PSI-6130, after three years of development, Sofia and his colleagues arrived at sofosbuvir in 2007. What’s remarkable, according to Sofia, is that it was not in fact a happy accident, but a product of explicit engineering. “It does exactly what we designed it to do, which is one of those things that hardly ever happens,” he said.

Sofia’s clinical colleagues at Pharmasset began testing sofosbuvir in human patients between 2010 and 2011. When Pharmasset’s medical advisory group reviewed the data, they realized for the first time that sofosbuvir could potentially treat hepatitis patients without interferon—considered a heresy at the time. Since then, others have conducted larger trials of sofosbuvir—studies named POSITRON, FUSION, FISSION, NEUTRINO, and VALENCE, playing on the idea that sofosbuvir is a nucleotide—which showed that the drug is effective against all six genotypes of hepatitis C, with minimal side effects. Last month, at The Liver Meeting in Washington, D.C., scientists presented studies showing that sofosbuvir could also help cure hepatitis C in harder-to-treat patients, like those who also have H.I.V. or more advanced liver disease. There will be more studies of sofosbuvir to come, including post-marketing trials that will look for previously undetected side effects—as well as research on how sofosbuvir can best be used in combination with other new drugs in the pipeline.

Sofosbuvir does have limits, however. The first genotype of hepatitis C has always been the most difficult to treat, and remains so, even with the advent of sufosbuvir. Most patients infected with that genotype still need a combination of interferon injections and ribavirin, at least until other, new drugs hit the market, which is anticipated to happen in the next year or two. More problematically for the hundred and fifty million people worldwide who suffer from hepatitis C, Franciscus and other advocates are worried that sofosbuvir and other new drugs in the pipeline may be too expensive. Gilead announced that the wholesale cost of sofosbuvir will be a thousand dollars a pill, with the total cost of treatment easily exceeding a hundred thousand dollars per patient. Insurance companies, meanwhile, may only cover treatment for hepatitis-C patients who already have liver damage.

Following the acquisition in 2011, Sofia worked with Gilead for about a year to manage the transition process, a time he doesn’t recount fondly. “When you develop something and you take very personal ownership of it, and see it move on to where you’re no longer involved in a direct way to what’s happening to that drug,” Sofia said, “well, it’s very difficult to go through that.”

Afterward, Sofia and some of his old Pharmasset colleagues started a new company, OnCore BioPharma, to develop cures for hepatitis B. Hepatitis B is another leading cause of liver cancer, and is far more transmissible from mother to child, during pregnancy and birth, than hepatitis C; many who succumb to hepatitis B were infected as infants. Currently, we only have drugs that suppress hepatitis B, but you may have to take them for the rest of your life to keep the virus in check.

I asked Sofia what he’d be calling his next drug. “I consider myself very lucky to have one drug, he replied. “When I was doing undergraduate research at Cornell, I was told that I had to be comfortable with failure because eighty per cent of what you’re going to do is going to fail.”

Celine Gounder is a physician, public-health specialist, and medical journalist.

Photograph: David Paul Morris/Bloomberg via Getty

Source

Physician Views: FDA throws up surprise labelling for Gilead Sciences' hepatitis C treatment Sovaldi – will it boost first year uptake?

Provided by FirstWord Pharma

(Ref: Physician Views Desk)
December 9th, 2013
By: Simon King

Confirmed late on Friday, FDA approval of Gilead Sciences' hepatitis C therapy Sovaldi (sofosbuvir) has been highly anticipated.

Nevertheless, the company managed to spring a surprise on both investors and rivals by securing labelling for Sovaldi as an all-oral therapy – in combination with ribavirin – for the large genotype 1 patient population (estimated 75 percent of US patient pool), when dosed over 24 weeks among patients who are deemed to be ‘ineligible’ to interferon.

This outcome is particularly surprising, noted International Strategy & Investment analyst Mark Schoenebaum, as Gilead had provided no indication that data to support this particular labelling had been submitted to the FDA. Expectation instead was for sofosbuvir to only be approved in genotype 1 patients in combination with interferon and ribavirin.

