Fatty Liver Disease Tied to Diabetes, Atherosclerosis

Medscape Medical News > Conference News

Miriam E. Tucker
April 11, 2014

LONDON, United Kingdom — Nonalcoholic fatty liver disease is an independent predictor of cardiometabolic risk, according to 2 new studies.

Taken together, these findings "contribute to a large body of evidence showing nonalcoholic fatty liver disease may pose a cardiovascular risk above and beyond that conferred by traditional risk factors," said Frank Lammert, MD, PhD, professor of internal medicine at the Saarlande University Medical Center in Homburg, Germany.

"I think the key message for clinical practice is that these diseases are closely correlated, and clinical practitioners should be aware of this," he told Medscape Medical News.

Dr. Lammert, who was not involved in either study, spoke during a press briefing here at European Association for the Study of the Liver International Liver Congress 2014, where results from the 2 studies were presented.

In the Japanese study, the presence of nonalcoholic fatty liver disease was associated with an increased risk for type 2 diabetes, and improvement in the disease over a 10-year follow-up period appeared to reduce the risk.

In the French study, nonalcoholic fatty liver disease was found to be a predictor of carotid atherosclerosis, independent of the classic cardiovascular risk factors. In patients with nonalcoholic fatty liver disease, carotid intima-media thickness (C-IMT), carotid plaques, and Framingham scores were greater.

Type 2 Diabetes

In the Japanese study, 3074 patients who did not have diabetes or hepatitis A or B and who did not consume excessive amounts of alcohol underwent 2 ultrasound health checks at least 10 years apart.

At baseline, 24% of the cohort was found to have nonalcoholic fatty liver disease, said Hajime Yamazaki, MD, from the Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan, who presented the results.

At a mean follow-up of 11.3 years, 16.1% of the 728 patients with nonalcoholic fatty liver disease at baseline had developed type 2 diabetes, compared with just 3.1% of the 2346 who did not. The crude odds ratio for the association was 6.05 (P < .001).

After multivariate analysis adjusted for a variety of confounders, including age, sex, body mass index, family history of diabetes, and dyslipidemia, the odds ratio remained significant, at 2.82 (P < .001).

Follow-up ultrasound showed improvement in 110 of the patients with nonalcoholic fatty liver disease at baseline; in the other 618, there was no improvement.

The reason for the improvement could not be determined from these data, but in most cases, it was likely the result of lifestyle changes, Dr. Yamazaki explained.

The incidence of type 2 diabetes lower in those whose condition improved than in those whose condition did not (6.4% vs 17.8%). The crude odds ratio for improvement in nonalcoholic fatty liver disease and type 2 diabetes was 0.31 (P = .004); on multivariate analysis, it was 0.30 (P = .003).

"The clinical message is that it is important to reduce fatty liver to prevent diabetes," he told Medscape Medical News.

This study is the largest and longest to show an association between nonalcoholic fatty liver disease and type 2 diabetes, and the first-ever to show a reduction in type 2 diabetes with improvement in fatty liver disease, he said.

This study was possible because ultrasound health checks are part of clinical practice in East Asian countries. It is unlikely that this type of study could be conducted elsewhere, but results would probably be similar in other populations, he explained.

Although cause and effect couldn't be assessed in this study, "for many of the patients — maybe for the majority — there is a causal link between liver disease and diabetes because the liver plays a central role in glucose homeostasis," Dr. Lammert pointed out.

Cardiovascular Disease

Results from the 2-part cross-sectional and longitudinal French study were presented by Raluca Pais, MD, PhD, from Université Pierre et Marie Curie and Hôpital de La Pitié-Salpêtrière in Paris.

The cross-sectional part involved 5671 patients 20 to 75 years of age who had 2 or more cardiovascular risk factors. All had undergone at least 1 carotid ultrasound to measure C-IMT and carotid plaques.

C-IMT was significantly higher in the 1871 subjects with nonalcoholic fatty liver disease than in the 3800 without the disease (0.64 vs 0.61 mm; P < .001), as were the prevalence of carotid plaques (44% vs 37%; P < 0.001) and Framingham risk scores (15 vs 8; P < 0.001). All were independent of age, sex, body mass index, hypertension, and tobacco use, Dr. Pais reported.

At 8-year follow-up in a subset of 1872 patients who had at least 2 C-IMT measurements, those with nonalcoholic fatty liver disease at baseline had a 34% increased risk for carotid plaques (P < .02).

These associations held true regardless of serum alanine aminotransferase levels, she said.

"Patients at risk for CVD should probably be screened for fatty liver, regardless of the transaminase levels, because nonalcoholic fatty liver disease is an independent predictor of cardiovascular risk, beyond traditional risk factors like metabolic syndrome," she told Medscape Medical News. "We don't know if nonalcoholic fatty liver disease is a marker or actively involved in the pathogenesis and progression of cardiovascular disease. It's at least a marker; for the rest, we don't yet have the answer."

Clinical Implications

During the briefing, Dr. Lammert advised that patients who enter a liver unit be assessed for cardiovascular risk and that those seen in cardiology settings be evaluated by a liver specialist.

"We should stratify the risk and define the subgroup of patients who would benefit from being treated by both a cardiologist and a hepatologist. It shouldn't happen by chance," he said.

He also advised that liver specialists focus on patients who present with nonalcoholic fatty liver disease without traditional cardiovascular risk factors, noting that at least 1 such genetic subgroup has been identified. "We need to define this better," said Dr. Lammert.

Dr. Yamazaki, Dr. Pais, and Dr. Lammert have disclosed no relevant financial relationships.

