Excerpts from a "Hepatology" commentary on the future of Taribavirn - by Paul Kwo, MD and Rakesh Vinayek MD.... (Thank you NATAP.org)

The Next Step for Taribavirin - Commentary        Hepatology Sept 24 2010   Paul Y Kwo and Rakesh Vinayek   Excerpts:   In this issue of Hepatology, Poordad and colleagues report the SVR rates of weight-based TBV compared to weight-based RBV in naïve genotype I HCV-infected patients. In this US Phase 2b randomized open-label controlled parallel group study, 278 naïve genotype I subjects were randomized to TBV 20, 25, or 30 mg/kg/day or RBV 800-1400 mg, pegIFN alfa-2b for 48 weeks. An early virologic response (EVR) defined as undetectable HCV RNA (< 39 I.U. at Week 12) or a 2 log reduction in baseline HCV RNA, the primary endpoint of the study, was comparable across all treatment arms. The SVR rate was also preserved across all treatment arms, ranging between 27 and 28%. The overall response rates in this trial were low though the high percentage of African Americans (20%) and those with advanced fibrosis may explain the lower SVR rates. It would be interesting to know the IL-28 composition of the treatment population as there may have been a high prevalence of unfavorable Il-28 CT or TT genotype patients present which could also explain in part the low SVR rates.   While SVR rates were not different between treatment arms, a lower relapse rate was seen with an incremental increase in the dose of TBV, similar to that observed with RBV. In addition, the per protocol SVR rates were substantially higher again demonstrating the importance of adherence to therapy to provide optimal SVR rates in the genotype I population. Lower anemia rates (defined as hemoglobin < 10 grams/dL) were seen in the TBV arms throughout the entire 48 weeks, with cumulative anemia rates being significantly lower across the two lower TBV arms (20 mg and 25 mg/kg) compared to weight-based RBV. However, as the dose of TBV was increased to 30 mg/kg, the anemia rate was numerically lower than with RBV but was not significant, other than at week 4, suggesting that higher doses TBV may lead to similar rates of anemia and other side effects observed with RBV. The pharmacokinetic analysis showed that this effect correlated with RBV plasma exposure. Furthermore, within the first 12 weeks of treatment when maintaining the dose of RBV has been shown to be most critical, significantly lower rates of anemia were observed with TBV compared with RBV (7-15% vs 24%, respectively) within the first 12 weeks of treatment although this translated clinically into comparable, not superior SVR rates in the TBV arms. Even though, fewer patients treated with TBV required dose reduction (13-28%) compared to 32% patients treated with RBV, it should also be noted that dropout rates for anemia were not different amongst the TBV arms compared to the RBV arms in this study, though this may be due to relatively small sample size. There does appear to be an increased rate of diarrhea in the TBV arms compared to RBV. This may be significant as some DAA agents are also associated with increased GI side effects and, as we enter an era where DAA agents and other drugs are combined, side effects could limit the efficacy of multi-drug combinations. Finally, while not statistically significant, insomnia was numerically higher in the TBV arms and should be a side effect of some concern in future trials. Thus, as significantly fewer dose reductions were noted only in the TBV 20 mg/kg arm as compared to the higher doses of TBV and RBV with similar SVR rates, the dose of 20 mg/kg may also require study in the future with DAA agents  So what does the future hold for taribavirin? Phase 2 and ongoing Phase 3 trials strongly suggest that DAA agents will be added to pegIFN and RBV to obtain higher SVR rates, albeit at the expense of higher rates of anemia and other side effects. Currently, the role of ESAs in the treatment of HCV with DAA agents is not yet precisely defined, though we await the results of ongoing trials. The inclusion of TBV into the HCV armamentarium may serve as an opportunity to combine with pegIFN and DAA agents to reduce the rates of anemia and avoid RBV dose reduction or introduction of ESAs. As RBV reduction or removal of RBV is associated with increased rates of breakthrough and development of resistance to DAA agents, TBV may have a role in populations particularly sensitive to ribavirin-related anemia , including those with advanced liver disease, older patients, patients who have undergone liver transplantation, HIV/HCV coinfected individuals, patients with hemoglobulinopathies and chronic renal failure 20. However, with the commencement of several trials comprising of multiple combinations of DAA agents with and without pegIFN/RBV, and the development of newer protease inhibitors with potentially lower rates of anemia, the role of TBV remains less precisely defined and could potentially have a finite life cycle. Studies with combinations of DAA agents with PEGIFN/RBV have been initiated and these studies will multiply. Whether or not RBV (and TBV) can be eliminated altogether remains to be determined.  Particularly in those patients with unfavorable treatment characteristics, RBV may remain a part of our therapeutic armamentarium for years to come; and, if so, TBV could be an option which has the potential to limit toxicity and potentially reduce costs. The ideal study may be to combine TBV with a DAA agent and pegIFN and compare it to RBV, to see if SVR rates can be preserved or improved by minimizing dose reductions and reducing the emergence of resistance. Given the long wait between the approval of pegIFN and RBV and yet unapproved DAA agents, one should not discount the potential contribution of TBV. Many promising agents have already been stopped in development due to lack of efficacy or toxicity 21-22. Thus, if TBV can be shown to preserve or improve efficacy rates in combination with DAAs and Peg IFN, with lower rates of anemia, the use of TBV in these clinical settings would be a welcome addition to the HCV armamentarium as we begin to expand the HCV populations that we treat.