Excluding interferon from the equation may theoretically boost the number of genotype 1 patients whom are treated with a sofosbuvir regimen in 2014, prior to the anticipated launch of all-oral therapies (such as Gilead's sofosbuvir + ledipasvir fixed-dose combination) at the end of next year. Particularly as a number of earlier FirstWord Physician Views polls had already suggested significant enthusiasm for the more unfavourable sofosbuvir+ interferon + ribavirin combination anyway.

Physician Views: Entering the post-interferon era – will Gilead Sciences dominate hepatitis C? and Physician Views: What opportunity for Gilead Sciences' hepatitis C therapy sofosbuvir before interferon-sparing regimens reach the market?

Nevertheless, there are a number of potential barriers to uptake for a genotype 1 sofosbuvir + ribavirin combination in 2014. Schoenebaum points out, for example, that quantifying the number of 'ineligible' interferon patients is difficult; will genotype 1 patients simply refuse interferon as they are aware that an interferon-sparing regimen is now technically available, or will physicians only use this regimen in patients who are known not to be able to tolerate interferon?

Furthermore, with a duration of 24 weeks, the sofosbuvir + ribavirin combination will be priced higher, at an estimated gross cost of around $168,000. This could cause an issue with payers, and Gilead is reportedly offering a patient support programme that will ensure that most commercially insured patients will have no more than a $5 co-pay, which will include patients who are charged larger co-insurance amounts.

In addition, approval for the sofosbuvir + ribavirin combination is supported by a relatively small clinical data set. Therefore, Schoenebaum argues that physicians may be reluctant to prescribe the combination, particularly as Gilead's fixed-dose product – which will be supported by more clinical data at launch and likely cost around $100,000 per patient – is probably some 12 months away.

To help provide some clarity on how this labelling for Sovaldi has been perceived by physicians and how it may influence their prescribing decisions in 2014, FirstWord is polling US-based gastroenterologists/hepatologists and infectious disease specialists on the following 5 questions...

How they perceive Sovaldi’s labelling (permitting combination use with ribavirin only, for a 24-week course of therapy in interferon-ineligible genotype 1 patients) to influence their use in genotype 1 patients during 2014

How they perceive this labelling to impact their treatment of warehoused genotype 1 patients in 2014

What factor would act as the main reason for them not using Sovaldi + ribavirin as a 24-week therapy in genotype 1 patients in 2014

Whether they believe that a genotype 1 patient saying that they did not want to be treated with interferon would constitute that patient to be 'interferon ineligible'

How much influence they expect payers to have on the eligibility of genotype 1 patients to receive the Sovaldi + ribavirin combination, particularly in light of the impending arrival of cheaper, fixed-dose combinations in late 2014/early 2015.

You will be able to read the results and analysis on Thursday.

Results and related analysis will be published for FirstWord Pharma PLUS subscribers to read, with the opportunity for non-FirstWord Pharma PLUS subscribers to purchase these findings.

To be notified when poll results and analysis become available, please click here.

As always, FirstWord would very much like to receive your feedback and suggestions.

Note: FirstWord Polls are powered by MedePolls, a fast-turnaround service to conduct instant polls of up to five questions with guaranteed samples that include physicians from dozens of specialities and over 100 markets. To conduct this poll with a different audience, or an entirely different poll, contact us at info@firstwordpharma.com.

To read more Physician Views articles, click here.

Source

Activists pounce on $1,000-a-day price for Gilead's hep C wonder drug, Sovaldi

Provided by FiercePharma

December 9, 2013 | By Tracy Staton

Doctors and patients have been waiting impatiently for the big FDA approval on Friday: Gilead Sciences' ($GILD) breakthrough hepatitis C treatment sofosbuvir, now dubbed Sovaldi. But so have some of Gilead's fiercest critics, and those groups came out swinging.

No one questions the promise of Sovaldi, the first drug approved to treat hep C patients without the difficult-to-tolerate interferon. The once-a-day pill offers many patients not only a shorter course of treatment but better results, too. That's why doctors have been "warehousing" some hep C patients--in essence, waiting to treat them until Gilead's new drug hit the market.

What's the catch? It's priced at $84,000 per 12-week treatment course. That's $1,000 a day.

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The pent-up demand for Sovaldi, coupled with its steep price, is expected to push sales to $2 billion--not at peak, not even at 5 years out, but next year, its first on the market. As TheStreet points out, that's an unprecedented feat. And one analyst thinks Sovaldi could actually hit $4.5 billion next year, or more than $1 billion per quarter, on average. Try to get your head around that.

