Gilead Sciences announces viral relapse in 12 week GS-7977 + RBV ELECTRON arm...

Gilead press release on 2/17/12. The press release that shook the HCV drug development world. Gilead announced that they had data for 8 out of 10 previous null-responder subjects  randomized to the 12 week GS-7977 + RBV arm in the ELECTRON trial. Out of the 8 patients, 6 developed viral relapse. Data on the other two patients is forthcoming. So, this counts out GS-7977 + RBV for 12 weeks as effective therapy for previous null responders. The questions that remain are: can therapy extended past 12 weeks do the job? (say 24, 36 or even 48)?  Does this regimen require the addition of one or more additional DAAs that target differing parts of the HCV replication process? Or the addition of interferon? Or both of the latter? This is clearly not a reason to panic (although, judging from the stock drop today, shareholders did do just that) but it did answer 'no' to an important question this study was designed to answer - is 12 weeks of GS-7977 + RBV enough to achieve an SVR in the null responder patient population?  Gilead will look at multiple combinations of treatment durations and drug combinations to find the one that achieves the best results. Gilead also has an excellent portfolio of HCV drugs that inhibit differing parts of the HCV replication process to pair with GS-7977.  So panic is definitely not warranted.


It is a warning to analysts who touted an inteferon-free GS-7977 + RBV as the answer to all patient types. Such statements were misleading to their investors. We can learn from the early research days of HIV. I don't want to say "I told you so", but "I told you so". The HCV virus is a highly replicating virus with no proof-reading mechanism capable of making every possible mutation of itself in the course of a day. As in HIV, one drug will not be able to stop the virus from replicating and will select out the mutations that are resistant to the drug and are most fit to survive in the presence of drug. It will take more than one drug targeting more than one part of the viral replication process to do the trick, and may also require the generalized immune response triggered by exogenous interferon as much as we'd like to see that go away. 

Gilead Announces Data for Genotype 1 Null Responder Hepatitis C Patients Enrolled in ELECTRON Study


– Viral Relapse Seen Post Treatment with GS-7977 Plus Ribavirin –

– Awaiting Data for Treatment-Naïve Genotype 1 Patients –
Press Release: Gilead Sciences, Inc.
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FOSTER CITY, Calif.--(BUSINESS WIRE)--

Gilead Sciences, Inc. (NASDAQ:GILD - News) announced today that the majority of hepatitis C genotype 1 patients with a prior “null” response to an interferon (IFN)-containing regimen enrolled in the ongoing ELECTRON study experienced viral relapse within four weeks of completing 12 weeks of treatment with GS-7977 plus ribavirin (RBV). Ten patients were randomized to this arm of the ELECTRON study and data are available for eight of the 10 patients at this time. Among these eight patients, six have experienced viral relapse. Two patients have not relapsed; however, they have only reached the two week post-treatment time point.

“These data answer an important question about the use of GS-7977 and ribavirin for the treatment of genotype 1 null responder patients, suggesting that additional direct acting antivirals may be necessary to effectively treat this patient population,” said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer. “We will continue to explore a number of therapeutic approaches to address this significant unmet medical need, including combinations with other oral antivirals.”

GS-7977 is a nucleotide analog polymerase inhibitor that is currently being studied for the treatment of chronic hepatitis C. A number of ongoing Phase 2 and Phase 3 studies are evaluating the safety and efficacy of the compound with and without RBV and/or pegylated interferon (Peg-IFN) in patients with genotypes 1-6 who are treatment naïve, treatment experienced, or have had a “null” response to Peg-IFN.

Genotype 2 and 3 data from the ELECTRON study were presented at the 62nd annual meeting of the American Association for the Study of Liver Diseases (The Liver Meeting 2011). Data from the genotype 1 null responder arm of the study will be presented at an upcoming scientific conference.

Results from ongoing studies in genotype 1 treatment-naïve patients will be available in the coming months. The first data evaluating GS-7977 plus RBV for 12 weeks in genotype 1 naïve patients will come from an arm of the QUANTUM study with 25 patients at the end of the first quarter of 2012. This will be followed in the second quarter by data from the ELECTRON study involving 25 patients and, early in the third quarter, data on GS-7977 and RBV treatment for 24 weeks from an arm of the QUANTUM study will become available.

Conference Call

 Gilead will host a conference call today, February 17, 2012 at 8:00 a.m. Eastern Time, to discuss these study results. To access the live call, please dial 1-866-825-1709 (U.S.) or 1-617-213-8060 (international). The conference passcode number is 71588571. Telephone replay is available approximately one hour after the call through 11:59 p.m. Eastern Time, February 20, 2012. To access, please call 1-888-286-8010 (U.S.) or 1-617-801-6888 (international). The conference passcode number for the replay is 64278864. 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 Gilead Sciences

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

Forward-Looking Statement

 This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, that are subject to risks, uncertainties and other factors, including the possibility of unfavorable results from the ELECTRON and QUANTUM studies, including in genotype 1 treatment-naïve patients, as well as other clinical trials evaluating GS-7977 with or without RBV and/or Peg-IFN or in combination with other antivirals; the anticipated timing for receiving clinical data and making regulatory filings; and Gilead’s ability to develop an all-oral antiviral regimen for HCV genotype 1 patients or a pangenotypic regimen for all HCV patients. As a result, GS-7977 may never be successfully commercialized. Further, Gilead may make a strategic decision to discontinue development of GS-7977 if, for example, it believes commercialization will be difficult relative to other opportunities in its pipeline. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2011, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

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.

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Contact:.
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Gilead Sciences, Inc.
Susan Hubbard, 650-522-5715 (Investors)
Amy Flood, 650-522-5643 (Media)

Gilead Sciences posts good news on PSI-7977...

