Achillion Pharmaceuticals announces preliminary proof-of-concept data with HCV NS5A inhibitor ACH-2928...

Looks like Achillion Pharmaceuticals' NS5A inhibitor is bearing fruit, with the company releasing three-day monotherapy proof-of-concept data for it's first generation NS5A inhibitor ACH-2928 as well as naming a second generation compound ACH-3102, which is slated for early trials in Q1/Q2 next year. CE0 Michael D. Kishbauch is aiming for "a proprietary interferon-free DAA combination regimen for the treatment of HCV within Achillion's pipeline." Looks like Achillion will have plenty to present at EASL 2012, as well as an intention to evaluate an all-oral comb including one of their protease inhibitors and an NS5A inhibitors.

Achillion Announces Preliminary Phase 1b Proof-of-Concept Data With ACH-2928 NS5A Inhibitor for the Treatment of Hepatitis C

Achieves 3.68 Log10 Reduction in HCV RNA After Three Days of Treatment

NEW HAVEN, Conn., Dec 5, 2011 (GlobeNewswire via COMTEX) -- Achillion Pharmaceuticals, Inc. ACHN +1.61% , a leader in the discovery and development of small molecule drugs to combat the most challenging infectious diseases, today reported proof-of-concept data from its Phase 1b clinical trial of ACH-2928, a first-generation NS5A inhibitor, demonstrating that patients treated with ACH-2928 achieved a mean maximum 3.68 log10 reduction in HCV RNA after three-day monotherapy of 60 mg once daily. The compound also demonstrated good safety and tolerability both in healthy volunteers and in patients with chronic hepatitis C (HCV).

ACH-2928, Achillion's first generation inhibitor of the NS5A protein, was discovered through the Company's NS5A inhibitor program. Achillion also recently nominated a second-generation NS5A inhibitor, ACH-3102, which is currently undergoing IND-enabling studies and is expected to be advanced into clinical trials during the first half of 2012.

"We believe NS5A inhibitors have emerged as an important component for an all-oral, direct acting antiviral (DAA) regimen," commented Michael D. Kishbauch, President and Chief Executive Officer of Achillion. "Furthermore, NS5A inhibitors, when combined with a protease inhibitor, have achieved sustained viral responses in clinical trials in tough to treat genotype 1 HCV populations. We believe this highlights the potential to form a proprietary interferon-free DAA combination regimen for the treatment of HCV within Achillion's pipeline."

ACH-2928 Phase 1 Program

In July 2011, Achillion initiated dosing in a randomized, double-blind, placebo-controlled phase 1a/1b clinical trial to investigate the safety, tolerability, pharmacokinetic profile and antiviral activity of ACH-2928. The trial consists of three segments: assessment of single ascending oral doses (SAD) in healthy volunteers, evaluation of 3 days of oral repeat doses in subjects with genotype 1a or 1b HCV, and a 5-day multiple ascending doses segment in healthy volunteers.

During the oral repeat doses segment in subjects infected with HCV, a total of 10 patients were enrolled with 2 patients (genotype 1a) receiving placebo and 8 patients (7 genotype 1a and 1 genotype 1b) treated with 3 doses of 60 mg ACH-2928 administered once daily. No serious adverse events (SAE) were reported and there were no patient discontinuations during treatment. The mean maximum HCV RNA decline during therapy was 3.68 log10 compared to a 0.54 log10 decline for patients receiving placebo. There were no viral breakthroughs observed during ACH-2928 monotherapy.

Preliminary data from the SAD trial segment demonstrated ACH-2928 was well tolerated at all doses evaluated up to and including the maximum dose of 500 mg. There were no serious adverse events, no clinically significant changes in vital signs, electrocardiograms (ECGs), or laboratory evaluations. All reported adverse events were classified as mild or moderate, and were transient in nature.

Based upon these preliminary results, the ongoing Phase 1 study will continue to evaluate the pharmacokinetic, pharmacodynamic, and antiviral profile of ACH-2928. These Phase 1 results have been submitted for presentation at a medical meeting being held during the second quarter of 2012. In parallel, Achillion is advancing its second generation NS5A inhibitor ACH-3102 through IND-enabling studies and the Company expects to initiate clinical development during the first half of 2012.

"As we continue to evaluate ACH-2928 in this Phase 1 study, we are also working rapidly to advance ACH-3102, which has shown in preclinical studies to possess the same potent activity against genotype 1a HCV as ACH-2928, as well as enhanced activity against resistant HCV mutants that have been observed in this patient population," stated Milind Deshpande, PhD, President of Research and Development and Chief Scientific Officer. "We believe these results validate our NS5A development program, and look forward to developing an all-oral combination for clinical evaluation that includes one of our protease inhibitors and an NS5A inhibitor next year."

About NS5A Inhibitors

The NS5A protein is a clinically validated target that serves multiple functions at various stages of the HCV life cycle including involvement in virion production, interaction with host proteins and association with interferon-resistance. Achillion's NS5A inhibitors, including ACH-2928 and ACH-3102, possess potent in vitro activity against all HCV genotypes and demonstrate, in preclinical studies, additive to synergistic activity when combined with NS3 protease inhibitors, NS5B polymerase inhibitors, and ribavirin. In preclinical studies, ACH-2928 and ACH-3102 have demonstrated excellent potency, in the pico-molar range, against HCV RNA replication, including potent activity against genotype 1a while ACH-3102 has been shown to possess enhanced activity against recognized genotype 1 resistant variants.

About HCV

The hepatitis C virus infects the liver and is the most common cause of viral hepatitis, which is an inflammation of the liver. It is currently estimated that more than 170 million people are infected with HCV worldwide and The American Association of Liver Disease estimates that up to 80 percent of individuals become chronically infected following exposure to the virus. If left untreated, chronic hepatitis can lead to permanent liver damage, which can result in the development of liver cancer, liver failure or death. Few therapeutic options currently exist for the treatment of HCV infection. The current standard of care is limited by its specificity for certain types of HCV, significant side-effect profile, and injectable route of administration.

About Achillion Pharmaceuticals

Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. Achillion's proven discovery and development teams have advanced multiple product candidates with novel mechanisms of action. Achillion is focused on solutions for the most challenging problems in infectious disease including hepatitis C and resistant bacterial infections. For more information on Achillion Pharmaceuticals, please visit www.achillion.com or call 1-203-624-7000.

Forward-Looking Statements

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other important factors, including statements with respect to the potency, safety and other characteristics of Achillion's NS5A inhibitors, which may not be duplicated in clinical studies, and Achillion's expectations regarding results, timing and duration of clinical trials and reporting of results from clinical trials of Achillion's NS5A inhibitors. Among the important factors that could cause actual results to differ materially from those indicated by such forward-looking statements are risks relating to: Achillion's ability to advance the development of its drug candidates under the timelines it anticipates in current and future clinical trials; to obtain patent protection for its drug candidates, and the freedom to operate under third party intellectual property; to establish commercial manufacturing arrangements and to identify, enter into and maintain collaboration agreements with appropriate third-parties; and to raise the substantial additional capital needed to achieve its business objectives. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2010 and its subsequent SEC filings.

In addition, any forward-looking statement in this press release represents Achillion's views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. Achillion disclaims any obligation to update any forward-looking statement, except as required by applicable law.

This news release was distributed by GlobeNewswire, www.globenewswire.com

SOURCE: Achillion Pharmaceuticals, Inc.



CONTACT: Glenn Schulman
Achillion Pharmaceuticals, Inc.
Tel. (203) 752-5510
gschulman@achillion.com
Investors:
Mary Kay Fenton
Achillion Pharmaceuticals, Inc.
Tel. (203) 624-7000
mfenton@achillion.com
Media:
Christin Culotta Miller
Ogilvy PR
Tel. (212) 880-5264
christin.miller@ogilvy.com

BMS and Tibotec team up HCV antivirals for phase II trial....

The HCV development partnership space is jumpin'! Medivir/Tibotec now has two partnerships, one with Gilead/Pharmasset in combination with their nuc PSI-7977 and now with BMS's daclatasvir. The question of what happens to the development of BMS's peg lambda is still a bit of a mystery.

December 02, 2011 07:30 AM Eastern Time

Bristol-Myers Squibb Enters Clinical Collaboration Agreement with Tibotec Pharmaceuticals for Phase II Combination Study in Patients Chronically Infected with Hepatitis C

NEW YORK--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) announced today that it has entered into a clinical collaboration agreement with Tibotec Pharmaceuticals, one of the Janssen Pharmaceutical Companies, to evaluate the utility of daclatasvir (BMS-790052), Bristol-Myers Squibb’s investigational NS5A replication complex inhibitor, in combination with Tibotec Pharmaceuticals' investigational NS3 protease inhibitor, TMC435, for the treatment of chronic hepatitis C virus (HCV).

Under the agreement the companies will evaluate the potential to achieve sustained viral response 12 and 24 weeks post treatment in patients with HCV genotype 1 in a study with three treatment regimens: an oral, once-daily treatment regimen of daclatasvir and TMC435 with pegylated-interferon alpha plus ribavirin; an oral, once-daily treatment regimen of daclatasvir and TMC435 with ribavirin and an oral, once-daily treatment regimen of daclatasvir and TMC435 alone. The study is planned to start in the first half of 2012.

“Bristol-Myers Squibb is dedicated to developing innovative treatment options for patients with serious diseases like HCV,” said Brian Daniels, senior vice president, Development. “We are pleased to work with Tibotec to advance the scientific understanding for the potential for an all-oral regimen of direct acting antivirals, which would be an important advancement for patients with HCV. This is a continuation of our leadership in forging partnerships to advance combination antiviral therapy.”

About daclatasvir (BMS-790052)

Discovered by Bristol-Myers Squibb through a genomics approach, daclatasvir is the first NS5A replication complex inhibitor to be investigated in clinical trials and is currently in Phase III development. Daclatasvir is part of a portfolio of investigational compounds that the company is developing for the treatment of hepatitis C.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.

