Enanta Joins Big Leagues: What are your goals for your next generation of HCV drugs?

Investment Commentary

Enanta Joins Big Leagues With Hepatitis C Drug

By AMY REEVES, INVESTOR'S BUSINESS DAILY

Posted 01/07/2014 07:15 PM ET

Since it went public in March, little biotech Enanta Pharmaceuticals has been in the middle of a clash between giants.

Enanta (ENTA) is the developer of ABT-450, a protease inhibitor that's one of three antiviral agents in AbbVie's (ABBV) cocktail of drugs in testing to treat the hepatitis C virus, HCV. AbbVie's is considered to be the nearest contender to Gilead Sciences' (GILD) Sovaldi, recently approved as part of the first officially sanctioned treatment for HCV that's all oral and doesn't include interferon.

The AbbVie-Enanta regimen has done as well as Sovaldi in trials, but analysts have debated how much its more complicated nature — it involves as many as five pills a day — will be a disadvantage on the market. Currently, analysts expect it to hit the market in 2015. They say it could be pulling in $2 billion a year by 2017.

That means a slew of milestone payments and royalties for Enanta, which is the rare development-stage biotech to be turning a profit thanks to the success it's already achieved in the pipeline.

Recently, CEO Jay Luly talked with IBD about the company's hepatitis C program as well as what's coming down the road.

IBD: How did Enanta get into the hepatitis C business?

Luly: We've been in the hep C business for over 10 years. We started with a single program, HCV protease, which is the one that we've partnered with AbbVie back in '06. Over the last decade, we've proliferated the number of targets. We're actually working on four different targets in HCV now.

IBD: Was the goal back then already to create the first interferon-free hepatitis C regimen?

Luly: Things have changed so rapidly. (From) when we first started working in protease, up until the time we signed the deal with (AbbVie), the assumption was that you would get a protease approved as a single agent, and then you would do combinations with it once it was approved. No one really imagined that the FDA was going to allow combination therapy on multiple investigational agents with none of them having been (previously) approved.

Even two and a half years ago, when Vertex (VRTX) and Merck (MRK) got approval (for Incivek), you still needed interferon if you were just using a protease alone. I'm not sure 10 years ago we would have imagined the field would have played out the way it did, but the way it's played out is probably much better than any of us had ever imagined, (with) the constructive nature of the FDA in exploring combinations earlier rather than later. That's really helped accelerate the whole field.

IBD: Can you explain how the AbbVie arrangement is structured?

Luly: It's had different phases. The discovery phase has mostly been accomplished and gave rise to ABT-450 and the next-gen protease inhibitor, ABT-493. Along with that, AbbVie paid an upfront licensing fee for our protease technology — that was a sizable upfront payment.

After that we stepped into clinical-development milestones. We've earned all of those milestones — that was about $55 million. Now we've moved on to the stage of regulatory milestones. We have $195 million in pre-commercial milestones on the 450 program. Those will be paid out starting with a (new drug application) filing targeted for the second quarter of (2014). We'll receive $40 million upon filing, and then we have $155 million more in approval milestones in the various territories.

Commercialization is targeted for early 2015. It's structured so that we receive double-digit royalties on the protease revenue.

IBD: People have been talking about the number of different drugs a patient has to take in AbbVie's regimen. Can you explain why it's necessary to have so many different agents at work?

Luly: For genotype 1 HCV, which is about 75% of the market in the large markets, you can't use a single agent to beat the virus. It's probably an expectation people had from the old HIV days when one agent wasn't enough — you needed to do a combination cocktail in order to be sure that you really hammered the virus. That's certainly turned out to be the case in HCV.

In the first regimen we're bringing forward with AbbVie, there are three different mechanisms of anti-HCV agents being used in the so-called 3D regimen. Optionally we've also studied adding on top of that ribavirin.

Gilead, on the other hand, is looking at a two-(anti)-HCV regimen, and also optionally studying it with ribavirin. It's really a question that gets answered ultimately by large clinical trials: Are three drugs in the combo the right number? Can you get away with two? Can you get away with two in some populations but not others? Do you need ribavirin? Going after genotype 1, it appears you need at least two drugs in the combination, and with some of the harder-to-treat populations you may need three or even more.

These HCV patients are not all the same. Some have a 1a virus; some have a 1b virus. Even within the 1a and 1b (groups), patients further stratify based on other factors. Some have more advanced disease, some have early disease, some have failed previous therapy, some are naive. So it's going to be interesting to see how all these different sub-populations settle down.

IBD: What are your goals for your next generation of HCV drugs?

Luly: Our first generation is really aiming at a very broad genotype 1 label — cirrhotics and all the different subtypes. But the next-gen program is looking beyond genotype 1. It is a pan-genotypic regimen. It also has activities against known resistance mutants that are out there.

It's shaping up in an interesting way where we have multiple regimens with AbbVie, but we're delighted to be — as a small-cap company — right in the thick of this all-oral race that's going on right now. It's actually very exciting.

IBD: Can you tell us about what you're doing with Novartis? That's also about hepatitis C, right?

Luly: You bet. With AbbVie we're partners on protease inhibitors; with Novartis (NVS) we're partners on NS5A inhibitors. If we pause for a minute and think, "Wait, the AbbVie cocktail has an NS5A in it too," that would be correct. We're in combinations with AbbVie that include some of their proprietary cocktail ingredients — (this) gives us more shots on goal that way than if we were doing it by ourselves. With Novartis, we're currently doing proof-of-concept studies with HCV patients. The goal would be to bring that forward into yet other combinations with agents of their pipeline.

Again, it gives us multiple shots on goal. We'll be able to participate in up to three different regimens with AbbVie, and we're hoping to duplicate additional shots with Novartis as well.

Read More At Investor's Business Daily:
http://news.investors.com/technology/010714-685548-enanta-ceo-jay-luly-interviewed.htm#ixzz2pqeYm8W6

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CME Video: Emerging Treatment Options for Hepatitis C Genotype 3,2 and 1 Patients

Hello folks,
Clinical Care Options (CCO) launched a series of video modules with three different case scenarios exploring HCV treatment choices, durations, and outcomes in genotype 3, 2, and 1 patients.

For instance in the first module the panel weighs in on the clinical trial data of investigational agents sofosbuvir and simeprevir in treatment naïve and experienced genotype 3 patients. The text only for "Case 1 " is provided below, an expert video discussion for each case is available in the module. 

Other topics include; treatment options for a new class of null responders who failed telaprevir or boceprevir and treating recurrent HCV after liver transplantation. 

A free quick registration is required 

Advanced HCV Treatment Topics
Fred Poordad, MD, moderates a case-based panel discussion exploring complex management issues in HCV-infected patients with Nezam H. Afdhal, MD, FRCPI, Douglas T. Dietrich, MD, Paul Y. Kwo, MD, and Norah Terrault, MD, MPH.

Released: 11/7/2013

Case 1: A Treatment-Experienced Patient With Genotype 3 HCV

Fred Poordad, MD:The patient is a 57-year-old white male with genotype 3a HCV infection and previous treatment failure on peginterferon 2a and ribavirin. He is now asking about his options for retreatment. He has no specific records of his past treatment, and his previous HCV RNA levels are unknown. He indicates he developed anemia while on therapy, with ribavirin being held for an unknown period. His current HCV RNA is 1.2 million IU/mL; liver enzyme studies determine his alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are elevated at 125 U/L and 114 U/L, respectively, but the rest of his laboratory examinations are within normal limits. His ultrasound shows his liver and spleen to be of normal size and a FibroTest identifies F0-F2 fibrosis. 

The first consideration is whether you would perform any additional tests to evaluate the patient’s liver histology?