First micro-RNA-Targeted Drug to treat HCV enters Phase II Clinical Trials...

HOERSHOLM, Denmark and SAN DIEGO, September 22, 2010 /PRNewswire/ --

- Santaris Pharma A/S initiates Phase 2a clinical trial with miravirsen (SPC3649) to assess safety and tolerability in treatment-naive patients with chronic Hepatitis C

- miravirsen is the first microRNA-targeted drug to receive Investigational New Drug (IND) acceptance from FDA, paving the way to conduct Phase 2 trials for treatment of Hepatitis C in the United States

- Developed using Santaris Pharma A/S Locked Nucleic Acid (LNA) Drug Platform, miravirsen inhibits miR-122, a microRNA important for Hepatitis C viral replication, thereby significantly reducing the levels of Hepatitis C virus

- Due to unique mechanism-of-action, miravirsen holds promise as new treatment option for Hepatitis C patients, including the 50% of patients not responsive to current standard of care(1)

Santaris Pharma A/S, a clinical-stage biopharmaceutical company focused on the discovery and development of RNA-targeted therapies, today announced that it has advanced miravirsen (SPC3649), the first microRNA-targeted drug to enter clinical trials, into Phase 2 studies to assess the safety and tolerability of the drug in treatment-naive patients infected with the Hepatitis C virus (HCV).

Paving the way to conduct the first clinical trials of a microRNA-targeted drug in the United States, Santaris Pharma A/S also received acceptance of its Investigational New Drug (IND) application from the U.S. Food and Drug Administration (FDA). In addition to the United States, the Phase 2a clinical trials will be conducted in the Netherlands, Germany, Poland, Romania, and Slovakia.

The World Health Organization estimates about 3% of the world's population has been infected with HCV and that some 170 million are chronic carriers at risk of developing liver cirrhosis and/or liver cancer(2). Approximately 3-4 million Americans are chronically infected with an estimated 40,000 new infections per year(1). In Europe, there are about 4 million carriers(2). The current standard of care, pegylated interferon in combination with ribavirin, is effective in only about 50% of those treated(1).

Developed using Santaris Pharma A/S proprietary Locked Nucleic Acid (LNA) Drug Platform, miravirsen is a specific inhibitor of miR-122, a liver specific microRNA that the Hepatitis C virus requires for replication. Miravirsen is designed to recognize and sequester miR-122, making it unavailable to the Hepatitis C virus. As a result, the replication of the virus is effectively inhibited and the level of Hepatitis C virus is reduced.