But that sort of price tag really riles people like Dr. Jennifer Cohn, medical director of the Doctors Without Borders access-to-medicines campaign. The international healthcare organization is already pushing Gilead to sell Sovaldi on the cheap--$500, including diagnostics--when it's launched in developing countries. Already, the legal activist group Initiative for Medicines, Access & Knowledge has filed an opposition to patent protection for Sovaldi in India, aiming to pre-empt Gilead's pricing power.

"We are very worried that Gilead will charge exorbitant prices in countries that are classified as 'middle-income,' even though they are home to around 75% of the world's poor," Cohn said in a statement. "Using patents to block affordable versions of sofosbuvir and pricing this drug out of reach of the most vulnerable groups who need it most is simply putting profits before people's lives."

Gilead has come under frequent fire for its pricing policies on AIDS treatments. Most recently, Doctors Without Borders and the AIDS Healthcare Foundation--along with a group of Democratic members of Congress--balked at the $28,000-a-year price on Gilead's four-in-one HIV pill Stribild. And that's after years of lobbying from activists looking for price breaks on the drugs.

Gilead has made some moves to open up access to its HIV treatments, including contributing some patents to the Medicines Patent Pool and licensing some drugs to generics makers for sale in India.

Those moves were a long time coming, however, and public health advocates are keen on winning concessions earlier on the hep C side. That's partly because so many patients in the developing world are coinfected with hep C and HIV--and, of course, because Sovaldi is such a big step forward for hep C treatment.

Gilead and plenty of others would argue that the company has spent billions developing the drug and has the right to make money on that investment. The pharma business is a business, after all. Stribild, for instance, has already made impressive progress toward its expected 2018 sales of $3.54 billion. Can Gilead's business interests and patients' interests find balance? That's the ultimate question.

- see the release from Gilead
- read the Reuters news
- check out FiercePharma's approval story
- get more from TheStreet

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J&J Launches HIV Drug Donation Program in Africa

Mon, 12/09/2013 - 10:10am

Janssen, the pharmaceutical companies of Johnson & Johnson, today announced a first-of-its-kind pediatric HIV treatment donation program to improve access to the company's approved HIV medicines for children and adolescents failing HIV treatment in sub-Saharan Africa. At a symposium entitled "When Children Need HIV Treatment Beyond First-Line: How Can We All Respond?" at the 17th International Conference on AIDS and STIs in Africa (ICASA), Ministries of Health (MOHs) in sub-Saharan Africa were invited to submit a formal Expression of Interest to participate in the charitable pediatric HIV treatment donation program.

Through this program, Janssen will donate its HIV medicines Prezista (darunavir) and Intelence (etravirine), including child-friendly formulations, free of charge to eligible countries with the clinical capacity and willingness to address second- and third-line pediatric HIV treatment. Each child enrolled will receive Janssen's donated HIV medicines as needed until they turn 19 at which point they will be transitioned into the adult national HIV program or other designated by the national HIV program for continued treatment.

The donation program is intended to be a first step in a broader collaborative effort to build awareness, incite action, and advance learning around second- and third-line pediatric HIV treatment in sub-Saharan Africa. Janssen is working with the Elizabeth Glaser Pediatric AIDS Foundation, the Partnership for Supply Chain Management (PFSCM), and MAP International to fully maximize the impact and reach of this initiative.

"The donation program is part of our longstanding commitment to help people living with HIV and enhance access to our medicines for those in need. Only a third of the 3 million children living with HIV are receiving medicines today, and of those children receiving treatment, a small but growing number are experiencing HIV treatment failures and are in need of new treatment options," said Paul Stoffels, chief scientific officer, Johnson & Johnson and worldwide chairman, Janssen. "We hope this innovative donation program is the first step in sparking further collaborative action across sub-Saharan Africa for children who are experiencing HIV treatment failure. Our vision is that these children receive the HIV treatment and care they need to stay healthy and grow to become healthy, productive young adults."