Douglas T. Dieterich, MD:I would certainly want more information because my own experience with FibroTest has been less than ideal. At my center, we typically use transient elastography because we have it available. I wouldn’t order a liver biopsy.

Paul Y. Kwo, MD:My view is that the results of a liver biopsy would be helpful. The serum markers present 1 part of the picture; however, in this instance, the management approach will depend on the liver histology, making the biopsy results very helpful.


Norah Terrault, MD, MPH:I agree that the patient’s fibrosis stage is critical information, and the F0-F2 score on the FibroTest leaves considerable room for uncertainty. The patient’s platelet count is also concerning. A biopsy may be useful to help determine whether to delay treatment. 

It is important to remember that every test has an error rate, and all the available data have to come together and make sense when you evaluate a given patient. If 1 of the tests does not seem consistent with other aspects of the patient presentation, it is important to seek more information until you are confident in making the right decision.

Fred Poordad, MD:In this case, we did biopsy the patient, and the results indicated Stage 3 fibrosis by Metavir score.

Disease Outcomes and Treatment Outcomes in Genotype 3 HCV

Fred Poordad, MD:Until recently, genotype 2 and genotype 3 HCV have been classified as a single entity. However, in recent years, differences between these genotypes have become more clearly recognized. Disease progression rates are faster in genotype 3 compared with genotype 2.[1] As long ago as 2007, Shiffman and colleagues[2] demonstrated that patients with genotype 2 HCV treated with peginterferon/ribavirin experience an approximately 10% higher rate of sustained virologic response (SVR) compared with those infected with genotype 3 HCV with the same regimen. Importantly, rapid virologic response (RVR) rates are lower in genotype 3 and, especially in patients with genotype 3 without RVR, 16 weeks of therapy is inadequate to achieve SVR.[2] Further, patients experience higher relapse rates with genotype 3.[3]

Nezam H. Afdhal, MD, FRCPI:Disease progression rates are really a difficult question and determining disease progression rates is complex. There are no good cohort studies that have followed untreated patients for 20 or 30 years to show this kind of retrospective data. However, numerically speaking, patients with genotype 3 HCV infection tend to have more liver disease at the time of presentation—whether that means the true rate of progression is different or not is unclear. Additionally, genotype 3 HCV infection is associated with more hepatic steatosis; does that affect progression? Genotype 3 HCV infection in the United States and Europe is a disease of young intravenous (IV) drug users, while in the rest of the world it is very predominant in India and Pakistan, where there is significant morbidity and mortality associated with cirrhosis, liver cancer, and liver failure from this disease. Overall, we do see a lot more disease in patients with genotype 3 HCV infection, but I am not sure if this is due to a difference in the rate of progression in this patient population.

Norah Terrault, MD, MPH:I agree that it is difficult to judge disease progression, but there are some emerging data that the genotype might be a predictor of outcomes. Whether this outcome is driven by genotype 3 HCV itself or by accompanying cofactors is unclear.

Fred Poordad, MD:Van der Meer and colleagues[4] demonstrated an approximately 2-fold increased risk of mortality in patients with genotype 3 HCV infection compared with patients without genotype 3 infection. Importantly, curing genotype 3 HCV results in a significantly lower mortality rate compared with patients who are treated but do not achieve an SVR. Furthermore, older patients with genotype 3 HCV, higher levels of fibrosis, diabetes, or a history of alcohol use are less likely to do well.[4]

Douglas T. Dieterich, MD:That has been my experience as well. Alcohol, diabetes, and genotype 3 HCV infection are all associated with steatosis in the liver which may increase the fibrosis rate, leading to higher mortality. As a consequence, patients with genotype 3 HCV who fail treatment with peginterferon/ribavirin are some of the most difficult to treat outside of a clinical trial.

Emerging Treatment Options for Genotype 3 HCV

Fred Poordad, MD:The interferon-free combination of the nucleoside analogue sofosbuvir with ribavirin has shown promise in the treatment of genotypes 2 and 3 HCV, and at the time of writing has been submitted for approval for these genotypes.

The phase III Fission trial was a randomized, open-label, active-control, noninferiority study comparing 12 weeks of sofosbuvir plus ribavirin with 24 weeks of peginterferon/ribavirin in treatment-naive patients with genotype 2 or 3 HCV infection. The overall SVR rates were 67% for both sofosbuvir plus ribavirin and peginterferon/ribavirin.[5] Subanalysis based on HCV genotype found that patients with genotype 2 infection had a 97% SVR rate with sofosbuvir plus ribavirin compared with 78% SVR rate with peginterferon/ribavirin. However, the sofosbuvir plus ribavirin regimen for patients infected with genotype 3 HCV achieved an SVR of 56% vs a 63% SVR rate with peginterferon/ribavirin. These results indicate the noninferiority endpoint was met, but for genotype 3 HCV infection, the data are clearly not as satisfying as hoped.

The blinded, active-controlled phase III FUSION study explored treatment with 12 weeks of sofosbuvir plus ribavirin, followed by 4 weeks of matching placebo, or 16 weeks of sofosbuvir plus ribavirin in treatment-experienced patients with genotype 2 or 3 HCV infection. After 12 weeks of treatment in patients with genotype 3 HCV infection, the SVR rate was only 30%.[6] However, the additional 4 weeks of treatment doubled the SVR rate to 62%.

Now, go to the next page to see a video of the faculty discussion of these data.

Continue to CCO........

2013 Pipeline Report - 28 HCV interferon-free regimens in development

Treatment Action Group 2013 Pipeline Report

At the 7th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention held in Kuala Lumpur, Malaysia the HIV i-Base/Treatment Action Group (Tag) released their comprehensive 2013 Pipeline Report. In the report both organizations advocate a global effort for national leaders and regulatory authorities to work together and expedite research needed to bring safe HIV, HCV and tuberculosis drugs to market.

For the HCV community, there is a particular article written by Tracy Swan from (Tag) which offers an update on the new HCV drugs currently in phases II/III trials.

The author writes:

"An impressive 26  new HCV drugs are being studied in phases II/III in at least 28 interferon-free regimens, which are bringing the potential of  faster, all-oral HCV cures rapidly toward approval for the world’s 185 million people living with HCV"

2013 Pipeline Report - Hepatitis C Drug Development Catapults Onward 

Excerpt from the press release;

In the 2013 “HCV Treatment Pipeline,” Tracy Swan (TAG) notes that the “confluence of a robust HCV drug pipeline, shortened regimens, and [shorter] posttreatment follow-up are extraordinary. The new FDA breakthrough therapy designation may speed things up as well. By the end of 2014, [new HCV drugs] from four different classes and fixed-dose combinations (FDCs) are likely to be approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), offering the potential for off-label mixing and matching.” An impressive 26 new HCV drugs are being studied in phases II/III in at least 28 interferon-free regimens, which are bringing the potential of faster, all-oral HCV cures rapidly toward approval for the world’s 185 million people living with HCV.

Swan notes, however, that not all optimal combinations are being studied, with some sponsors preferring combinations of their own proprietary compounds, while many sponsors take too long to study their new drugs in people coinfected with HIV and HCV, and those with cirrhosis.

In her companion chapter, “Low- and Middle-Income Countries Defuse Hepatitis C, the ‘Viral Time Bomb,’” Karyn Kaplan (TAG) describes how a worldwide movement is forming to ensure that when new all-oral HCV cures are approved, that governments, health systems, and providers will be ready for them. Kaplan points to recent progress instigated by HCV activists in countries such as Egypt, Georgia, Thailand, and Ukraine.

