Seven steps to a healthy liver

Dr Paramesh Rangesh, April 21, 2012

Liver is the one of the most important organs in the body and plays a pivotal role in overseeing almost all bodily functions. Weighing about 1.5 kilograms, it stores minerals, vitamins and manufactures new proteins when needed. The liver also produces bile, which aids in the process of fat digestion. The organ is responsible for breaking down therapeutic ingredients in medicine, so that it can be quickly absorbed by the body. Its supportive role in building coagulation capability helps in forming blood clots.

Interestingly, the liver can also completely regenerate itself. From just 25 per cent functionality, it can still rebuild itself into a fully-functional liver. Here are some healthy factors that will nurture the liver:

* Healthy diet: a diet rich in magnesium, iron, and carbohydrates will keep the liver healthy and help in detoxifying the body. Drinking plenty of water throughout the day is also essential.

* Avoid alcohol: Consuming large amounts of alcohol can lead to three serious conditions — alcoholic hepatitis, alcoholic cirrhosis and a fatty liver. Keep alcohol intake to a bare minimum or avoid alcohol altogether.

* Avoid drugs: recreational drugs severely damage liver cells. Some prescription drugs can also be hepatotoxic, so do not exceed the recommended dosage of medication, unless advised by a doctor.

* Organic foods: organic fruits and vegetables are high in antioxidants that protect the liver as well as help in its cleansing processes. Try to include organic foods in your diet.

* Avoid environmental pollutants: toxic fumes from paint thinners, bug sprays and other aerosols can enter the body through tiny blood vessels in your lungs and are carried to your liver, which can cause injury to the organ. Wear a protective mask when using these products.

* Exercise

* Get vaccinated: remember to vaccinate yourself against viral liver disease like hepatitis A and B.

The liver loves...

* Garlic: it is known to activate liver enzymes that flush away toxins from the body.

* Green, leafy vegetables: they are high in chlorophylls —spinach, mustard greens, broccoli and cabbage are great detoxifiers. Others like chicory and bitter melon help in increasing bile production.

* Turmeric: it is not only good for your curries, but boosts liver detoxification by flushing out known dietary carcinogens.

* Lemon and lime: they contain very high amounts of Vitamin C, which aids the body in synthesising toxic material into substance that can be absorbed by water. Drinking freshly-squeezed lemon or lime juice in the morning helps stimulate the liver.

* Beets and carrots: they help the liver by eliminating toxins like heavy metals from the body. They are also high in plant-flavanoids and beta-carotene that improve overall health.

Source

EASL 2012: Oral HCV Combo Effective for Genotype One

By Michael Smith, North American Correspondent, MedPage Today

Published: April 20, 2012

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania.

 

Action Points

• 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.
• In this small study, a combination oral therapeutic regimen, without interferon-alfa, including a investigational protease inhibitor and an investigational polymerase inhibitor was well tolerated and very effective in treatment of naive noncirrhotic patients with genotype 1 HCV.

An all-oral treatment regimen for hepatitis C had high response rates among patients with a hard-to-treat type of virus, a researcher reported.

After 12 weeks of therapy with two investigational direct-acting agents and ribavirin, 91% of patients with genotype one virus went on to have a sustained virologic response (SVR) 24 weeks later, according to Eric Lawitz, MD, of Alamo Medical Research in San Antonio.

It's the first time such a regimen -- given without interferon-alfa -- has shown such high response rates among patients with that type of HCV, Lawitz said at the meeting of the European Association for the Study of the Liver in Barcelona.

The regimen included one standard drug, ribavirin, as well as ABT-450/r, which is given with ritonavir (Norvir) and inhibits the viral NS3 protease inhibitor, and ABT-072, a non-nucleoside NS5B polymerase inhibitor.

In a small study of 11 patients who had not previously been treated for the virus, all showed sharp declines in hepatitis C RNA within three weeks of starting the 12 weeks of therapy and all had undetectable virus from week five through the end of treatment.

One patient relapsed by week eight after the end of treatment, but 91% were still virus-free at week 24 post-therapy and 82% were still clear by 36 weeks, Lawitz said.

He did, however, flag one case of a patient relapsing after the 36-week mark -- a case that has raised eyebrows at the meeting.

Lawitz said the drug's makers are not worried that the case will affect development of the drug, other experts said it may raise a red flag about approvals based on relatively short follow-up times.

"I suspect there are, or will be, others," according to Paul Pockros, MD, of the Scripps Clinic in La Jolla, Calif., who was not part of the study. "If it is one-off, the FDA will say it's fine, but if there are more, it could negatively affect" approvals for all of the new direct-acting agents, Pockros told a reporter.

Until recently, drug studies in hepatitis C used relatively long follow-ups, but in 2011, the FDA said future trials could use SVR 12 weeks after the end of therapy as an endpoint, because relapse usually occurs within that time.

Among the 10 patients with 48-week data available, there have been no more relapses, Lawitz reported.

The drug combination was well-tolerated. Most reported adverse events were mild and the most common were headache, fatigue, nausea, and dry skin. No patient stopped therapy because of adverse events.

There were two cases of transient bilirubin elevation, which took place during the first week of therapy but returned to normal with continued treatment.

The study was sponsored by Abbott Laboratories.

Several authors are employees of the company, which took part in data interpretation and approval of the presentation.

Primary source: EASL
Source reference:
Lawitz E, et al "A 12-week interferon-free regimen of ABT-450/r, ABT-072, and ribavirin was well tolerated and achieved sustained virologic response in 91% treatment-naïve HCV IL28B-CC genotype-1-infected subject" EASL 2012.

Source

Janssen launches EMEA division to market hepatitis C drug

Published: 20/04/2012

Janssen Pharmaceutica has set up a new division to market its hepatitis C product TMC435 to patients in Europe, the Middle East and Africa.

Janssen, which is itself a subsidiary of healthcare giant Johnson & Johnson (J&J), said the Janssen Therapeutics EMEA division will be based in Beerse, Belgium, and will bring together experts from across the region to tackle the disease.

At the heart of this will be the development and commercialisation of TMC435, an investigational protease inhibitor that the company is developing with its partner Medivir as a new class of hepatitis C treatment.

It is currently in late phase III clinical development in combination with current treatment option pegIFN/ribavirin.

Jane Griffiths, Janssen EMEA company group chair said: “The World Health Organization describes hepatitis C as a ‘viral time bomb’.

“That is why we have created a dedicated division, which will commercialise TMC435 and help meet hepatitis C patients’ needs. Janssen Therapeutics EMEA is on a mission to bring new options to successfully treat patients with this devastating disease.”

Outside the EMEA, J&J’s other subsidiary Tibotec plans to market the drug if approved.

The launch of Janssen Therapeutics EMEA coincides with European Association for the Study of the Liver (EASL) International Liver Congress 2012 in Barcelona.

At the congress, Janssen presented new retrospective analysis of phase III data for its other hepatitis C treatment Incivo (telaprevir).

The drug, which is approved in Europe to treat chronic hepatitis C in combination with pegIFN/ribavirin, demonstrated that a similar sustained virologic response (SVR) rate was achievable even if the dosage of ribavirin was lowered.

This could have benefits for people with hepatitis C, according to Janssen, as ribavirin is linked to incidents of anaemia in patients taken the combination of treatments.

Professor Mark Sulkowski, professor of medicine at Johns Hopkins University School of Medicine, Baltimore, said: “These results demonstrate that the reduction of ribavirin to help manage treatment-related anaemia when treating with telaprevir did not compromise the chance of clearing the virus.”

There will be an interview with Jane Griffiths in the May issue of Pharmaceutical Market Europe.

Source

J&J Open to Expanding Hepatitis C Cooperation With Vertex

By Makiko Kitamura on April 20, 2012

Johnson & Johnson (JNJ) (JNJ)’s Janssen unit said it may explore widening cooperation on hepatitis C withVertex Pharmaceuticals Inc. (VRTX) (VRTX) that may develop in tandem with a separate partnership with Medivir AB (MVIRB) on the disease.

“We remain open to see if we can expand our collaboration,” Gaston Picchio, vice president of Janssen’s global clinical virology and hepatitic disease area, said in an interview today in Barcelona, where he’s attending the European Association for the Study of the Liver annual meeting. “Vertex has announced plans for developing interferon-free therapies. We are partners, so that puts us in a better position to be a part of that,” should studies prove to be promising.