Posted 2/2/12 on Businessweek.com - PSI-7977 + Ribavirin in genotype 1 looking good four weeks in. Expect full data explosion at CROI next month.

Gilead Gains on Positive Data From Experimental Hepatitis C Drug
February 02, 2012, 8:47 PM EST
By Ryan Flinn

Feb. 2 (Bloomberg) -- Gilead Sciences Inc., the drugmaker that acquired Pharmasset Inc. last month for its experimental hepatitis C treatments, gained in extended trading after saying one of the therapies produced positive clinical trial results.
Patients with genotype 1 hepatitis C -- the most common in North America -- had no detectable signs of the virus after four weeks on the drug, PSI-7977, Norbert Bischofberger, Gilead’s chief scientific officer, said today on the Foster City, California-based company’s earnings call. An earlier study of the medicine, gained in the $10.8 billion Pharmasset purchase, cured all patients with genotype 2 and 3.
Drugmakers including Gilead, Merck & Co., Vertex Pharmaceuticals Inc. and Bristol-Myers Squibb Co., are striving to develop a new class of oral cures for hepatitis C to replace older drugs that require injections. Bristol-Myers recently agreed to spend $2.5 billion to buy Inhibitex Inc. for its experimental hepatitis C therapies.
“It looks like Gilead will race ahead and continue to lead because it’s drug 7977 continues to support potential 100 percent cure rates,” Michael Yee, an analyst with RBC Capital Markets in San Francisco, said in an interview. “The data disclosed in genotype 1, an important population for which there was no good data yet, continues to show they can support a multibillion-dollar drug franchise with 7977.”
The drug was tested in combination with ribavirin, a medication currently used in treating the disease. The therapy was given to patients who hadn’t taken other drugs and those whose illness wasn’t helped by other treatments.
The company will present further data on the clinical trial at an infectious diseases conference next month in Seattle.
Gilead rose as much as 6.4 percent to $52.45 after closing at $49.31 in New York trading.
--Editor: Andrew Pollack
To contact the reporter on this story: Ryan Flinn in San Francisco at rflinn@bloomberg.net
To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net

Gilead nears completion of Pharmasset deal

From Boston.com: Gilead edges closer to acquiring Pharmasset and it's prized portfolio of HCV drugs. I can smell the co-formulations brewing from here. 

Gilead nears completion of Pharmasset deal
January 12, 2012

FOSTER CITY, Calif.—Gilead Sciences has acquired about 95 percent of the outstanding shares in Pharmasset as it draws closer to closing its $11 billion deal for the drug developer.

Gilead, based in Foster City, Calif., said about 72 million Pharmasset shares have been tendered. Gilead announced in November that it would pay $137 per share in cash for the, a Princeton, N.J. drug developer.

Pharmasset Inc. has three potential hepatitis C treatments in clinical testing, including a candidate labeled PSI-7977 in late-stage testing. Analysts see promise in the drug because doctors may be able prescribe the pill in a combination with other treatments that does not involve interferon, an injection that comes with rough side effects.

Hepatitis C is a virus that can lead to life-threatening liver damage and is the main cause of liver transplants in the United States. Analysts expect it to become a bigger health problem as baby boomers ages.

Gilead Sciences Inc. plans to buy additional shares of Pharmasset directly from the company, which has no drugs on the market. The acquisition is expected to close in the first quarter.

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)

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

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

Pharmasset awarded fast track status for polymerase inhibitor PSI-938...

(Good news for Pharmasset, as the FDA awards it's polymerase inhibitor PSI-938 fast track status, which would shorten the review period from 10 months to six months. Pharmasset also announces the start of an interferon-free, dual polymerase inhibitor trial of PSI-938 in combination with it's PSI-7977 compound in the Q3 of this year)

PSI-938 Receives Fast Track Designation from the FDA for the Treatment of Chronic Hepatitis C Infection

PRINCETON, N.J., Aug. 24, 2011 /PRNewswire via COMTEX/ -- Pharmasset, Inc. /quotes/zigman/101019/quotes/nls/vrus VRUS +0.02% has received fast track designation from the U.S. Food and Drug Administration (FDA) for PSI-938 for the treatment of chronic hepatitis C virus (HCV) infection. PSI-938 is an oral guanosine nucleotide analog polymerase inhibitor of HCV.

In March 2011, Pharmasset presented data from the NUCLEAR study demonstrating that PSI-938 has potent antiviral activity and is generally safe and well tolerated, both as monotherapy and in combination with Pharmasset's lead nucleotide analog, PSI-7977. The NUCLEAR study was conducted in treatment naive subjects with genotype 1 HCV who were treated for 14 days with either PSI-938 or a combination of PSI-938 and PSI-7977 with 92% achieving HCV RNA <15IU/mL, the limit of detection, in the combination arms. Pharmasset plans to initiate QUANTUM, an interferon-free combination trial with PSI-938 and PSI-7977 in the third quarter of 2011.

Under the FDA Modernization Act of 1997, fast track designation may facilitate the development and expedite the review of a drug candidate that is intended for the treatment of a serious and life-threatening condition and demonstrates the potential to address an unmet medical need for such a condition. PSI-938 was granted the fast track designation primarily due to the need for HCV treatments with improved tolerability, safety and efficacy over the existing standard of care for both treatment-naive and treatment-experienced patients.

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 four Phase 2b trials in patients with HCV genotypes 1 through 6, including abbreviated duration interferon and interferon-free regimens. Our purine, PSI-938, an unpartnered guanosine nucleotide analog, recently reported safety and efficacy data from 14 days of monotherapy as well as 14 days in combination with the pyrimidine, PSI-7977. An SVR-endpoint study of the purine-pyrimidine combination is anticipated to begin in the third quarter of 2011. Mericitabine (RG7128) continues in three Phase 2b trials and one interferon-free trial being conducted through a strategic collaboration with Roche.