The press release is available here

2013 "HCV Treatment Pipeline" - By Tracy Swan

Hepatitis C Drug Development Catapults Onward 
By Tracy Swan

Highlights:
HCV Treatments in Phase II and Phase III
The Best Combinations
Interferon-Free Regimens in Development for HCV Genotype 1
Interferon-Free Regimens in Development - HCV Genotypes 2, 3, & 4
Cross-company Trials
Next in Line: Simeprevir, Faldaprevir, and Sofosbuvir
Without a PEG to Stand on: The Sofosbuvir Saga Goes on
Biting the (Magic) Bullet
Twinkle, Twinkle, Little (Lone) Star
AbbVie: All Hands on Deck
Bristol-Myers Squibb: All In!
(Genotype) 3 is the new 1
SVR in HCV Genotypes 2 and 3
Cirrhosis: From Frontier to Proving Ground
HIV/HCV Coinfection
Faldaprevir plus PEG-IFN/RBV
Simeprevir plus PEG-IFN and RBV
From Excess to Access
Where Should All the Research Go?

Access the report here.........

Next Chapter:
Low-  and Middle-Income Countries Defuse Hepatitis C, the “Viral Time Bomb” 

Update
2013 SVR Rates

AbbVie's ABT-450- Breakthrough Therapy Designation from the U.S. Food and Drug Administration Granted to Investigational HCV Regimen

Related:
AbbVie gains inside 'breakthrough' track at FDA for hot hep C combo
The company says that the FDA has picked its antiviral combo--with and without ribavirin-- as a new breakthrough therapy worthy of a swift review and perhaps a shortened clinical trial process ahead of a regulatory decision. 

Breakthrough Therapy Designation from the U.S. Food and Drug Administration Granted to Investigational HCV Regimen Containing Protease Inhibitor ABT-450

WATERTOWN, Mass.--(BUSINESS WIRE)--

Enanta Pharmaceuticals, Inc., (ENTA), a research and development-focused biotechnology company dedicated to creating small molecule drugs in the infectious disease field, today announced that AbbVie’s investigational direct-acting antiviral (DAA) combination regimen with and without ribavirin for the treatment of genotype 1 (GT1) hepatitis C virus (HCV) infection has been designated as a Breakthrough Therapy by the U.S. Food and Drug Administration (FDA). ABT-450, Enanta’s lead HCV protease inhibitor identified in its ongoing collaboration with AbbVie, is one of three DAAs in the regimen.

   
The all-oral, triple-DAA combination regimen is currently being studied in Phase 3 clinical trials that are being conducted by AbbVie. The Phase 3 program includes more than 2,000 patients with genotype 1 HCV infection, with trial sites in 29 countries. The DAAs in the trials include ABT-450/r (protease inhibitor and ritonavir) combined with two of AbbVie’s proprietary investigational DAAs, ABT-267 (NS5A inhibitor) and ABT-333 (non-nucleoside polymerase inhibitor), and are being dosed with and without ribavirin.
   
According to the FDA, Breakthrough Therapy designation is intended to expedite the development and review of drugs for serious or life-threatening conditions. The criteria for Breakthrough Therapy designation include preliminary clinical evidence demonstrating a drug may have substantial improvement on at least one clinically significant endpoint compared to available therapy. A Breakthrough Therapy designation conveys all of the fast track program features, as well as more intensive FDA guidance on an efficient drug development program.¹

About Hepatitis C Virus (HCV)
Hepatitis C is a liver disease affecting over 170 million people worldwide. The virus is typically spread through direct contact with the blood of an infected person. Hepatitis C increases a person’s risk of developing chronic liver disease, cirrhosis, liver cancer and death. There is an acute need for new HCV therapies that are safer and more effective for many variants of the virus.
   
Collaboration with AbbVie (formerly the research-based pharmaceutical business of Abbott Laboratories
In December 2006, Enanta and Abbott announced a worldwide agreement to collaborate on the discovery, development and commercialization of HCV NS3 and NS3/4A protease inhibitors and HCV protease inhibitor-containing drug combinations. Under the agreement, AbbVie (as the successor to Abbott) is responsible for all development and commercialization activities for ABT-450. Enanta received a $57 million upfront payment upon signing the collaboration agreement, has received all clinical milestone payments, and is eligible to receive an additional $195 million in payments for regulatory milestones, as well as double-digit royalties worldwide on any revenue allocable to the collaboration’s protease inhibitors. Also, for any additional collaborative HCV protease inhibitor product candidate developed under the agreement, Enanta holds an option to modify the U.S. portion of it rights to receive milestone payments and worldwide royalties. With this option, Enanta can fund 40 percent of U.S. development costs and U.S. commercialization efforts (sales and promotion costs) in exchange for 40 percent of any U.S. profits ultimately achieved after regulatory approval instead of receiving payments for U.S. commercial regulatory approval milestones and royalties on U.S. sales.
   
About Enanta
Enanta Pharmaceuticals is a research and development-focused biotechnology company that uses its robust chemistry-driven approach and drug discovery capabilities to create small molecule drugs in the infectious disease field. Enanta is discovering and developing novel inhibitors designed for use against the hepatitis C virus (HCV). These inhibitors include members of the direct acting antiviral (DAA) inhibitor classes – protease (partnered with AbbVie), NS5A (partnered with Novartis) and nucleotide polymerase – as well as a class of host-targeted antiviral (HTA) inhibitors targeted against cyclophilin. Additionally, Enanta has created a new class of antibiotics, called Bicyclolides, for the treatment of multi-drug resistant bacteria, with a current focus on developing an intravenous and oral treatment for hospital and community MRSA (methicillin-resistant Staphylococcus aureus) infections.
   
Forward-Looking Statement Disclaimer
This press release contains forward-looking statements, including statements with respect to the Breakthrough Therapy designation that the FDA has given to AbbVie’s regimen containing ABT-450 for treatment of genotype 1 HCV infection and milestones and royalties that Enanta is eligible to receive on ABT-450 and any additional collaboration protease inhibitor products. Statements that are not historical facts are based on our management’s current expectations, estimates, forecasts and projections about our business and the industry in which we operate and our management’s beliefs and assumptions. The statements contained in this release are not guarantees of future performance and involve certain risks, uncertainties and assumptions, which are difficult to predict. Therefore, actual outcomes and results may differ materially from what is expressed in such forward-looking statements. Important factors that may affect actual results include the development and commercialization efforts of AbbVie for HCV treatment regimens containing ABT-450 or any additional collaboration protease inhibitor product, regulatory actions affecting clinical development or treatment regimens containing ABT-450 or any additional collaboration protease inhibitor product, and clinical development of competitive product candidates. Enanta cautions investors not to place undue reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this release, and Enanta undertakes no obligation to update or revise these statements, except as may be required by law.
   
¹U.S. Food and Drug Administration. Frequently Asked Questions: Breakthrough Therapies. 2013.

AASLD- Abbott hepatitis C oral drugs bring high cure rates in trial

Abbott hepatitis C drugs bring high cure rates in trial

 

Ransdell Pierson Reuters

11:34 a.m. CST, November 10, 2012

(Reuters) - A trio of oral medicines from Abbott Laboratories Inc to treat hepatitis C produced unprecedented cure rates in patients who had failed to benefit from standard treatment, as well as very high cure rates for newly treated patients, Abbott said on Saturday.

Detailed data from the mid-stage trial, called Aviator, were released Saturday at the annual meeting of the American Association for the Study of Liver Disease (AASLD) in Boston.

Investors and patients have very high hopes for the Abbott drugs - a protease inhibitor called ABT-450, a polymerase inhibitor ABT-333 and ABT-267 from a class known as NS5A inhibitors. They are used without interferon, an injectable standard treatment that causes flu-like symptoms.

Abbott said it plans to move ahead with large Phase III studies of the three drugs, used either with or without the standard antiviral pill ribavirin, based on favorable results seen in patients treated for eight weeks or twelve weeks in the Aviator study. Patients in the study had the most common, and hardest-to-treat, strain of hepatitis C known as Genotype 1.