"Advancing miravirsen, the first microRNA-targeted drug to enter clinical trials, into Phase 2 studies in patients with Hepatitis C demonstrates Santaris Pharma A/S leadership in developing RNA-targeted medicines," said Arthur A. Levin, Ph.D., Vice President, Chief Development Officer and President, US Operations. "Receiving IND acceptance from the FDA to conduct the first clinical trials with a microRNA-targeted drug in the United States brings Santaris Pharma A/S one step closer to potentially providing a growing number of patients chronically infected with HCV with a more effective and better tolerated treatment option."

The LNA Drug Platform is the only technology with both mRNA and microRNA targeted drugs in clinical trials, reinforcing the broad utility of the platform. The unique combination of small size and very high affinity, which is only achievable with LNA-based drugs, allows this new class of drugs to potently and specifically inhibit RNA targets in many different tissues without the need for complex delivery vehicles. LNA-based drugs are a promising new type of therapy that enables scientists to develop drugs to attack previously inaccessible pathways.

"Using our LNA Drug Platform to advance the first microRNA-targeted therapy into human clinical trials was certainly a scientific breakthrough," said Henrik Oerum, Ph.D., Vice President and Chief Scientific Officer of Santaris Pharma A/S. "We are extremely pleased with the results of the Phase I trials and excited to progress miravirsen into Phase 2 clinical trials. Because of its unique mechanism of action and tolerability profile, miravirsen has the potential to be an effective treatment option for patients with HCV."

The randomized, double-blind, placebo-controlled, ascending multiple-dose Phase 2a study will assess the safety and tolerability of miravirsen and is designed to enroll up to 55 treatment-naive patients with chronic Hepatitis C virus genotype 1 infection. Secondary endpoints include pharmacokinetics of miravirsen and its effect on viral load. Miravirsen will be given as subcutaneous injections weekly or every other week for four weeks.

Data from Phase 1 clinical studies with miravirsen in healthy volunteers show that the drug is well tolerated. A recent study published in Science demonstrated that miravirsen successfully inhibited miR-122 and dramatically reduced Hepatitis C virus in the liver and in the bloodstream in chimpanzees chronically infected with the Hepatitis C virus(3). Miravirsen provided continued efficacy in the animals up to several months after the treatment period with no adverse events and no evidence of viral rebound or resistance.

In addition to miravirsen, Santaris Pharma A/S has a robust product pipeline targeting mRNAs and microRNAs both internally as well as in partnerships and collaborations with miRagen Therapeutics (cardiovascular diseases), Shire plc (rare genetic disorders), Pfizer (undisclosed therapeutic areas), GlaxoSmithKline (viral disease) and Enzon Pharmaceuticals (oncology).

About microRNAs

MicroRNAs have emerged as an important class of small RNAs encoded in the genome. They act to control the expression of sets of genes and entire pathways and are thus thought of as master regulators of gene expression. Recent studies have demonstrated that microRNAs are associated with many disease processes. Because they are single molecular entities that dictate the expression of fundamental regulatory pathways, microRNAs represent potential drug targets for controlling many biologic and disease processes.

About Locked Nucleic Acid (LNA) Drug Platform

The LNA Drug Platform and Drug Discovery Engine developed by Santaris Pharma A/S combines the Company's proprietary LNA chemistry with its highly specialized and targeted drug development capabilities to rapidly deliver potent single-stranded LNA-based drug candidates against RNA targets, both mRNA and microRNA, for a range of diseases including metabolic disorders, infectious and inflammatory diseases, cancer and rare genetic disorders. The LNA Drug Platform overcomes the limitations of earlier antisense and siRNA technologies to deliver potent single-stranded LNA-based drug candidates across a multitude of disease states. The unique combination of small size and very high affinity, which is only achievable with LNA-based drugs, allows this new class of drugs to potently and specifically inhibit RNA targets in many different tissues without the need for complex delivery vehicles. LNA-based drugs are a promising new type of therapy that enables scientists to develop drugs to attack previously inaccessible clinical pathways. The most important features of LNA-based drugs include excellent specificity, providing optimal targeting; increased affinity to targets providing improved potency; and strong pharmacology upon systemic delivery without complicated delivery vehicles.