European Association for the Study of the Liver (EASL) International Liver Congress 2014: Abstracts 23 and 26. Presented April 10, 2014.

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Video: Jean-Michel Pawlotsky on the New EASL HCV Treatment Guidelines

ILC Press·

Published on Apr 11, 2014

An interview with Jean-Michel Pawlotsky, Former EASL Secretary General, who led the consolidation of the new EASL treatment guidelines for hepatitis C launched at The International Liver CongressTM 2014.

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'3D' HCV Combo Almost Perfect

Published: Apr 11, 2014

By Michael Smith, North American Correspondent, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor,
Perelman School of Medicine at the University of Pennsylvania

Action Points

• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
• The combination of a protease inhibitor (ABT-450) and a drug that delays its degradation (ritonavir), plus two inhibitors of hepatitis C virus replication (ombitasvir and dasabuvir) achieved high SVR₁₂ rates with low rates of treatment discontinuation in treatment-experienced, noncirrhotic HCV genotype 1-infected patients, including prior null responders.

LONDON -- An investigational drug combination cured almost all patients with the form of hepatitis C (HCV) that is most common in North America, researchers said.

In two major phase III studies, cure rates after 12 weeks of treatment with the so-called 3D combination ranged from 95.3% to 100% depending on patient subgroups, investigators reported here at the annual meeting of the European Association for the Study of the Liver and online in the New England Journal of Medicine.

Cure rates -- with a cure defined as no detectable HCV RNA 12 weeks after the end of treatment, or SVR₁₂ -- appeared to be independent of patient and viral characteristics in the industry-supported trials.

The results are highly promising and likely to hold up in clinical practice, once the combination is approved, according to William Carey, MD, of the Cleveland Clinic.

But, Carey told MedPage Today, the studies included only patients with HCV genotype 1. Although that accounts for about 70% of the cases in North America, "that means there's 30% of people who have a different genotype and these results are not directly applicable" to them, he said.

The combination until recently has been known by its nickname 3D -- or by a soup of numbers and letters -- because the drugs involved had yet to be named by the manufacturer, AbbVie of North Chicago, Ill.

Two of them now have names -- ABT-267, an NS5A inhibitor, is now ombitasvir and the non-nucleoside polymerase inhibitor ABT-333 is now called dasabuvir. The as-yet-nameless third drug is ABT-450, a protease inhibitor boosted with ritonavir (Norvir).

The combination is given with ribavirin, a nonspecific antiviral drug.

With cure rates approaching 100%, the combination is one of the stars of this meeting, with two plenary session presentations and a late-breaker oral talk, as well as others, devoted to it.

The Sapphire I and Sapphire II studies are parallel randomized placebo-controlled trials that tested the combination in patients with genotype 1 HCV who did not have cirrhosis.

Sapphire I, led by Jordan Feld, MD, of the University of Toronto in Canada, looked at outcomes in patients who had not been previously treated. Sapphire II, led by Stefan Zeuzem, MD, of Johann Wolfgang Goethe University in Frankfurt, Germany, studied patients who had failed earlier therapy.

Sapphire I enrolled 631 patients and assigned three-quarters of them to the active drug, while the remainder were given matching placebo for 12 weeks, after which they were switched to the active regimen for an open-label study.

The primary endpoint was a comparison with outcomes from historical trials involving telaprevir (Incivek) with pegylated interferon-alfa and ribavirin, where the SVR₁₂ was 78%, Feld reported.

The SVR₁₂ rate in the active treatment arm was 96.2% overall, which was superior to the historical control rate, he reported. Nor was there little difference by subgenotype -- 95.3% among patients with genotype 1a and 98.0% among those with genotype 1b.

Rates were similarly high in all subgroups, including those defined by sex, race, age, fibrosis score, and HCV RNA level.

Few patients stopped therapy because of adverse events -- 0.6% in each study group, but those in the active treatment arm had significantly more nausea, pruritus, insomnia, diarrhea, and asthenia than placebo patients (P<0.05 for all comparisons).

Grade 1 declines in hemoglobin occurred in 47.5% of patients in the 3D arm; grade 2 drops occurred in 5.8%, Feld reported. In contrast, 2.5% of placebo patients had grade 1 declines.

"I would say this was a highly, highly effective regimen," commented Alessio Aghemo, MD, PhD, of the University of Milan and a member of the association's governing board.

The design of Sapphire II was similar, except that patients had to have failed a previous attempt at treatment with peginterferon and ribavirin.

Zeuzem and colleagues enrolled 394 patients, including 115 who had relapsed after previous therapy, 86 who had had only a limited response, and 193 who had not responded at all.

Again three-quarters were assigned to the 3D combination for 12 weeks, while the rest got a matching placebo before being switched to the active treatment in an open-label, 12-week extension.

Results were also similar to those seen in Sapphire I and, if anything, a little better: an overall SVR₁₂ rate of 96.3%, with 96% in genotype 1a and 96.7% in genotype 1b, Zeuzem reported.

The type of previous failure did not seem to matter: 95.3% among patients with a prior relapse, 100% among patients with a prior partial response, and 95.2% among patients with a prior null response.

As in Sapphire I, SVR₁₂ rates were high and similar across subgroups.

The SVR₁₂ rates were superior to the historical comparison rate of 65% among treatment failures who had been retreated with telaprevir, peginterferon, and ribavirin.

Pruritus occurred more frequently in 13.8% of 3D patients, which was significantly different (at P=0.03) from the 5.2% among placebo patients.