Treatment of pediatric HIV remains significantly neglected in sub-Saharan Africa. Responding to the challenge of HIV treatment-experienced children requires a comprehensive effort to help guide countries in the provision of necessary and appropriate care for this neglected population.  This includes improving understanding of the problem, expanding national treatment guidelines beyond first-line, increasing healthcare capacity for pediatric HIV treatment and monitoring, and ensuring that availability of co-administered HIV medicines remains a priority.

The submission period for the Expression of Interest by country MOHs to participate in the drug donation initiative will run from Jan. 15 until Feb. 14, 2014. An independent, third-party review committee of international experts in pediatric HIV will review all applications to determine country eligibility to receive the donation.  Country approvals will be announced in March 2014. Countries interested in more information or submitting an Expression of Interest should visit:www.pedaids.org/treatmentdonation.

Date: December 9, 2013

Source: Johnson and Johnson

Source

Gilead Sciences: A Unique Stallion

Peovided by Seeking Alpha

Dec 9 2013, 11:12  |  about: GILD

Prohost Biotech

Taking down Gilead (GILD) seems to be beyond the reach authors of tales intended to frighten investors into selling this outstanding stock. The attempts have been repetitive but short of success. Gilead is a stallion. Unlike stallions, the horses whose muscular superiority over other horses is genetically derived, Gilead’s power is acquired through a unique culture that embraces the power of intuition, self-confidence, common sense and courage. Using an optimal amount of faith, the firm turned intuition into inspiration and using courage and wisdom, the Stallion carried out inspired tasks fated unattainable by others.

Thanks to the megastar’s contribution in the treatment of AIDS through its mega anti-retroviral pills, millions of desperate AIDS patients’ death sentences are being nullified. The use of multiple highly active antiretroviral therapy (HAART) turned the torturer and killer disease into a chronic disease, decreasing the patient's total HIV burden, preserving the immune system’s function and avoiding the opportunistic infections that used to assume the killer’s role of AIDS victims before the HAART drugs.

Mentioning the firm’s intuition and insight in the beginning of this article was not meant as a crafted artistic text to just praise a firm, but a reality demonstrated in Gilead’s decisions in general. A well-illustrated inspired act, though, is Gilead’s decision to pay an obscene amount of money to buy Sovaldi (sofosbuvir) - the pill that the FDA granted approval a couple of days ago. All analysts, stockholders and all Gilead’s fans, including Prohost believed that the decision made no sense; especially that Gilead has its own drug discovery technology. As the drug was passing the tests of clinical trials and approaching approval, all those who disapproved of the firm’s decision realized how insightful was Gilead and how shortsighted they were.

Recalculating, we grasped the fact that millions of more hopeless HCV infected people who had declined to take previous treatments from fear of side effects will be willing to take the Sovaldi combination that would cure them in a 12-weeks. Assessing the cost of treatment while considering the cost of the untreated progressive HCV infection, the cost of the all-oral combination looked meager in comparison with the cost of the progressive disease, the complication of cirrhosis, including the hospitalization for hemorrhagic episodes, for liver transplant, the cost of transplant complications and of the possibility of HCV infection of the transplanted liver and of cancer. More important is avoiding the cost patients pay in their agony caused by intolerable symptoms, and caused by the expectation of cancer and death.

Regarding the finances, It is estimated that the drug will bring a little less than in $2 billion in revenues during its penetration. The revenues are now expected to reach over $6 billions a couple of years in the future.

Edward Cox, director of the Office of Antimicrobial Products in the FDA’s drug evaluation center, seems to have stated, ““The approval of Sovaldi represents a significant shift in the treatment paradigm for some patients with chronic hepatitis C

Some analysts believe now that the $11 billion Gilead paid for the drug is now estimated to bring in more than $100 billion in sales revenues over a decade.

The sofosbuvir cocktail taken for 12 weeks cured 90 percent of patients with genotypes 1, 4, 5 and 6 who hadn’t been treated before, Sovaldi is also approved for genotypes 2 and 3, which account for as many as 25 percent of infections, in combination with ribavirin.

The stallion has reached the finish line before the other horses. Let’s not talk about other horses now. It is Gilead’s week. When the celebration ends, we will try to find another stallion among the other horses. We are sure we will find a few.