Bristol-Myers Squibb Forward-Looking Statement

This press release contains “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995, regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that the compound described in this release will move from early stage development into full product development, that clinical trials of this compound will support a regulatory filing, or that the compound will receive regulatory approval or become a commercially successful product. Forward-looking statements in the press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb’s business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2010, its Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise.

Contacts

Bristol-Myers Squibb
Media:
Jennifer Fron Mauer, 609-252-6579
jennifer.mauer@bms.com
or
Investors:
John Elicker, 609-252-4611
john.elicker@bms.com
or
Teri Loxam, 609-252-3368
teri.loxam@bms.com

Company Information Center
Bristol-Myers Squibb Company

NYSE:BMY

Journal article in Hepatology on green tea flavonoid that may prevent HCV reinfection post-liver transplant...

Some promising news published online in the journal Hepatology discussing in vivo research on the green tea catechin epigallocatechin-3-gallate (EGCG) that could possibly block HCV viral attachment to hepatocytes to prevent hepatitis C reinfection post-transplant.

Contact: Dawn Peters
healthnews@wiley.com
781-388-8408
Wiley-Blackwell

Green tea flavonoid may prevent reinfection with hepatitis C virus following liver transplantation


German researchers have determined that epigallocatechin-3-gallate (EGCG)—a flavonoid found in green tea—inhibits the hepatitis C virus (HCV) from entering liver cells. Study findings available in the December issue of Hepatology, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases, suggest that EGCG may offer an antiviral strategy to prevent HCV reinfection following liver transplantation.

HCV infection can lead to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) or primary liver cancer. HCV is one of the most common causes of chronic liver disease and a primary indication for liver transplantation, affecting up to 170 million individuals worldwide according to estimates from the World Health Organization (WHO). Prior studies report that nearly 2% of the world population is infected with chronic HCV and up to 20% of the population in some countries.

While standard treatment with interferon with ribavirin and newer protease inhibitors may clear infection in some individuals, a substantial number of patients still may not respond to these therapies. For individuals receiving liver transplants due to complications from HCV, reinfection of the healthy donor liver remains a significant concern. Antiviral strategies that target HCV in its early stages are urgently needed to prevent graft reinfection and improve long-term outcomes for patients.

To address this critical issue, Dr. Sandra Ciesek and Dr. Eike Steinmann from the Hannover Medical School in Germany investigated the effect of the EGCG molecule, which is a major component of green tea, in preventing HCV from attaching to liver cells. "Green tea catechins such as EGCG and its derivatives epigallocatechin (EGC), epicatechingallate (ECG), and epicatechin (EC) have been shown to exhibit antiviral and anti-oncogenic properties," explains Dr. Ciesek. "Our study further explores the potential effect these flavonoids have in preventing HCV reinfection following liver transplantation."

Results showed that unlike its derivatives, EGCG inhibits entry of HCV into liver cells. The authors suggest that EGCG may impede HCV cell entry by acting on the host cell as the green tea catechin was not found to alter the density of virus particles. Pretreatment of cells with EGCG before HCV inoculation did not reduce the infection; however application during inoculation inhibited the rapid spread of the HCV. Lastly, researchers showed that EGCG inhibits viral attachment—the initial step in the HCV infection process. "The green tea antioxidant EGCG inhibits HCV cell entry by blocking viral attachment and may offer a new approach to prevent HCV infection, particularly reinfection following liver transplantation." concludes Dr. Ciesek.


###


Full Citation: The Green Tea Polyphenol Epigallocatechin-3-Gallate (EGCG) Inhibits Hepatitis C Virus (HCV) Entry." Sandra Ciesek, Thomas von Hahn, Che C. Colpitts, Luis M Schang,Martina Friesland, Jörg Steinmann, Michael P. Manns, Michael Ott, Heiner Wedemeyer, Philip Meuleman, Thomas Pietschmann and Eike Steinmann. Hepatology; Published Online: November 30, 2011 (DOI: 10.1002/hep.24610); Print Issue Date: December 2011. http://onlinelibrary.wiley.com/doi/10.1002/hep.24610/abstract.

Author Contact: To arrange an interview with Dr. Sandra Ciesek or Dr. Eike Steinmann, please contact Jo Schilling at jo.schilling@twincore.de.

This study is published in Hepatology. Media wishing to receive a PDF of the article may contact healthnews@wiley.com.

About the Journal

Hepatology is the premier publication in the field of liver disease, publishing original, peer-reviewed articles concerning all aspects of liver structure, function and disease. Hepatology's current impact factor is 10.885.Each month, the distinguished Editorial Board monitors and selects only the best articles on subjects such as immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases and their complications, liver cancer, and drug metabolism. Hepatology is published on behalf of the American Association for the Study of Liver Diseases (AASLD). For more information, please visit http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1527-3350 .

About Wiley-Blackwell

Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the world's leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit www.wileyblackwell.com or our new online platform, Wiley Online Library (wileyonlinelibrary.com), one of the world's most extensive multidisciplinary collections of online resources, covering life, health, social and physical sciences, and humanities.

Hep C Protease Inhibitors May Not Be Cost-Effective For Some First-Time Treatment Takers

From http://www.hepmag.com, a synopsis of an AASLD study authored byZiad Gellad, MD, MPH, of Duke University Medical Center that argues triple therapy may not be the most cost-effective stragtegy for genotype 1 patients with the IL-28B CC genotype. As we know, patients with the CC genotype are more likely to respond to peg-interferon and ribavirin alone, at a significant cost savings compared to starting these patients on a HCV protease inhibitor. According to Gellad, " for first-time treatment takers with the IL-28B CC genotype, adding Incivek “is unlikely to be cost-effective under current cost and efficacy conditions”

Hepatitis C virus (HCV) protease inhibitors are not cost-effective for first-time treatment takers with HCV genotype 1 and the IL-28B CC genotype, according to analysis conducted by Ziad Gellad, MD, MPH, of Duke University Medical Center in Durham, North Carolina, and his colleagues. They reported their findings on Monday, November 7, at the 62nd annual meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco. According to the study authors, people with the IL-28B CC genotype are more likely to be cured with pegylated interferon and ribavirin alone than people with the IL-28B CT or TT genotypes, for whom the addition of either Incivek (telaprevir) or Victrelis (boceprevir) may be more cost effective.

A 24- to 48-week course of pegylated interferon and ribavirin ranges from $18,000 to $30,000. As Gellad noted, “adding Incivek (telaprevir) or Victrelis (boceprevir)”—both recently approved HCV protease inhibitors—“more than doubles the cost of therapy, to a range of $48,000 to $85,000.”

An advantage of Incivek and Victrelis is that they can improve the effectiveness of treatment when added to a combination of pegylated interferon and ribavirin. This is particularly true for people with the IL-28B CT or TT genotype, which is believed to reduce the effectiveness of pegylated interferon, which remains a backbone of hepatitis C treatment. Conversely, those with the IL-28B CC genotype are much more likely to respond effectively to pegylated interferon-ribavirin therapy. Thus, it remains unclear if adding either Incivek or Victrelis to pegylated interferon/ribavirin—provided that the patient has an IL-28B CC genotype and is starting therapy for the first time—translates into added effectiveness worth the additional cost of either drug.

The authors created a model that allowed them to analyze three HCV treatment strategies. The first strategy involved 48 weeks of treatment with pegylated interferon plus ribavirin. The second strategy involved 24 weeks of pegylated interferon and ribavirin according to response-guided therapy (RGT) rules, which take into consideration viral load measurements at weeks four and 12 of treatment. The third strategy involved 12 weeks of Incivek in combination with either 24 or 38 weeks of pegylated interferon plus ribavirin.

According to the analysis by Gellad’s team, the cure rates among first-time treatment takers with the CC genotype were similar, yet the costs of each regimen varied considerable. Among those who qualified for 24 weeks of RGT with pegylated interferon and ribavirin alone, the cure rate was expected to be roughly 71 percent at a cost of $46,785. The cost increased to $54,931 when interferon/ribavirin was used for a total of 48 weeks, with an expected cure rate of 66 percent. If retreatment was necessary in either circumstance, roughly 87 percent to 91 percent would be cured.

Starting hepatitis C treatment with an Incivek-inclusive regimen was expected to cure 89 percent of HCV-positive individuals with the CC IL-28B genotype—at a cost of $68,788. According to estimates of lifetime treatment costs and quality-adjusted life-years (QALYs) measurements, however, the gain did not differ significantly compared with the other two strategies.

Adding Incivek to pegylated interferon and ribavirin was cost-effective for first-time treatment takers in certain circumstances, Gellad and his colleagues noted, such as when it enhanced the early response to hepatitis C treatment (known as extended rapid virologic response, or eRVR). An eRVR—when hepatitis C viral load is undetectable at treatment week 4 and remains that way at week 12—is a strong predictor of being cured. Incivek was considered cost-effective when it boosted the eRVR rate to 89 percent. For people who did not have an eRVR, Incivek was cost effective if it could increase cure rates to over 80 percent. In addition, the authors considered Incivek to be cost-effective for retreating people who relapsed or did not respond to dual therapy.

In summary, for first-time treatment takers with the IL-28B CC genotype, adding Incivek “is unlikely to be cost-effective under current cost and efficacy conditions,” said Gellad, who concluded by recommending research to compare effectiveness of treatment with and without an HCV protease inhibitor in this group.

University of Liverpool launches an iPhone app for HCV DAA drug interactions...

(Finally, an app that is immediately practical! The new HEP i-Chart app launched by University of Liverpool researchers assists patients and providers alike in keeping up to date with possible drug-drug interactions between the new Direct Acting Antivirals for Hepatitis C and other medications and herbs. More info at http://www.hep-druginteractions.org/ )

The University of Liverpool has launched an iphone app, HEP i-chart, that provides Hepatitis C (HCV) patients with quick and easy access to the latest information about drug interactions.