Three patients in the active-regimen group dropped out owing to adverse events including one patient with a serious renal adverse event that investigators thought was not related to the study drugs, Zeuzem reported.

Hemoglobin declines of grade 2 (from 8 to less than 10 grams per deciliter) and grade 3 (6.5 to less than 8) were observed in 4.7% and 0.3% of 3D patients, respectively, but none stopped treatment owing to anemia, he said.

"It's a very important study," Aghemo told reporters, "because it shows that previous treatment failure can be overcome with the 3D regimen with "incredibly high SVR rates (and) an excellent safety profile."

Both studies were supprted by AbbVie.

Feld disclosed relevant relationships with the company, as well as with Boehringer Ingelheim, Gilead Sciences, Vertex Pharmaceuticals, Achillion Pharmaceuticals, Bristol-Myers Squibb, Idenix Pharmaceuticals, Janssen Pharmaceuticals, Merck, Roche, and Santaris Pharma.

Zeuzem disclosed relevant relationships with the company, as well as with Bristol-Myers Squibb, Boehringer Ingelheim, Gilead Sciences, Vertex Pharmaceuticals, Idenix Pharmaceuticals, Janssen Pharmaceuticals, Merck, Roche, Novartis, and Santaris Pharma.

Aghemo disclosed relevant relationships with Gilead, AbbVie, Janssen, Merck, and Roche.

Primary source: New England Journal of Medicine
Source reference: Feld JJ, et al "Treatment of HCV with ABT-450/r–ombitasvir and dasabuvir with ribavirin" N Eng J Med 2014; DOI: 10.1056/NEJMoa1315722.

Additional source: New England Journal of Medicine
Source reference:Zeuzem S, et al "Retreatment of HCV with ABT-450/r–ombitasvir and dasabuvir with ribavirin" N Eng J Med 2014; DOI: 10.1056/NEJMoa1401561.

Source

Also See: AbbVie to Present Detailed Phase III Results from SAPPHIRE-I and SAPPHIRE-II Studies in Chronic Hepatitis C Patients at the 2014 International Liver Congress™

$1,000-a-Day Hepatitis C Miracle Drug Gets a Major Price Cut, Just Not In the U.S.

Provided by The Wire

By Polly Mosendz
4 hours ago

Health department workers in New Hampshire set up a temporary clinic to handle a hepatitis C outbreak in 2012. (AP PHOTO/JIM COLE)

India, Egypt and Brazil have secured access to Sovaldi, the incredibly effective, but also incredibly expensive hepatitis C treatment, for one percent of its cost in America. The 12-week treatment program that runs U.S. insurance companies $84,000 per cycle, will be just $840 in those nations. Burma, Kenya, Mozambique and Iran will pay slightly more: $900 for the full treatment program, or 1.1 percent of the standard price. 

However, American insurance companies, which have bristled at the price being charged by the drug's maker, Gilead Sciences, will continue to pay full freight. In fact, they will essentially be subsidizing the cost for less developed nations where need is greater, but ability to pay is far less.

The majorly reduced price will be especially beneficial to Egypt, which has one of the world’s highest rates of hepatitis C infections. The government has treated more than 350,000 patients at their own expense in the last six years. Wahin Doss, a member of the National Hepatology and Tropical Medicine Institute in Egypt, spearheaded the treatment program, which had a 50% success rate. Doss was instrumental to negotiating the deal with Gilead.

While the company initially wanted a higher rate, they settled at one percent due to the size of the market: “We told them we could compensate price for volume, said Doss. "All companies want to enter Egypt because of the huge market, but we are not letting them in unless they offer good prices. We hope to treat a million patients in Egypt.”

The company’s reduced prices came after the World Health Organization worked with Gilead directly to help spread the drug's usage. So what determines who gets a discount and who doesn't? It's simple. Gilead admits their “global pricing model is based on a country’s ability to pay.” 

While the countries that most need and cannot afford the drug were greatly helped, many other nations may not be able to negotiate such as low price. Isabelle Meyer-Andrieux, an advisor at Doctors Without Borders, finds that “a major concern for us is the price for middle-income countries,” such as Ukraine and China. Meyer-Andrieux believes that the wealthier countries, which had a lower rate of hepatitis C infection, will earn Gilead enough to subsidize the reduced price in developing countries: “They don’t have to treat so many patients to reimburse the $11 billion.” Of the 130 million to 185 million people in the world with hepatitis C, about ninety percent of them reside in the world’s poorest nations, as this 2013 article from the journal Science shows.

The World Health Organization hopes that with the price will be further deceased for middle income countries through tiered pricing and generic versions of the medication. So far the tiered pricing has set the British cost to $57,000 for a full treatment, Germany to $66,000 and Canada to $55,000.  Though the tiered pricing certainly offers some reduction in cost, many health leaders are left unimpressed by the so-called discounts. “When you're starting from such an exorbitant price in the U.S., the price Gilead will offer middle-income countries like Thailand and Indonesia may seem like a good discount. But it will still be too expensive for many of these countries to scale up treatment”, said Rohit Malpani of Doctors Without Borders.

As for the $1,000 a day American price for the extremely effective (and life-saving) medication, Gilead is holding firm that they “think the price is fair. It’s a one-time cost that is your lifetime cost.” In a letter on March 20, Representative Henry Waxman called for Gilead to explain their United States pricing structure to Congress, as part of an inquiry that remains ongoing.

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VIDEO: WHO guidelines focus on low- and middle-income countries

Provided by Healio

April 11, 2014

LONDON — Stefan Wiktor, MD, team leader of the WHO Global Hepatitis Program, discussed the new hepatitis C treatment guidelines issued by WHO at the International Liver Congress in London.