Vertex said on April 18 that it will start enrolling patients in a mid-stage study combining three medicines, excluding interferon, a core component of the current standard of care. Vertex and competitors including Gilead Sciences Inc. (GILD) (GILD),Bristol-Myers Squibb Co. (BMY) (BMY) and Abbott Laboratories (ABT) (ABT) are racing to develop next-generation treatments for hepatitis C that exclude interferon because of flu-like side effects.

Vertex and J&J collaborated to develop telaprevir, marketed as Incivek by Vertex in North America and as Incivo by Janssen in other regions including Europe. The drug was approved by regulators last year as a treatment for hepatitis C in combination with interferon and ribavirin.

Medivir Project

J&J, which has its headquarters in New Brunswick, New Jersey, is also developing the protease inhibitor TMC435 with Huddinge, Sweden-based Medivir, which has said mid-stage trials of the drug in interferon-free combinations with Gilead’s 7977 and with Bristol-Myers’s daclatasvir experimental drugs are starting in the second quarter.

While J&J and Medivir are also developing the TMC647 polymerase inhibitor, Vertex’s VX-222 compound in the same class of drugs is further along in development. VX-222 is one of the three drugs included in Cambridge, Massachusetts-based Vertex’s mid-stage interferon-free treatment study.

Meanwhile, J&J is also “committed” to improving the labeling of Incivo by conducting further trials that examine less frequent dosage as well as efficacy in patients also infected by the HIV virus and those who have had liver transplants, Picchio said.

To contact the reporter on this story: Makiko Kitamura in Barcelona via mkitamura1@bloomberg.net 

To contact the editor responsible for this story: Phil Serafino at pserafino@bloomberg.net

Source

Partner Up or Get Passed Up

By Brian Orelli, The Motley Fool

Posted 9:26AM 04/20/12 Posted under: Investing

I can only imagine the conversation:

Bristol-Myers Squibb (NYS: BMY) : "Hey partner, we've got a new hepatitis C drug candidate from our acquisition of Inhibitex. Want to combine it with your drug?"

Johnson & Johnson (NYS: JNJ) : "Sure, why not? Maybe it'll give us an edge against Gilead Sciences (NAS: GILD) , the front-runner in the quest for an all-oral hepatitis C treatment. But make sure you give it a really complicated name; INX-189 was too easy."

BMS: "Already done."

The duo expanded their partnership beyond combining BMS' daclatasvir with J&J's TMC435 to include a combination of TMC435 with BMS-986094, the compound formally known as INX-189. The companies also agreed that if daclatasvir and TMC435 work well in a phase 2 trial, they'll move it into a phase 3 trial.

The quest for an all-oral hepatitis C treatment to replace Merck's (NYS: MRK) PegIntron and Roche's Pegasys, which have to be injected, will likely require multiple drugs from different drugmakers. Hepatitis C drugs come in different classes that disrupt the virus in different ways. A few companies -- Gilead and Roche, for instance -- seem to have a drug in enough categories to develop a cocktail on their own, but that assumes they have the best (or at least good enough) drugs to get a decent cure rate. The current standard of care that combines an injectable drug with Vertex Pharmaceuticals' (NAS: VRTX) Incivek cures around 70% of patients, so any all-oral treatment would have to meet or exceed that.

Flying solo also poses a problem for timing. Gilead, for instance, is reportedly considering going it alone even though its GS-7977 works really well with Bristol's daclatasvir, as it has a drug of its own in the same class as daclatasvir. That choice will likely result in getting to the market slower.

Sure, combining drugs means sharing profits, but I think that's a good trade-off for the potential to be best in class and not let any other combination products pass you up.

Now if we can just get easy-to-remember trade names for all these drugs.

Source

World Liver Day 2012: Things you ought to know about your liver

Dr Ashwin Mallya, Apr 19, 2012 at 8:03 AM

Your liver is a one and a half kg organ that sits behind your right rib cage. If you did not have your liver, you would not be able to process nutrients like carbohydrates, proteins, fats, vitamins and minerals from your food. Your body would not get rid of all the toxins and microbes. Your blood would probably never clot! The liver plays a vital role in maintaining the body’s metabolic balance.

As the liver performs a variety of important functions it is extremely vulnerable to a variety of metabolic, toxic, microbial, circulatory and cancerous insults. Awareness of the liver’s functions and what all can cause liver disease can help you take the road to great health.

Let’s start with a few commonly known diseases that can affect the liver:

1. Fatty Liver: This disease was traditionally known to occur in association with excessive alcohol intake but now the non-alcoholic variant is reaching epidemic proportions in the developed countries. Known to occur in association with metabolic syndrome consisting of hypertension, diabetes, obesity and hyperlipidemia this disease occurs because of faulty fat metabolism in the liver. Prevention is the best treatment and if uncontrolled can even end up in liver failure.
2. Viral hepatitis is an infection of the liver that is caused by a group of viruses that have particular affinity for the liver. Out of these, hepatitis A and E are caused by eating food contaminated with the virus. Hepatitis B, C and D are acquired through blood, body fluids and by unprotected sexual contact.
3. Alcoholic hepatitis is inflammation (swelling) of the liver due to ingestion of alcohol.
4. Cirrhosis or scarring of the liver is caused mostly due to alcohol intake, viral infection due to hepatitis B and C , bile duct disease or iron overload. It is among the top 10 causes of death in the world. The liver ceases to function normally due to irreversible damage. It progresses gradually and can lead to end stage liver disease.
5. Drug induced damage caused due to the various medicines we take and chemicals we are exposed to. As liver is the major detoxifying organ in the body, it is subject to an enormous variety of drugs and chemicals. Always be careful when consuming medicines. Even over the counter medications like paracetamol can cause fulminant liver failure. Never take medications beyond the recommended dosage. It is always better to consult a doctor before taking medications and follow up at the slightest evidence of ill health. Certain herbal medications could also cause damage to the liver and so can medications for tuberculosis.
6. Liver cancer can be caused by many factors including viral infections (hepatitis B and C), chronic alcoholism, certain food contaminants, genetic factors, cirrhosis of the liver.

What are the symptoms of liver disease?

This depends on the onset and rapidity of progression of liver damage.

In case of acute liver damage (due to drugs, toxins, viral hepatitis A, B or E), there may be fever with yellowish discoloration of sclera (the white of the eye), skin and urine. In most cases this may be self-limiting. In a small percentage, this may progress to fulminant liver failure leading to coma, altered blood clotting, kidney failure, secondary infections and may even require liver transplantation.

In chronic liver damage (due to hepatitis B, C or alcohol), the symptoms would be more gradual in onset:

• Jaundice or yellowish discoloration of skin and the white of the eye.
• Swelling especially in the legs and feet due to low protein levels.
• Enlargement of breasts known as gynecomastia (in a male).
• Reddish spider like discolorations (spider nevi) beneath the skin especially over the chest.
• Accumulation of fluid (ascites) in the abdomen giving it a protruded appearance.
• Problems with clotting of blood
• Vomiting of blood or blood in stools
• Altered senses with change in behavior, confusion, forgetfulness and other symptoms related to the brain also known as hepatic encephalopathy.
• Gradual worsening of kidney function

The above symptoms are not comprehensive and it is best to consult a doctor at the earliest onset of any of the above.

Tips for a healthy liver:

Diet and Alcohol: A balanced diet with low fat content would be well suited to prevent fatty liver. Alcohol is best avoided.

Exercise: Plays a role in controlling cholesterol and in the metabolism of fat thus indirectly protecting the liver.

Vaccination: Hepatitis B is preventable by vaccination. Three shots of the hepatitis B vaccine taken over three months can provide long term protection against the dreaded disease.

Hygienic food and drinking water: Hepatitis A and E are known to spread via the oral route. Think twice before having road side delicacies! Boil the water that you intend to drink. It is the best way to prevent communicable diseases.

Avoid self-medication: Various drugs can damage the liver if taken indiscriminately

Regular check-ups: Once diagnosed with liver disease, be regular in follow ups with the doctor. Reversible damage can become irreversible if neglected.