Hepatitis C was first discovered in the 1980s when it became apparent that there was a new virus (not the already known hepatitis A or B) causing liver damage. Hepatitis C causes inflammation and swelling of the liver. It is estimated that over 170million individuals – representing 3% of the world's population – are chronically infected with the Hepatitis C virus (HCV). Statistically, as many people are infected with HCV as are with HIV.

Since its identification, drug treatment to eradicate the virus has advanced greatly, especially in the last few years. Two new drugs have recently been licensed for treatment of HCV, and there are more drugs in development.

HEP i-chart is based on the website (http://www.hep-druginteractions.org/) developed at the University by Professor David Back and Professor Saye Khoo which provides a comprehensive online guide to the interactions between anti-hepatitis drugs and other drugs. It is a tool that provides Hepatitis C patients and healthcare professionals with immediate access to up-to-date information on potential drug interactions between HCV drugs, and other drugs that the patient may be prescribed as well as over-the-counter, recreational or herbal medications.

Existing HCV drugs, newly licensed drugs and drugs in development can have interactions with each other and with other drugs which can impact on their effectiveness – sometimes with serious consequences. For this reason, some drug combinations must not be used, whilst others must be given with caution, possibly requiring adjustment or monitoring.

Professor of Pharmacology, David Back, said: "We are delighted to launch with our partners – KnowledgePoint360, MSD and Janssen- this new i-phone application that provides Hepatitis C patients and healthcare professionals with instant and easy access to information about HCV drug interactions which is relevant and reliable and up-to-date. This resource is especially important as new HCV drug treatments are approved and come into use."

Professor Graham Foster, President of the British Association for the Study of the Liver (BASL) said: "This new app, HEP i-chart, is a timely and much-needed resource for HCV patients as the number of new drugs which are available to treat Hepatitis C increases."

Gilead Sciences to Acquire Pharmasset, Inc. for $11 Billion

This is a game-changer in HCV drug development. Gilead, long a commercial juggernaut in the HBV and HIV commercial space, purchases Pharmasset whose HCV development portfolio includes it's AASLD show-stopper nucleotide analog PSI-7977. Gilead already has an impressive HCV drug development program in place and with it's expertise in antiviral co-formulation, one can foresee leveragin that expertise to Gilead's full advantage in developing all-oral HCV antiviral compounds. It will be interesting to see how the competition reacts. It could be game-over for many otherwise fledgling development programs whose molecules just won't be able to compete


Gilead Sciences to Acquire Pharmasset, Inc. for $11 Billion

- Accelerates Development of All-Oral Regimen for the Treatment of HCV -
- Leverages Gilead's Infrastructure and Expertise in Antiviral Drug Development, Manufacturing and Commercialization -

FOSTER CITY, Calif. & PRINCETON, N.J., Nov 21, 2011 (BUSINESS WIRE) --

Gilead Sciences, Inc. (Nasdaq:GILD) and Pharmasset, Inc. (Nasdaq:VRUS) announced today that the companies have signed a definitive agreement under which Gilead will acquire Pharmasset for $137 per share in cash. The transaction, which values Pharmasset at approximately $11 billion, was unanimously approved by Pharmasset's Board of Directors. Gilead plans to finance the transaction with cash on hand, bank debt and senior unsecured notes. The company expects the transaction, when completed, to be dilutive to Gilead's earnings through 2014 and accretive in 2015 and beyond. Further guidance will be provided when the transaction closes, which is expected to be in the first quarter of 2012.

Pharmasset currently has three clinical-stage product candidates for the treatment of chronic hepatitis C virus (HCV) advancing in trials in various populations. The company's lead product candidate, PSI-7977, an unpartnered uracil nucleotide analog, has recently been advanced into two Phase 3 studies in genotype 2 and 3 patients. Both studies will utilize 12 weeks of treatment with PSI-7977 in combination with ribavirin. One study will compare this all-oral regimen against 24 weeks of the standard-of-care pegylated interferon/ribavirin in treatment-naïve patients, and the second study will compare the all-oral regimen to placebo in interferon-intolerant/ineligible patients. A third Phase 3 study in genotype 1 patients will be initiated in the second half of 2012, the design of which is dependent on the outcome of Phase 2 studies which are evaluating PSI-7977 in various combinations in genotype 1-infected patients. If successful, this strategy could lead to an initial U.S. regulatory approval of PSI-7977 in 2014. PSI-938, an unpartnered guanosine nucleotide analog, is being tested in a Phase 2b interferon-free trial as monotherapy and in combination with PSI-7977 in subjects with HCV of all viral genotypes. Mericitabine (RG7128), a cytidine nucleoside analog, is partnered with Roche and is being evaluated in three Phase 2b trials. Roche is responsible for all aspects of the development of mericitabine.

"The acquisition of Pharmasset represents an important and exciting opportunity to accelerate Gilead's effort to change the treatment paradigm for HCV-infected patients by developing all-oral regimens for the treatment of the disease regardless of viral genotype," said John C. Martin, PhD, Chairman and Chief Executive Officer of Gilead. "Pharmasset presented compelling Phase 2 data earlier this month further characterizing the strong efficacy and safety profile of PSI-7977. The compound, together with Pharmasset's other pipeline candidates, represents a strong strategic fit with Gilead's vision, pipeline and capabilities. This transaction will serve to drive the long-term growth of our business, and we look forward to working closely with the Pharmasset team to advance a broad clinical program in HCV to address the unmet needs of patients and the medical community."

"We are excited to join together with Gilead, which shares our commitment to providing HCV patients with new, highly efficacious and safe oral therapies," said Schaefer Price, President and Chief Executive Officer, Pharmasset. "We are very encouraged by the data from our Phase 2 studies of PSI-7977 and believe strongly in the potential of this compound to be a component in the transformation of the treatment of chronic HCV. Gilead's established expertise and leadership in the field of antiviral drug development and commercialization, coupled with the company's existing portfolio of promising compounds for HCV, make this partnership an ideal step to fully realize the potential of our promising molecules as part of future all-oral combination therapies for millions of patients in need around the world."

Gilead's research and development portfolio includes seven unique molecules in various stages of clinical development for the treatment of HCV. Pegylated interferon in combination with ribavirin is currently part of the standard of care treatment for patients with chronic hepatitis C. Gilead is focused on advancing multiple compounds with different mechanisms of action and resistance profiles in combinations that will support delivery of an all-oral regimen that would eliminate the need for pegylated interferon. Three separate all-oral Phase 2 studies are currently ongoing, and Gilead expects clinical data from these studies to become available in 2012 and early 2013. Pharmasset's compounds are complementary to Gilead's existing HCV portfolio, and the transaction will help advance Gilead's effort to develop an all-oral regimen for the treatment of HCV.

Terms of the Transaction

Under the terms of the merger agreement, a wholly-owned subsidiary of Gilead will promptly commence a tender offer to acquire all of the outstanding shares of Pharmasset's common stock at a price of $137 per share in cash. Following successful completion of the tender offer, Gilead will acquire all remaining shares not tendered in the offer through a second step merger at the same price as in the tender offer.

The consummation of the tender offer is subject to various conditions, including a minimum tender of at least a majority of outstanding Pharmasset shares on a fully diluted basis, the expiration or termination of the waiting period under the Hart Scott Rodino Antitrust Improvements Act, and other customary conditions. The tender offer is not subject to a financing condition.

The $137 per share price in the transaction represents an 89% premium to Pharmasset's closing share price on Friday, November 18, 2011, the last trading day prior to announcement, and 59% to Pharmasset's all time high closing stock price.

Gilead has received commitments from Bank of America Merrill Lynch and Barclays Capital in connection with financing of the transaction.

Barclays Capital and Bank of America Merrill Lynch are acting as financial advisors to Gilead in the transaction. Morgan Stanley & Co. LLC is acting as the financial advisor to Pharmasset. Skadden, Arps, Slate, Meagher & Flom LLP is serving as legal counsel to Gilead and Sullivan & Cromwell LLP is serving as legal counsel to Pharmasset.

Conference Call

Gilead will host a conference call today, Monday, November 21, 2011, at 8:00 a.m. Eastern Time, to discuss the proposed acquisition. To access the live call, please dial 1-800-599-9829 (U.S.) or 1-617-847-8703 (international). The conference passcode number is 61526607. Telephone replay is available approximately one hour after the call through 11:00 a.m. Eastern Time, November 24, 2011. To access, please call 1-888-286-8010 (U.S.) or 1-617-801-6888 (international). The conference passcode number for the replay is 39677531. The information provided on the teleconference is only accurate at the time of the conference call, and Gilead will take no responsibility for providing updated information.

About Pharmasset

Pharmasset is a clinical-stage pharmaceutical company committed to discovering, developing and commercializing novel drugs to treat viral infections. Pharmasset's primary focus is the development of oral therapeutics for the treatment of hepatitis C virus (HCV) infection. Pharmasset's research and development efforts are focused on nucleoside/tide analogs, a class of compounds which act as alternative substrates for the viral polymerase, thus inhibiting viral replication.

About Gilead Sciences

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

Forward-Looking Statement

This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, that are subject to risks, uncertainties and other factors. All statements other than statements of historical fact are statements that could be deemed forward-looking statements, including all statements regarding the intent, belief or current expectation of the companies' and members of their senior management team. Forward-looking statements include, without limitation, statements regarding business combination and similar transactions, prospective performance and opportunities and the outlook for the companies' businesses, including, without limitation, the ability of Gilead to advance Pharmasset's product pipeline or develop an all-oral antiviral regimen for HCV, performance and opportunities and regulatory approvals, the anticipated timing of data from clinical data; the possibility of unfavorable results of the companies' clinical trials; filings and approvals relating to the transaction; the expected timing of the completion of the transaction; the ability to complete the transaction considering the various closing conditions; and any assumptions underlying any of the foregoing. Investors are cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties and are cautioned not to place undue reliance on these forward-looking statements. Actual results may differ materially from those currently anticipated due to a number of risks and uncertainties. Risks and uncertainties that could cause the actual results to differ from expectations contemplated by forward-looking statements include: uncertainties as to the timing of the tender offer and merger; uncertainties as to how many of Pharmasset's stockholders will tender their stock in the offer; the possibility that competing offers will be made; the possibility that various closing conditions for the transaction may not be satisfied or waived, including that a governmental entity may prohibit, delay or refuse to grant approval for the consummation of the transaction; the effects of the transaction on relationships with employees, customers, other business partners or governmental entities; other business effects, including the effects of industry, economic or political conditions outside of the companies' control; transaction costs; actual or contingent liabilities; and other risks and uncertainties detailed from time to time in the companies' periodic reports filed with the Securities and Exchange Commission, including current reports on Form 8-K, quarterly reports on Form 10-Q and annual reports on Form 10-K. All forward-looking statements are based on information currently available to the companies, and the companies assume no obligation to update any such forward-looking statements.