FORWARD-LOOKING: Material presented here is for informational purposes only. Nothing in this article should be taken as a solicitation to purchase or sell securities. Before buying or selling any stock you should do your own research and reach your own conclusion. Further, these are our 'opinions' and we may be wrong. We may have positions in securities mentioned in this article. You should take this into consideration before acting on any advice given in this article. If this makes you uncomfortable, then do not listen to our thoughts and opinions. The contents of this article do not take into consideration your individual investment objectives so consult with your own financial adviser before making an investment decision. Investing includes certain risks including loss of principal.

Disclosure: None

Source

MSF response to the U.S. FDA approval of the drug sofosbuvir, to be marketed by Gilead for the treatment of hepatitis C

Provided by MSF Access Campaign

6 December 2013

Public health groups have moved to block unwarranted patents in India

Pricing in developing countries a serious concern

Sofosbuvir, a ‘direct-acting antiviral’ for hepatitis C, results in significantly higher cure rates in a shorter period of time than current therapy, and for some genotypes of hepatitis C, eliminates the need to use the injectable drug pegylated interferon, which is difficult to administer and causes multiple side effects. Sofosbuvir will be priced exorbitantly, with estimates of up to $80,000 for a 12-week treatment course in the US. While prices in developing countries are still unknown, they are likely to far exceed what patients and governments can afford.

MSF has begun treating several patients in India with hepatitis C (who are co-infected with HIV), using today’s available drugs, but would like to access sofosbuvir for patients in India and several other countries to make expanding treatment in its medical projects feasible.

A ‘patent opposition’ for sofosbuvir was filed in India on 21 November 2013 by the legal group I-MAK, Initiative for Medicines, Access & Knowledge, in an effort to ensure more affordable versions of the drug can be made in India, which is often called the ‘pharmacy of the developing world.’

Further, a recent study released by researchers at Liverpool University at the American Association for the Study of Liver Diseases conference in November found that sofosbuvir is relatively simple and cheap to produce, at $68-$136 for a 12-week treatment course, making the prices Gilead is projected to charge all the more unacceptable.  At the projected price of up to $80,000 per treatment course, it would cost as much as $256 billion to treat all 3.2 million people infected with hepatitis C in the US alone. Even at a fraction of such prices, these drugs will be priced out of reach of governments and millions of people in developing countries.

“This drug is of public health importance but it won’t do much good if it’s unaffordable for the more than one hundred million people with hepatitis C in developing countries. We know from our experience treating HIV in developing countries that treatment must be simple and affordable, so we urge Gilead to act so that a full treatment course plus diagnostics costs no more than $500 in developing countries. We are very worried that Gilead will charge exorbitant prices in countries that are classified as ‘middle-income,’ even though they are home to around 75 percent of the world’s poor.  Using patents to block affordable versions of sofosbuvir and pricing this drug out of reach of the most vulnerable groups who need it most is simply putting profits before people’s lives.”
- Dr. Jennifer Cohn, Medical Director, MSF Access Campaign 

Source

Idenix Pharmaceuticals (Nasdaq:IDIX) Patent Infringement Lawsuit Vs. Gilead Sciences, Progenics Pharmaceuticals (Nasdaq:PGNX) Topline Data From Study

By riddock57

Dec 8, 2013 6:05:21 PM PST

Idenix Pharmaceuticals, Inc. (Nasdaq:IDIX)

Hepatitis means inflammation of the liver. There are many causes of hepatitis. For example, drinking too much alcohol, various drugs and chemicals, and also several different viruses can cause hepatitis.

Hepatitis C, a virus which is carried in the bloodstream to the liver, is one of several hepatitis viruses and is generally considered to be among the most serious of these viruses. Hepatitis C is passed through contact with contaminated blood — most commonly through needles shared during illegal-drug use.

Chronic hepatitis C is a blood-borne infectious disease of the liver that affects approximately 3.2 million people in the United States

On Friday, Gilead Sciences, Inc. reported that the FDA has approvedSovaldi(TM) (sofosbuvir) 400 mg tablets, a once-daily oral nucleotide analog polymerase inhibitor for the treatment of chronic hepatitis C(CHC) infection as a component of a combination antiviral treatment regimen.

The Wholesaler Acquisition Cost (WAC) of a 28-tablet bottle of Sovaldi in the United States is $28,000

IDIX recently reported that it has filed two lawsuits against Gilead: a patent infringement lawsuit in the U.S. District Court in Boston, Massachusetts and a separate patent infringement and interference lawsuit in the U.S. District Court in Wilmington, Delaware.