This World Liver day, let’s strive not to abuse our liver, one of the most useful organs that we have. Let’s treat it with the love and respect it deserves.

Source

Patients seek refuge from overpriced treatment of hepatitis

Blame doctors, health officials and pharmaceutical companies of fleecing patients.

By Our Correspondent

Published: April 21, 2012

ISLAMABAD: Patients suffering from hepatitis B and C demanded on Friday that the government fix the price of Pegasys injection at Rs5,000, to preclude doctors and pharmacies from exploiting them.

A protest against the artificial price of life saving drugs including Pegasys was held outside the National Press Club on Friday.

The protest was attended by a large number of patients and human rights activists.

They said the actual price of the injection, manufactured by a multinational company, is not more than Rs3,000. However it is being sold in the market at inflated prices of Rs13,000.

They claimed the doctors prescribing the injection were receiving half of the price as kickbacks, while the rest of the money is distributed among importers, health officials, distributors and retailers.

“This is an organised crime against helpless patients who cannot afford four doses per month,” they asserted.

Over 10% of the county’s population is suffering from the deadly disease, which is mostly caused by reusing disposable syringes, transfusion of unscreened blood and use of unsterilised equipment in hospitals and clinics.

Pharmaceutical companies take full advantage of the situation by selling their drugs at exorbitant rates and barring the entry of affordable medicines in the market at the same time, the protesters said.

In addition, these companies have been found to be ignorant towards conducting research to produce cheaper medicines, claimed a protester.

Addressing the procession, Sawera Foundation Patron-in-chief Mian Ahmed said the government has been unable to control the pharmaceutical industries, which have been resisting development of indigenous drugs manufacturing.

He suggested allowing medicines to be imported from India and China would increase competition and hence fair valuation of medicines. “The same injection will cost Rs1,500 if we import it from India,” said Ahmed.

Nineteen-year-old Parveen, a resident of katchi abadi in F-11, said she was diagnosed with hepatitis C during pregnancy last year but could not afford the expensive treatment.

Parveen got the disease when she had her tooth removed from a roadside dentist in Golra Sharif.

“I will continue living with the disease for the rest of my life as I make only Rs3,000 per month,” she added.

Published in The Express Tribune, April 21^st, 2012.

Source

EASL 2012: Safety OF TELAPREVIR or Boceprevir IN COMBINATION WITH Peginterferon alfa/Ribavirin, in CIRRHOTIC NON RESPONDERS.

Abstract

Title
Safety OF TELAPREVIR or Boceprevir IN COMBINATION WITH Peginterferon alfa/Ribavirin, in CIRRHOTIC NON RESPONDERS. FIRST RESULTS OF THE FRENCH EARLY ACCESS PROGRAM (ANRS CO20-CUPIC)

Speaker:
Christophe Hezode

Author:
C. Hezode¹*, C. Dorival², F. Zoulim³, T. Poynard⁴, P. Mathurin⁵, S. Pol⁶, D. Larrey⁷, P. Cacoub⁴, V. de Ledinghen⁸, M. Bourlière⁹, P.H. Bernard¹⁰, G. Riachi¹¹, L. Alric¹², D. Samuel¹³, Y. Barthe², H. Fontaine⁶, F. Carrat², J.-P. Bronowicki¹⁴, ANRS CO20 CUPIC study group

Affiliation:
¹Hôpital Henri Mondor, Inserm U955, Université Paris-Est, Creteil, ²Hôpital Saint-Antoine, Inserm U707, UPMC-Paris6, Paris, ³Hospices Civils de Lyon, Lyon, ⁴Hôpital de la Pitié-Salpêtrière, Paris, ⁵Hôpital Claude Huriez, Lille, ⁶Hôpital Cochin, Inserm U1016, Université Paris Descartes, Paris, ⁷Hôpital Saint-Eloi, Montpellier, ⁸Hôpital Haut-Lévèque, Pessac, ⁹Fondation Hôpital Saint Joseph, Marseille, ¹⁰Hôpital Saint André, Bordeaux, ¹¹Hôpital Charles Nicolle, Rouen, ¹²Hôpital Purpan, Toulouse, ¹³Hôpital Paul Brousse, Villejuif, ¹⁴Hôpital de Brabois, Nancy, France. *christophe.hezode@hmn.aphp.fr

Phase III trials have shown that Telaprevir (TVR) is associated with frequent dermatological disorders and anemia, whereas Boceprevir (BOC) is associated with frequent anemia. However, few cirrhotic patients were included in these trials. We report the safety profiles of TVR or BOC in combination with peginterferon (PEG-IFN) and ribavirin (RBV) in the French Early Access Program for the use of protease inhibitors (PI).

Methods: Patients with compensated child A cirrhosis, HCV genotype 1 infection and prior relapse or partial response to PEG-IFN/RBV regimen were prospectively included to receive either 12 weeks of TVR, PEG-IFN-alfa2a/RBV and 36 weeks of PEG-IFN-alfa2a/RBV, or 4 weeks of PEG-IFN-2b/RBV and 44 weeks of BOC, PEG-IFN-2b/RBV without randomization which precludes any comparison between the two molecules. Safety analysis is restricted to patients with at least 8 weeks of treatment.

Results: Female-to-male ratio was 0.4 and mean age was 57 years in each group. Safety profiles are summarized in the table.

Conclusions: The safety profile of TVR or BOC with PEG-IFN/RBV in cirrhotic patients was poor and associated with increased SAE rates (30% to 51%) compared to those reported in phase III trials (9% to 14%). These data strongly suggest that triple therapy must be administered cautiously with intensive safety monitoring in these patients.

	TVR n=169	BOC n=138
Median treatment / PI duration (days)	112.0 / 85.0	113.0 / 84.0
Serious adverse events (SAE) / Discontinuation(AE)	87 (51%) / 20 (12%)	41 (30%) / 10 (7%)
Death	3 (2%)	1 (1%)
Anemia Grade 2(8.0-<10.0g/dL) / Grade 3-4(<8.0g/dL)	54 (32%) / 23 (14%)	39 (28%) / 8 (6%)
EPO use / Blood transfusion	94 (56%) / 32 (19%)	71 (51%) / 8 (6%)
Neutropenia Grade3-4(<1000/mm3) / G-CSF use	21 (12%) / 5 (3%)	14 (10%) / 7 (5%)
Thrombopenia Grade 3-4(<50000/mm3) / Thrombopoietin use	37 (22%) / 1 (1%)	10 (7%) / 1 (1%)
Rash Grade 3 / SCAR	11 (7%) / 0 (0%)	1 (1%) / 0 (0%)
Grade 3-4 infection / other AEs	4 (2%) / 90 (53%)	1 (1%) / 44 (32%)

[safety profile]

Source

EASL 2012: Poster Presentations, Slides and Press Releases

 

All links will open into a new window taking you to the NATAP website

1. EASL: The efficacy and safety of the interferon-free combination of BI 201335 and BI 207127 in genotype 1 HCV patients with cirrhosis: Interim analysis from SOUND-C2 - (04/20/12)
   
   
2. EASL: GS-7977 + PEG/RBV in HCV Genotype 1: The ATOMIC Trial An End To Response-Guided Therapy - (04/20/12)
   
   
3. EASL: GS-7977 Phase 2 Trials: Concordance of SVR4 with SVR12 and SVR24 in HCV Genotypes 1-3 - (04/20/12)
   
   
4. EASL: Peginterferon Lambda-1A (Lambda) Compared With Peginterferon Alfa-2A (Alfa) in Treatment- Naive Patients With HCV Genotypes 2 or 3: First SVR24 Results From EMERGE Phase IIb - (04/20/12)
   
   
5. EASL: Dual Oral Therapy with NS5A Inhibitor Daclatasvir (BMS-790052) and NS3 Protease Inhibitor Asunaprevir (BMS-650032) in HCV Genotype 1b-Infected Null Responders or Patients Ineligible/Intolerant to Peginterferon/Ribavirin - (04/19/12)
   
   
6. EASL: TMC435 with peginterferon and ribavirin in treatment-experienced HCV genotype 1 patients: the ASPIRE study, a randomised Phase IIb trial - (04/19/12)
   