Additional Information and Where to Find It

The tender offer described in this document has not yet commenced. This announcement is neither an offer to purchase nor a solicitation of an offer to sell shares of Pharmasset. At the time the offer is commenced, Gilead will file a Tender Offer Statement on Schedule TO with the U.S. Securities and Exchange Commission, and Pharmasset will file a Solicitation/Recommendation Statement on Schedule 14D-9 with respect to the offer. Pharmasset stockholders and other investors are urged to read the tender offer materials (including an Offer to Purchase, a related Letter of Transmittal and certain other offer documents) and the Solicitation/Recommendation Statement because they will contain important information which should be read carefully before any decision is made with respect to the tender offer. The Offer to Purchase, the related Letter of Transmittal and certain other offer documents, as well as the Solicitation/Recommendation Statement, will be made available to all stockholders of Pharmasset at no expense to them. The Tender Offer Statement and the Solicitation/Recommendation Statement will be made available for free at the Commission's web site at www.sec.gov. Free copies of these materials and certain other offering documents will be made available by Gilead by mail to Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, attention: Investor Relations.

In addition to the Offer to Purchase, the related Letter of Transmittal and certain other offer documents, as well as the Solicitation/Recommendation Statement, Gilead and Pharmasset file annual, quarterly and special reports, proxy statements and other information with the Securities and Exchange Commission. You may read and copy any reports, statements or other information filed by Gilead or Pharmasset at the SEC public reference room at 100 F Street, N.E., Washington, D.C. 20549. Please call the Commission at 1-800-SEC-0330 for further information on the public reference room. Gilead's and Pharmasset's filings with the Commission are also available to the public from commercial document-retrieval services and at the website maintained by the Commission at www.sec.gov.

For more information on Gilead Sciences, please visit the company's website at www.gilead.com or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.



SOURCE: Gilead Sciences, Inc.

Gilead
Susan Hubbard, 650-522-5715 (Investors)
Amy Flood, 650-522-5643 (Media)
or
Pharmasset
Richard E.T. Smith, 609-865-0693 (Investors)
or
Sard Verbinnen & Co
Andrew Cole/Chris Kittredge, 212-687-8080 (Media)

The Motley Fool preaches pragmatism to potential Achillion suitors...

This Biotech Stock Rose for All the Wrong Reasons
By Brian Orelli | More Articles
November 18, 2011

Achillion Pharmaceuticals (Nasdaq: ACHN ) might get bought, according to an article by Bloomberg. Shares jumped by as much as 17% today in response to the report, although it's pulled back a little since then.

And this is news because?

Achillion has three drugs in the clinic, which all treat hepatitis C, a disease that's quickly moving toward cocktail therapies as a standard of care. Pharmasset (Nasdaq: VRUS ) has separate partnerships with Johnson & Johnson (NYSE: JNJ ) and Bristol-Myers Squibb (NYSE: BMY ) to test its drug in combination with the big pharmas. Roche just bought Anadys Pharmaceuticals for its hepatitis C drug to be used in combination with its drugs and with drugs developed by Merck (NYSE: MRK ) , with which it has a partnership. Vertex Pharmaceuticals (Nasdaq: VRTX ) licensed compounds from Alios BioPharma. And the list goes on.

I'd expect Achillion to be talking with potential partners, and I'd expect that many of those companies would entertain the idea of purchasing the company at the right price.

What I don't expect is for a company's CEO to go blabbing to the media about it. There's just no reason for it.

And there's no reason for investors to jump onboard expecting that a sale is imminent. BioSante Pharmaceuticals' (Nasdaq: BPAX ) CEO made similar comments to the same news organization, causing its shares to spike in July, but shares have since fallen 40% from the high set that month.

Achillion expects to report interim phase 2 data by the end of the year for its lead compound ACH-1625. Most -- dare I say all -- potential buyers would want to see that data before making a purchase. And unless the purchase price was out of this world, Achillion's board would be crazy to agree to a sale with the data on the horizon. Assuming it's positive, the data will only make the company more valuable as a potential takeout target.

If you're going to purchase shares of Achillion, I'd consider looking for a pullback before jumping in. You might not get one -- sometimes rumors are true, and the phase 2 data will be available soon -- but I don't see how Achillion is more valuable after the Bloomberg report than it was yesterday.

Medscape article: Adverse CNS Effects of HCV Treatment Discourage Adherence

Medscape interviews clinical psychologist Jeffrey J. Weiss, PhD, MS, from Mount Sinai School of Medicine in New York City and Raymond Chung, MD,vice chief of the gastrointestinal unit and medical director of the liver transplant program at Massachusetts General Hospital in Boston regarding a large prospective study looking at CNS effects of Peg + riba and the resulting effect on adherence because of depression and/or 'brain fog'.

Adverse CNS Effects of HCV Treatment Discourage Adherence

Neil Canavan

November 18, 2011 (San Francisco, California) — Patients infected with hepatitis C virus (HCV) can experience a marked decline in neuropsychological cognitive function in the first 14 weeks of combination pegylated interferon and ribavirin therapy. This poses a potential treat to treatment adherence, said clinical psychologist Jeffrey J. Weiss, PhD, MS, from Mount Sinai School of Medicine in New York City, here at The Liver Meeting 2011: American Association for the Study of Liver Diseases 62nd Annual Meeting.

These data are from a large prospective study looking at early treatment discontinuation and the onset of neuropsychiatric symptomatology in HCV monoinfected and HCV/HIV coinfected treatment-naïve patients receiving combination pegylated interferon/ribavirin therapy, Dr. Weiss explained.

"A lot of work has focused on depression, and not to the decrements in cognitive function," said Dr. Weiss. A host of neuropsychiatric symptoms should be considered when initiating a new treatment.

"In this era of direct-acting antivirals, when we're asking patients to take medications 3 times a day (every 6 to 9 hours)..., we need to be aware that, just at baseline, 40% to 50% of patients...[have] substantial deficits in cognitive functioning."

This investigation established the degree of neurocognitive decline during the first 12 and 48 weeks of treatment. Both HCV-infected and HCV/HIV-coinfected patients were evaluated. Neuropsychological instruments were used to explore which domains of cognitive functioning are most affected by combination pegylated interferon/ribavirin treatment, and whether being coinfected with HIV adds to the decrements in cognitive functioning.

There were no significant differences at baseline between the HCV-infected and HCV/HIV-coinfected cohorts for age, sex distribution, ethnicity, HCV RNA viral load, HCV genotype, or stage of liver disease. There were also no differences between the 2 groups at baseline for neuropsychological scores. However, although the same percentage of patients in the HCV and HCV/HIV cohorts reported depression, HCV patients had significantly worse depression scores.

After treatment, global neuropsychological function declined significantly in HCV patients during the first 24 weeks of HCV treatment. Domains with the greatest declines were memory, executive function, and motor function. "The HCV monoinfected group also had a greater decline in neuropsychological function than the coinfected group in the first 12 weeks," said Dr. Weiss. "This is probably due to more depression among HCV patients at baseline."

How a patient's declining neuropsychological function affects their behavior is key, and can depend on clinical history, Dr. Weiss explained. "Patients who have a history of cognitive dysfunction might respond less to the onset of new symptoms. Patients with a significant pathology who are already well engaged in psychiatric treatment tend to do quite well on [antiretroviral] treatment because they are familiar with the symptoms and are being well managed." Those who are high functioning at baseline will have more trouble; to be successfully managed, the healthcare provider must be aware of the potential for central nervous system (CNS)-related treatment nonadherence.

CNS and the Hepatologist

Raymond T. Chung, MD, vice chief of the gastrointestinal unit and medical director of the liver transplant program at Massachusetts General Hospital in Boston, agrees that the hepatologist must be part psychiatrist. "We field these patients rather then pass them off since there can often be overlap with true advanced hepatic disease and hepatic encephalopathy."

He is mindful of the potential impact of HCV medications. "It has been a modest issue with both HCV/HIV and HCV alone." Symptoms are often called "brain fog," Dr. Chung explained. "This fog does get in the way, in high-functioning individuals, of their ability to carry out intricate calculative functions and memory at work, for instance." It would not be surprising for such a patient to become frustrated and consider forgoing medication, he observed.

Dr. Chung considers the issue manageable if it is proactively addressed. However, like many clinicians at the meeting, he's looking more toward preventing than managing adverse effects by eliminating pegylated interferon from standard HCV treatment.

Dr. Weiss reports being a consultant for Vertex Pharmaceuticals and Kadmon Pharmaceuticals. Dr. Chung has disclosed no relevant financial relationships.

The Liver Meeting 2011: American Association for the Study of Liver Diseases (AASLD) 62nd Annual Meeting. Abstract 972. November 6, 2011.

Medscape Medical News © 2011 WebMD, LLC
Send comments and news tips to news@medscape.net.

UBS analysts see bright future in GSK's Promacta for HCV treatment-associated thrombocytopenia...

Article from Bloomberg.com. UBS analysts see potential 'blockbuster' status from GSK's Eltrombopag in the treatment of HCV treatment-associated thrombocytopenia.