Wiktor said the WHO guidelines are different from others being introduced because they focus on low- and middle-income countries.

“In these countries, most people who have hepatitis C are not being treated and in some countries, [patients] are receiving standard interferon, which is really substandard care, in a sense,” Wiktor told Healio.com

The group that convened to establish the guidelines included representatives from low- and middle-income countries, who felt it was important to include recommendations for “all the existing treatments.” The guidelines include recommendations on current treatments and new drug options in the forefront, Wiktor said.

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Merck’s Investigational Chronic Hepatitis C Combination Therapy MK-5172/MK-8742 Demonstrates Antiviral Activity in Hard-to-Cure Patients with HCV Genotype 1 Infection

Clinical Findings Support Initiation of C-EDGE Phase 3 Program

Friday, April 11, 2014 1:00 am EDT

"These findings provide additional clinical evidence regarding the potential of MK-5172/MK-8742 in treating a broad spectrum of HCV patients."

WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside of the United States and Canada, today announced interim results from the ongoing C-WORTHy study, a multi-arm Phase 2 clinical trial evaluating the efficacy and safety of an all-oral, once-daily regimen combining MK-5172, an investigational hepatitis C virus (HCV) NS3/4A protease inhibitor, and MK-8742, an investigational HCV NS5A replication complex inhibitor, among patients with chronic HCV Genotype 1 infection (GT1). Interim analysis of hard-to-cure¹ patients administered MK-5172/MK-8742 with and without ribavirin (RBV) for 12 or 18 weeks showed sustained viral response² (SVR), 4 to 8 weeks after the completion of therapy (SVR4/8):

• HCV GT1 infected, treatment-naïve cirrhotic patients, MK-5172/MK-8742 treated - 97 percent (28/29 and 29/30) for 12 and 18 weeks, and MK-5172/MK-8742 plus RBV - 90 percent (28/31) and 97 percent (30/31) for 12 and 18 weeks, respectively.
• HCV GT1 infected prior-null responder patients (with or without cirrhosis), MK-5172/MK-8742 treated - 91 percent (30/33) and 97 percent (29/30) for 12 and 18 weeks, respectively, and MK-5172/MK-8742 plus RBV treated 94 percent (30/32) and 100 percent (32/32) for the 12 and 18 weeks, respectively.
• Treatment-naïve, non-cirrhotic patients with HCV/HIV co-infection, MK-5172/MK-8742 treated for 12 weeks - 90 percent (26/29) and MK-5172/MK-8742 plus RBV for 12 weeks 97 percent (28/29).

These data were presented at the 49th Annual Meeting of the European Association for the Study of the Liver (EASL), also known as The International Liver Congress™ 2014 in London, UK.

“There is still a need for further options for the most difficult-to-cure patients, including those with cirrhosis and HCV/HIV co-infection,” said Dr. Eric Lawitz, MD, vice president, Scientific and Research Development, The Texas Liver Institute, and clinical professor of medicine, University of Texas Health Science Center in San Antonio. “These findings provide additional clinical evidence regarding the potential of MK-5172/MK-8742 in treating a broad spectrum of HCV patients.”

C-WORTHy Study Design

C-WORTHy is a randomized, dose-responsive, parallel-group, multiple-site, double-blind clinical trial comparing different patient populations exposed to different durations of treatment of MK-5172 (100 mg once daily) in combination with MK-8742 (50 mg once daily) with or without RBV in subjects with chronic HCV infection. A total of 471 patients with chronic HCV GT1 and HCV RNA levels of ≥10,000 IU/mL were enrolled in C-WORTHy and randomized across 16 arms. These results examine hard-to-cure subpopulations, including treatment-naïve patients with liver cirrhosis (12- and 18-week arms, with and without RBV), prior-null responder patients with and without cirrhosis (12- and 18-week arms, with and without RBV) and patients with HIV/HCV co-infection (12-week arms).

Key Findings for MK-5172/MK-8742

Viral suppression (HCV RNA levels less than 25 IU/mL) was demonstrated for treatment-naïve patients with cirrhosis, prior-null responder patients with and without cirrhosis and HIV/HCV co-infected patients by Treatment Week (TW)12. These levels were maintained at rates between 90 and 100 percent across patient subgroups through the completion of dosing and at the four-week treatment follow-up time point (FU4).

The most common adverse events observed among treatment-naïve patients with cirrhosis and prior-null responder patients with and without cirrhosis were fatigue (23% and 28%, respectively), headache (24% and 24%, respectively), and asthenia (8% and 19%, respectively). The most common adverse events observed among HIV co-infected patients were headache (8%), asthenia (8%), fatigue (7%), and sleep disorder (7%). There were no early discontinuations due to drug-related adverse events and no clinically significant abnormalities observed in routine laboratory analysis of hematologic markers.

About Merck’s Phase 3 HCV Program: C-EDGE

Based on the results of the Phase 2 clinical program, Merck has initiated Phase 3 clinical trials for MK-5172/MK-8742. The Phase 3 program, called C-EDGE, will evaluate the safety and efficacy of MK-5172/MK-8742 with and without ribavirin in various genotypes and across a broad range of patient populations with chronic HCV. Study cohorts will include: C-EDGE TN (GT1, GT4-6; treatment-naive ± cirrhosis), C-EDGE CO-INFXN (GT1, GT4-6; treatment-naive ± cirrhosis with HIV/HCV co-infection), C-EDGE RECOVERY (GT1, GT4-6; treatment-naive ± cirrhosis; ± HIV/HCV co-infection on opiate substitution therapy), and C-EDGE TE (GT1, GT4-6; prior failed treatment with peginterferon/ribavirin; ± HIV/HCV co-infection). Study information can be found at www.clinicaltrials.gov.