   
7. EASL: TMC435 in patients infected with HCV genotype 1 who have failed previous pegylated interferon / ribavirin treatment: Virologic analyses of the ASPIRE trial - (04/19/12)
   
   
8. EASL: Potent Viral Suppression With the All-Oral Combination of Daclatasvir (NS5A Inhibitor) and GS-7977 (Nucleotide NS5B Inhibitor), +/- Ribavirin, in Treatment-Naive Patients With Chronic HCV GT1, 2, or 3 (100% SVR gt1, 91% gt2) - (04/19/12)
   
   
9. EASL: A 12-Week Interferon-Free Regimen of ABT-450/r, ABT-072, and Ribavirin was Well Tolerated and Achieved Sustained Virologic Response in 91% Treatment-Naïve HCV IL28B-CC Genotype-1-Infected Subjects - (04/19/12)
   
   
10. EASL: All-Oral Combination of Investigational Hepatitis C (HCV) Compounds Daclatasvir and GS-7977 Achieved Sustained Virologic Response (SVR4) in 100% of Genotype 1 and 91% of Genotype 2 and 3 Treatment-Naïve Patients in Phase II Study - press release - (04/19/12)
    
    
11. EASL: Gilead Announces Early Sustained Virologic Response Rates for GS-7977 Plus Ribavirin in Genotype 1 Treatment-Naïve Hepatitis C Patients - press release - (04/19/12)
    
    
12. EASL: Gilead Announces Sustained Virologic Response Data for 12-Week Regimen of GS-7977 Plus Pegylated Interferon and Ribavirin in Genotype 1 Hepatitis C Patients - press release - (04/19/12)
    
    
13. EASL: Gilead Announces Early Sustained Virologic Response Rates for GS-7977 Plus Ribavirin in Genotype 1 Treatment-Naïve Hepatitis C Patients - press release - (04/19/12)
    
    
14. EASL: Viral cure achieved without interferon in up to 82% of hepatitis C patients (GT-1a & -1b*): protease inhibitor BI 201335 and the polymerase inhibitor BI 207127, both with and without ribavirin (Boerhinger Ingelheim) - press release - (04/19/12)
    
    
15. EASL: First ever data investigating interferon-free treatment in hepatitis C patients who have liver cirrhosis shows high viral cure rate: protease inhibitor BI 201335 plus the polymerase inhibitor BI 207127 plus ribavirin (Boerhinger Ingelheim) - (04/19/12)
    
    
16. EASL: Confirmation That Quadruple Therapy With Daclatasvir (NS5A Inhibitor), Asunaprevir (NS3 Inhibitor) and Peginterferon/Ribavirin Results in a High Rate of SVR4 in HCV Genotype 1 Null Responders - (04/19/12)
    
    
17. EASL: Abbott Presents Positive Results from Interferon-Free Phase 2 "Co-Pilot" Study for the Treatment of Hepatitis C - Press Release - (04/19/12)

EASL 2012: Video Chronic Hepatitis C: A Global Public Health Crisis

Published on Apr 20, 2012 by SaluteDomaniTV

Chronic hepatitis c is a viral infection of the liver that affects approximately 130 to 1170 million people around the world.

If left untrated, Hcv infection is potentially serious disease that can damage the liver over time and lead cirrhosis, end stage liver disease and liver cancer.

Victrelis -boceprevir is approved for treatment of Hcv genotype 1 infection, in combination with peginterferon alfa and ribavirin in adult patients with compensated liver disease who are previously untreated or who have failed previous therapy.

EASL 2012: New data provides hope for HCV non-responders

Provided by News-Medical.Net

Published on April 20, 2012 at 8:35 AM

New data from a number of clinical trials presented for the first time at the International Liver Congress- 2012 provides hope for previously difficult to treat hepatitis C (HCV) patient populations.

In the first multicentric study of the efficacy and safety of the protease inhibitors (PI) Boceprevir or Telaprevir in patients with severe HCV genotype 1 (GT1) recurrence after liver transplantation, results show that 57% of patients achieve undetectable hepatitis C viral loads 24 weeks after treatment (SVR24) with pegylated Interferon-alfa-2b (PegIFN-α-2b), ribavirin (RBV) and either Boceprevir or Telaprevir. Interactions between immunosuppressants and PIs were easily controlled.

Further new data shows that, in HCV GT1 and HIV co-infected patients, the addition of Boceprevir to PegIFN-α-2b and RBV results in higher rates of undetectable HCV RNA levels compared to treatment with only PegIFN-α-2b and RBV alone. At the end of treatment (week 48), 63.9% of patients receiving Boceprevir, PegIFN-α-2b and RBV had undetectable HCV RNA, compared to 29.4% in the control arm. The study found the safety and tolerability profile of Boceprevir, PegIFN-α-2b and RBV was consistent with that observed in HCV-monoinfected patients.

The combination of these findings provides new hope for various difficult to treat hepatitis C populations. Professor Mark Thursz, EASL's Secretary General commented on the exciting new data: "Patients with HIV co-infection and patients who have been transplanted for HCV infection often have more aggressive disease and have been harder to treat. Worries about drug-drug interactions have caused concern about the use of protease inhibitors in these groups. The new trial data shows that the benefits of direct anti-virals can now be experienced by a wider group of patient populations."

In a study of chronic HCV GT1 patients previously unresponsive to treatment with PegIFN and RBV alone , new data shows TMC435 - an oral, once-daily, investigational HCV NS3/4A protease inhibitor - combined with PegIFN-alfa-2a and RBV achieves significantly higher SVR24 rates compared with placebo. In the hardest to treat group of prior null-responders with cirrhosis, TMC435, PegIFN-alfa-2a and RBV treatment shows 61-80% SVR24 compared to 23% with placebo.

In other exciting data presented at the congress, the authors of a study on PSI-7977, a uridine nucleotide analog, propose that it may signal an end to response guided therapy in HCV GT1 patients. Response-guided therapy is a paradigm for treating chronic HCV infections in which treatment decisions are based on how rapidly HCV responds to treatment. With response-guided therapy, patients who rapidly clear virus from their bloodstream are eligible to receive a shorter duration of therapy, while slower responders receive standard or extended durations of therapy.

In earlier studies, PSI-7977 has been associated with greater than 90% SVR (sustained virological response undetectable HCV RNA level 24 weeks after treatment) in HCV GT1, GT2, or GT3 patients, independent of predictors of poor responsiveness to interferon. In new data presented at the congress, the study authors show HCV GT1, GT4, or GT6 patients treated with PSI-7977 and PEG/RBV achieved 97% RVR (rapid virological response - undetectable HCV RNA level after four weeks of treatment), with no viral breakthrough or relapse observed to date in subjects completing at least 10 weeks of PSI-7977.

Source: European Association for the Study of the Liver

Source

New Drug Combination Possible For Hepatitis C

from Patricia: I love what Dr. Friedman has to say here about the behavior of Gilead and BMS in light of the excellent trials results released yesterday at the International Liver Conference. He has hit the nail on the head. They are playing with people’s lives here …

Submitted by Annabel Tautou on Fri, 04/20/2012 - 07:57

It has been recently revealed in a report that there has been a new drug combination made that can effectively treat hepatitis C in the time to come. This has even proved to work well in a small scale trial. This means that in the time to come, it might surely be able to prove its worth as a potential way to treat or at least work towards securing the body, when it comes to the affliction of this disease.

“The only appropriate motivation should be what is the best and fastest way to get cures, not what is best for the shareholders”, revealed Dr. Scott Friedman, chief of liver diseases at the Mount Sinai School of Medicine in New York.

Though it is too early to jump to any conclusions as of now, it might still be a very positive step in the time to come. It might be able to form an effective way to cure the disease and might even prevent it from occurring in the time to come.

There are currently a number of companies trying their best to formulate such medicines that work towards eradicating this disease from the world. There is however need for more efforts to be made by one and all for collectively being able to fight the disease in the time to come, rather than fighting on which company has been able to form the drug.

The cure percentage for the drug has been greatly improved by the introduction of the pills by Vertex Pharmacy firm, which gave out its drug last year. It remains to be seen how the firms trying to develop cures shall be able to find it in the time to come and how cure methods can be made better for the disease.