Glaxo’s Promacta May Turn Into Blockbuster Medicine, UBS Says

By Makiko Kitamura

Nov. 7 (Bloomberg) -- GlaxoSmithKline Plc’s Promacta blood disorder medicine may generate as much as $2 billion in annual sales if the U.K.’s largest drugmaker can expand its use to the treatment of a condition associated with hepatitis C, according to UBS AG.

The medicine, already approved for sale in the U.S. to raise platelet counts in patients with a rare blood disorder, is being studied to extend use to patients with thrombocytopenia, a blood complication stemming from hepatitis C treatments. Glaxo will present results from the last of three stages of clinical testing required for regulatory approval on the new use at a medical meeting in San Francisco today.

As many as 170 million people worldwide are chronically infected with the hepatitis C virus, which can lead to cirrhosis of the liver and liver cancer, according to the World Health Organization. Glaxo’s Promacta would enable hepatitis C patients to be treated with antiviral medicines for longer periods of time, turning the drug into a “potential blockbuster,” said Gbola Amusa, a health-care analyst at UBS in London.

“Depending on how positive the data are, this could generate an additional $2 billion in annual sales,” Amusa said. Promacta had sales of 51 million pounds ($82 million) through the end of September, compared with 31 million pounds in 2010.

The study results are slated to be presented at the American Association for the Study of Liver Diseases’ annual Liver Meeting at 3:15 p.m. San Francisco time.

Sales Estimate

If the data are positive, an approval by regulators may come as early as the end of next year, Amusa said. The sales estimate assumes that antiviral medicines including interferon will continue to dominate hepatitis C treatments, Amusa said. Abbott Laboratories last month presented interim study results for a new alternative therapy that does not use interferon.

“Undoubtedly, this would be a big potential opportunity for the drug if it demonstrates strong results,” said Gustav Ando, a health-care analyst at consulting company IHS Global Insight in London. “We remain somewhat cautious until we see some of the side-effects data.”

Any potential damage to the liver in terms of toxicity along with blood clotting are of concern, Amusa and Ando said.

Glaxo said on Oct. 26 it plans to file as many as 10 drugs for approval next year. The compounds in late-stage development include Relovair, which Glaxo is developing as a successor to the Advair asthma inhaler. Advair, Glaxo’s best-selling product, generated 19 percent of total revenue in the first half of the year.

Three Glaxo products have been cleared for sale this year, including Benlysta, a therapy for the auto-immune disease lupus that was approved by U.S. regulators in March. The company’s global sales in the quarter ended Sept. 30 rose 4.3 percent to 7.1 billion pounds from a year earlier.

--Editors: Bruce Rule, Kristen Hallam

To contact the reporter responsible for this story: Makiko Kitamura in London at mkitamura1@bloomberg.net

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

Milk Thistle shows no effect according to data presented at AASLD...

(From MEDPAGE.com: Data from AASLD concludes that silymarin. the active compound in the botanical Milk Thistle long believed to have antiviral and liver rejuvenating effects has neither compared to placebo. Important info for patients long misled by claims from unscrupulous vendors)

SAN FRANCISCO -- A botanical agent used in the treatment of liver disorders had no detectable effect on hepatitis C virus (HCV) disease activity in comparison with placebo in patients with previously treated chronic disease, results of a randomized trial showed.

Patients treated for six months with either of two doses of silymarin had little change in levels of the liver enzyme alanine transaminase (ALT). About 4% of patients in each silymarin arm and in the placebo group met the primary endpoint of a decline in ALT to ≤45 IU or at least a 50% decline from baseline.

"Similarly, symptom scores and quality of life measures were unchanged during silymarin treatment," Michael W. Fried, MD, of the University of North Carolina in Chapel Hill, reported here at the American Association for the Study of Liver Diseases meeting.

The trial was perhaps the first to use a single, well-described silymarin preparation, and the doses employed in the study were five to seven times higher than customary doses, he added.

Silymarin is an extract of milk thistle and has long been used as a treatment for various types of liver disorders. A mixture of flavonolignans, silymarin has demonstrated anti-inflammatory and immunodulatory properties in vitro, as well as activity against the HCV core and virus-associated gene expression.

The substance has been evaluated in clinical trials as a therapeutic aid for cirrhosis, alcoholic liver disease, and viral hepatitis. However, the results have been inconsistent.

"Previous studies have been confounded by a lack of well-defined efficacy endpoints, inclusion of heterogeneous populations of patients with liver disease, and use of nonstandardized silymarin preparations," said Fried.

To address some of the shortcomings of previous clinical studies, the investigators designed a trial to evaluate silymarin as a potential aid in the treatment of chronic HCV that had not responded to interferon-based therapy.

All of the 154 patients enrolled at four centers in the U.S. had a history of treatment with interferon-based therapy and had not achieved a sustained virologic response. The patients had quantifiable HCV RNA and a serum ALT ≥65 IU.

The silymarin preparation used for the trial is produced in the Netherlands under the brand name Legalon 140 and is approved as a prescription drug in some European and Asian countries. The customary dose is 140 mg three times a day.

Eligible patients were randomized to one of two doses of silymarin (420 or 700 mg) or placebo. Patients in the high-dose silymarin arm took five capsules of the botanical agent three times daily. Patients randomized to the standard dose took three silymarin capsules and two placebo capsules three times each day, and patients in the placebo arm took five matching capsules three times daily.

The high-dose arm was based on results from a phase I dose-finding trial "in order to provide the highest likelihood of finding a therapeutic benefit," said Fried.

The primary endpoint, measured after 24 weeks, was a decline in serum ALT to ≤45 IU (the upper limit of normal) or a decline of at least 50% from baseline and <65 IU (1.5 times the upper limit of normal).

The patients were randomized to the three treatment arms. The three groups did not differ with respect to baseline demographic and clinical characteristics. Median age was 55, about 70% were white, about 90% had HCV genotype 1, about a fourth of the patients had evidence of cirrhosis, and 40% to 45% had a history of milk thistle use.

Adherence was good, said Fried, as about 90% of the study participants consumed more than 80% of their medication doses.

After six months, one person in the placebo group had a serum ALT ≤45 IU, as did two patients in each of the silymarin arms. Additionally, two patients in the placebo and high-dose silymarin groups had at least a 50% decline in baseline ALT to <65 IU, as did one patient in the 420-mg silymarin arm.

The proportion of patients who met either definition of the primary endpoint was 3.8% (two of 52) in the placebo group, 4% (two of 50) in the 420-mg silymarin arm, and 3.8% (two of 52) in the high-dose silymarin arm.

The three groups also did not differ significantly with respect to the mean change in ALT, change in HCV RNA, or scores on a battery of quality-of-life instruments. A graph of serum ALT levels throughout the six months showed virtually superimposable lines for the three groups.

The placebo and silymarin groups also did not differ significantly in their adverse-event profiles. The most common types of adverse events were gastrointestinal, musculoskeletal, dermatologic, infection, and physical injury. Six patients in the 420-mg silymarin arm and five in the 700-mg arm had serious adverse events, compared with one in the placebo group.

During the discussion that followed the presentation, Fried expressed doubt that using even higher doses of silymarin might lead to better results, as suggested by a member of the audience.

AASLD president T. Jake Liang, MD, said the study is informative because the results showed not only that silymarin performed no better than placebo in a well-controlled clinical trial but also that the substance is not harmful for people who take it for liver conditions.

HCV leaps ahead of HIV as leader of cause of death in the U.S.

From POZ.com. HCV surpasses HIV as a leading cause of death in the US, according to the CDC

November 10, 2011

Hepatitis C Surpasses HIV as Cause of Death in U.S.

It’s official. Chronic hepatitis C virus (HCV) infection is associated with more deaths than HIV infection, according to sobering new data presented by the U.S. Centers for Disease Control and Prevention (CDC) on Tuesday, November 8, at the 62nd annual meeting of the American Association for the Studies of Liver Diseases (AASLD) in San Francisco.

The discouraging findings, presented by Scott Holmberg, MD, MPH, chief of the CDC’s Division of Viral Hepatitis Epidemiology and Surveillance Branch, come from data involving 21.8 million deaths reported to the National Center for Health Statistics between 1999 and 2007. The only cases included in the analysis involved reports that specified HIV, AIDS, HCV or hepatitis B virus (HBV) infection as possible contributors to the deaths.

Encouragingly, death rates associated with chronic HBV infection—a major cause of liver failure and liver cancer—remained relatively flat between 1999 and 2007. In 2007, for example, about 1,800 U.S. residents died of HBV-related complications, which translated into less than one chronic hepatitis B-attributable death per 100,000 people in this country.

Death rates related to HIV infection continue to fall. Whereas HIV contributed to 6 per 100,000 deaths in 1999, the rate dropped to less than four per 100,000 deaths in 2007.

Hepatitis C–related deaths have increased sharply, Holmberg’s team reported. Whereas HCV contributed to roughly 3 per 100,000 deaths in 1999, the HCV-related death rate exceeded 4 per 100,000 people in the United States by 2007.

With respect to crude numbers, roughly 12,700 HIV-related deaths were reported to the National Center for Health Statistics in 2007. More than 15,000 HCV-related deaths were reported to the center that year.

Most viral hepatitis deaths occurred in people in the prime of their lives. About 59 percent of people who died of complications related to hepatitis B were between the ages of 45 and 64. The impact of chronic hepatitis C was even more substantial—roughly 73 percent of the deaths related to HCV were in baby boomers.

Not surprisingly, death rates were highest among certain populations. For example, people coinfected with both HBV and HCV faced a 30-fold increase in the risk of death from liver disease or related complications. Alcohol abuse was associated with a four-fold increase in the risk of death. Coinfection with HIV nearly doubled the risk of death from HBV-related complications and quadrupled the risk of death from HCV-associated liver disease.

“[Achieving] declines in mortality similar to those seen with HIV,” Holmberg’s group concluded, “will require new policy directions and commitment to detect and link infectious persons to care and successful treatment.”

New MEDSCAPE article sheds more light on PSI-7977 and the ELECTRON trial...