Merck’s Commitment to HCV

For more than 25 years, Merck has been at the forefront of the response to the HCV epidemic. Merck employees are dedicated to applying their scientific expertise, resources and global reach to deliver healthcare solutions that support people living with HCV worldwide.

About Merck

Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside of the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebook and YouTube.

Merck Forward-Looking Statement

This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of Merck’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; Merck’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of Merck’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck’s 2013 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

¹ Defined as treatment-naïve patients with liver cirrhosis, prior-null responder patients with and without cirrhosis and patients with HIV/HCV co-infection

² Defined as HCV RNA below the limit of quantification or below the limit of detection at the last visit on record – 4, 8, 12, or 24 weeks after the completion of therapy

Contact:

Merck

Media Contacts:

Caroline Lappetito, 267-305-7639

Sarra Herzog, 201-669-6570 or

Investor Contacts:

Carol Ferguson, 908-500-1101

Justin Holko, 908-423-5088

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Viral Hepatitis More Deadly Than HIV In Europe

London, 11 April 2014

London, UK, Friday 11 April 2014: Mortality from viral hepatitis is significantly higher than from HIV/AIDS across EU countries, according to results from The Global Burden of Disease Study 2010 (GBD 2010) which was announced forthe first time today at the International Liver Congress^TM 2014¹.

GBD 2010 is the most recent version of a large epidemiological study funded by the Bill and Melinda Gates Foundation and coordinated by the Institute for Health Metrics and Evaluation (IHME) at the University of Washington.

In the EU, in 2010, there were more than 10 times as many deaths due to viral hepatitis as there were HIV-attributable deaths. Hepatitis C Virus (HCV) and Hepatitis B Virus (HBV) are estimated to have caused nearly 90,000 deaths that year in the EU (HCV nearly 57,000 deaths, HBV nearly 31,000 deaths), while there were just over 8,000 deaths from HIV/AIDS.

Presenting these thought-provoking figures, EASL’s Vice-Secretary Dr. Laurent Castera from the department of Hepatology, Hôpital Beaujon in Paris said: “GBD 2010 is making a critical contribution to our understanding of present and future health priorities for countries and the global community. Although HIV/AIDS undeniably remains a key global health priority, the higher mortality from viral hepatitis than from HIV/AIDS in the EU means that hepatitis B andC must clearly now be counted among the top global and local priorities for health.”“

Additional resources are needed to prevent, detect and treat hepatitis B and C in order to address these imbalancesin major preventable causes of human death,” Dr Castera added.

The Global Burden of Disease Study 2010 is the largest ever systematic effort to describe the global distribution and causes of a wide array of major diseases, injuries, and health risk factors. GBD 2010 has collated estimates of 291 diseases and injuries and 1,160 sequelae to identify the causes of human death worldwide

Using country-level and regional causes of death, mortality attributed to HBV, HCV and HIV/AIDS between 1990 and 2010 has been compared across Europe, by region and for specific countries. These findings have then beencompared to global trends.

Globally, deaths from both viral hepatitis and HIV increased from 1990-2010 with HIV/AIDS ranking 6th (1.47 milliondeaths) and viral hepatitis B and C combined ranking 9th, with 1.29 million deaths in 2010.

Whereas HIV-related deaths in the EU fell by more than half following the late 1990s, in Eastern Europe HIV mortality has risen sharply. “This goes some way to explaining why mortality from viral hepatitis does not appear to be higher than that of HIV/AIDS in other areas of Europe outside of the EU,” concluded Dr Castera.

Disclaimer: the data referenced in this release is based on the submitted abstract. More recent data maybe presented at the International Liver Congress™ 2014.

- Ends -

Notes to Editors

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 Congress^TM 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
• Organisation of a Mentorship program and Masterclass to support young investigators starting out on their career path
• Participation in a number of policy initiatives at European level

About The International Liver Congress^TM 2014

The International Liver Congress™ 2014, the 49th annual meeting of the European Association for the study of the Liver, is being held at ExCel London from April 9 – 13, 2014. The congress annually attracts in excess of 9000 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field.

For further information on the studies, or to request an interview, please do not hesitate to contact the EASL Press Office on:

Email: easlpressoffice@cohnwolfe.com

Helena Symeou  +44 7976 562 430

Courtney Lock +44 7894 386 422

1. B.C. Cowie et al., EUROPEAN RESPONSES IN FOCUS: COMPARING VIRAL HEPATITIS AND HIV RELATED DEATHS IN EUROPE 1990-2010 IN THE GLOBAL BURDEN OF DISEASE STUDY 2010. Abstract presented at International Liver Congress^TM 2014

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Gilead’s Sovaldi® Demonstrates Efficacy and Safety Among Chronic Hepatitis C Patients with Advanced Liver Disease

- Benefit in Patients with Decompensated Cirrhosis and Recurrent HCV Infection Following Liver Transplantation --

LONDON--(BUSINESS WIRE)--Apr. 11, 2014-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced data from two Phase 2 studies and a compassionate access study in which a regimen containing once-daily Sovaldi^® (sofosbuvir) 400 mg was administered for the treatment of chronic hepatitis C virus (HCV) infection in patients with advanced liver disease. These data are being presented this week at the 49th Annual Meeting of the European Association for the Study of the Liver (The International Liver Congress 2014) in London.