Some 93 percent of patients who failed prior therapy had a sustained virologic response (SVR), meaning they were considered cured, after 12 weeks of taking the trio of new drugs, plus ribavirin.

"Nobody anywhere has broken the 50 percent mark in (cure rates) for this population," Scott Brun, a senior Abbott research executive said in an interview. "These are robust results."

Abbott said it aims to be the first company to market an interferon-free regimen to patients with Genotype 1 infections.

Four of 448 patients in the study discontinued treatment due to adverse events, a dropout rate that Abbott said suggested the medicines were very well tolerated.

About 97 percent of previously untreated patients were considered cured after 12 weeks of treatment with the three Abbott drugs, plus ribavirin. Moreover, similarly impressive cure rates were seen among patients taking the three drugs, plus ribavirin, for 8 weeks.

Without ribavirin, 87 percent of previously untreated patients were considered cured after 12 weeks on Abbott's three drugs, Abbott said.

Rival drugmaker Gilead Sciences Inc stole a bit of Abbott's thunder on Saturday by releasing data showing a 100 percent cure rate among previously untreated genotype 1 patients who took only two of its oral treatments, plus ribavirin, for 12 weeks.

A pair of new hepatitis C drugs approved last year, Vertex Pharmaceuticals Inc's Incivek and Merck & Co's Victrelis, significantly boosted cure rates and cut treatment duration to as low as 24 weeks for some patients. But the protease inhibitors must still be taken with interferon, an injected drug that often causes severe flu-like symptoms that lead many hepatitis patients to delay or discontinue treatment.

Gilead, Bristol-Myers Squibb Co and Vertex are racing to develop interferon-free treatment regimens. They are expected to become blockbuster products, if approved, because of their far shorter treatment times and better cure rates, compared with existing drug regimens.

Many analysts view Gilead as current leader both on timing and perceived advantages of its experimental hepatitis C program.

An estimated 3 million Americans are believed infected with the virus, which quietly damages the liver over years or decades and is the biggest reason for liver transplants in the United States. Abbott said as many as 170 million people worldwide are infected.

(Reporting by Ransdell Pierson; Editing by Vicki Allen and Jackie Frank)

Abbott Press Release

Abbott Presents Promising Phase 2b Interferon-free Hepatitis C Results at 2012 Liver Meeting®

• Investigational Triple-DAA Regimen plus Ribavirin Treatment for 12 Weeks Demonstrated High SVR₁₂ Rates in Intent-to-Treat Analysis
• Phase 3 Registrational Program Currently Enrolling

November 10, 2012

Abbott Park, Illinois (NYSE: ABT) — Results from Abbott’s phase 2b clinical trial, "Aviator," demonstrated high sustained viral response rates at 12 weeks post-treatment (SVR₁₂) in all 8- and 12-week arms, with combinations of direct acting antivirals (DAAs) given with and without ribavirin (RBV). Results will be presented at the President's Press Conference and the latebreaking clinical trials session at the Liver Meeting, the Annual Meeting of the American Association for the Study of Liver Disease (AASLD) in Boston.

Based on promising results from Aviator, Abbott has selected triple-DAA regimens, with and without ribavirin, to move forward into phase 3 clinical trials. Topline intent-to-treat results for the 12-week, triple-DAA regimen with ribavirin are as follows:

SVR₁₂ in treatment-naïve genotype 1 (GT1) patients was 97.5 percent (77 of 79), and 93.3 percent (42 of 45) in GT1 null responder patients

In GT1a patients, SVR₁₂ was achieved in 96 percent (52 of 54) of treatment naïve patients and 89 percent (25 of 28) of null responder patients

In GT1b patients, SVR₁₂ was achieved in 100 percent of treatment naïve (25 of 25) and null responder patients (17 of 17)

In addition, results from the 12-week triple-DAA regimen without RBV in treatment naïve patients showed:

SVR₁₂ was achieved in 87.3 percent (69 of 79) of GT1 patients
SVR₁₂ in GT1a patients was 83 percent (43 of 52)
SVR₁₂ in GT1b patients was 96 percent (24 of 25)

"Based on the high SVR₁₂ results with Abbott’s triple-direct acting antiviral regimen in GT1 patients, it appears we are moving closer to potential oral treatment regimens that do not require interferon to treat HCV," said Kris Kowdley, M.D., director of the Liver Center of Excellence in the Digestive Disease Institute at Virginia Mason Medical Center, and Clinical Professor of Medicine at the University of Washington in Seattle. "This is encouraging news for the many patients who are unable or unwilling to take interferon."

About Study M11-652 (Aviator)

This phase 2b study assesses the safety, and efficacy of ABT-450/r (dosed 100/100mg to 200/100mg QD), ABT-267 (25mg QD), ABT-333 (400mg BID) and ribavirin in non-cirrhotic treatment-naïve patients and prior peg-interferon/ribavirin null responders for 8, 12 or 24 weeks. Enrollment was open to GT1-infected patients regardless of IL28B host genotype and ribavirin dosing was weight-based. Results from the treatment groups are summarized in the chart below.

	Treatment-Naïve					Null Responders
Duration	8 weeks	12 weeks				12 weeks
Regimen	ABT-450/r ABT-267 ABT-333 RBV	ABT-450/r ABT-333 RBV	ABT-450/r ABT-267 RBV	ABT-450/r ABT-267 ABT-333	ABT-450/r ABT-267 ABT-333 RBV	ABT-450/r ABT-267 RBV	ABT-450/r ABT-267 ABT-333 RBV
Number dosed	80	41	79	79	79	45	45
Relapses	9	4	5	5	1	5	0
Breakthroughs	0	1	1	1	0	0	3
Lost to Follow up (LTFU) or withdrew consent	1	1	2	4	1	0	0
SVR12 (ITT)1	87.5% (70/80)	85.4% (35/41)	89.9% (71/79)	87.3% (69/79)	97.5% (77/79)	88.9% (40/45)	93.3% (42/45)
SVR12 (OD)2	88.6% (70/79)	87.5% (35/40)	92.2% (71/77)	92% (69/75)	98.7% (77/78)	88.9% (40/45)	93.3% (42/45)
SVR12 (ITT) GT1a	84% (47/56)	79% (23/29)	85% (44/52)	83% (43/52)	96% (52/54)	81% (21/26)	89% (25/28)
SVR12 (ITT) GT1b	96% (23/24)	100% (12/12)	100% (27/27)	96% (24/25)	100% (25/25)	100% (18/18)	100% (17/17)

ITT (Intent-to-treat) population: includes all patients who received at least one dose of study drug

OD (Observed data): Excludes patients with values missing for reasons other than virologic failure or discontinuation due to AEs

"The 93.3 percent SVR₁₂ seen with triple-DAA therapy with ribavirin in previous null responder patients in Aviator is noteworthy given the limited treatment options with interferon-based therapies for this patient population," said Scott Brun, M.D., divisional vice president, Infectious Disease Development, Abbott. "As the data from the Aviator study have matured, we are encouraged that we have continued to see high SVR₁₂ rates. Results from Aviator have allowed Abbott to confidently move into larger, confirmatory Phase 3 trials with the goal of being the first company to bring an interferon-free treatment regimen to genotype 1 patients."

Aviator Safety Results

Four of 448 patients (one percent) in the 8- and 12-week arms discontinued due to adverse events. Of five serious AEs (1 percent), one (arthralgia or joint pain) was possibly study drug-related. In the trial, the most common adverse events were fatigue (28 and 27 percent) and headache (28 and 31 percent) for treatment naïve and null responders respectively.

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.