Pharmasset launched a broadside in the HCV drug development wars during AASLD, revealing that some patients may be able to achieve and SVR without the use of interferon. This was according to nterim results from the phase II ELECTRON trial, looking at Pharmasset's nucleotide inhibitor PSI-7977 in various combinations with ribavirin and interferon/no interferon in different Hepatitis C genotypes. In one arm, PSI-7977 plus ribavirin was administered for 12 weeks in 10 genotype 2 and 3 patients. This article sheds further light on those patients - in short, they were genotype 2/3, tx-naïve without cirrhosis. They had a mean age of 47 years, mean baseline HCV RNA was 6.49 log10 IU/mL, and roughly 43% had the favorable 'CC genotype' associated with favorable response to standard interferon-based therapy. The author also interviews lead PI Edward Gane, MD and gets 'too good to be true?' thoughts from Michael Bernstein, MD who was involved in the NM-286 clinical trials.

From Medscape Medical News
New HCV Drug Achieves 100% Cure Rate Without Interferon

Neil Canavan

November 9, 2011 (San Francisco, California) — An interferon-free regimen for the treatment of infection with hepatitis C virus (HCV) might soon be available, according to data from the ELECTRON trial, presented here at The Liver Meeting 2011: American Association for the Study of Liver Diseases 62nd Annual Meeting.

In ELECTRON — 1 of 2 phase 2 studies of the investigational compound PSI-7977 (Pharmasset) reported here — an interferon-free regimen of PSI-7977 plus ribavirin achieved a 100% sustained viral response (SVR) at 12 weeks in all study subjects.

"PSI-7977 has the potential to dramatically change the treatment paradigm for HCV," said lead study investigator Edward Gane, MD, from Auckland City Hospital in New Zealand.

PSI-7977 is a uridine nucleotide analog polymerase inhibitor that is administered once daily with or without food. It has demonstrated robust activity in patients infected with HCV genotype 1 when used in combination with pegylated-interferon and ribavirin after a 12-week course.

Activity with this agent used as a monotherapy has also been reported.

"The aim of the ELECTRON trial was to determine the shortest duration of interferon, if any, required to achieve SVR when PSI-7977 plus ribavirin are administered for 12 weeks," Dr. Gane explained.

ELECTRON investigators recruited 40 patients who were randomized to 1 of 4 treatment groups: PSI-7977 400 mg plus ribavirin for 12 weeks plus interferon for 0, 4, 8, or 12 weeks.

Patients were treatment-naïve, noncirrhotic, infected with HCV genotype 2 or 3, and stratified by interleukin (IL)28B single-nucleotide polymorphisms (SNP) and HCV RNA levels. Mean age was 47 years and mean baseline HCV RNA was 6.49 log10 IU/mL, with 42.5% exhibiting the CC genotype at the IL28B SNP.

"We selected a genotype 2/3 population because this represents a population that would be more easily rescued with interferon in the event of virologic breakthrough," Dr. Gane explained.

Results after treatment initiation were dramatic. "All patients achieved a rapid virologic response, with over 80% being nondetectable at 2 weeks," reported Dr. Gane.

All patients had undetectable HCV at 3 weeks; furthermore, all patients achieved end-of-treatment response. No cases of treatment resistance were observed.

"Even following cessation of interferon, or with no interferon, there were no virologic breakthroughs on treatment." Also encouraging was the fact that all patients in the study experienced a rapid normalization of alanine aminotransferase.

There were no serious adverse events, and the mild to moderate events observed were attributed to either interferon or ribavirin. Significant improvements in safety and tolerability were seen in the interferon-free treatment group. No safety signals for PSI-7977 were observed, and there were no treatment-related discontinuations.

Results of the 12-week analysis prompted study investigators to add an exploratory treatment group of open-label PSI-7977 monotherapy for 12 weeks (n = 10). "The response was the same as with combination treatment with ribavirin," said Dr. Gane. Although this study is ongoing, 6 of 10 patients have achieved SVR at 4 weeks.

"These data clearly demonstrate that PSI-7977 exhibits high potency and has a high barrier to resistance," Dr. Gane said, noting that the drug is being advanced in phase 3 investigations in all HCV genotypes.

Too Good to be True?

Michael Bernstein, MD, director of the hepatitis clinic at the Coney Island Hospital, Brooklyn, New York, has doubts about PSI-7977. "If you use it with ribavirin and no interferon, you get a 100% SVR; if you use it alone, you get a 100% SVR."

Dr. Bernstein accepts the efficacy of PSI-7977 for the moment, but is concerned that ELECTRON isn't powered to say much about the tolerability or resistance profiles of the drug.

"What we've found with most of these [polymerase inhibitors] is that if you use them by themselves, you get resistance; if you don't, they can be very difficult to tolerate," said Dr. Bernstein. "There was a drug being investigated at Mount Sinai — a polymerase inhibitor, NM286 — and those patients got severe diarrhea and could not tolerate it. According to the ELECTRON study, everything was perfect — no gastrointestinal issues, no apparent adverse events of any kind, and it worked 100% of the time without interferon, or ribavirin.... If it's true, it will be great. The holy grail is to try to rid HCV treatment regimens of interferon."

Although sincerely impressed, Dr. Bernstein, who has seen many drugs come and go, suspects that as larger phase 3 trials of PSI-7977 are conducted, polymerase-associated adverse events, tolerability issues, and treatment resistance patterns will emerge.

Dr. Gane reports advisory board relationships with Pharmasset, Gilead, Roche, Janssen-Cilag, and Boehringer-Ingelheim. Dr. Bernstein has disclosed no relevant financial relationships.

The Liver Meeting 2011: American Association for the Study of Liver Diseases (AASLD) 62nd Annual Meeting: Abstract 34. Presented November 6, 2011.

Pharmasset's HCV nucleotide analog PSI-7977 poised to raise the bar for HCV DAAs....

By far the biggest buzz at AASLD thus far has been the performance of Pharmasset's PSI-7977, a nucleotide analog being studied in various combinations for the treatment of chronic hepatitis C. Pharmasset released Phase II data at AASLD showing 100% SVR in a small group of genotype 2/3 patients in combination with ribavirin but without the need for interferon. The success despite the lack of interferon raised hopes for a truly interferon-free pan-genotypic treatment for HCV with once daily dosing and a minimum amount of side effects. The drug has a long way to go in development, but this data certainly buoyed hopes of patients, HCV providers and investors alike. One hopes that the data for prior non-responders (especially null-responders) and genotype 1 patients fair as well.

Twelve Weeks Interferon-Free PSI-7977 Regimen Cures 100 Percent Hep C Genotype 2/3

A twelve-week course of Pharmasset’s once-daily experimental nucleotide analog PSI-7977, combined with ribavirin, cured 10 of 10 people living with genotype 2/3 hepatitis C virus (HCV) who used the regimen—without pegylated interferon—in a Phase II clinical trial. The highly encouraging results were reported Sunday, November 6, at the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco.

Compared with the three other groups included in the study, which involved taking PSI-7977 plus ribavirin with either four, eight or 12 weeks of pegylated interferon, significant improvements in safety and tolerability were also documented among those using PSI-7977 plus ribavirin alone, according to Edward Gane, MD, of the Auckland City Hospital in Auckland, New Zealand, and his ELECTRON study colleagues.

Results from early studies of PSI-7977 have been promising. In the PROTON study, PSI-7977 combined with pegylated interferon plus ribavirin resulted in sustained virologic responses (SVRs)—viral cures—in 96 percent of study volunteers with HCV genotype 2/3 and 91 percent of those with HCV genotype 1 (the most common yet hardest-to-treat form of the virus in the United States).

ELECTRON, initiated in December 2010, was conducted to determine the shortest duration of pegylated interferon—if any—required to achieve SVRs when PSI-7977 plus ribavirin are given for 12 weeks. HCV genotype 2/3 patients were initially selected for this unorthodox study—pegylated interferon has long been a mainstay agent in hepatitis C drug regimens—given pegylated interferon and ribavirin tend to be much more effective for individuals with genotype 2/3 virus and could be called upon in the event of poor responses to PSI-7977/ribavirin in the study.

No “rescue” therapy proved necessary. At virtually all study time points—weeks 4, 8 and 12 during therapy and weeks 4, 8, 12 and 24 following the completion of treatment—100 percent of the patients in each group maintained undetectable HCV viral loads. Eleven patients received PSI-7977/ribavirin plus 12 weeks of pegylated interferon, 10 received PSI-7977/ribavirin plus eight weeks of pegylated interferon, nine received PSI-7977/ribavirin plus pegylated interferon and ten received PSI-7977/ribavirin without pegylated interferon.

Gane noted that HCV viral load suppression was rapid in all four treatment groups—virtually everyone had HCV below the level of detection within three weeks of beginning treatment.

At least one side effect—including headache, fatigue, depression, insomnia, anxiety, irritability, muscle soreness and upper respiratory tract infections—was more likely to be documented in those in the 12-week pegylated interferon group (72 percent), compared with those who didn’t receive any pegylated interferon (40 percent).

Similarly, whereas moderate-to-severe drops in neutrophils—a type of white blood cell—was documented in roughly 70 percent of those in the 12-week pegylated interferon group, no volunteers in the interferon-free PSI-7977/ribavirin group experienced this toxicity. Interferon-free PSI-7977 plus ribavirin also had much less of an impact on hemoglobin levels, a marker of anemia.

Also encouraging, all patients in the study experienced a rapid normalization of ALT, a key liver enzyme. Among those in the interferon-free treatment group, normal ALT levels were documented in all patients by the end of the third week of treatment.

In summary, Gane noted, “PSI-7977 [400 milligrams once daily] remains very well tolerated with no attributable safety signal, no treatment discontinuations and no treatment emergency laboratory abnormalities.” As for potency, he concluded that PSI-7977/ribavirin “elicited rapid suppression” of HCV viral load in study volunteers with HCV genotype 2 or 3 and that all 40 patients in the study achieved an SVR, regardless of whether or not interferon was used. Additionally, not a single case of drug-resistant virus emerged during the study.