For full press release, click on the attached link.

Pharmasset & Tibotec team up HCV drugs in clinical collaborative agreement...

Pharmasset all over the news this week, they definitely seem to be teaming up with the right folks in their development of their nucleotide analog PSI-7977... with their own nuc PSI-938, with BMS's NS5a inhibitor and now with Medivir/Tibotec's TMC435. The HCV DAA development space is definitely heating up!

Pharmasset Enters into a Clinical Collaboration Agreement with Tibotec Pharmaceuticals for a Combination Study in Patients Chronically Infected with Hepatitis C


- Study to evaluate the combination of PSI-7977 and TMC435 with and without ribavirin in prior null responder, genotype 1 HCV patients

PRINCETON, N.J., July 6, 2011 /PRNewswire/ -- Pharmasset, Inc. (NASDAQ: VRUS), announced today that it has entered into a clinical collaboration agreement with Tibotec Pharmaceuticals to evaluate in a Phase 2 study the safety and efficacy of PSI-7977, Pharmasset's investigational nucleotide polymerase inhibitor, in combination with TMC435, Tibotec Pharmaceuticals' investigational protease inhibitor, for the treatment of chronic hepatitis C virus (HCV).

This phase 2 proof of concept study will evaluate the potential to achieve sustained virologic response 12 weeks post treatment with an all oral, once-daily, interferon-free treatment regimen in patients infected with genotype 1 HCV. Specifically, the study will assess the safety, pharmacokinetics and pharmacodynamics of 12 and 24 weeks of PSI-7977 in combination with TMC435, with and without ribavirin, in patients chronically infected with HCV genotype 1 who had a prior null response to peginterferon alfa and ribavirin treatment. The study is planned to start in the second half of 2011.

"We are excited to be working with Tibotec to simplify and improve HCV treatment," stated Bill Symonds, PharmD, Pharmasset's Senior Vice President of Clinical Pharmacology and Translational Medicine. "PSI-7977 is now being studied in interferon-free combinations with each of the three leading classes of direct-acting antivirals: Tibotec's protease inhibitor, Bristol-Myers Squibb's NS5a inhibitor, and our own nucleotide, PSI-938. This advances one of our key goals at Pharmasset: to develop our nucleotide analogs as the backbone of interferon-free HCV therapy."

About PSI-7977

PSI-7977 is a prodrug of a uracil nucleotide analog polymerase inhibitor we are developing for the treatment of chronic HCV infection. PSI-7977 has completed a 28 day phase 2a trial in combination with peg-interferon and ribavirin (Peg-IFN/RBV) and is currently being tested in four phase 2b studies: the PROTON trial in combination with peg-IFN/RBV in HCV genotype 1, 2 or 3 patients; the ATOMIC trial with peg-IFN/RBV in HCV genotypes 1,4,5,6; the ELECTRON trial, an interferon sparing /interferon free study in HCV genotypes 1,2 and 3 and a study with Bristol-Myers Squibb's NS5a inhibitor, BMS-790052, as part of an interferon free regimen. Pharmasset also anticipates initiating its own interferon free trial with PSI-7977 and PSI-938, a guanine nucleotide polymerase inhibitor in the third calendar quarter 2011.

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 three Phase 2b trials in patients with HCV genotypes 1 through 6, including abbreviated duration interferon and interferon-free regimens. Our purine, PSI-938, an unpartnered guanosine nucleotide analog, recently reported safety and efficacy data from 14 days of monotherapy as well as 14 days in combination with the pyrimidine, PSI-7977. An SVR-endpoint study of the purine-pyrimidine combination is anticipated to begin in the third quarter of 2011. Mericitabine (RG7128) continues in two Phase 2b trials and one interferon-free trial being conducted through a strategic collaboration with Roche.

Pharmasset
Richard E. T. Smith, Ph.D.
VP, Investor Relations and Corporate Communications
Office: +1 (609) 865-0693

Pharmasset 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.

RELATED LINKS
http://www.pharmasset.com

Pharmasset's PSI-7977 deemed having "Blockbuster potential"...

Hold your horses, I think an analyst used this to describe VX-222 at one time...

Associated Press
Pharmasset climbs as analyst raises target
Associated Press, 07.05.11, 12:23 PM EDT

NEW YORK -- Shares of hepatitis C drug developer Pharmasset Inc. rose Tuesday after a Canaccord Genuity analyst raised his price target on the stock.

THE SPARK: Analyst George Farmer assumed coverage of the stock, maintaining a "Buy" rating and raising the price target to $160 per share from $57. He said Pharmasset ( VRUS - news- people )'s hepatitis drug candidate PSI-7977 has "blockbuster potential" and its pipeline is promising, as another hepatitis C treatment has also looked very effective in earlier studies.

THE BIG PICTURE: The Princeton, N.J., company said last month that it will expand a trial of PSI-79777 to see if it is effective for patients who have not responded to other hepatitis C drugs and to see if it can eliminate the virus in eight weeks instead of the normal 12 weeks. The changes indicate the drug is working well in the study. PSI-7977 is years away from reaching the market, as Pharmasset plans to report mid-stage trial results later in 2011 and will have to conduct late-stage trials after that.

SHARE ACTION: Pharmasset stock rose $3.59, or 3.2 percent, to $116.33 in midday trading. Shares have traded between $23.56 and $135.92 over the past year.