About Santaris Pharma A/S

Santaris Pharma A/S is a privately held clinical-stage biopharmaceutical company focused on the discovery and development of RNA-targeted therapies. The Locked Nucleic Acid (LNA) Drug Platform and Drug Discovery Engine developed by Santaris Pharma A/S combine the Company's proprietary LNA chemistry with its highly specialized and targeted drug development capabilities to rapidly deliver potent single-stranded LNA-based drug candidates across a multitude of disease states. The Company's research and development activities focus on infectious diseases and metabolic disorders, while partnerships with major pharmaceutical companies include a range of therapeutic areas including cancer, cardiovascular disease, infectious and inflammatory diseases, and rare genetic disorders. The Company has strategic partnerships with miRagen Therapeutics, Shire plc, Pfizer, GlaxoSmithKline, and Enzon Pharmaceuticals. As part of its broad patent estate, the Company holds exclusive worldwide rights to all therapeutic uses of LNA. Santaris Pharma A/S, founded in 2003, is headquartered in Denmark with operations in the United States. Please visit http://www.santaris.com for more information.

FDA issues draft guidelines for STAT-C/DAA development ...

The FDA has just issued a draft of potential guidelines for companies developing STAT-C / DAA drugs for Hepatitis C.  This is for comment only, the FDA will issue their final guidelines toward the end of the year.  The draft can be viewed on the FDA website.

LabCorp Enhances HCV Testing Services with the Launch of IL-28B Test

Assay is Commercially Available for Patient Testing and Clinical Trials BURLINGTON, N.C.--(BUSINESS WIRE [1])-- Laboratory Corporation of America^® Holdings (LabCorp^®) (NYSE: LH) announced today the nationwide availability of a genetic test to detect the presence of a single polymorphism within the IL-28B gene that has been reported to help predict a person’s response to certain hepatitis C virus (HCV) therapies.

“This test represents an important addition to the management and treatment of HCV infections, and complements the current company test portfolio for this disease,” indicated Dr. Mark Brecher, LabCorp’s Chief Medical Officer. “The ability to detect the polymorphism within the IL-28B gene may help predict the response to treatments, leading to an improvement in patient care and a reduction in treatment costs.”
An estimated 3.2 million people in the United States and 170 million people worldwide are infected with HCV. The recommended treatment regimen for chronic infection includes pegylated interferon-based therapies. However, some patients experience limited efficacy, treatment is often poorly tolerated and the side effects prevent some patients from completing therapy. Therefore, identifying patients who may be likely to have a favorable response to treatment is a high priority.

The importance of the IL-28B genetic polymorphism was first reported in the journal Nature (September 2009) by scientific teams from Merck and Duke University. Specific variants in this gene have been associated with an approximately 2-3 fold greater rate of sustained viral suppression in response to treatment with combination pegylated interferon alfa/ribavirin therapy among patients infected with HCV genotype 1 with a CC genotype as compared with either the CT or TT genotypes. HCV genotype 1 is the most common form of the virus, accounting for approximately 70 percent of HCV cases in the U.S.

The test is now available for patient testing through LabCorp’s Centers of Excellence, Monogram Biosciences and The Center for Molecular Biology and Pathology (CMBP). The test is also available through Esoterix Clinical Trials Services for clinical trials. LabCorp has licensed global rights to this marker from Merck.

Viral Matters on Twitter & LinkedIn...

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The Street speaks: Forbes article on Vertex lead over Merck in STAT-C/DAA drugs...