Of the six main genotypes of hepatitis C, genotypes 1, 2 and 3 are the most widespread. Genotype 1 is the most common genotype in the U.S. and the most difficult to treat with interferon based therapies. Patients with genotypes 2 and 3 are more likely than individuals with genotype 1 to respond to therapy with peg-interferon or the combination of peg-interferon and ribavirin.

About Abbott's HCV Development Programs

Abbott's HCV portfolio includes investigational medicines with three different mechanisms of action, including protease (ABT-450/r), polymerase (ABT-333) and NS5A (ABT-267) inhibitors, currently being studied in clinical trials. ABT-450 is being developed with low dose ritonavir which enhances the pharmacokinetic properties of ABT-450. The use of ritonavir 100mg with ABT-450 for the treatment of HCV is investigational.

ABT-450 was discovered during the course of a collaboration between Abbott and Enanta Pharmaceuticals for HCV protease inhibitors and regimens that include protease inhibitors. ABT-450 is being developed by Abbott for use in combination with Abbott's other investigational medicines for the treatment of HCV. Abbott is well-positioned to explore combinations and co-formulations of these medicines.

On Monday, November 12 at 5:30 p.m. EST, Abbott will host an investor webcast to discuss the phase 2b Aviator data, as well as our recently initiated phase 3 registrational program. The webcast can be accessed on Abbott’s investor relations website at abbottinvestor.com.

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 Important Safety Information and Full Prescribing Information.

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.

---

Media: Tracy Sorrentino Roseanne Durril	(847) 937-8712 (847) 938-6114
Financial: Larry Peepo Liz Shea	(847) 935-6722 (847) 935-2211

UPDATE: Abbott Hepatitis C Regimen Suppresses Virus in New Study

Investment Commentary

UPDATE: Abbott Hepatitis C Regimen Suppresses Virus in New Study

--Abbott reports positive data for three all-oral hepatitis drugs from clinical trial

--Results help Abbott choose regimen for late stage studies

--Positive data also reported for Bristol-Myers drugs

(Adds details about Bristol-Myers drugs in fourth and 18th-19th paragraphs, analyst comments in 20th paragraph, and updates stock prices.)

By Peter Loftus

An experimental all-oral drug regimen developed by Abbott Laboratories (ABT) suppressed the hepatitis C virus in most patients in a new clinical trial.

The results helped guide Abbott to decide on a regimen based on three experimental drugs that the company is taking into larger, late stage clinical trials. Abbott hopes to begin selling a new hepatitis C therapy in 2015, assuming trial results are positive and regulators give the green light, and the company has suggested annual sales could eventually exceed $2 billion.

Abbott, Gilead Sciences Inc. (GILD) and others are racing to introduce the next generation of drugs for an expected multibillion-dollar hepatitis C market. A selling point for drugs in development is they can be taken orally, minus an injectable component of the current standard treatment, a treatment that patients have difficulty tolerating.

The new Abbott results--together with new hepatitis C drug data from Bristol-Myers Squibb Co. (BMY)--suggest Gilead still faces solid competition to its perceived status as the leader in the hepatitis C race.

A summary of the results of the new Abbott study was posted online Monday by the American Association for the Study of Liver Diseases in advance of its November conference, where the full data will be presented.

Hepatitis C is a viral disease that attacks the liver, and is believed to afflict about 180 million people world-wide, with more than four million in the U.S., according to the National Institute of Allergy and Infectious Diseases. At-risk groups include people who had blood transfusions before 1992, when a screening test for the virus was developed.

Abbott has previously reported positive results from midstage studies of its various experimental hepatitis C drugs.

The new study, titled "Aviator," tested three experimental Abbott drugs in a midstage, or Phase 2b, clinical trial of people with hepatitis C. One of the drugs, ABT-450, is a so-called protease inhibitor, which is in the same class of drugs as two that went on sale last year--Merck & Co.'s (MRK) Victrelis and Vertex Pharmaceuticals Inc.'s (VRTX) Incivek. Incivek is marketed outside the U.S. by Johnson & Johnson (JNJ) as Incivo. ABT-450 was given along with a boosting agent known as ritonavir.

The other two experimental drugs used in the latest study are ABT-267, known as an NS5A inhibitor, and ABT-333, a non- nucleoside NS5B inhibitor. Also, some patients were given the drug ribavirin, which is a staple of current hepatitis C therapy.

The trial tested various combinations of these drugs for varying durations up to 24 weeks of treatment, in both patients who had undergone prior treatment and those new to treatment.

The study tracked how many patients had a sustained virologic response 12 weeks after the end of treatment, a measure known as SVR12. Sustained virologic response is roughly equivalent to being virus-free or having nearly undetectable viral levels.

The regimen with the highest SVR12 rates contained the Abbott experimental drugs--ABT-450 with ritonavir, ABT-267 and ABT-333--plus ribavirin for 12 weeks.

This regimen led to an SVR12 rate of 99% in 77 patients who hadn't received prior treatment, and 93% among 41 patients who hadn't responded well to therapy containing the injectable drug interferon. A small number of patients in each of these groups didn't have 12-week follow-up results or hadn't yet reached 12 weeks post-treatment, so the final SVR12 rates could change when those results come in.

The SVR12 rates for other therapy groups in the 571-patient study ranged from 89% to 92%, according to the AASLD summary.

About 1% of patients discontinued treatment because of adverse events. The most common adverse events were fatigue and headaches.

Abbott will test this regimen, with and without ribavirin, in late stage, or Phase 3, clinical trials. In one of these trials,ABT-450, ritonavir and ABT-267 will be coformulated in a single pill, which will reduce the pill count from that of the Phase 2 study. The 300-patient trial is expected to begin recruiting soon.

Scott Brun, Abbott's divisional vice president of infectious disease development, said the company was encouraged by the results, which need to be confirmed in the larger studies.

New data on orally administered hepatitis C drugs developed by Bristol-Myers Squibb Co. (BMY) also appeared positive. A 12-week regimen containing Bristol's daclatasvir, asunaprevir and BMS-791325 produced a sustained virologic response in 94% of one group of patients four weeks after treatment, according to a summary posted by AASLD.

Bristol experienced a major setback in August when it scrapped development of a once-promising hepatitis C drug obtained in its $2.5 billion purchase of Inhibitex earlier this year. Bristol cited safety concerns that arose in a clinical trial.

Analysts said the new data released Monday suggest Bristol may still be able to move forward with other drugs in an all-oral regimen, despite the recent setback.
http://online.wsj.com/article/BT-CO-20121015-710044.html

More then 90% Cured In Small Hepatitis C Study

More than 90% cured in small hep. C study

By Bill Berkrot, Reuters
Source

Last Updated: April 4, 2012 1:15pm

A small study has yielded hepatitis C cure rates higher than 90% in previously untreated patients.

A combination of experimental oral hepatitis C treatments being developed by Abbott Laboratories led to cure rates higher than 90 percent in previously untreated patients, according to data from a small mid-stage study.

The data, to be presented at a major European liver meeting later this month, puts Abbott firmly in the crowded race to produce a short duration, interferon-free treatment regimen for the serious liver disease.

Abbott shares rose nearly 2 percent on a down day for the broader market. Shares of some companies developing rival drugs, such as Gilead Sciences Inc and Idenix Pharmaceuticals Inc fell.

“This demonstrates unprecedented cure rates for the most common form of hepatitis C infection. And we were able to achieve those rates with only a 12-week duration of therapy,” said Scott Brun, Abbott’s divisional vice president for infectious disease development.

Abstracts, or brief summaries, of studies to be presented at the European Association for the Study of the Liver (EASL) meeting in Barcelona were made available on Wednesday.

“At EASL it’s going to be very clear that we’ve reached a really transformational moment for patients with HCV (hepatitis C virus),” Brun said.