The Massachusetts infringement lawsuit alleges that Gilead infringes two U.S. patents co-owned byIDIX (6,914,054 and 7,608,597) that cover methods of treating the hepatitis C virus using 2'-methyl nucleosides. In this lawsuit, IDIX is seeking a declaration that Gilead's imminent distribution, importation, use, sale or offer to sell drugs-containing sofosbuvir, a 2'-methyl nucleoside compound, infringes IDIX's patents.

The Delaware infringement and interference lawsuit alleges that Gilead infringes a separate U.S. patent co-owned by IDIX (7,608,600) that covers methods of treating the hepatitis C virus using 2'-methyl-2'-fluoro nucleosides. IDIX is seeking a declaration that Gilead's imminent distribution, importation, use, sale or offer to sell drugs-containing sofosbuvir infringes the IDIX '600 patent. Additionally, the Delaware lawsuit asserts a claim for interfering patents between the IDIX '600 patent and a U.S. patent (8,415,322) owned by a Gilead subsidiary, Gilead Pharmasset LLC. IDIX is seeking to have the Gilead '322 patent declared invalid.

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Despite Increasing Cost Sensitivity of EU5 Payers, Sofosbuvir and Simeprevir are Poised to Reshape the Hepatitis C Virus Market by End of 2015

Developers of New Agents Must Show Superiority Over Marketed Therapies and Expect Tough Pricing and Reimbursement Negotiations, According to a New Report from Decision Resources

BURLINGTON, Mass., Dec. 9, 2013 /PRNewswire/ -- Decision Resources, one of the world's leading research and advisory firms for pharmaceutical and healthcare issues, finds that surveyed gastroenterologists across the EU5 (France, Germany,Italy, Spain and the United Kingdom) anticipate prescribing Gilead's sofosbuvir to approximately 20 percent of their hepatitis C virus genotype 1 (HCV-1) patients and Janssen/Medivir's simeprevir to approximately 7 percent of these patients by the end of 2015. Surveyed specialists also indicated that they expect to prescribe sofosbuvir-based regimens to more than one-third of their HCV-2 and HCV-3 patients in this timeframe. Additionally, with sofosbuvir anticipated to be the first approved drug not requiring combination usage with interferon (IFN) in HCV-2 and/or HCV-3 patients, surveyed physicians expect that close to two-thirds of sofosbuvir-treated patients will receive it as part of IFN-free regimens by the end of 2015.

(Logo: http://photos.prnewswire.com/prnh/20130103/MM36784LOGO)

Currently available first-generation protease inhibitors (Janssen's Incivo and Merck/Roche's Victrelis) and pegylated IFNs (Roche's Pegasys and Merck's PegIntron) receive government reimbursement and coverage in the EU5 markets. However, country-specific cost-effectiveness analyses and prescribing parameters that tie guideline adherence to reimbursement are increasingly being implemented and inform physician prescribing practices. These mechanisms demonstrate the growing importance of health technology assessment, value-based pricing and patient access programs and will continue to be key market access hurdles in the evaluation, reimbursement and uptake of all future HCV therapies.

The new European Physician and Payer Forum report entitled The Impending Inteferon-Free Era of Hepatitis C Virus Treatment: How Will All-Oral Regimens Shape EU5 Prescribing, and What Market Access Challenges Will They Face? also finds that individual European markets have implemented varying mechanisms for aggressively promoting the rational use of HCV medicines, including hospital-based prescribing (France), national online registers to track the use of costly therapies (Italy) and reimbursement oversight boards (United Kingdom).

"The revolutionary developments in the treatment of HCV in the coming years will bring to the market tremendous improvements in efficacy, tolerability and convenience of HCV regimens. However, in the cost-constrained EU5 markets, drug developers will need to balance payer authorities' price expectations with uptake potential for maximum return on investment," said Decision Resources Analyst David Holman, Ph.D. "As competition escalates in the HCV market, budget constraints at regional, local and institutional levels must all be carefully considered."