Source

Also See:

1. Have BMS and Gilead found the 'killer app' for hep. C?
2. Collaboration on Hepatitis Drugs Lags
3. Gilead, Bristol Put Profits Ahead of Best Care for Hep C Patients

Have BMS and Gilead found the 'killer app' for hep. C?

Marc Iskowitz

April 19, 2012

Scientists are getting closer to finding the killer app in treating hepatitis C, but it may be too soon to pick a winner.

Bristol-Myers Squibb and Gilead said this morning that an all-oral therapy joining together two drugs the companies are each developing suppressed the virus in more than 95% of patients across a broad spectrum of genotypes.

The drug combo of daclatasvir from BMS and Gilead's GS-7977 reached a 100% sustained virologic response (SVR), or cure rate, at week four in one common subgroup, genotype 1 patients who have not been previously treated with interferon—an injectable associated with flu-like side effects.

The 100% cure rate held even when ribavirin, another traditional mainstay of treatment, was left out of the mix, bettering a roughly 90% SVR rate seen for an Abbott triple therapy in a trial a few weeks ago.

“It obviously doesn't get any better than this,” cheered ISI analyst Mark Schoenebaum in a quick note to investors this morning after BMS and Gilead announced their results. Data from the Phase II combo trial are “best case,” he added, in that only 2% of respondents to an informal survey he fielded earlier this month said they expected the 100% SVR rate.

The findings accelerated momentum in an already fast-moving category, in which drugmakers are swooping up assets to pad HCV pipelines and experimenting with a variety of regimens and combinations. Last November Gilead agreed to pay almost $11 billion for biotech firm Pharmasset's GS-7977, and BMS in January said it was buying Inhibitex for about $2.5 billion and getting access to that firm's potential HCV drug, INX-189.

The direct-acting antivirals (DAAs) from BMS, Gilead and Abbott are showing the best efficacy and tolerability to date.

Not that there haven't been speed bumps along the way. In February, Gilead's ‘7977 had come under assault when data showed that six out of six subjects treated with the pipeline drug, who were prior null responders to other HCV therapy, had experienced a relapse of their disease.

Analysts had predicted that patients who are naïve to therapy would be easier to treat with a non-interferon regimen than null responders, and the Gilead/BMS data furthered this notion. Several analysts now believe daclatasvir, an NS5a inhibitor, and ‘7977, a nucleotide analog (or “Nuc” as the class is called), may form the best treatment “backbone” option across all genotypes.

“It appears that the ‘killer app' in HCV is probably an NS5A plus a nuc without ribavirin,” Schoenebaum declared.

The newer protease inhibitors—Vertex's Incivek and Merck's Victrelis, both launched in 2011—look like they will be vulnerable to the all-oral regimens, but not for a few years.

“These results obviously reinforce the expectation that DAA-only (IFN and RBV-sparing) regimens will likely quickly supplant current HCV treatments when they become available in the 2015/2016 timeframe,” wrote Deutsche Bank's Barbara Ryan in a note today.

In a Thursday dispatch to investors, Credit Suisse's Catherine Arnold said the data also “takes a little shine off” Abbott's HCV program, “but we still view it as a competitive presence.” The triple therapy combines the firm's protease inhibitor ABT-450 + non-nucleoside polymerase inhibitor ABT-333 + ribavirin.

While the Gilead/BMS combination sets the bar high for competitors, scientists are still debating where the best treatment synergy lies, and firms are awaiting more data before finalizing their commercial plans.

The Gilead/BMS combo “represents the most compelling all-oral, interferon-free data in the highly visible [HCV] marketplace,” noted Arnold. “Despite this strong data,” she added, “a partnership is unlikely in the near term as both companies wait for additional data sets related to their HCV assets to fully evaluate their options.”

Ryan cautioned that other factors—side effects, dosing convenience and, of course, cost—“will be important considerations in determining market share. In our opinion, it is premature to conclude who the ultimate winners and losers will be in the ‘new' HCV market on the basis of the data available to date.” Ryan doesn't think any one or two players will dominate the field. Null and non-responders could also be a factor in determining long-term HCV dominance.

Results from a cocktail joining Gilead's ‘7977 and ribavirin also surprised, hitting an SVR rate of 88%—far better than the 50% the Street had expected, according to Schoenebaum. Abbott's all-oral triple combo may be another good backbone option, while daclatasvir so far looks like a solid add-on option—one that has pan-genotype efficacy and excellent tolerability—and BMS is exploring multiple pairing options (including with its own Nuc, INX-189).

Other Nucs in development include Vertex's ALS-2200 and ALS-2158, and biotech firm Idenix's IDX184, which can be combined with its NS5A inhibitor, IDX719.

Source

Also See:

1. Collaboration on Hepatitis Drugs Lags
2. Gilead, Bristol Put Profits Ahead of Best Care for Hep C Patients

EASL 2012:Sequana Medical's ALFApump(R) System Proves to Be a Safe and Efficacious Breakthrough Technology in Ascites Management

PRESS RELEASE

April 20, 2012, 4:00 a.m. EDT

Data presented at the International Liver Disease Meeting demonstrated that the ALFApump System significantly decreases the need for Large Volume Paracentesis and can reduce hospital visits

ZURICH, Apr 20, 2012 (BUSINESS WIRE) -- Sequana Medical announced that initial results from the PIONEER Clinical Study of its ALFApump System were presented today at the 47th annual European Association for Study of the Liver Meeting in Barcelona. The data demonstrated that the ALFApump System is a safe and effective device for management of ascites in patients with advanced cirrhosis. The PIONEER study is a prospective, multi-centre, open label study of patients with refractory ascites due to liver cirrhosis conducted at nine centres in four European countries. Sequana Medical's ALFApump System is the first and only system for the automatic and continual removal of ascites. Refractory ascites affects over 100,000 patients in Europe and the US every year and the number of patients is growing at an annual rate of 10% due to the accelerating incidence of hepatitis and obesity-related liver disease.

Dr. Jose Such, Chief of Hepatology at the Hospital General, University de Alicante, Spain, presented initial data in a session entitled "Description of an Automated Low-Flow Ascites (ALFA) pump system for the treatment of ascites in patients with cirrhosis. Preliminary Report". In addition to safety and efficacy, the data showed that the ALFApump System significantly reduced the median number of paracentesis procedures from 3.4 in the month prior to pump implant to just 0.2 per month and there was a 91% reduction in the volume removed by paracentesis.

Ascites is a common complication among patients with late-stage liver disease and is the leading reason for hospitalization among patients with cirrhosis. Paracentesis, which involves inserting a large-bore needle into the abdomen to drain 5-10 litres of accumulated ascites, is the most common procedure for the treatment of ascites. However, paracentesis has to be repeated frequently, often every 7-10 days, as it doesn't prevent the re-accumulation of ascites. This repeated procedure is burdensome both to the patient and healthcare service provider.

"The ALFApump System was developed to bring significant benefits to both patients and physicians, and has the potential to become the new standard of care for management of refractory ascites", said Dr. Noel L. Johnson, CEO of Sequana Medical. "I am quite pleased that the EASL Board selected the abstract describing the initial data from the ALFApump Pioneer Study for oral presentation at this year's International Liver Congress."

The ALFApump System consists of a subcutaneously implanted battery-powered pump connected to a catheter placed in the abdominal cavity which automatically and continually collects ascites and moves it to the bladder, where it is eliminated from the patient through normal urination.

"I am delighted to have had the opportunity to present these promising results from the Pioneer Study at the EASL congress", stated Dr. Jose Such. "The ALFApump System is proving to be a safe and efficacious device that will improve the lives of thousands of patients with refractory ascites by freeing them from the burden of repeat visits to the hospital for paracentesis."

The ALFApump System was granted CE Mark in 2011 and is currently being introduced into leading hepatology centres across Europe.

About Sequana Medical:

Founded in 2006, Sequana Medical AG is a Swiss medical device company backed by NeoMed Management, VI Partners, Biomed Invest, Capricorn Health Tech and Entrepreneur's Fund, dedicated to improving patient lives through innovative technologies to manage fluid overload in patients suffering from liver disease, cancer and congestive heart failure.

SOURCE: Sequana Medical

Source

Collaboration on Hepatitis Drugs Lags

David Paul Morris/Bloomberg News

A machine purifying a drug at a Gilead Sciences laboratory in California.