The Phase II trial of previously untreated patients, known as Co-Pilot, combined Abbot’s protease inhibitor ABT-450 boosted by the antiviral drug ritonavir with its polymerase inhibitor ABT-333 and ribavirin, a drug that is part of all current hepatitis C regimens.

Patients received the combination therapy for 12 weeks and were checked 24 weeks later for signs of the virus in the blood to determine if there was a sustained virologic response, or SVR. Any patients that achieved an SVR 24 weeks after completing treatment are deemed to be cured.

Eighteen of the 19 patients who received a 250 milligram dose of ABT-450 as part of their combination achieved SVR, or 95 percent, while 13 of 14 patients who got a 150 mg dose of ABT-450 were deemed to be cured, or 93 percent.

“We would acknowledge that the 4-drug combination from Abbott sets a high bar for competitors,” BMO Capital Markets analyst Jim Birchenough said in a research note.

He noted that Gilead shares were down in response to the Abbott data, but expressed confidence that a Gilead combination therapy will ultimately be able to match Abbott’s efficacy.

In a third arm of the study that involved patients who had failed to be helped by the former standard treatment of interferon and ribavirin, eight of 17 patients achieved SVR for a cure rate of 47 percent.
“In our view, the response rate in previous non-responders may not be competitive,” said Wells Fargo analyst Larry Biegelsen, who called the treatment naive data “very strong.”

Abbott is also testing a drug from a promising class known as NS5A inhibitors in various all-oral combinations that it believes may improve cure rates for prior non-responders.

“For a first step it’s very encouraging,” Brun said of the new data in non-responders. “If you’re able to add the potent NS5A inhibitor into the mix we think there’s the potential to do even better and that’s currently under study.”

There were no serious side effects seen in the study, with the most common side effects fatigue, nausea and headache.

LEAP FORWARD
The treatment of hepatitis C took a major leap forward last year with the approval of new drugs from Vertex Pharmaceuticals Inc and Merck & Co that led to far-higher cure rates with the potential for shorter treatment durations than interferon and ribavirin, which had to be taken for 48 weeks and cured about 40 percent of patients.

Vertex’s Incivek led to cure rates as high as 80 percent in previously untreated patients. But both new drugs must be taken with interferon and ribavirin, and the shortest treatment regimen is currently 24 weeks, with many patients still requiring 48 weeks.

Interferon, an injected drug, causes miserable flu-like symptoms that lead many patients to discontinue treatment and many more to put off treatment altogether. If left untreated, hepatitis C can lead to cirrhosis, liver cancer, and death. It is also the most common reason for liver transplants.

Analysts believe an interferon-free therapy with a high cure rate and shorter treatment duration is likely to be a multibillion-dollar seller. That has led to fierce competition among drugmakers.
Gilead and Bristol-Myers Squibb Co recently spent billions to buy companies developing such drugs. Vertex, Merck and several other smaller companies are also working on various interferon-free combinations.

Gilead shares were down 2.5 percent at $46.88, while shares of Idenix were off more than 11 percent at $9.09. Abbott shares were up 0.4 percent at $61.40 after climbing to a multi-year high of $62.55 earlier on Wednesday.

Far larger trials will be needed to confirm the efficacy and safety of the Abbott drugs, and the company said it is on track to begin pivotal Phase III testing in early 2013.

But the data Abbott will present at EASL this month clearly signals that it intends to be a major player in the field.

EASL:Abbott to Present Positive Phase 2 Results from Multiple Interferon-Free Studies of Combination Regimens for the Treatment of Hepatitis C

April 4
EASL ABSTRACTS NOW READY TO VIEW
Click Here
.
Public
The abstracts will be available on the EASL website, http://www.easl.eu as of today.
..
Abbott to Present Positive Phase 2 Results from Multiple Interferon-Free Studies of Combination Regimens for the Treatment of Hepatitis C

April 04, 2012

Abbott Park, Illinois (NYSE: ABT) — Abbott will present clinical trial results from two different interferon-free, Phase 2 studies for the treatment of hepatitis C (HCV) 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. Abstracts for the meeting were published online today.

In the study known as "Co-Pilot," different doses of ABT-450/r, plus ABT-333 and ribavirin administered for 12 weeks showed sustained virological response at 12 weeks post treatment (SVR₁₂) in 95 percent and 93 percent of treatment-naïve genotype 1 (GT1) patients. In these patients, response was independent of HCV subtype, host IL28B genotype or dose of ABT-450/r. In addition, SVR₁₂ was achieved in 47 percent of patients who were previous non-responders to past HCV treatment.

In a separate study, known as "Pilot," 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).

Full results with longer-term follow-up data from both studies will be presented at the meeting. Abstracts are available at www.easl.eu.

"We are extremely encouraged to see this level of sustained response with only 12 weeks of therapy in patients who were new to treatment, and to see a response in patients who had failed past treatment because options to cure this population are limited," said Fred Poordad, M.D., chief of hepatology at Cedars-Sinai Medical Center in Los Angeles, and the lead investigator for Co-Pilot and an investigator for Pilot. "These data suggest that an interferon-free, all-oral regimen of direct-acting antiviral medications could be an important new treatment option for HCV, and we look forward to presenting additional data at the meeting."

"At this meeting, Abbott will present some of the first sustained viral response data for short course, interferon-free regimens for the treatment of HCV. The data suggest that with a 12-week regimen containing just two of our direct-acting antiviral medicines, and no peginterferon, we can achieve high cure rates in treatment-naïve, genotype 1 patients," said Scott Brun, M.D., divisional vice president, Infectious Disease Development, Abbott. "Abbott's HCV pipeline includes several compounds in different drug classes and we have the flexibility to study a variety of multi-drug regimens for HCV, with a focus on interferon-free treatments. Abbott is committed to exploring a wide variety of options in our portfolio with the goal of developing optimized regimens to help patients."

Current treatments for HCV remain interferon-based and a significant number of HCV patients are unable or unwilling to take interferon due to contraindications and/or side effects. 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.

These two studies represent an important part of Abbott’s broader HCV development program. Larger Phase 2 clinical trials are ongoing, and Abbott expects to present additional data later this year. In addition to its partnership with Enanta Pharmaceuticals on ABT-450 and protease inhibitors, 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.

Study M12-746 (Co-Pilot)

Fred Poordad, et al.; Saturday, April 21, 15:30-17:30 CET / 8:30-10:30 a.m. CDT.

"12-Week Interferon-Free Regimen of ABT-450/r+ABT-333+Ribavirin Achieved SVR₁₂ in More Than 90% of Treatment-Naïve HCV Genotype-1-Infected Subjects and 47% of Previous Non-Responders"

• The objectives of this Phase 2 study were to assess safety and tolerability of 12-week, interferon-free regimens in HCV GT1 patients who were either treatment-naïve or previous non-responders. The trial had three arms with three primary endpoints – rapid virological response (RVR) at week 4 and SVR at weeks 4 and 12.
• Enrollment was open to GT1-infected patients regardless of IL28B host genotype and ribavirin dosing was weight-based.
• 95 percent (18 of 19) of treatment-naïve patients infected with HCV GT1
  (17 GT 1a, 2 GT 1b) achieved SVR₁₂ with ABT-450/r 250/100 mg dosed once daily (QD) + ABT-333 400 mg dosed twice daily (BID) + ribavirin (Arm 1).
• 93 percent (13 of 14) of treatment-naïve patients infected with HCV GT1
  (11 GT 1a, 3 GT 1b) achieved SVR₁₂ with ABT-450/r 150/100 mg QD + ABT-333 400 mg BID + ribavirin (Arm 2).
• One patient in Arm 1 discontinued due to asymptomatic isolated ALT/AST elevations at week 2. One patient in Arm 2 discontinued due to noncompliance in week 1. All remaining patients in Arms 1 and 2 completed treatment and achieved SVR₁₂. In Arm 3, six patients experienced viral breakthrough while on treatment and three patients relapsed after treatment stopped.
• In the trial the most common adverse events were fatigue (42 percent), nausea (22 percent) and headache (20 percent).
• 47 percent (8 of 17) of patients with HCV GT1 (16 GT 1a, 1 GT 1b) who had previously not responded to other HCV treatments achieved SVR₁₂ with
  ABT-450/r 150/100 mg QD + ABT-333 400 mg BID + ribavirin (Arm 3).