Further results from ELECTRON are expected. The study has been amended, adding several new treatment groups. One group is exploring PSI-7977 used as monotherapy—without pegylated interferon or ribavirin—to treat genotype 2/3 infection. Preliminary data reported by Gane's team suggest that four patients in this group have maintained undetectable HCV levels four weeks after discontinuing treatment.

Another group is studying PSI-7977 in combination with pegylated interferon plus ribavirin, again in genotype 2/3 patients, but for only eight weeks.

Three additional groups are now enrolling patients. One is studying 12 weeks of PSI-7977 plus ribavirin, without interferon, in HCV genotype 2/3 patients who weren't able to clear the virus with 24 weeks of previous pegylated interferon/ribavirin therapy. A second is evaluating PSI-7977 plus ribavirin in HCV genotype 1 patients beginning therapy for the first time. The third group consists of individuals with HCV genotype 1 null responders (patients who responded very poorly to prior pegylated interferon/ribavirin treatment); they will receive PSI-7977/ribavirin for a total of 12 weeks.

Pharmasset recently announced its Phase III clinical trial program. Two studies—FISSION and POSITRON—will further explore the safety and efficacy of PSI-7977 plus ribavirin, but without pegylated interferon, in approximately 725 people with genotype 2/3 HCV infection. A third study will explore PSI-7977 in HCV genotype 1 patients, with the design of the study determined by the ongoing ELECTRON clinical trial and another study still under way.

Read the full article here: http://www.aidsmeds.com/articles/psi7977_svr_hcv_1667_21405.shtml

The Motley Fool comments on the next generation of Hepatitis C drug therapy...

The Motley Fool's take on the future of HCV drug development, buyouts and partnerships. Once the fodder for small biotechs, Big Pharma has their eye on the marketplace. That means plenty of action in the coming months in the quest to usurp Telaprevir's crown.

Gunning for the Leaders

By Brian Orelli
October 31, 2011

Merck's (NYSE: MRK ) Victrelis and Vertex Pharmaceuticals' (Nasdaq: VRTX ) Incivek have been on the market for only five months, and the threats to unseat them keep coming.

Data on some of the next-generation hepatitis C drugs will be presented at the end of this week, when the annual meeting of the American Association for the Study of Liver Diseases kicks off. Add in top-line data that's been released recently and expected results in the next few months, and the hepatitis C space is looks like it'll get really crowded, really quickly.

The biotech front-runner
Pharmasset (Nasdaq: VRUS ) has grabbed most of the spotlight. The company has a drug, RG7128, partnered with Roche, but most of the focus has been on PSI-7977 that it owns in its entirety. The company will present data at the meeting including results using PSI-7977 as a monotherapy. Reducing or eliminating peginterferon, which must be used with Incivek and Victrelis, is a goal of every next-generation hepatitis C regimen because of nasty side effects with peginterferon.

Achillion Pharmaceuticals (Nasdaq: ACHN ) will make multiple presentations at the meeting, with its phase 2 compound, ACH-1625, being the most interesting. Idenix Pharmaceuticals has a pair of presentations at the meeting.

No shortage of pharma competition
Unfortunately for the smaller biotechs, Big Brother is interested in the space as well.

Earlier this month, Abbott Labs (NYSE: ABT ) said it has a drug combination that might be able to deliver cure rates as high as 90% without peginterferon. Don't write off the others just yet, though. It was a fairly small trial, and the data from more patients might not be as impressive.

Bristol-Myers Squibb (NYSE: BMY ) recently presented data for one of its compounds, BMS-790052. In a phase 2 trial, 83% of patients taking the two highest doses of BMS-790052 had undetectable viral levels 24 weeks after treatment, compared with just 25% who took just peginterferon alfa and ribavirin. But the results with BMS-790052 required adding it to peginterferon and ribavirin.

The upside to pharma's interest
Fortunately for biotechs, combination treatments are likely to be key to ridding patients of the virus. Resistance issues are common, but they can be avoided by combining medications that attack the virus in different ways.

No doubt Roche's acquisition of Anadys earlier this month was driven by its desire to get a hold of Anadys' hepatitis C treatment, setrobuvir. While we might see more acquisitions in the works, partnerships -- especially non-exclusive ones -- could be the best solution for both sides. Pharmasset has used the double-dipping strategy making pacts with both Johnson & Johnson (NYSE: JNJ ) and Bristol-Myers to combine their hepatitis C treatments with PSI-7977.

The problem with non-exclusive pacts is that they may not provide biotechs with much cash to fund their own development. On the other hand, if a biotech doesn't make too many of them, it could lead to a takeout offer.

Which combo is the combo?
It's hard to know which combination will eventually win out. When you start adding multiple drugs to each other, there's bound to be side-effect issues that aren't a problem when they're used individually. Hepatitis C is a little less life-threatening than HIV, so the FDA will demand a cleaner side-effect profile than they have for cocktails that treat HIV.

And while finding the most potent combination is important, it's useful only if they complement each other's resistance issues; knocking the virus down to undetectable levels in 100% of the patients isn't particularly useful if the virus just rebounds once it mutates in a way to avoid the drugs' inhibitory properties.

Rather than trying to guess which company will eventually profit, buying a basket of hepatitis C drugmakers might be the best move. If a combo treatment is going to eventually work, why not a combination of investments?

Biotica nominates cyclophilin inhibitor BC556 for development....

Biotica Technology Limited announces development of cyclophilin inhibitor BC556 for treatment of chronic Hepatitis C. Biotica claims to offer an advantage with a high barrier to resistance, low potential for drug interactions and PK suitable for once-daily dosing.

PRESS RELEASE
Oct. 31, 2011, 12:09 p.m. EDT
Biotica nominates drug candidate, BC556, a cyclophilin inhibitor to treat Hepatitis C
Cyclophilin inhibition provides a high barrier to viral resistance in combination therapy


LONDON, Oct 31, 2011 (BUSINESS WIRE) -- Biotica Technology Limited (Biotica), a privately-held biotechnology company that discovers and develops polyketide therapeutics, today announces the nomination of its drug candidate, BC556, a cyclophilin inhibitor to treat Hepatitis C virus (HCV) infection. BC556 offers many benefits over existing treatments and, in combination with drugs acting by other mechanisms, offers the potential of an interferon-free regimen for treatment of HCV infection.

BC556 is a highly potent inhibitor of HCV replication across viral genotypes, its pharmacokinetic profile is consistent with once-daily oral dosing and the compound exhibits a very high barrier to selection of viral resistance. As in HIV therapy, successful treatment of HCV is likely to involve combination of drugs acting by different mechanisms. BC556 benefits from reduced interaction with drug transporters and metabolizing enzymes responsible for drug-drug interactions, and therefore is a suitable compound for combining with other drugs in a treatment cocktail. BC556 was selected from Biotica's new Sangamide class of cyclophilin inhibitors. Sangamides are analogs of the naturally-occurring polyketide Sanglifehrin A, produced using Biotica's proprietary polyketide engineering technology.

"It is our strong belief that only a combination therapy, as in the treatment of HIV, will offer patients a fully-efficacious treatment for hepatitis C,'' commented Edward Hodgkin, Biotica's CEO. "As such, Biotica will develop and commercialise BC556 in combination with other drugs with the aim to provide a therapy with a high barrier to resistance, pan-genotype efficacy, oral dosing, and without the side effects seen with interferon-based therapy.''

- Ends -

Notes to editors

About Biotica Technology Limited

Biotica is a privately-held biotechnology company that discovers and develops polyketide therapeutics. It has a growing pipeline of novel therapeutic programs supported by clinical validation. These include nPT-mTOR (unique rapamycin analogs), nPT-CyP (cyclophilin inhibitors for HCV) and nPT-ery (anti-inflammatory erythromycin analogs partnered with GlaxoSmithKline). All of Biotica's projects employ its proprietary novoPT(TM) technology, which enables it to select from the many known polyketides with biological activity and make a range of derivatives that are either difficult or impossible to make by medicinal chemistry methods. For additional information visit www.biotica.com .

About Hepatitis C

Hepatitis C virus infection (HCV) is a chronic blood-borne infection which attacks the liver with potentially fatal effects. The World Health Organisation estimates that up to 170 million people worldwide are infected with HCV, making the virus a health concern of global magnitude. Vaccines for HCV are not available and the infection is only curable in certain patients.

The current standard of care (SoC) treatment for HCV is the well-established combination therapy of interferon-alpha (a protein therapeutic immune stimulant) and ribavirin (a broad spectrum anti-viral). This protocol has serious side effects and shortfalls in efficacy. SoC only achieves a sustained clearance and virological response (SVR) rate of 45% in HCV genotype 1 (the predominant genotype of the virus in Western countries). In addition, the chronic side effects of the treatment (fatigue, influenza-like symptoms, etc.), present compliance issues for patients over the 48-week course. Indeed, the severity of the side effects is such that 60 to 80 percent of patients are forced to reduce dosing, or cease treatment entirely. It is noteworthy that a recent report of US Veterans [State of Care for Veterans with Chronic Hepatitis C, Nov 2010] states that up to 100,000 patients are delaying HCV treatment awaiting better therapies in development that offer greater efficacy and better side-effect profiles.

SOURCE: Biotica Technology Limited

Pharmasset expands PSI-7977 ELECTRON trial for treatment of HCV...