The first study, Study GS-US-334-0125 (Oral #068), is an ongoing open-label Phase 2 clinical trial evaluating HCV patients with cirrhosis and portal hypertension, with or without decompensation, who were randomized 1:1 to an immediate treatment arm in which Sovaldi and ribavirin (RBV) was administered for 48 weeks (n=25) or to a deferred treatment arm in which this regimen was initiated after a 24-week observation period (n=25). Eighty percent of participants were treatment-experienced.

Of the 22 patients who completed 24 weeks of therapy, 95 percent (n=21/22) achieved virologic suppression on treatment. Additionally, patients taking Sovaldi-based therapy experienced trends in clinical and laboratory parameter improvements compared to patients in the observation arm. Sovaldi-based therapy was well tolerated in the study, and only one patient discontinued treatment due to an adverse event. The most common adverse events occurring in more than 25 percent of patients included nausea and pruritis. Patients in both arms of the study will be followed to determine their 12-week sustained virologic response rates (SVR12) after 48 weeks of Sovaldi-based therapy.

Study GS-US-334-0126 (Poster #1232), was a single-arm open-label Phase 2 trial in which patients with established recurrent HCV infection following liver transplantation received up to 24 weeks of therapy with Sovaldi plus RBV (escalating doses starting at 400 mg/day). The majority of patients had genotype 1-HCV infection (n=33/40) and 88 percent (n=35/40) were treatment-experienced.

Seventy percent (n=28/40) of patients in this study achieved SVR12. The most common adverse events occurring in more than 20 percent of patients were fatigue, headache, arthralgia (joint pain) and diarrhea. There were no deaths, graft losses or episodes of organ rejection among post-liver transplantation patients, and no drug-drug interactions were reported between Sovaldi and immunosuppressive agents.

A third, compassionate access study (Oral #62), evaluated Sovaldi therapy among 104 post-transplant patients with severe recurrent HCV, including fibrosing cholestatic hepatitis, who had exhausted all other treatment options and received pre-approval access to Sovaldi via Gilead’s compassionate use program. Patients received up to 48 weeks of Sovaldi plus RBV, with some patients also receiving pegylated interferon (peg-IFN) (180 μg/week) at their physician’s discretion. The majority of patients in the study experienced clinical improvements on treatment. Overall, 62 percent of patients achieved SVR12. Sovaldi-based therapy was well tolerated.

“The patients included in these analyses are historically among the most difficult to cure, and many have had no appropriate treatment options until now,” said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer, Gilead Sciences. “These data demonstrate that Sovaldi-based oral therapy can improve outcomes, has a favorable safety profile and is well tolerated among hepatitis C patients with severe liver disease.”

Additional information about Study GS-US-334-0125 and Study GS-US-334-0126 can be found at www.clinicaltrials.gov.

About Sovaldi

Sovaldi is an oral nucleotide analog inhibitor of the HCV NS5B polymerase enzyme, which plays an essential role in HCV replication. Sovaldi is a direct-acting agent, meaning that it interferes directly with the HCV life cycle by suppressing viral replication.

Sovaldi was approved in the United States on December 8, 2013 and in the European Union on January 17. In the United States, Sovaldi is approved for the treatment of chronic hepatitis C infection as a component of a combination antiviral treatment regimen. Efficacy has been established in subjects with HCV genotype 1, 2, 3 or 4 infection, including those with hepatocellular carcinoma meeting Milan criteria (awaiting liver transplantation) and those with HCV/HIV-1 co-infection. Treatment response varies based on baseline host and viral factors. Monotherapy is not recommended for treatment of chronic hepatitis C. Studies GS-US-334-0125 and GS-US-334-0126 evaluated investigational uses of Sovaldi, for which safety and efficacy have not yet been established.

IMPORTANT SAFETY INFORMATION

Contraindications

Sovaldi combination treatment with ribavirin or with peginterferon alfa plus ribavirin is contraindicated in women who are pregnant or may become pregnant and men whose female partners are pregnant because of the risk for birth defects and fetal death associated with ribavirin. Contraindications to peginterferon alfa and ribavirin also apply to Sovaldi combination treatment. Refer to the prescribing information of peginterferon alfa and ribavirin for a list of their contraindications.

Warnings and Precautions

• Pregnancy: Use with Ribavirin or Peginterferon Alfa/Ribavirin: Ribavirin therapy should not be started unless a report of a negative pregnancy test has been obtained immediately prior to initiation of therapy. Female patients of childbearing potential and their male partners must use two forms of non-hormonal contraception during treatment and for at least 6 months after treatment has concluded. Routine monthly pregnancy tests must be performed during this time. Refer to the prescribing information for ribavirin.

• Use with Potent P-gp Inducers: Rifampin and St. John’s wort should not be used with Sovaldi as they may significantly decrease sofosbuvir plasma concentration, reducing its therapeutic effect.

Adverse Reactions

Most common (≥20 percent, all grades) adverse reactions for:

• Sovaldi + peginterferon alfa + ribavirin combination therapy were fatigue, headache, nausea, insomnia, and anemia
• Sovaldi + ribavirin combination therapy were fatigue, and headache

Drug Interactions

In addition to rifampin and St. John’s wort, coadministration of Sovaldi is not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of sofosbuvir, reducing its therapeutic effect.