Study M12-267 (Pilot)

Eric Lawitz et al.; Thursday, April 19, 16:00-18:00 CET / 9:00-11:00 a.m. CDT.

"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"

• 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 1,000-1,200 mg/day was weight-based 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 SVR_24.
• In the trial, the most common adverse events reported were headache, fatigue, nausea and dry skin. There were no premature discontinuations.

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

In addition to the oral presentations, Abbott has six poster presentations at ILC 2012:
.

• Tami Pilot-Matias et al.; Friday, April 20 (11:00-11:30, 12:30-14:00, 15:30-16:00 CET)
  "In vitro combinatory effect of HCV NS3/4A protease inhibitor ABT-450, NS5A inhibitor ABT-267, and non-nucleoside NS5B polymerase inhibitor ABT-333"
• Robert W. Baran et al.; Friday, April 20 (11:00-11:30, 12:30-14:00, 15:30-16:00 CET)
  "Hepatitis C Virus Patient Reported Outcomes (HCVPRO): Development and Validation of a Disease-Specific Patient Reported Outcomes Instrument for Health-Related Quality of Life Measurement"
• Eric Lawitz et al.; Saturday, April 21 (11:00-11:30, 12:30-13:30, 15:00-15:30 CET)
  "Safety and antiviral activity of ABT-267, a novel NS5A inhibitor, during 3-day monotherapy: first study in HCV genotype-1 (GT1)-infected treatment-naïve subjects"

• J Greg Sullivan et al.; Saturday, April 21 (11:00-11:30, 12:30-13:30, 15:00-15:30 CET)
  "ABT-267 combined with pegylated interferon alpha-2a/ribavirin in genotype 1 (GT1) HCV-infected treatment-naïve subjects: 12 week antiviral and safety analysis"
• Eric Lawitz et al; Saturday, April 21 (11:00-11:30, 12:30-13:30, 15:00-15:30 CET)
  "ABT-450/ritonavir (ABT-450/r) combined with pegylated interferon alpha-2a/ribavirin after 3-day monotherapy in genotype 1 (GT1) HCV-infected treatment-naïve subjects: 12-week sustained virologic response (SVR₁₂) and safety results"
• Fred Poordad et al.; Saturday, April 21 (11:00-11:30, 12:30-13:30, 15:00-15:30 CET)
  "ABT-072 or ABT-333 combined with pegylated interferon/ribavirin after 3-day monotherapy in HCV genotype 1 (GT1)-infected treatment-naïve subjects: 12-week sustained virologic response (SVR₁₂) and safety results"

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 aviumcomplex (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 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.

---

Media: Tracy Sorrentino Roseanne Durril	(847) 937-8712 (847) 938-6114
Financial: Lawrence Peepo Elizabeth Shea	(847) 935-6722 (847) 935-2211

Hepatitis News Ticker-Video;Side Effects Telaprevir-Incivek and Boceprevir-Victrelis

Hepatitis C Side Effect Management: Lauren Thomas, RN, NP-C with Liver Specialists of Texas
by Dr. Joe Galati on September 26, 2011
Lauren Thomas, RN, NP-C, discusses in the video the management of side effects associated with hepatitis C therapy. The triple therapy, which includes pegylated interferon, ribavirin and a protease inhibitor (either telaprevir or boceprevir) are discussed. This video is geared for patients, family members, and healthcare providers involved in the care of hepatitis C patients and their treatment. Proper management of the medication side effects if key to successful treatment, and clearance of the HCV virus. Your comments are welcomed, letting us know what additional topics you would like included in the educational series.



Also See Hepatitis C Drug Incivek (telaprevir); What are the side effects ?

Enanta's Lead NS5A Inhibitor Candidate for HCV, EDP-239, Selected as One of Windhover's Top 10 Infectious Disease Projects to Watch
WATERTOWN, Mass., Sept. 26, 2011 /PRNewswire/ --
Enanta Pharmaceuticals, Inc. announced today that its lead development candidate from its NS5A hepatitis C virus (HCV) inhibitor program, EDP-239, has been recognized on Windhover's list of the "Top 10 Most Interesting Infectious Disease Projects to Watch." EDP-239 was chosen by independent experts at Windhover Information and Herndon Company.

NS5A, a clinically-validated target, is a non-structural viral protein that is essential to viral replication. Research efforts have shown that targeting NS5A gives rise to profound antiviral activity, and as a result, this protein has emerged as an important target for antiviral drug development. Enanta's NS5A program and intellectual property estate in the HCV field were derived from its internal drug discovery efforts.

"Enanta appreciates Windhover's recognition of our EDP-239 program for HCV, which showcases the strength of our internal drug discovery efforts aimed against important infectious disease targets," said Jay Luly, Ph.D, president and chief executive officer, Enanta Pharmaceuticals. "We are on-track to initiate a Phase 1 clinical trial for EDP-239 in the coming months, following preclinical studies that demonstrated picomolar potency against multiple genotypes of the virus, an excellent safety profile and a preclinical pharmacokinetic profile amenable to once-a-day dosing in humans."

"Selected companies have been screened using a strict set of judging criteria for the Top 10 award and represent what our committees considered the most attractive infectious disease opportunities the industry has to offer," said David Cassak, Vice President, Content, Windhover Conferences, a division of Elsevier Business Intelligence. "Winners have met rigorous criteria, including: unmet medical need, market potential, diversity of indications, strong science, multi-level partnering opportunities (biotech and pharma), potential for new opportunities beyond initial indications and corporate stability."

About the Hepatitis C Virus
Hepatitis C is a liver disease affecting over 170 million people worldwide. The virus is spread through direct contact with the blood of an infected person. Hepatitis C increases a person's risk of developing chronic liver disease, cirrhosis, liver cancer and death. Liver disease associated with HCV infection is growing rapidly, and there is an acute need for new therapies that are safer and more effective. Specifically targeted antiviral therapies for HCV, such as NS3/4a protease and NS5A inhibitors, may have the potential to increase the proportion of patients in whom the virus can be eradicated.

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 developing novel protease, NS5A, nucleoside(tide) polymerase, and cyclophilin-based inhibitors targeted against the Hepatitis C virus (HCV). Additionally, the Company has created a new class of macrolide 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 http://www.enanta.com/.

For Enanta Investor Relations, please contact:Paul Mellett617-607-0761
For Enanta Public Relations, please contact MacDougall Biomedical Communications:Kari Watson508-647-0209 or kwatson@macbiocom.com
SOURCE Enanta PharmaceuticalsBack to top
RELATED LINKS http://www.enanta.com/

From NATAP

Recruiting A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of ABT-450 With Ritonavir (ABT-450/r) When Given Together With ABT-333 and Ribavirin (RBV) in Treatment-Naïve and Non-responder Subjects With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection
An Open-Label Pilot Study to Evaluate the Antiviral Activity, Safety and Pharmacokinetics of ABT-450 With Ritonavir (ABT-450/r) Dosed in Combination With ABT-333 and Ribavirin (RBV) in Treatment-Naive and Non-responder Subjects With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection

Images in Clinical Medicine
Porphyria Cutanea Tarda
Chih-Chieh Chan, M.D., and Sung-Jan Lin, M.D., Ph.D.
N Engl J Med 2011; 365:1128
September 22, 2011
A 51-year-old man with a history of heavy alcohol use, chronic hepatitis C virus (HCV) infection, and hepatic cirrhosis presented to his physician with an 8-month history of periorbital hair growth. On examination, healing crusts and scars were evident in sun-exposed areas. He described skin photosensitivity and intermittent painful blistering over the nape of the neck, the forearms, and the backs of the hands (Panel A).