Pharmasset expands it's ELECTRON trial by adding two interferon-free arms and modifying another one. The changes include a PSI-7977 monotherapy arm (!!!) for Tx-naive genotype 1 patients; a PSI-7977 + RBV arm in Tx-experienced GT 2/3 patients and modifying a treatment arm for null responders by adding an interferon-free PSI-7977 + RBV arm. This announcement caused investors to flee Vertex Pharmaceuticals, which saw a 7% slide today.

press release

Oct. 10, 2011, 6:45 a.m. EDT

Pharmasset Announces Further Expansion of ELECTRON Trial in Hepatitis C

--**Added PSI-7977 monotherapy arm in treatment-naive patients with HCV GT1
--**Added PSI-7977/RBV arm in treatment experienced patients with HCV GT2/3
--**Modified previously-announced treatment regimen in HCV GT1 prior null responders to explore IFN-free regimen of PSI-7977/RBV


PRINCETON, N.J., Oct. 10, 2011 /PRNewswire via COMTEX/ -- Pharmasset, Inc. announced today the addition of two treatment arms to the ELECTRON trial of PSI-7977, a nucleotide analog polymerase inhibitor, for the treatment of chronic hepatitis C (HCV). The rapid and consistent antiviral effects and high barrier to resistance demonstrated with PSI-7977 to date provided the rationale for additional exploratory regimens in this setting. The protocol amendment adds one arm exploring 12 weeks of PSI-7977 monotherapy in treatment naive patients with HCV genotype 1 (GT1), and one arm of PSI-7977 and ribavirin (RBV) in treatment-experienced patients with HCV genotype 2 (GT2) or genotype 3 (GT3). In addition, the previously announced arm in HCV GT1 patients with a prior "null" response to an interferon (IFN) containing regimen, which was planned to assess PSI-7977/IFN/RBV, has been modified to an IFN-free 12-week regimen of PSI-7977/RBV.

"We look forward to reporting SVR12 results from Part 1 and interim data from the PSI-7977 monotherapy arm of ELECTRON on Sunday, November 6th, 2011 at the upcoming 2011 American Association for the Study of Liver Diseases (AASLD) annual meeting. The preliminary results to be discussed at AASLD led us to expand the study to add an arm of PSI-7977 monotherapy for HCV GT1," said Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "We and others continue to explore the potential of PSI-7977 for IFN-free and monotherapy treatment regimens in a broader group of individuals living with HCV of all genotypes and regardless of their response to prior treatment."

In addition to previously announced interferon-free studies of PSI-7977 by Bristol Myers Squibb and Tibotec, The National Institute of Health (NIH) recently initiated an interferon-free 24 week study of PSI-7977 400mg QD with and without ribavirin, in 60 treatment naive patients with HCV genotype 1 (GT1) in the US.

About ELECTRON

ELECTRON is an exploratory study of PSI-7977 for the treatment of chronic HCV infection. Part 1 of the trial is evaluating 12-week regimens of interferon-free PSI-7977 400mg QD with ribavirin (RBV), and three abbreviated duration peginterferon (Peg-IFN) regimens of 4, 8, or 12 weeks in treatment-naive patients with HCV GT2 or GT3. The primary endpoint of the trial is the safety and tolerability of PSI-7977 400mg QD and RBV for 12 weeks, administered with or without Peg-IFN. On May 11, 2011, Pharmasset announced the completed enrollment of Part 1 of ELECTRON:

PSI-7977 400 mg with Peg-IFN and RBV for 12 weeks (GT2/3)

PSI-7977 400 mg with RBV for 12 weeks, Peg-IFN weeks 1-8 only (GT2/3)

PSI-7977 400 mg with RBV for 12 weeks; Peg-IFN weeks 1-4 only (GT2/3)

PSI-7977 400 mg with RBV for 12 weeks (GT2/3)

In Part 2 of ELECTRON, a 5th cohort was added to explore PSI-7977 monotherapy in treatment naive patients with HCV GT2 or GT3:

PSI-7977 400 mg monotherapy for 12 weeks (n=10 GT2/3)

Following on the previously reported 100% SVR12 in treatment-naive subjects with HCV GT2/3 (PROTON), a 6th cohort was added to ELECTRON to explore an 8-week duration of PSI-7977Peg-IFN/RBV. The previously announced 7th cohort in HCV GT1 patients with a prior "null" response to Peg-IFN, has been modified to an interferon-free 12-week regimen of PSI-7977/RBV.

PSI-7977 400 mg with Peg-IFN/RBV for 8 weeks (n=10 GT2/3 treatment-naive)

PSI-7977 400 mg with RBV for 12 weeks (n=10 GT1 null)

In Part 3 of ELECTRON, two additional IFN-free regimens will be explored in treatment-naive patients with HCV GT1 and in treatment-experienced patients with HCV GT2 or GT3.

PSI-7977 400 mg monotherapy for 12 weeks (n=25 GT1 treatment-naive)

PSI-7977 400 mg with RBV for 12 weeks (n=25 GT2/3 treatment-experienced)

About Pharmasset

Pharmasset is a clinical-stage pharmaceutical company committed to discovering, developing, and commercializing novel drugs to treat viral infections. Pharmasset's primary focus is the development of oral therapeutics for the treatment of hepatitis C virus (HCV) infection. Our research and development efforts are focused on nucleoside/tide analogs, a class of compounds which act as alternative substrates for the viral polymerase, thus inhibiting viral replication. We currently have three clinical-stage product candidates advancing in trials in various populations. Our pyrimidine, PSI-7977, an unpartnered uracil nucleotide analog, is currently under study in five Phase 2b trials, including abbreviated duration interferon and interferon-free regimens, in subjects with all HCV genotypes. Our purine, PSI-938, an unpartnered guanosine nucleotide analog, is in QUANTUM, a Phase 2b interferon-free trial of PSI-7977 and PSI-938 in subjects with all HCV genotypes. Mericitabine (RG7128) continues in three Phase 2b trials and one interferon-free trial being conducted through a strategic collaboration with Roche.

ContactRichard E. T. Smith, Ph.D.VP, Investor Relations and Corporate CommunicationsOffice: +1 (609) 865-0693

Forward-Looking Statements

Pharmasset "Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995: Statements in this press release that are not historical facts are "forward-looking statements," that involve risks, uncertainties, and other important factors, including, without limitation, the risk of cessation or delay of any of the ongoing or planned clinical trials and/or our development of our product candidates, the risk that the results of previously conducted studies involving our product candidates will not be repeated or observed in ongoing or future studies involving our product candidates, the risk that our collaboration with Roche will not continue or will not be successful, and the risk that any one or more of our product candidates will not be successfully developed and commercialized. For a discussion of risks, uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in our Annual Report on Form 10-K for the fiscal year ended September 30, 2010 and our Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission and discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission.

SOURCE Pharmasset, Inc.

Copyright (C) 2011 PR Newswire. All rights reserved

Enanta's Lead NS5A Inhibitor Candidate for HCV, EDP-239, Selected as One of Windhover's Top 10 Infectious Disease Projects to Watch

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 via COMTEX/ -- 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 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 Pharmaceuticals
Copyright (C) 2011 PR Newswire. All rights reserved

Small Cap Network.com on Hepatitis C drug development....

The Hepatitis C Race Is On: MRK, VRTX, VRUS, ACHN, PFE, IDIX

By James E. Brumley

Published: September 21, 2011 10:24:49 AM PDT

The race for an effective hepatitis C treatment may not be as high-profile as, say efforts to find a cure for cancer or HIV. It's a bigger market than most may imagine though, judging from the number of companies doing R&D in the arena. Here's a quick look at the key one.

Merck & Co., Inc. (NYSE:MRK) has one of only two FDA-approved hepatitis C drugs. Its version is called Victrelis - a protease inhibitor. It was only approved in May, so there's no sales momentum yet. If the efficacy seen in Phase II testing is any clue though, it should be a revenue driver. Merck said two-thirds of patients receiving Victrelis in combination with other treatments had a strong virologic response in that the virus was no longer detected in the blood six months weeks after the treatment was stopped.

Vertex Pharmaceuticals Incorporated (NASDAQ:VRTX) has the other FDA-approved hepatitis C treatment. Theirs is called Incivek - another protease inhibitor. Vertex's entry in the race seems even better than Merck's; nearly 80% of patients saw no sign of the irus in the blood 24 weeks after treatment.

Pharmasset, Inc. (NASDAQ:VRUS) is anything but a household name, and its drug is only in Phase II testing. But, PSI-7977 (a nucleoside polymerase inhibitor) is very promising. When used in combination with interferon and ribavirin, Pharmasset produces a 12-week sustained virological response rate of 91% for previously untreated hepatitis C patients.

Achillion Pharmaceuticals, Inc. (NASDAQ:ACHN) actually has several versions of its treatment currently anywhere from pre-clinical studies to Phase II trials. They're all built on the same basic platform though; all act as protease inhibitors. The underlying mechanism for these compounds is novel, targeting the NS4A protein of HCV. By inhibiting this target, Achillion Pharmaceuticals says the formation of a functional replicase complex (a key step in viral replication of the viral RNA genome) is blocked. ACH-1625 is the one to watch closely now.

Update/Correction: Achillion is exploring two distinct programs - protease inhibitors and NS5A inhibitors. The protease inhibitor program includes its lead Phase 2 compound ACH-1625, while the Phase 1 program is evaluating a novel pan-genotypic compound designated ACH-2684. The second class of compounds the company is developing are NS5A inhibitors, and is the backbone ACH-2928 (also in Phase 1 development).

Pfizer Inc. (NYSE:PFE) is in the hepatitis C race, but for a company of it size and financial backing, it's surprisingly lagging. Its polymerase inhibitor (PF-868554) is only in Phase II trials right now. Given the lateness of the effort and the fact that Pfizer has multiple partners on this front, it's hard to say HCV is a priority its going to push forward in a meaningful way.

Finally, Idenix Pharmaceuticals, Inc. (NASDAQ:IDIX) has a small army of hepatitis C treatment in the hopper (four in all, but they're all significantly different than one another). The one that's furthest along is IDX184, currently in Phase II, while work on IDX320 has been halted for the time being. Idenix Pharmaceuticals began 12-week trials of IDX184 in July of this year, and is expected to share interim results sometime in the fourth quarter. IDX184 has also been halted - albeit temporary - in the past by the FDA over safety concerns.

The hepatitis C market could be worth as much as $10 billion within five years, according to industry analysts. It affects tens of million of people worldwide every year.