Pharmasset Announces the Expansion of the ELECTRON Trial in Chronic Hepatitis C

Pharmasset adding arms to it's genotype 2/3 ELECTRON trial looking at shorter durations of therapy in addition to inteferon-free monotherapy for it's PSI-7977 nucleotide analog. Nucs traditionally have a very high barrier to resistance in comparison to non-nucs, but with a virus capable of making every possibly mutation of itself in the course of a day, is nuc monotherapy without an immune system modulator or another viral life cycle-specific inhibitor enough, even in the relatively easy-to-treat G2 and 3 virus? If it's not, what are the odds of a PSI-7977 resistant quasispecies developing and the corresponding fitness level compared to wild type of those variants? Guess we'll find out soon enough. If anyone can shed further enlightenment, please do.

PRINCETON, N.J., June 8, 2011 /PRNewswire/ -- Pharmasset, Inc. (Nasdaq: VRUS) announced today the addition of three treatment cohorts 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 provide the rationale for additional exploratory regimens in this setting. This amendment will add one arm exploring 12 weeks of PSI-7977 monotherapy (without peginterferon and ribavirin) and two arms of interferon-sparing therapy: one for 8 weeks of PSI-7977 plus peginterferon and ribavirin (Peg-IFN/RBV) in patients with HCV genotype 2 (GT2) or 3 (GT3) and one for 12 weeks of PSI-7977 plus Peg-IFN/RBV in patients with HCV genotype 1 (GT1) prior null responses.

"The combination data reported at EASL demonstrated that SVRs were achievable with two oral DAAs in the absence of peginterferon and ribavirin," stated Bill Symonds, PharmD, Pharmasset's Senior Vice President of Clinical Pharmacology and Translational Medicine, "We continue to explore the potential for removing peginterferon and ribavirin from the HCV treatment regimen. Given the encouraging data we are seeing in ELECTRON, we have decided to expand the study to investigate PSI-7977 monotherapy, as well as shorter treatment regimens based on the promising data we reported at EASL from PROTON."

Pharmasset anticipates reporting results from the first four arms of the trial (n=40) during the second half of 2011. We have submitted a number of abstracts to the 2011 American Association for the Study of Liver Diseases (AASLD) meeting, including data from the ELECTRON and PROTON trials.

About the Trial

The ELECTRON trial 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 PSI-7977 400mg QD in combination with ribavirin (RBV) only, and in separate arms with abbreviated durations of Peg-IFN for 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 in patients with HCV GT 2 or GT 3:

* PSI-7977 400mg with RBV for 12 weeks (no peginterferon);
* PSI-7977 400mg with RBV for 12 weeks; Peg-IFN weeks 1-4 only;
* PSI-7977 400mg with RBV for 12 weeks, Peg-IFN weeks 1-8 only;
* PSI-7977 400mg with Peg-IFN and RBV for 12 weeks.


In Part 2 of ELECTRON, Pharmasset will enroll an additional 30 patients into exploratory regimens of monotherapy and abbreviated durations of total therapy. Following on the first four Cohorts of ELECTRON a 5th cohort will be added to explore 7977 400mg monotherapy in treatment-naive patients with HCV GT2 or GT3:

* PSI-7977 400mg monotherapy for 12 weeks.


With the previously reported 100% SVR12 in naive GT2/3 subjects in PROTON, a 6th and 7th cohort will be added to ELECTRON to explore shorter treatment durations in both GT2/3 naive subjects and HCV GT1 subjects who have documented null responses (less than 2 log(10) IU/mL reduction in HCV RNA after 12 weeks of Peg-IFN/RBV):

* PSI-7977 400mg with Peg-IFN/RBV for 8 weeks
* PSI-7977 400mg QD with Peg-IFN/RBV for 12 weeks.


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 three Phase 2b trials in patients with HCV genotypes 1 through 6, including abbreviated duration interferon and interferon-free regimens. Our purine, PSI-938, an unpartnered guanosine nucleotide analog, recently reported safety and efficacy data from 14 days of monotherapy as well as 14 days in combination with the pyrimidine, PSI-7977. An SVR-endpoint study of the purine-pyrimidine combination is anticipated to begin in the third quarter of 2011. Mericitabine (RG7128) continues in two Phase 2b trials and one interferon-free trial being conducted through a strategic collaboration with Roche.

Contact
Richard E. T. Smith, Ph.D.
VP, Investor Relations and Corporate Communications
Office: +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.

Analysts speculate on PSI-7977 possibly receiving earlier than anticipated FDA approval...

From Forbes.com

Associated Press
Ahead of the Bell: Pharmasset shares rise
Associated Press, 06.03.11, 09:02 AM EDT

NEW YORK -- A Citi Investment Research analyst said Friday that Pharmasset Inc.'s leading hepatitis C drug candidate could be approved sooner than expected, and he nearly tripled his price target on Pharmasset shares.

Shares of the Princeton, N.J., company rose $3.33, or 3.3 percent, to $104.20 in pre-market trading.

Analyst Yaron Werber said the drug candidate, which is designated PSI-7977, could be approved as soon as mid-2014 to treat two relatively rare types of hepatitis C.

Werber previously thought PSI-7977 wouldn't reach the market until late 2015, and he raised his target on Pharmasset ( VRUS - news - people ) to $200 per share from $71 to reflect the chances of an earlier approval, which would boost sales of the drug.

Werber said PSI-7977 could get to the market sooner if it is approved to treat hepatitis C genotypes 2 and 3, which make up a minority of cases. In late May, Pharmasset started a mid-stage clinical trial of PSI-7977 as a treatment for hepatitis C genotypes 1, 2, and 3. Genotype 1 makes up about 70 percent of hepatitis C diagnoses. Werber said he thinks the drug "will have solid data and will be one of the dominant drugs in hepatitis C."

The analyst said Pharmasset should present study data in November and should start late-stage studies in early 2012. He thinks the company will be profitable in 2016.