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 longer-term results from clinical trials evaluating Sovaldi for the treatment of HCV among patients with advanced liver disease, and the risk that healthcare providers, payers or insurers may not recognize the benefits of Sovaldi over other agents. As Sovaldi is used over longer periods of time by treatment-experienced patients with underlying health problems taking numerous other medicines, Gilead may find new issues such as safety, resistance or drug interaction issues, which may require it to provide additional warnings or contraindications in the label, which could reduce the market acceptance of Sovaldi. 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 Annual Report on Form 10-K for the year ended December 31, 2013, 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.

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 (Europe))

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EASL Recommendations on Treatment of Hepatitis C 2014

April 11, 2014

Hepatitis C virus (HCV) infection is one of the main causes of chronic liver disease worldwide. The long-term impact of HCV infection is highly variable, ranging from minimal histological changes to extensive fibrosis and cirrhosis with or without hepatocellular carcinoma (HCC).... (read more by viewing or downloading EASL recommendations)

Full version:

EASL Recommendations on Treatment of Hepatitis C 2014 (download pdf)

Summary:

EASL Recommendations on Treatment of Hepatitis C 2014 (download pdf)

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New Data Reveals Positive Outcomes for Hep C Transplant Patients

London, United Kingdom, Friday 11 April 2014: New research announced at the International Liver Congress^TM 2014 today provides new hope for the notoriously difficult-to-treat population of liver transplant patients with recurring hepatitis C (HCV).^[1]

As part of a compassionate use program, 104 post-liver transplant patients with recurring HCV who had exhausted all treatment options and had poor clinical prognoses, received sofosbuvir (SOF) and ribavirin (RBV) with pegylated interferon (PEG) included at the physicians’ discretion for up to 48 weeks. Among patients whose clinical outcomes have been reported, 62% achieved SVR12. Additionally, 62% of patients had improvements in clinical conditions associated with hepatic decompensation (e.g., ascites and encephalopathy) and/or improvement in liver function tests. SOF+RBV±PEG was well-tolerated and led to high rates of virologic suppression.

EASL’s European Policy Councillor Professor Patrizia Burra of the Multivisceral Transplant Unit, Padova University Hospital, Padua, Italy said: “There are currently no effective treatment options for this patient group. However, this new trial involving the nucleotide polymerase inhibitor sofosbuvir (SOF) has demonstrated promising results, providing further evidence of its clinical potential.”

“For patients with advanced hepatitis C liver disease, liver transplants offer a second chance,” continued Professor Burra, “and for those who continue to suffer post-surgery, it’s important for us to keep following up all avenues possible to improve their quality of life.”

Other research revealed at the International Liver Congress^TM 2014 showed that most patients with mild hepatitis C recurrence diagnosed one year after liver transplant have excellent long-term outcomes.^[2]

In the second study, 172 patients who were diagnosed with mild hepatitis C recurrence one year after undergoing liver transplant surgery between 1999 and 2012 were followed for six and a half years with all relevant transplant-related, donor and recipient variables recorded. The cumulative probability of HCV-related graft loss five and 10 years after liver transplant were 3% and 10%, respectively.

However one third of these patients are still at risk of going on to develop cirrhosis, further demonstrating the need for antiviral therapy pre or post-transplant.

Hepatitis C infection is a common cause of liver transplantation, with virus-related diseases comprising 40% of primary indications for liver transplantation in Europe among patients with cirrhosis.^[3]

More than 5,500 liver transplantations are currently performed in Europe per year.^[3]

Disclaimer: the data referenced in this release is based on the submitted abstract. More recent data may be presented at the International Liver Congress™ 2014.

- Ends -

Notes to Editors

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 Congress^TM 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
• Organisation of a Mentorship program and Masterclass to support young investigators starting out on their career path
• Participation in a number of policy initiatives at European level

About The International Liver Congress^TM 2014

The International Liver Congress™ 2014, the 49th annual meeting of the European Association for the study of the Liver, is being held at ExCel London from April 9 – 13, 2014. The congress annually attracts in excess of 9000 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field.

For further information on the studies, or to request an interview, please do not hesitate to contact the EASL Press Office on:

Email: easlpressoffice@cohnwolfe.com

Helena Symeou  +44 7976 562 430

Courtney Lock +44 7894 386 422

1. X.FORNS ET AL. SOFOSBUVIR COMPASSIONATE USE PROGRAM FOR PATIENTS WITH SEVERE RECURRENTHEPATITIS C INCLUDING FIBROSING CHOLESTATIC HEPATITIS FOLLOWING LIVER TRANSPLANTATION. ABSTRACTPRESENTED AT THE INTERNATIONAL LIVER CONGRESS™ 2014

2. M.GAMBATO ET AL. LONG TERM OUTCOME OF MILD HEPATITIS C RECURRENCE AFTER LIVER TRANSPLANTATION: A LARGEPROSPECTIVE STUDY. ABSTRACT PRESENTED AT THE INTERNATIONAL LIVER CONGRESS™ 2014

3. EU BURDEN OF LIVER DISEASE: A REVIEW OF AVAILABLE EPIDEMIOLOGICAL DATA. EUROPEAN ASSOCIATION FOR THE STUDYOF THE LIVER. 2013. HTTP://WWW.EASL.EU/ASSETS/APPLICATION/FILES/54AE845CAEC619F_FILE.PDF ACCESSED 16.02.14.