Manufacturers seeking to penetrate the EU5 HCV market must also optimize pivotal trial design, preferably offering head-to-head comparison against currently marketed protease inhibitors, and should provide thorough cost-effectiveness analyses on their products. Such data is increasingly vital in all EU5 countries as cost-constrained healthcare authorities strive to draw out value for money.

About Decision Resources
Decision Resources (www.decisionresources.com) is a world leader in market research publications, advisory services and consulting designed to help clients shape strategy, allocate resources and master their chosen markets. Decision Resources is a Decision Resources Group company.

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

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

SOURCE Decision Resources

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EASL publishes revised clinical practice guidelines to optimise the management of hepatitis C virus

PUBLIC RELEASE DATE: 9-Dec-2013

Contact: Courtney Lock
easlpressoffice@cohnwolfe.com
44-207-331-5317
European Association for the Study of the Liver

EASL publishes updated clinical practice guidelines to optimise the management of hepatitis C virus infection.

The European Association for the Study of the Liver (EASL) today publishes their revised Clinical Practice Guidelines (CPGs) on the management of hepatitis C virus infection (HCV) (1). The EASL guidelines, which supersede the previous version published in 2011, are designed to help physicians and other healthcare providers optimise their management of patients with acute and chronic HCV.

It is estimated that approximately 160 million individuals, i.e. 2.35% of the world's population, are chronically infected with HCV. In the European Union alone, between 7.3 and 8.8 million people are infected with HCV, double the previous estimate made in 1997. The prevalence varies across the region with higher rates seen in the south and the east, making HCV a critical area of attention for hepatologists as one fifth of HCV-infected patients are at risk of developing cirrhosis or liver cancer (2).

HCV CPG co-chair reviewer and consultant hepatologist at Queen Elizabeth Hospital, Birmingham, Professor David Mutimer said: "As our understanding of HCV increases and therapies evolve, more complex treatment strategies are necessary to achieve the primary goal of curing the infection.

"Since EASL published the last HCV CPG in 2011, two protease inhibitors have been approved for use in patients infected with HCV genotype 1. These first-generation direct-acting antivirals are the first of many direct acting antiviral drugs which will revolutionise treatment for HCV patients, including those who failed to respond to previous therapies. The new guidelines provide essential information on the recommended use of these newly licensed drugs to help prescribers deliver optimal care for their HCV patients."

Based on a systematic review of existing literature, the CPGs provide best practice recommendations on a number of key areas:

• Current standard of care and developing therapies
• Diagnosis of acute and chronic hepatitis C
• Goals and endpoints of HCV therapy
• Indications for treatment and who should be treated
• Treatment strategies for different viral genotypes
• Treatment monitoring including virological response-guided triple, and dual therapy
• Monitoring treatment safety
• Treatment of special groups including HIV co-infection, hepatitis B co-infection and patients with other co-morbidities such as severe liver disease

The guidelines also contain significant discussion about people who inject drugs (PWID*) providing an overview of the published literature relating to the treatment of these patients, and covering issues such as:

• Re-infection following successful HCV treatment in patients at high risk (such as PWID)
• The burden of chronic HCV and advanced liver disease among ageing cohorts of PWID

Professor Mutimer added: "With HCV spread among PWID now accounting for the vast majority of incident cases in developed countries, and with modelling studies suggesting that treatment for PWID could reduce transmission, it is critical that physicians review and adopt these guidelines when managing this important group of patients."

Commenting on the CPGs, EASL Secretary General Professor Markus Peck-Radosavljevic said "EASL is dedicated to promoting hepatology research and education to improve the worldwide treatment of liver disease. As treatment for hepatitis C continues to progress rapidly with the development and approval of new therapies, it's vital to ensure that our series of Clinical Practice Guidelines reflect best practice to drive better clinical outcomes.

"As there have been several key clinical and scientific advances over the past two years, these guidelines build upon the recommendations reported by the EASL HCV panel of experts in 2011. EASL encourage clinicians to refer to these new HCV guidelines for the most up-to-date, evidence based methods to offer patients first class treatment."

###

The guidelines will also be published in the Journal of Hepatology (Vol. 60 Issue. 2 February, 2014) and presented during a session of the International Liver CongressTM 2014 in London (April 9 – 13).

About EASL

EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.