New trials looking at treating HCV genotypes 1,2,3,4 and 5 with Pharmasett's PSI-7997

New studies that popped up in Clinical Trials.gov looking at Pharmasett's PSI-7977 with and without Peg in Genotypes 1, 2, 3, 4 and 5. Many thanks to the good people over at NATAP.org for the heads' up on these trials.


PSI-7977 With Pegylated Interferon and Ribavirin Hepatitis C Virus (HCV) Genotypes 1,4,5,6 (ATOMIC)


Open-Labeled Study of PSI-7977 and RBV With and Without PEG-IFN in Treatment-Naïve Patients With HCV GT2 or GT3

Could an all-oral agent to treat HCV be on the way?

Two week interim data for Pharmasset's Interferon/Ribavirin-free nuc-nuc combo is a long way from an SVR, but so far the company has earned bragging rights by having 15/16 subjects in this early phase trial go undetectable after two weeks. This is seemingly a pretty potent combo in comparison to Vertex's data with it's nuc VX-222 + Telaprevir + Peg Interferon + Ribavirin. Depending on the arm, that data topped out at 38-57% undetectability after 14 days in comparison to 94% with PSI-938 and PSI-7977. Pharmasset’s new landmark was enough for investors to spin like tops and goose the stock to new heights. Keep in mind that investors don’t always act rationally and It’s difficult to predict outcomes as all we know regarding viral kinetics and positive/negative predictive values comes from regimens that contain peg-inf plus ribavirin as its therapeutic backbone. If PSI-938 and PSI-7977 can retain 94% undetectable at four weeks, I’ll be proportionally reassured regarding this combo’s future. It will be interesting how the company defines when it’s time to stop therapy given that there isn’t an immunomodulator aboard. At what time points will the company declare EOT and SVR? An all oral combo would be an amazing paradigm shift for this disease state and will set the bar extremely high for drug developers looking to get into the HCV therapeutic category, but there’s a long road ahead.

Pharmasset Hep C Data Wows Investors

Adam Feuerstein
03/08/11 - 11:46 AM EST
PRINCETON, N.J. (TheStreet) -- Pharmasset(VRUS) shares are soaring on the release of new but very preliminary data that hints at a breakthrough, all-oral cure for hepatitis C.

Treatment with two oral drugs developed by Pharmasset resulted in 15 of 16, or 94%, of patients reporting undetectable levels of the hepatitis C virus after 14 days, according to interim results from a study released Monday.

These early data on the two Pharmasset drugs -- PSI-938 and PSI-7977 are the best reported to date by any company seeking to develop a new, all-oral therapy for hepatitis C. This Pharmasset effort is drawing even more attention because it potentially eliminates the need for patients to be treated with long-acting interferon, one of two drugs currently used to treat hepatitis C but which is difficult for patients to tolerate and causes many side effects.

Pharmasset shares rose 24% on Monday and were up another 8% to $66.92 on Tuesday.

The PSI-938 and PSI-7977 combination data were released Monday in a research abstract released online by the European Association for the Study of the Liver (EASL), which holds its annual meeting March 30 through April 3.

EASL makes research abstracts for its annual meeting freely available to the public but prohibits journalists from writing about the data contained in the research abstracts until they are presented at the annual meeting. TheStreet refuses to adhere to EASL's media embargo since these hepatitis C data are freely available online now and are impacting the stock prices of publicly traded companies developing hepatitis C drugs.

While investors are displaying great enthusiasm for the Pharmasset all-oral drug combination, the data from the study are very early. One particular risk seen in other, similar studies that omit long-acting interferon is the development of mutated hepatitis C virus that can quickly become resistant to drug treatment.

None of the patients treated in the Pharmasset study have reported rebounding levels of hepatitis C virus, according to the research abstract, but so-called viral rebound may emerge as patients are treated longer, or when treatment is stopped and these patients are followed long-term to determine if they are truly cured.
Pharmasset owns full rights to both PSI-938 and PSI-7977. The company is developing another hepatitis C drug, RG7128, in partnership with Roche.

"We believe the full data of a 14-day combination of PSI-7977 / PSI-938 to be presented at the upcoming EASL could show proof of principle for a nuc-nuc combination and position Pharmasset as one of the front runners in the race to develop an interferon-free regimen, which is considered a Holy Grail in hepatitis C treatment," said Leerink Swann analyst Howard Liang in a note to clients Tuesday.

The EASL meeting at the end of the month will also feature data from other companies seeking to develop various combination treatments for hepatitis C.

Vertex Pharmaceuticals(VRTX) is studying a "quad" regimen consisting of two experimental drugs, VX-222 and telaprevir, combined with the current standard of care, long-acting interferon and ribavirin. An EASL research abstract released Monday reported treatment with Vertex's "quad" therapy resulted in 38-57% of patients with undetectable virus after two weeks and 86-87% undetectable after four weeks.

One potential competitive disadvantage to the Vertex quad is that patients still need to be treated with long-acting interferon, which requires weekly injections. Vertex previously reported disappointing results from an all-oral Hep C drug regimen that eliminated interferon.

Telaprevir is currently under review by regulators in the U.S. and Europe. The U.S. Food and Drug Administration is expected to make an approval decision on or before May 23.

Gilead Sciences(GILD) and Bristol-Myers Squibb(BMY) will also be presenting new data from Hep C combination drug studies at the EASL meeting later this month.

--Written by Adam Feuerstein in Boston.

BMS and Pharmasset to combine BMS-790052 and PSI-7997 HCV DAA candidates for proof-of-concept study...

Pharmasset and BMS initiate first cross-company study combining two QD oral, direct-acting antivirals together both with and without ribavirin.


Bristol-Myers Squibb and Pharmasset are to carry out a proof-of-concept study evaluating their respective investigational drug candidates BMS-790052 and PSI-7977 as oral combination therapy for chronic hepatitis C (HCV). BMS-790052 is BMS’ NS5A replication complex inhibitor. Pharmasset’s PSI-7977 is a nucleotide polymerase inhibitor.