Vertex Maintains Lead Over Merck In Hepatitis C

By MATTHEW HERPER

Vertex Pharmaceuticals looks to be the big winner in the race to develop new treatments for hepatitis C. Analysts on Wall Street have moved on to worrying how big Vertex will win, and what that leaves for its main competitor, Merck.

New data, released via press release today after the stock market closed, show that 65% of patients who were not cured by previous treatments did have an overall cure, known as a sustained virologic response (SVR), on Vertex’s drug telaprevir. This result is at the top end of Wall Street’s expectations, and Vertex shares rose 1.4% in after-hours trading.


“These are the kinds of advances we see in internal medicine only once every ten to fifteen years,” said Stefan Zeuzem, who ran the study for Vertex’s European marketing partner, Johnson & Johnson. He is chief of the department of medicine at JW Goethe University Hospital in Frankfurt.

Thirty-one percent of telaprevir patients who had gotten no benefit at all from previous treatments with the current hepatitis C regimen, a combination of interferon and antiviral drug ribavirin, had SVRs. Only 5% of these “null responders” got an SVR when treated with interferon, ribavirin, and a placebo. So giving telaprevir increased the response rate six-fold.

Still, this 31% number was a little worse than Wall Street expected. Mark Schoenebaum, who covers Vertex for International Strategy & Investment, had predicted that 55% of “nulls” would get an SVR. (Update: Schoenebaum said on a conference call in August this was the “upper limit” of what investors should expect.) Lawrence Biegelsen, an analyst who covers J&J for Wachovia, and pegged the number at a something like 40% of the null patients.

But in a note to investors this evening, Schoenebaum called today’s result “very strong.” In its study of patients who had been pre-treated, he wrote, Merck’s boceprevir had achieved an SVR rate of 66%, about in line with the 65% achieved by telaprevir. But the comparison is deceiving, he wrote, because Merck’s trial design essentially excludes “nulls.” The fair comparison, he writes, is the 78% SVR rate telaprevir achieved in patients who saw their virus levels go down during a previous treatment, but were not cured.
Still, Schoenebaum says that Vertex shares are fairly valued at their current price. He argues that newer agents will supplant telaprevir much faster than anyone expects. His thesis is that, as occurred with HIV, new regimens of convenient combination pills will emerge and win much of the market. He has written that Bristol-Myers Squibb could be a major threat in this regard. Vertex is working at developing combinations for exactly this reason.

Hepatitis C drugs are tough to take, causing flu-like side effects and anemia. Telaprevir can cause a significant rash, which is serious in 5% of patients.

When the first drugs to treat hepatitis C emerged they cured only 6% of patients. Current regimens cure about 40% of patients with the version of the disease included in this trial. New treatments like boceprevir and telaprevir promise to increase that to 60% or 70%. That really is amazing progress.

Idenix compounds put on 'clinical hold' after three serious adverse events...

CAMBRIDGE, Mass., Sept. 7 /PRNewswire-FirstCall/ -- Idenix Pharmaceuticals, Inc. (Nasdaq: IDIX), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today announced that the company received verbal notice on Friday, September 3, 2010 from the U.S. Food and Drug Administration (FDA) that the IDX184 and IDX320 programs have been placed on clinical hold. A clinical hold is an order issued by the FDA to the sponsor to delay a proposed clinical investigation or to suspend an ongoing investigation. This decision was made after Idenix notified the FDA of three serious adverse events that occurred during a drug-drug interaction study of the combination of IDX184 and IDX320 in healthy volunteers. These observed serious adverse events were elevated liver function tests detected in three subjects during post exposure safety visits. The liver function tests have returned to nearly normal levels in all three subjects during follow-up. All planned studies of IDX184 and IDX320 to date have been completed and there are currently no healthy volunteers or patients receiving IDX184 or IDX320. Idenix will submit full data to the FDA from recently completed preclinical and clinical studies, including 3-month chronic toxicology studies of IDX184, a 14-day study of IDX184 in combination with pegylated interferon/ribavirin (PegIFN/RBV), a 3-day proof-of-concept study of IDX320 in hepatitis C (HCV) infected patients, and the IDX184 and IDX320 drug-drug interaction study in healthy volunteers in order to assess next steps in the development of both compounds.