The patient's urine had pink fluorescence under a Wood's lamp, suggesting the presence of uroporphyrin (Panel B, a urine sample from the patient [indicated by an asterisk] and one from a normal control subject [N] under white light; Panel C, the same two urine samples under ultraviolet A light). A diagnosis of porphyria cutanea tarda was confirmed when marked uroporphyrinuria was shown on laboratory analysis. Porphyria cutanea tarda results from decreased activity of the uroporphyrinogen decarboxylase enzyme. Although the mechanism is unknown, the sporadic form of the disease is strongly associated with chronic HCV infection. Facial hypertrichosis is common and may serve as a diagnostic clue.

Although treatment of the patient's chronic HCV infection was considered inadvisable by his hepatologist, low-dose oral hydroxychloroquine, skin photoprotection, and alcohol cessation successfully controlled the cutaneous eruptions within 6 months.
Chih-Chieh Chan, M.D.Sung-Jan Lin, M.D., Ph.D.National Taiwan University Hospital, Taipei,
Taiwan 009015@ntuh.gov.tw

New Hepatitis C Drugs
Published on Sep 19, 2011 by wdsutv
According to the Centers for Disease Control, an estimated 3.2 million americans have chronic Hepatitis C infections. The FDA recently approved two new drugs for treatment.


HIV

Rapid Immune Test Cuts HIV Care Drop-Outs
By eliminating bottlenecks, a rapid immune system test sharply cut the proportion of people who dropped out of HIV care before starting treatment, researchers reported.

Transplant

Old, diseased organs no barrier to donation
by: Marianne Betts
From: Herald Sun
September 26, 2011 12:00AM
ORGANS from old and diseased donors are increasingly being transplanted into gravely ill Australians.

The oldest donor last year was 84, and record numbers of organs are being transplanted from donors with cancer, diabetes and hepatitis, the Australian and New Zealand Organ Donation Registry 2011 Report reveals.

Despite an increase in organ donations, 1600 Australians are awaiting a transplant and many will die before they get one.

Last year, half the nation's 309 donors had been smokers, 14 had cancer, 20 had hepatitis B, two had hepatitis C, 29 had diabetes and 86 had high blood pressure.
In Australia, hepatitis B and C, cancer and the arenavirus have been passed on through infected donor organs and recipients have died.

Nine livers were transplanted from donors with hepatitis B or C.
Austin Hospital liver transplant unit director Professor Bob Jones said while some recipients might not have had hepatitis, others already would have had the disease.
He said there was a risk of hepatitis being passed from donor to recipient through a transplant.
"It's all about balancing the degree of risk - you have to balance these risks versus the risk of dying waiting," he said.

"If a patient is dying in ICU and has 24 hours to live and the only donor has hepatitis B, we will discuss it with the family."

Some elderly donors were suitable - a dying 30-year-old woman received a 78-year-old's liver, and two or three years later, it was still working "beautifully", he said.
Royal Australasian College of Surgeons transplant surgery chair Jonathan Fawcett said each year the average age of donors was rising.

"In the mid-1990s, (surgeons) were reluctant to use organs retrieved from donors over 50, but now it's common to use organs from donors well into their 60s," Mr Fawcett said.
Victorian medical director of organ and tissue donation Dr Helen Opdam said: "Ten years ago, we would not entertain using organs from someone who was a heavy smoker or a heavy drinker. "Now we will, as long as they are functioning well."

Marijuana

Prescription for Pot - A Debate on the Merits of Medical Marijuana
The use of marijuana for medicinal purpose has been a hotly debated topic in the United States. While cannabis is still listed as an illegal narcotic under Federal Law, 16 states and the District of Columbia have statutes decriminalizing medicinal marijuana as a therapy for specific ailments. Recently, the American Medical Association released a report urging review of marijuana as a Schedule 1 controlled substance, noting that physicians should be protected from prosecution for recommending marijuana and that further studies should be conducted into marijuana’s use as medicine.To provide further insight on this controversy, MD Magazine Peers & Perspectives convened two leading experts in the field to debate the merits or lack thereof of medical marijuana: Joel W. Hay, PhD, professor of clinical pharmacology and pharmaceutical economics and policy at the Shafer Center for Health Policy and Economics in the School of Pharmacy at the University of Southern California, and Joseph I. Sirven, MD, professor and chairman of the department of neurology at the Mayo Clinic in Arizona. The panel was moderated by Peter Salgo, MD. This transcript has been condensed and edited for clarity and length...Continue Reading

Pharmaceutical

Podcast: Dollars for Docs Update
by Minhee ChoProPublica, Sep. 19, 2:44 p.m.
ProPublica’s Charles Ornstein, Tracy Weber and Dan Nguyen join the podcast this week to talk about their recently updated Dollars for Docs database – a project tracking big pharma’s payments to physicians.

ProPublica recently published a major update to our Dollars for Docs news application [1] – a database tracking money physicians have received from some of the pharmaceutical industry’s largest companies to promote their products.
Currently, the database lists $761.3 million in payments from 12 companies, which account for about 40 percent of U.S. sales. But in 2013, all drug and medical device companies will have to disclose what they are paying doctors for promotional talks, consulting, research, meals and more. Until then, ProPublica’s Dollars for Docs team – Charles Ornstein, Tracy Weber and Dan Nguyen – hope their project will shed some light on the industry’s ties to physicians. They join the podcast this week to explain the technical complexity of this project, why pharmaceutical companies enlist physicians to promote their products to begin with, and why patients have a right to know this information.

Click Below To Listen Or Read Transcript



UK-Man arrested over Nurofen contamination
Detectives investigating how packs of Nurofen Plus were found to contain antipsychotic and anti-epileptic drugs are questioning a man in custody.
Scotland Yard said the suspect, 30, from Bromley in south London, was arrested on Friday on suspicion of contamination of goods. He is being held in a south London police station.
Reckitt Benckiser, the drug's manufacturer, recalled the product on August 26 and halted distribution after discovering five boxes contained other companies' medicines.
It estimated some 250,000 packets were still in customers' hands.
Four of the affected boxes were found to contain the antipsychotic drug Seroquel XL 50mg and one packet contained Pfizer's anti-epileptic medication, Neurontin, in 100mg capsules.
The Met's Specialist Crime Directorate (SCD), which tackles serious and organised crime, is leading the probe and has been examining the entire production line of the drug as part of the inquiry.

AP IMPACT: Hospital drug shortages deadly, costly
By LINDA A. JOHNSONAP Business Writer
TRENTON, N.J. (AP) - A drug for dangerously high blood pressure, normally priced at $25.90 per dose, offered to hospitals for $1,200. Fifteen deaths in 15 months blamed on shortages of life-saving medications.
A growing crisis in the availability of drugs for chemotherapy, infections and other serious ailments is endangering patients and forcing hospitals to buy from secondary suppliers at huge markups because they can't get the medications any other way.
An Associated Press review of industry reports and interviews with nearly two dozen experts found the shortages - mainly of injected generic drugs that ordinarily are cheap - have delayed surgeries and cancer treatments, left patients in unnecessary pain and caused hospitals to give less effective treatments. That's resulted in complications and longer hospital stays.....

Healthy You

Nutrition experts out of the Harvard School of Public Health and Harvard Health Publications in Boston developed a blueprint for healthy eating that they call The Harvard Healthy Eating Plate




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