By ANDREW POLLACK

Published: April 19, 2012

A combination of two pills proved extremely effective in treating hepatitis C in a small trial, raising hopes among researchers that the disease will be curable without an injected drug that has debilitating side effects.

But the combination might not find its way to the market because one pill is owned by Gilead Sciences and the other by Bristol-Myers Squibb. The companies have not agreed to collaborate, to the chagrin of some doctors.

“The only appropriate motivation should be what is the best and fastest way to get cures, not what is best for the shareholders,” said Dr. Scott Friedman, chief of liver diseases at the Mount Sinai School of Medicine in New York, who was not involved in the trial.

Dr. Douglas J. Manion, a senior vice president for Bristol-Myers, said his company was “keen” on working with Gilead but that “thus far, they have been unwilling to engage in that collaboration.”

Norbert W. Bischofberger, executive vice president for research and development at Gilead, said his company wanted to wait several months for data on other treatment options before deciding what path to take.

“We told them it’s too early to jump wildly into this collaboration,” he said.

Both executives spoke separately by telephone from the International Liver Congress in Barcelona, Spain, where data on the drug combination was presented.

Gilead and Bristol are among the leaders of one of the most heated races in the pharmaceutical industry — to develop an all oral treatment for hepatitis C, a liver-damaging virus that infects three million to four million Americans.

New pills introduced last year by Vertex Pharmaceuticals and Merck have sharply improved the cure rate, to about 60 to 80 percent. But those drugs must still be used alpha interferon, which is injected weekly for up to a year and can cause flulike symptoms.

Many companies are trying to develop combinations of pills — similar to those used to treat H.I.V. — that would eradicate the virus without the need for interferon.

Results from several companies presented at the Barcelona conference have given doctors confidence that this will indeed be possible, with the first such combinations reaching the market perhaps by 2014.

Dr. Melissa Palmer, who was a practicing liver specialist until last fall, said that the trials were small and patients were usually not followed long enough to see if they were truly cured.

“It’s going to be important to wait a longer time to see if these results are sustainable,” said Dr. Palmer, who is now a consultant to investors.

Nonetheless, investors were busily predicting from the Barcelona data which companies will capture the billions of dollars a year in possible sales. Besides Gilead and Bristol, some mentioned Abbott Laboratories, which also presented strong preliminary data.

Gilead, a leader in drugs for AIDS, paid $11 billion a few months ago to acquire Pharmasset, based on very preliminary data on its hepatitis drug, now called GS-7977. Subsequent data was not as good and Gilead’s stock sank.

But the data announced on Thursday appeared to restore confidence in 7977. Shares of Gilead gained 12 percent to $52.25. Shares of Bristol rose 1 percent to $33.93.

All 29 of the patients with the strain of the virus that is most common in the United States had no detectable virus in their blood four weeks after finishing 24 weeks of treatment with GS-7977 and Bristol’s pill, daclatasvir. The figure was 28 out of 30 patients with two other virus strains. Each pill was taken once a day.

Doctors usually wait 12 to 24 weeks after finishing treatment to declare a cure, since there can be relapses.

Dr. Bischofberger said that before deciding whether to work with Bristol on a larger trial, Gilead wanted to wait a few months for data showing whether the same two drugs would work with only 12 weeks of treatment instead of 24.

He said he also wanted to see whether Gilead could improve results of using GS-7977 with ribavirin, a drug that is part of the existing treatment.

A combination of GS-7977 with ribavirin, which is generic, would be far less expensive than a combination with daclatasvir, he said, because new hepatitis drugs are expected to cost tens of thousands of dollars for a course of treatment.

A combination with ribavirin would also mean that Gilead would not have to split revenues with Bristol, making it easier to recoup the money it spent to buy Pharmasset.

Dr. Bischofberger said that once both 7977 and daclatasvir won approval, doctors could use them together, so patients would not be shortchanged if the companies did not collaborate.

Source

Also See: Gilead, Bristol Put Profits Ahead of Best Care for Hep C Patients

EASL 2012: Recapitulation of the entire hepatitis C virus life in engineered mouse cell lines

Public release date: 19-Apr-2012

Contact: Travis Taylor
easlpressoffice@cohnwolfe.com
44-789-438-6428
European Association for the Study of the Liver

A US study presented today at The International Liver CongressTM 2012 demonstrates that the entire HCV lifecycle can be recapitulated in murine cells, implying that HCV permissive mouse models could soon be developed.(1)

The data suggests that HCV replication in the murine environment is limited by innate immune responses. Inactivating these pathways and the expression of the appropriate entry factors and miR-122 creates murine fibroblasts that can be infected and support replication.

The study also corroborates previous data that the expression of apoE promotes production of infectious virus.

Although mouse orthologs of MAVS and TRIF could be cleaved by the HCV NS3/4A protease, this was not enough to establish robust HCV replication.

In contrast, impairment of type I and type III IFN signaling enhanced the permissiveness of murine fibroblasts for persistent HCV replication.

The in-depth study of hepatitis C pathogenesis and immune responses is currently hampered by the lack of suitable small animal models. This study is a positive step to addressing this issue.

###

References

1. Vogt A, Recapitulation of the entire Hepatitis C virus life in engineered mouse cell lines. Abstract presented at the International Liver CongressTM 2012

Source

EASL 2012: Gut Microbiota Transplantation may Prevent Development of Diabetes and Fatty Liver Disease

PRESS RELEASE

April 19, 2012, 5:00 a.m. EDT

BARCELONA, Spain, April 19, 2012 /PRNewswire via COMTEX/ -- Exciting new data presented today at the International Liver Congress™ 2012 shows the gut microbiota's causal role in the development of diabetes and non-alcoholic fatty liver disease (NAFLD), independent of obesity[1]. Though an early stage animal model, the French study highlights the possibility of preventing diabetes and NAFLD with gut microbiota transplantation - the engrafting of new microbiota, usually through administering faecal material from a healthy donor into the colon of a diseased recipient.[2]

To view the Multimedia News Release, please click:

http://multivu.prnewswire.com/mnr/prne/easl/53808/

In the 16 week study, two groups of germ free mice received gut microbiota transplants; one set from donor mice displaying symptoms of insulin resistance and liver steatosis (responders), the other from normal mice (non responders). The donor mice were selected due to their response to being fed a high fat diet.

The germ free group that received microbiota from symptomatic mice (responder receivers - RR) showed higher levels of fat concentration in the liver as well as being insulin resistant. The germ free group that received microbiota from healthy mice (non-responder-receivers - NRR) maintained normal glucose levels and sensitivity to insulin.

EASL Scientific Committee Member Dr Frank Lammert said: "The factors leading to Non-Alcoholic Fatty Liver Disease (NAFLD) are poorly understood, but it is known that NAFLD and Type 2 diabetes are characterised, respectively, by liver inflammation and metabolic disorders like insulin resistance."

"This study shows that different microbiota cause different metabolic responses in animals. By implanting microbiota from healthy mice, the study authors prevented the development of liver inflammation and insulin resistance, both indications of liver disease and diabetes. Thus, gut microbiota transplants could have a therapeutic role in the development of these diseases."

The RR mice also showed lower levels of microorganisms than usually found in the healthy gut. Lachnospiraceae was identified as the species most important in developing fatty liver and insulin resistance.

At present, the intestinal microbiota is considered to constitute a "microbial organ": one that has pivotal roles in the body's metabolism as well as immune function. Therefore transplantation aims to restore gut functionality and re-establish a certain state of intestinal flora.

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™ 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

iLiver iPhone app - a free medical app developed by EASL, with content fully authored, validated and accredited by 42 independent liver specialists

About The International Liver Congress™ 2012

The International Liver Congress™ 2012, the 47th annual meeting of the European Association for the study of the Liver, is being held at the Centre Convencions Internacional (CCIB) in Barcelona from April 18 - 22, 2012. The congress annually attracts over 8,300 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.