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AbbVie to Present Detailed Phase III Results from SAPPHIRE-I and SAPPHIRE-II Studies in Chronic Hepatitis C Patients at the 2014 International Liver Congress™

-SVR(12) rates of 96 percent were achieved in both SAPPHIRE-I (new to therapy) and SAPPHIRE-II (treatment-experienced with pegylated interferon and ribavirin) in adult patients with genotype 1 chronic hepatitis C virus infection

-All treatment-experienced sub-populations in the SAPPHIRE-II study achieved SVR(12) rates of 95-100 percent

-SAPPHIRE-I and SAPPHIRE-II results were published online in The New England Journal of Medicine

Apr 11, 2014

LONDON, April 11, 2014 /PRNewswire/ -- AbbVie (NYSE: ABBV) announced that detailed results from its phase III pivotal study, SAPPHIRE-I, will be presented today at the International Liver Congress™ (ILC) 2014 and featured in the ILC press conference. Results from the pivotal phase III study, SAPPHIRE-II, were also presented at the congress yesterday. Additionally, results from both SAPPHIRE-I and SAPPHIRE-II have been published online in The New England Journal of Medicine.

In the SAPPHIRE-I (N=631) and SAPPHIRE-II (N=394) placebo-controlled studies, adult, non-cirrhotic patients with chronic genotype 1 (GT1) hepatitis C virus (HCV) infection receiving the investigational AbbVie regimen with ribavirin (RBV) for 12 weeks achieved sustained virologic response rates 12 weeks post-treatment (SVR₁₂) of 96.2 percent (n=455/473) and 96.3 percent (n=286/297), respectively.

In SAPPHIRE-II, treatment-experienced sub-populations randomized to the AbbVie regimen with RBV were prior null responders (49.2 percent), prior relapsers (29.0 percent) and prior partial responders (21.9 percent) to pegylated interferon and RBV. 

"Patients with chronic hepatitis C who have not responded well to treatment in the past have historically been more difficult to treat," said Stefan Zeuzem, M.D., lead clinical investigator on SAPPHIRE-II and Chief of the Department of Medicine at the J.W. Goethe University Hospital in Frankfurt, Germany. "These data show very promising results in people who are infected with either subtype of the GT1 hepatitis C virus and who are either new to therapy or treatment-experienced."

SAPPHIRE-I and SAPPHIRE-II Results

	SAPPHIRE-I SVR12 (n=473)	SAPPHIRE-II SVR12 (n=297)
All GT1	96.2% (n=455/473)	96.3% (n=286/297)*
GT1a	95.3% (n=307/322)	96.0% (n=166/173)
GT1b	98.0% (n=148/151)	96.7% (n=119/123)
Treatment-experienced (GT1a and GT1b)
Prior null responders	n/a	95.2% (n=139/146)
Prior relapsers	n/a	95.3% (n=82/86)
Prior partial responders	n/a	100.0% (n=65/65)

*Subgenotype could not be determined for one patient

In SAPPHIRE-I, high response rates were seen across patients with certain variable characteristics, including gender, race, body mass index, fibrosis stage and baseline HCV viral load, as some of these patients have historically had a reduced response to treatment.

"These data provide further evidence that AbbVie's regimen can achieve high SVR₁₂ rates across a range of GT1 patients with varying prior treatment experience and response," said Scott Brun, M.D., Vice President, Pharmaceutical Development, AbbVie. "We are excited to be able to share these results at the ILC and as publications in The New England Journal of Medicine."

Discontinuations due to adverse events were reported in 0.6 percent of patients in both arms in SAPPHIRE-I and in 1.0 percent of patients receiving the AbbVie regimen in SAPPHIRE-II and no patients receiving placebo. The most commonly reported treatment-emergent adverse events (>10 percent in either arm) for both SAPPHIRE-I and SAPPHIRE-II were fatigue, headache, nausea, asthenia, insomnia, pruritus and diarrhea. Additional common adverse events occurring in the studies were rash in SAPPHIRE-I and dyspnea, cough and myalgia in SAPPHIRE-II. In SAPPHIRE-I, the adverse events that occurred with a significantly greater frequency in the treatment arm compared to placebo were pruritus, insomnia, diarrhea, nausea and asthenia; in SAPPHIRE-II, only pruritus.

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

About Study M11-646 (SAPPHIRE-I)
SAPPHIRE-I is a global, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 12 weeks of treatment with AbbVie's regimen with RBV in non-cirrhotic, GT1a and GT1b HCV-infected adult patients new to therapy.

The study population consisted of 631 patients: 473 were randomized to the AbbVie regimen with RBV for 12 weeks, and 158 patients were 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 AbbVie regimen with RBV for 12 weeks.

Of the 473 patients randomized to the AbbVie regimen with RBV, one case (0.2 percent) of on-treatment virologic failure occurred and seven patients (1.5 percent) experienced post-treatment relapse. In addition, three patients (0.6 percent) were lost to follow-up and seven patients (1.5 percent) discontinued the study prematurely. Patients lost to follow-up were considered treatment failures.

About Study M13-098 (SAPPHIRE-II)
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 AbbVie's regimen with RBV in non-cirrhotic, GT1a and GT1b HCV-infected, treatment-experienced adult patients who previously failed treatment with pegylated interferon and RBV.

The study population consisted of 394 patients: 297 were randomized to the AbbVie regimen with RBV for 12 weeks, and 97 patients were 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 AbbVie regimen with RBV for 12 weeks.

Of the 297 patients randomized to the AbbVie regimen with RBV, there were no cases of on-treatment virologic failure and seven patients (2.4 percent) experienced post-treatment relapse. Of these patients, six were prior null responders and one was a prior relapser. Three patients (1.0 percent) prematurely discontinued therapy due to adverse events and one patient (0.3 percent) prematurely discontinued the study.

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

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

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

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

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

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

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

See approved product labels for more information.

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

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

Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," in AbbVie's 2013 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission.

AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

SOURCE AbbVie

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

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