EASL's main focus on education and research is delivered through numerous events and initiatives, including:

The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide

Meetings including Monothematic and Special conferences, Post Graduate Courses and other endorsed meetings that take place throughout the year

Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology

Journal of Hepatology published monthly

Participation in a number of policy initiatives at European level

*PWID refers to recreational drug use

1. Mutimer D. et al. (2013) EASL Clinical Practice Guidelines: Management of Hepatitis C virus infection. Available at http://www.easl.eu/_clinical-practice-guideline

2. Hepatitis. Net Doctor. Available at http://www.netdoctor.co.uk/diseases/facts/hepatitis.htm. Accessed 25 November 2013.

Source

Simeprevir and (Especially) Sofosbuvir Are Great Leaps Forward — and They Will Cost Plenty

HIV and ID Observations

An ongoing dialogue on HIV/AIDS, infectious diseases, all matters medical, and some not so medical

Hepatitis C has been potentially curable for decades, but it’s hardly been easy. “I feel like I’m slowly killing myself,” said one of my patients, memorably, during week 24 of a planned bazillion-week course of interferon-ribavirin. (Actually it was only 48 weeks, but seemed like a bazillion weeks.)

Then in 2011 came the addition of telaprevir or boceprevir to the interferon-ribavirin, which made a cure more likely, but the treatment even worse. Rashes. Need for fatty meals. Tons of pills. Taste disturbance. Anal discomfort. (“Like shitting glass,” another memorable quote.) Anemia. And for the providers, having to manage these side effects and the complex “response-guided therapy” algorithms was no picnic.

Now, with the approval of simeprevir in November and in particular sofosbuvir Friday, HCV cure just got a whole lot easier. Both are one pill a day. Both have far fewer side effects than any existing HCV drug. Sofosbuvir adds the benefit of having almost zero important drug-drug interactions. (Simeprevir has many.)

The main problem with these new treatments is, frankly, their cost. They are very expensive — 12 weeks of simeprevir will be $65,000, of sofosbuvir $80,000. These costs are offset somewhat by reduced need for monitoring with safer therapies, a shorter course of interferon and ribavirin (if you go that route), and presumably down the road, prevented cases of cirrhosis, hepatocellular carcinoma, and liver transplantation.

And of course, few individuals will actually pay full price out of pocket for these treatments, just like few actually pay for their MRIs or their angioplasties or their stay in the ICU. Treating HCV is not like cosmetic surgery; it’s potentially lifesaving. And as with other expensive but lifesaving treatments, we’re hoping there will be generous patient-assistance programs for those who can’t pay.

But for those without coverage, people in other countries, or those charged with managing pharmacy budgets, this cost is a major hurdle.

All of which leaves me thinking that as of December 8, 2013, these are the best options for genotype 1 HCV infection (cost estimates approximate):

1. Simeprevir + sofosbuvir for 12 weeks. PROS: More than 90% cure rate in the COSMOS study. Two pills once daily (it’s amazing even to write that.) CONS: The COSMOS study was very small. Simeprevir can lead to photosensitivity and has many drug-drug interactions. The Q80K polymorphism may reduce response to simeprevir. This regimen is not “FDA approved.” Cost = $145,000.
2. Sofosbuvir + ribavirin for 24 weeks. PROS: Cured 76% of HIV/HCV co-infected patients in the PHOTON-1 study. May well do better in HCV mono-infected. Regimen is “FDA approved” for interferon-ineligible patients, which could help get insurance coverage. CONS. Ribavirin, and all its side effects. 24 weeks seems long compared to 12 weeks. Response rate is lower than other options listed here, which would require re-treatment. Cost (not including ribavirin) = $160,000.
3. Sofosbuvir + interferon + ribavirin for 12 weeks: PROS: 90% cure rate in NEUTRINO study. Only 12 weeks of interferon and ribavirin. Cost = $90,000. CONS: Interferon. Ribavirin. Enough said.

All are a lot better than what we had just last week. All of them contain sofosbuvir. And all are expensive.

What is the best way to treat HCV genotype 1 today?

• Sofosbuvir + simeprevir for 12 weeks
• Sofosbuvir + ribavirin for 24 weeks
• Sofosbuvir + peg-interferon + ribavirin for 12 weeks
• Still going to wait for more options …

Go to the bottom of the page here to vote ……