References

1. Le Roy T et al. Gut microbiota transplantation demonstrates its causal role in the development of type 2 diabetes and fatty liver. Abstract presented at the International Liver Congress™ 2012

2. Khoruts A and Sadowsky MJ, Therapeutic transplantation of the distal gut microbiota. Mucosal Immunology 2011;4:4-7

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  Travis Taylor +44(0)7894-386-422 Vicky O'Connor +44(0)7894-386-428

Video: http://multivu.prnewswire.com/mnr/prne/easl/53808/

SOURCE European Association for the Study of the Liver

Source

EASL 2012: Abbott Presents Positive Results from Phase 2 "Pilot" Study of an Interferon-Free Combination Regimen for the Treatment of Hepatitis C

Results among the Most Mature Data for an Interferon-Free Regimen, Including 36-Week Post-Treatment Sustained Viral Response for a 12-Week Treatment Regimen

April 19, 2012

Abbott Park, Illinois (NYSE: ABT) and Watertown, Massachusetts — Complete data from the study known as "Pilot" – Abbott's initial interferon-free study of its direct-acting antiviral agents for the treatment of hepatitis C (HCV) – showed that 91 percent of genotype 1 infected, treatment-naïve patients taking ABT-450/r and ABT-072 combined with ribavirin administered for 12 weeks, achieved sustained viral response at 24 weeks (SVR24). 82 percent of patients achieved SVR36. This is among the first 12-week, interferon-free HCV regimen with 36-week post-treatment data in genotype 1 patients. Results were presented today at the International Liver Congress 2012 (ILC 2012), the annual meeting of the European Association for the Study of the Liver (EASL), April 18-22 in Barcelona, Spain.

"The sustained viral response rates in this study are very encouraging as there are currently no treatment options for patients with HCV who cannot take or are intolerant to interferon," said Eric Lawitz, M.D., medical director at Alamo Medical Research in San Antonio, and the lead investigator for the study. "This is one of the earliest looks at mature data and it continues to demonstrate that a 12-week combination regimen of direct-acting antiviral treatments has the potential to offer high cure rates while eliminating the use of interferon."

Current treatments for HCV remain interferon-based. A significant number of HCV patients are unable or unwilling to take interferon due to contraindications and/or side effects, which may include flu-like symptoms, depression and insomnia. Specifically targeted antiviral therapies for HCV, such as protease inhibitors and non-nucleoside polymerase inhibitors, may have the potential to increase the proportion of patients in whom the virus can be eradicated.

About Study M12-267 (Pilot) and Key Findings

• The objectives of the 12-week, Phase 2 study were to assess the safety, tolerability, pharmacokinetics and antiviral activity of ABT-450/r 150/100 mg QD and ABT-072 400 mg QD + ribavirin administered for 12 weeks.
• The study was conducted in 11 treatment-naïve adults with host IL28B "CC" genotype from multiple ethnic backgrounds with non-cirrhotic HCV GT1
  (8 GT 1a, 3 GT 1b). Ribavirin dose was weight-based (1,000-1,200 mg/day) and dosed twice daily.
• The primary endpoint was percentage of patients with HCV RNA <25 IU/mL from week 4 through 12. Other trial endpoints include early virologic response, RVR and SVR through 24 weeks.
• 100 percent of patients maintained HCV RNA levels <25 IU/mL from weeks 4 through 12 of treatment, and all had undetectable HCV RNA from week 5 to the end of treatment.
• 91 percent of patients (10 of 11) achieved SVR24.
• One relapse was observed 8 weeks post therapy and a second 36 weeks post therapy; overall, 82 percent of patients (9 of 11) achieved SVR₃₆.
• No additional relapses were seen among the 10 patients with 48-week post-treatment data available / where SVR₄₈ results were available.
• In the trial, the most common adverse events were headache (36%), fatigue (27%), nausea (27%) and dry skin (27%). Most adverse events were mild in severity and there were no discontinuations due to adverse events.
• Two bilirubin elevations, which consisted of indirect bilirubin with no associated transaminase elevations (i.e. no indication of liver damage), were reported during the study. The bilirubin elevations occurred one week after starting treatment and resolved with continued dosing.

"Abbott is proud to present some of the first sustained viral response data for short course, interferon-free regimens for the treatment of HCV," said Scott Brun, M.D., divisional vice president, Infectious Disease Development, Abbott. "With a research portfolio that encompasses multiple direct-acting antiviral treatments in different drug classes, Abbott has the ability to quickly study a variety of combination regimens for HCV, with a focus on interferon-free regimens, to determine which has the greatest potential to help the largest number of patients."

ABT-450 is being developed with low dose ritonavir which enhances the pharmacokinetic properties of ABT-450. The use of ritonavir 100 mg with ABT-450 for the treatment of HCV is investigational.

ABT-450 was discovered during the course of collaboration between Abbott and Enanta Pharmaceuticals for protease inhibitors. ABT-450 is being developed by Abbott for use in combination with Abbott's non-nucleoside polymerase inhibitors (ABT-333 and ABT-072) and NS5A inhibitor (ABT-267). Additional data from larger, ongoing Phase 2 clinical trials is expected later this year.

About the Hepatitis C Virus

Hepatitis C is a liver disease affecting as many as 170 million people worldwide. The virus is primarily spread through direct contact with the blood of an infected person. HCV increases a person's risk of developing chronic liver disease, cirrhosis, liver cancer and death; and liver disease associated with HCV infection is growing rapidly.

Ritonavir Use in Treatment of HIV

Ritonavir is in a class of medicines called the HIV protease inhibitors. Ritonavir is used in combination with other anti-HIV medicines to treat people with human immunodeficiency virus (HIV) infection. Ritonavir is for adults and for children greater than 1 month in age and older.

Ritonavir does not cure HIV infection or AIDS and does not reduce the risk of passing HIV to others. People taking ritonavir may still get opportunistic infections or other conditions that happen with HIV infection. Some of these conditions are pneumonia, herpes virus infections, and Mycobacterium avium complex (MAC) infections.

Ritonavir Safety in Treatment of HIV

Patients should not take ritonavir with certain medicines, as these can cause serious or life-threatening problems such as irregular heartbeat, breathing difficulties, or excessive sleepiness. Patients should not take ritonavir if they have had a serious allergic reaction to any of its ingredients. Some patients taking ritonavir may develop liver and pancreas problems, which can cause death.

Patients may develop large increases in triglycerides and cholesterol, diabetes, high blood sugar, changes in body fat, increased bleeding in people with hemophilia, allergic reactions, and/or changes in heart rhythm. Patients may develop signs and symptoms of infections that they already have after starting anti-HIV medicines.

For more information, please see the Important Safety Information and full Prescribing Information for ritonavir.

About Enanta

Enanta Pharmaceuticals is a research and development company that uses its novel chemistry approach and drug discovery capabilities to create best in class small molecule drugs in the infectious disease field. Enanta is discovering and developing novel inhibitors and combinations of inhibitors targeted against the hepatitis C virus (HCV). These inhibitors include members of the direct acting antiviral (DAA) inhibitor classes– protease (partnered with Abbott), NS5A (partnered with Novartis), nucleotide polymerase, and a host targeted antiviral (HTA) inhibitor class targeted against cyclophilin. Additionally, the company has created a new class of antibiotics, called Bicyclolides, which overcomes bacterial resistance. Antibacterial focus areas include overcoming resistance to superbugs, treating respiratory tract infections, and developing intravenous and oral treatments for hospital and community MRSA infections. Enanta is a privately held company headquartered in Watertown, Mass. Enanta's news releases and other information are available on the company's web site at www.enanta.com.

About Abbott's HCV Development Programs

In addition to its partnership with Enanta Pharmaceuticals for protease inhibitors, including ABT-450 and ABT-450 containing regimens, Abbott has internal programs focused on additional viral targets. Abbott currently has investigational medicines with three different mechanisms of action in its ongoing clinical trials, including protease, polymerase and NS5A inhibitors. Abbott is well-positioned to explore combinations of these compounds, a strategy with the potential to markedly transform current treatment practices by shortening therapy duration, improving tolerability and increasing cure rates.

About Abbott

Abbott (NYSE: ABT) is a global, broad-based health care company devoted to the discovery, development, manufacturing and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs approximately 91,000 people and markets its products in more than 130 countries.