The proof-of-concept study will evaluate whether the once-daily oral therapy with the drug duo, either with or without concomitant ribavirin therapy, can lead to a sustained viral response 24 weeks post-treatment in patients chronically infected with HCV genotypes 1, 2, and 3. The trial is expected to start during the first half of 2011. The partners claim it will be the first cross-company study combining two oral, direct-acting antivirals.

At the start of November BMS reported positive data from an open-label Phase IIa trial evaluating a combination of BMS-790052 with its own NS3 protease inhibitor BMS-650032 in HCV genotype 1 patients who had previously not responded to standard HCV therapy with interferon and ribavirin (pegIFNα/RBV). The study showed that when given alongside pegIFNα/RBV treatment, a combination of BMS-790052/BMS-650032 led to 9/10 patients achieving complete early virologic response (cEVR, defined as undetectable viral load) by week 12.

Pharmasset’s PSI-7977, meanwhile, is a uracil nucleotide analog inhibitor of the NS5B polymerase. The drug is currently undergoing Phase IIb evaluation. In December 2010 Pharmasset announced the start of a Phase IIb interferon-sparing trial evaluating PSI-7977 in combination with ribavirin (RBV), and with either 0, 4, 8, or 12 weeks of pegIFNα, as therapy in treatment-naïve patients infected with HCV genotype 2 or 3.

Just last week the firm separately reported positive data from another Phase IIb study, which showed that combining PSI-7977 with pegIFNα/RBV therapy resulted in potent viral suppression in patients with HCV genotype 2 or 3, over 12 weeks. Pharmasset says it plans to initiate a separate Phase IIb combination study during 2011, to evaluate PSI-7977 in combination with pegIFNα/RBV over 24 weeks. PSI-7977 is separately being evaluated in a 14-day Phase I trial as combination therapy with the firm’s guanine nucleotide analog, PSI-938.

Update on Pharmasset's PSI-7977 and PSI-938....

UPDATE 1-Pharmasset says HCV drugs show promise
7:48am EST

* PSI-7977 shows rapid viral suppression

* PSI-938 found to be well tolerated

Jan 6 (Reuters) - Pharmasset Inc (VRUS.O: Quote, Profile, Research, Stock Buzz) said interim analyses of clinical studies of its two drugs for chronic hepatitis C showed promise.

A mid-stage study of the drug, codenamed PSI-7977, showed rapid viral suppression with all patients remaining below limit of detection at the end of treatment. No serious adverse events were reported.

The drug was granted "fast track" designation in August. Fast-track status is designed to expedite the review of drugs to treat serious diseases and fill unmet medical needs. [id:nSGE67B0JZ]

The company said it expects to start a 24-week mid-stage study of the drug in the second quarter of 2011.

An early-stage study of the drug, codenamed PSI-938, as a monotherapy was found to be safe and well-tolerated, Pharmasset said.

The Princeton, New Jersey-based company's shares, which have risen 50 percent in the last three months, closed at $46.59 on Wednesday on Nasdaq. (Reporting by Shravya Jain in Bangalore; Editing by Sriraj Kalluvila)

Pharmasset exploring interferon-sparing Phase II trial for it's nucelotide analog PSI-7977 for Genotype 2/3 HCV...

Possible great niche for PSI-7977 in Genotype 2/3 subjects, possibly cutting the duration of therapy in half for these patients and possibly taking the interferon component out of the equation. -Chris

Pharmasset Initiates Exploratory Interferon Sparing Clinical Trial of PSI-7977 for Chronic Hepatitis C


Exploratory phase 2 trial in patients with HCV genotype 2 or 3 to receive PSI-7977 400mg QD and ribavirin, with 0-12 weeks of pegylated interferon

Interim data expected in first half of 2011

PRINCETON, N.J., Dec. 14, 2010 /PRNewswire/ -- Pharmasset, Inc. (Nasdaq: VRUS) announced today that dosing has begun in an exploratory study of PSI-7977, a nucleotide analog polymerase inhibitor, for the treatment of chronic hepatitis C (HCV). The trial will evaluate PSI-7977 400mg QD in combination with ribavirin (RBV), with 0, 4, 8, or 12 weeks of pegylated interferon alfa 2a (Peg-IFN) in treatment-naive patients infected with HCV genotype 2 or 3.
"Based on the encouraging efficacy, safety and resistance data from the Phase 2a trial with PSI-7977 in combination with pegylated interferon and ribavirin, we initiated a study to explore shorter durations of interferon, including an interferon-free regimen in treatment naïve patients with HCV genotype 2 or 3," stated Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "An important limitation to the current treatment of HCV patients is the use of interferon with its associated side effect profile. We believe that PSI-7977's high barrier to resistance and the lack of a significant effect of IL28B genotype in the Phase 2a trial provide us an opportunity with PSI-7977 to explore shorter durations of interferon, and potentially even removing it from the treatment regimen altogether."

About the Trial
The trial is anticipated to enroll approximately 40 patients infected with HCV genotype 2 or 3 who have not previously been treated. The primary endpoint of the trial will be the assessment of safety and tolerability of PSI-7977 400mg QD and RBV for 12 weeks, administered with or without pegylated interferon (Peg-IFN) in treatment naïve patients with HCV genotypes 2 or 3. The trial will be conducted in New Zealand. Patients will be randomized into one of 4 arms:

-- PSI-7977 400mg QD in combination with RBV for 12 weeks (no interferon);
-- PSI-7977 400mg QD in combination with RBV for 12 weeks, with only 4 weeks of Peg-IFN;
-- PSI-7977 400mg QD in combination with RBV for 12 weeks, with only 8 weeks of Peg-IFN;
-- PSI-7977 400mg QD in combination with Peg-IFN and RBV for 12 weeks.

Patients will be stratified by HCV genotype and IL28B status to ensure balance across cohorts.
Pharmasset anticipates reporting interim data from this trial in the first half of 2011.

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 on the development of oral therapeutics for the treatment of hepatitis C virus (HCV). Our research and development efforts focus on nucleoside/tide analogs, a class of compounds which act as alternative substrates for the viral polymerase, thus inhibiting viral replication. We currently have four clinical-stage product candidates. RG7128, a cytosine nucleoside analog for chronic HCV infection, is in two Phase 2b clinical studies in combination with Pegasys(R) plus Copegus(R) and is also in the INFORM studies, the first series of studies designed to assess the potential of combinations of small molecules without Pegasys(R) and Copegus(R) to treat chronic HCV. These clinical studies are being conducted through a strategic collaboration with Roche. Our other clinical stage HCV candidates include PSI-7977, an unpartnered uracil nucleotide analog that has recently initiated dosing in a Phase 2b study in patients with HCV genotypes 1, 2, or 3, and PSI-938, an unpartnered guanosine nucleotide analog which recently completed a 7-day monotherapy study. We also have in our pipeline an additional purine nucleotide analog, PSI-661, in advanced preclinical development.

Pharmasset Initiates Dosing in a Combination Study of PSI-7977 and PSI-938 for Chronic Hepatitis C...

First study to look at a combination of of a purine and a pyrimidine nucleotide analog (PSI-938 and PSI-7977 respectively). Pharmasset believes the combination of two 'nucs' has a potential higher barrier to resistance, making it attractive to use in combo with other STAT-C/DAA drugs. The company plans a Phase II trail looking at the combination without interferon mid-2011 - Chris

- Phase 1 combination study of a pyrimidine (PSI-7977) and purine (PSI-938) nucleotide analog in patients with chronic hepatitis C

- Interim data expected in first quarter of 2011

PRINCETON, N.J., Nov. 30, 2010 /PRNewswire-FirstCall/ -- Pharmasset, Inc. (Nasdaq: VRUS) announced today that dosing has begun in Part 2 of a Phase 1 study. This is the first clinical study combining a purine (PSI-938) and a pyrimidine (PSI-7977) nucleotide analog for HCV, and is designed to evaluate once daily doses of PSI-7977 and PSI-938 in patients with HCV who have not been treated previously.

"We are excited to be initiating this combination study with two proprietary nucleotide analogs for HCV," stated Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "Based on our in vitro data, we believe the combination of two nucleotide analogs could provide potent antiviral activity across multiple HCV genotypes and could also have a higher barrier to resistance compared to other DAA combinations. We believe nucleotide analogs have a number of key attributes that may make them ideal partners for other DAA combinations, in addition to a 'nuc-nuc' combination."

About the Phase 1 Trial

In Part 1 of the Phase 1 multiple ascending dose study of PSI-938, suppression of HCV RNA below the limit of detection (LOD, <15 IU/mL) was observed in over half of the patients who received PSI-938 at daily doses of 200 mg or 300 mg for seven days. Part 2 of the study is designed to evaluate the combination of PSI-938 and PSI-7977. The primary objective is to assess the safety, tolerability and pharmacokinetics of PSI-938 administered alone for 14 days, and in combination with PSI-7977 for 7 to 14 days. The secondary objective is to evaluate viral kinetics of HCV RNA during monotherapy and combination nucleotide dosing. Approximately forty patients are expected to be enrolled into four cohorts as follows:

* PSI-938 QD administered as monotherapy for 14 days, followed by;
* PSI-938 QD for 7 days followed by PSI-938 plus PSI-7977 QD for 7 days and
* PSI-7977 QD for 7 days followed by PSI-938 plus PSI-7977 QD for 7 days, followed by;
* PSI-938 plus PSI-7977 QD for 14 days


We expect to report preliminary results from Part 2 of this Phase 1 study during the first quarter of calendar year 2011. We also expect to initiate a Phase 2 study of PSI-938 in combination with PSI-7977 during mid-2011. This Phase 2 study proposes to explore durations of PSI-938 and PSI-7977 in interferon-free combinations with an SVR endpoint.

Pharmasset releases Phase 1 data on HCV nucleotide inhibitor PSI-938

Reports Positive Preliminary Antiviral Data with PSI-938 for the Treatment of Hepatitis C 
10/28/2010

PRINCETON, N.J., Oct. 28 /PRNewswire-FirstCall/ -- Pharmasset, Inc. (Nasdaq: VRUS) reported positive preliminary results today from its phase I monotherapy trial of PSI-352938 ("PSI-938") for the treatment of chronic hepatitis C (HCV). PSI-938 is a guanosine nucleotide analog polymerase inhibitor in development for the treatment of chronic HCV infection.

PSI-938 Phase 1 Multiple Ascending Dose Study Overview

In August 2010, Pharmasset initiated a phase 1 multiple ascending dose study with PSI-938 administered once daily (QD) or twice daily (BID) for 7 days. The trial was conducted at two US centers as a blinded, randomized, and placebo-controlled study in 40 patients chronically infected with HCV genotype 1. The primary objective was to assess the safety, tolerability, and pharmacokinetics of PSI-938 administered over 7 days. The secondary objective was to assess antiviral activity by measuring the change in HCV RNA. Patients were randomized within each cohort to receive either PSI-938 (8 patients per cohort) or placebo (2 patients per cohort). Four dose cohorts of PSI-938 (100 mg QD, 200 mg QD, 300 mg QD and 100 mg BID) have been completed.