Abbott Contacts
Media:
Tracy Sorrentino
Roseanne Durril
(847) 937-8712
(847) 938-6114

Financial:
Lawrence Peepo
Elizabeth Shea
(847) 935-6722
(847) 935-2211

Enanta Contacts
Media:
Kari Watson
(781) 235-3060

Financial:
Paul Mellett
(617) 607-0761

Source

EASL 2012: Two studies show true impact of liver disease across Europe

Provided by News-Medical.Net

Published on April 19, 2012 at 6:46 AM

Two studies presented at the International Liver Congress- 2012 show the true impact that liver disease has across Europe. One highlights the financial cost of liver disease to the community and the second highlights the high mortality rates associated with cirrhosis.

A naturalistic, multicenter, retrospective, Cost of Illness study (COME) was developed to assess costs occurring in 1,088 patients over six months. Patients enrolled had liver diseases including hepatitis C, cirrhosis, hepatitis B, hepatic carcinoma and other hepatic diseases (cholestasis, NASH etc.). The study found that liver disease cost the EU on average at least -644.77 per patient per month. Hospitalisations account for 50.6% of the overall mean direct costs per month, with treatment accounting for 41.2% of costs. In addition, patients and family caregivers lost an average of 1.15 days per patient per month of productivity, an important indirect cost.

EASL Vice Secretary Professor Markus Peck-Radosavljeic commented: "These results demonstrate the real life costs involved in the treatment and ongoing management of patients with liver disease. Liver disease is an increasing problem and having concrete information on the financial impact can help us plan our treatment strategies more effectively and more importantly, might engage health authorities more to invest into preventive action like reducing harmful alcohol consumption and fight obesity."

The study concludes that although treatment costs account for just over 40% of direct costs, the use of efficient treatments is necessary to reduce worsening of patients' health, direct and indirect costs.

In a separate study the EASL-CLIF consortium report that 28 day mortality for Acute-on-Chronic liver failure (ACLF) is 35.5%. The consortium set out to address questions around ACLF, a poorly defined syndrome characterized by acute deterioration of cirrhosis, representing a main cause of hospitalisation and death. At present, no diagnostic criteria and information on prevalence, pathogenesis or prognosis are available. The consortium aimed to develop a new score (CLIF-SOFA, derived from the existing sequential organ failure assessment score) to assess the severity and number of organ failures.

1,379 patients, admitted to 29 hospitals due to complications of cirrhosis, were enrolled in this observational prospective European CANONIC study. Data presented at The International Liver Congress-2012 reports on results of the first 920 cases.

Four grades of ACLF were identified:

• ACLF-1: renal failure or a nonrenal organ failure associated with creatinine 1.5-2 mg/dL and/or grade I-II encephalopathy
• ACLF-2: 2 organ failures
• ACLF-3: 3 organ failures
• ACLF-4: 4-6 organ failures

The overall prevalence of ACLFwas 22.6% with twenty-eight-day mortality of ACLF patients at 35.3% compared (but as high as 85.7% in ACLF-4 patients) to only 4.1% in patients without ACLF. ACLFoften developed in patients with previously compensated (21%) or recently decompensated (< 3 months, 18%) cirrhosis and was significantly associated with bacterial infections and active alcoholism, but not gastrointestinal hemorrhage. Hepatitis, TIPS, paracentesis without albumin and surgery were infrequent precipitating events. In about 20% of cases no precipitating event was identified. ACLF was associated with an inflammatory reaction (both in infected and not infected patients) as estimated by increased WBC and plasma C-reactive protein levels.

Source: European Association for the Study of the Liver

Source

Modest Alcohol Consumption Lowers Risk and Severity of Liver Disease

News Release

Date: April 19, 2012

People with nonalcoholic fatty liver disease (NALFD) who consume alcohol in modest amounts – no more than one or two servings per day – are half as likely to develop hepatitis as non-drinkers with the same condition, reports a national team of scientists led by researchers at the University of California, San Diego School of Medicine.

The findings are published in the April 19, 2012 online issue of The Journal of Hepatology.

Two forms of nonalcoholic fatty liver disease (NAFLD) are depicted in these images of liver biopsies from adults, taken from this study. The first (top) shows nonalcoholic fatty liver only. The second (bottom) shows nonalcoholic steatohepatitis (NASH), a more serious condition with potential to progress to cirrhosis. Images courtesy of Elizabeth Brunt, MD, of Washington University in Saint Louis.

NALFD is the most common liver disease in the United States, affecting up to one third of American adults. It’s characterized by abnormal fat accumulation in the liver. The specific cause or causes is not known, though obesity and diabetes are risk factors. Most patients with NAFLD have few or no symptoms, but in its most progressive form, known as nonalcoholic steatohepatitis or NASH, there is a significantly heightened risk of cirrhosis, liver cancer and liver-related death.

NALFD is also a known risk factor for cardiovascular disease (CVD). Patients with NAFLD are approximately two times more likely to die from coronary heart disease than from liver disease. The study’s authors wanted to know if the well-documented heart-healthy benefits of modest alcohol consumption outweighed alcohol’s negative effects.

“We know a 50-year-old patient with NAFLD has a higher risk of CVD,” said Jeffrey Schwimmer, MD, associate professor of clinical pediatrics at UC San Diego, director of the Fatty Liver Clinic at Rady Children’s Hospital-San Diego and senior author. “Data would suggest modest alcohol consumption would be beneficial (in reducing the patient’s CVD risk) if you don’t take liver disease into account. When you do take liver disease into account, however, the usual medical recommendation is no alcohol whatsoever.”

Schwimmer and colleagues discovered that the benefits of modest alcohol consumption were compelling, at least in terms of reducing the odds of patients with NAFLD from developing more severe forms of the disease. Patients with NASH are 10 times more likely to progress to cirrhosis, the final phase of chronic liver disease. Cirrhosis is the 12th leading cause of death in the U.S., killing an estimated 27,000 Americans annually.

“Our study showed that those people with modest alcohol intake – two drinks or less daily – had half the odds of developing NASH than people who drank no alcohol,” said Schwimmer. “The reasons aren’t entirely clear. It’s known that alcohol can have beneficial effects on lipid levels, that it increases ‘good’ cholesterol, which tends to be low in NAFLD patients. Alcohol may improve insulin sensitivity, which has a role in NAFLD. And depending upon the type of alcohol, it may have anti-inflammatory effects.”

The study also found that in patients with NAFLD, modest drinkers experienced less severe liver scarring than did lifelong non-drinkers.

The study did not evaluate the effects of different types of alcohol, such as beer or spirits. Schwimmer said to do so would require a much larger study. Also, the study’s findings do not apply to children. All of the participants in the study were age 21 and older.

The current paper is based on analyses of 600 liver biopsies of patient’s with NAFLD by a national panel of pathologists who had no identifying clinical information about the samples. The study excluded anyone who averaged more than two alcoholic drinks per day or who reported consuming five or more drinks in a day (binge-drinking) at least once a month. All of the patients were at least 21 years of age.

Schwimmer said the findings indicate patients with liver disease should be treated individually, with nuance.

“For a patient with cirrhosis or viral hepatitis, the data says even small amounts of alcohol can be bad. But that may not be applicable to all forms of liver disease. Forty million Americans have NAFLD. Physicians need to look at their patient’s overall health, their CVD risk, their liver status, whether they’re already drinking modestly or not. They need to put all of these things into a framework to determine risk. I suspect modest alcohol consumption will be an appropriate recommendation for many patients, but clearly not all.”

Co-authors are Winston Dunn, departments of Pediatrics and Medicine, UC San Diego and Gastroenterology and Hepatology, Department of Medicine, University of Kansas Medical Center; Arun J. Sanyal, Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University Medical Center; Elizabeth M. Brunt, John Cochran VA Medical Center, Saint Louis and Division of Gastroenterology, Saint Louis University School of Medicine; Aynur Unalp-Arida, Department of Epidemilogy, Johns Hopkins Bloomberg School of Public Health; Michael Donohue, Division of Biostatics and Bioinformatics, Department of Family and Preventive Medicine, UC San Diego; and Arthur J. McCullough, Department of Gastroenterology and Hepatology, Cleveland Clinic.

Funding for this research came, in part, from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Child Health and Human Development and the National Cancer Institute.

# # #

Media Contact: Scott LaFee, 619-543-6163, slafee@ucsd.edu

Source