PSI-938 Antiviral Activity Summary

Preliminary Antiviral Response Observed Following PSI-938 Administered as Monotherapy for 7 Days
Dose	n	Median Change in HCV RNA at Day 8	Range	Number of Subjects with HCV RNA
		(log10 IU/mL)	(log10 IU/mL)
100 mg QD	8	-4.31	-2.66 to -5.12	1	3
200 mg QD	8	-4.64	-3.49 to -5.35	5	7
300 mg QD	8	-3.94	-3.43 to -5.29	4	4
100 mg BID	8	-4.59	-3.94 to -5.08	2	3
Placebo	8	-0.05	+0.17 to -0.29	0	0
LOD = limit of detection (<15 IU/mL) LOQ = limit of quantification (<43 IU/mL)

PSI-938 demonstrated potent antiviral activity with a mean HCV RNA change from baseline of 4.31 log10 IU/mL, 4.64 log10 IU/mL, 3.94 log10 IU/mL and 4.59 log10 IU/mL in patients receiving 100 mg QD, 200 mg QD, 300 mg QD and 100 mg BID for seven days, respectively. HCV RNA declined consistently throughout the 7-day dosing period, with no viral breakthrough. For the 16 subjects who received PSI-938 200 mg QD or 300 mg QD for 7 days, more than half (9 of 16) of the subjects on PSI-938 monotherapy achieved HCV RNA below the limit of detection (15 IU/mL) and 11 out of 16 patients achieved HCV RNA below the limit of quantification (43 IU/mL).

PSI-938 Pharmacokinetic and Safety Summary

Pharmacokinetics parameters were similar between healthy subjects in the single ascending dose study and HCV infected patients in the seven-day multiple ascending dose study. PSI-938 at all doses provided good systemic exposure and continue to support once-daily administration.

PSI-938 was generally safe and well tolerated across all doses studied to date with no serious adverse events and no discontinuations. There were no dose-related trends in adverse events through the dose escalations, no grade 4 treatment emergent laboratory changes, and no trends in clinical laboratory abnormalities.

PSI-938 SAD and preclinical data

The Phase 1a single ascending dose study conducted earlier this year assessed single doses of PSI-938 ranging from 100 mg to 1600 mg or matching placebo in healthy male and female volunteers. No dose-limiting toxicity was identified. Safety and pharmacokinetic data supported progression of PSI-938 to the 7-day monotherapy trial. Full data from the SAD trial will be presented at the upcoming AASLD Annual Liver Meeting in Boston, MA, October 29-November 3, 2010 (poster #1890).

Preclinically, both PSI-938 and Pharmasset's other guanosine analog, PSI-661, which is in late preclinical development, have demonstrated similar potency against wild-type HCV or HCV with the S282T mutation, which can be selected by RG7128 and PSI-7977 in vitro. Although the S282T has not been detected in treatment-naive individuals with HCV, nor selected in clinical trials with any of Pharmasset's nucleoside/tide analogs, the potential for interferon-sparing regimens may increase the focus on antivirals with complementary resistance profiles.

"We are very encouraged by the preliminary efficacy and safety data with PSI-938, our purine nucleotide analog for HCV," said Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "These data provide the first confirmatory evidence that a nucleoside/tide analog can exhibit substantial early antiviral activity in monotherapy as has been observed with compounds in other DAA classes. Unlike other classes of DAAs to date, our nucleotide analogs also provide a higher barrier to resistance and clinically-validated antiviral activity across a broad range of HCV genotypes, characteristics not yet demonstrated with other classes of DAA. We continue to believe that nucleoside/tide analogs will become the backbone of HCV therapy. In addition, similar to HIV, the combination of two complementary nucleoside/tide analogs could provide a differentiated therapy for HCV patients in the future."

PSI-938 and PSI-7977 Combination Study

In this quarter, Pharmasset plans to initiate a short-term study to assess the combination of PSI-938 and PSI-7977. The trial will be conducted in the US, as a blinded, randomized, placebo-controlled study in approximately 50 patients chronically infected with HCV genotype 1. The primary objective will be to assess the safety, tolerability, and pharmacokinetics of PSI-938 and PSI-7977 alone and in combination. Preliminary results are expected in the first half of 2011.

Conference Call and Webcast

Members of Pharmasset's management team will host a conference call today, October 28, 2010, at 8:00 a.m. ET to discuss the preliminary results of the multiple ascending dose trial with PSI-938. Investors may listen to the webcast of the conference call live on the "Events & Presentations" section of Pharmasset's website, www.pharmasset.com. Alternatively, investors may listen to the call by dialing 877-771-7028 from locations in the U.S. and 973-200-3092 from outside the U.S. The webcast replay will be available for at least 72 hours following the call.

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 on the development of oral therapeutics for the treatment of hepatitis C virus (HCV). Our research and development efforts focus on nucleoside/tide analogs, a class of compounds which act as alternative substrates for the viral polymerase, thus inhibiting viral replication. We currently have four clinical-stage product candidates. RG7128, a cytosine nucleoside analog for chronic HCV infection, is in two Phase 2b clinical studies in combination with Pegasys(R) plus Copegus(R) and is also in the INFORM studies, the first series of studies designed to assess the potential of combinations of small molecules without Pegasys(R) and Copegus(R) to treat chronic HCV. These clinical studies are being conducted through a strategic collaboration with Roche. Our other clinical stage HCV candidates include PSI-7977, an unpartnered uracil nucleotide analog presently in a Phase 2b study, and PSI-938, an unpartnered guanosine nucleotide analog in Phase 1. We also have in our pipeline an additional purine nucleotide analog, PSI-661, in advanced preclinical development. Racivir, for the treatment of HIV, has completed a Phase 2 clinical study.

Pegasys® and Copegus® are registered trademarks of Roche.