"We have not yet received a formal letter from the FDA, nor has the Agency had an opportunity to review the safety and efficacy data from recently completed clinical trials with IDX184 and IDX320. Based upon our discussions with the Agency, we are primarily focused on three cases of elevated liver function tests observed during our drug-drug interaction study of the combination of IDX184 and IDX320 in healthy volunteers," said Jean-Pierre Sommadossi, Ph.D., Idenix Chairman and Chief Executive Officer. "Based upon the safety and antiviral activity we observed in the IDX184 14-day study and the IDX320 3-day proof-of-concept study, both in HCV-infected patients, we remain committed to the future potential of these drug candidates. We will work closely with independent experts and our external safety committee to better understand the cause of these serious adverse events in the combination study of IDX184 and IDX320 and to provide the FDA with more information in order to expedite their review and resolve this matter as quickly as possible."
Full data presentations of IDX184, IDX320 and IDX375 studies will be presented at the annual meeting of the American Association for the Study of Liver Diseases (AASLD), which will be held at the end of October in Boston.

Phase I: IDX184/IDX320 Combination
Idenix completed a two-week Phase I, randomized, double-blind, placebo-controlled study to evaluate the safety and pharmacokinetic drug-drug interaction between IDX320 and IDX184 in healthy volunteers. Two cohorts were evaluated in the study with 10 subjects in each cohort randomized eight to active drug and two to placebo. Subjects in the first cohort received 400 mg once-daily of IDX320 for the first week, subsequently adding 100 mg once-daily of IDX184 for the second week. Subjects in the second cohort received 100 mg once-daily of IDX184 plus placebo for the first week, subsequently adding 400 mg once-daily of IDX320 for the second week. The combination of IDX184 and IDX320 was generally safe and well tolerated during the 14 days of treatment. Liver function abnormalities deemed to be serious adverse events were detected in three subjects during the post exposure safety visits. Liver function tests in these subjects have returned to nearly normal during follow-up. Pharmacokinetic drug-drug interactions between IDX184 and IDX320 were not considered to be clinically significant. Neither the plasma exposure of IDX184 and its metabolite, 2'-methylguanosine, nor IDX320 plasma exposure explain these three serious adverse events.

Phase IIa: IDX184, a liver-targeted HCV nucleotide prodrug
This 14-day, Phase IIa clinical trial evaluated 50 to 200 mg doses of IDX184 in combination with PegIFN/RBV in treatment-naive HCV genotype 1-infected patients. At Day 14, mean (+/- standard deviation) viral load reductions were 1.5 (+/- 1.3) logs for placebo (n=16), 2.7 (+/- 1.3) logs for 50 mg IDX184 QD (n=16), 4.0 (+/- 1.7) logs for 50 mg IDX184 BID (n=8), 4.2 (+/- 1.9) logs for 100 mg QD (n=8), 4.1 (+/- 1.2), for 150 mg QD (n=15), 4.1 (+/-1.4) logs for 100 mg BID (n=8) and 3.7 (+/- 1.2) logs for 200 mg QD (n=8). In the cohorts of 100 mg, 150 mg, and 200 mg daily doses in combination with PegIFN/RBV, 50%, 40% and 25%, respectively, of patients achieved undetectable virus levels (<15 IU/mL) by Day 14. Liver injury parameters (ALT and AST) improved with all doses of IDX184. The side effect profile of the three drug combination was consistent with the known side effect profile of PegIFN/RBV alone. The most common adverse events reported were fatigue, myalgia, headache and nausea.
Phase I/II: IDX 320, an HCV protease inhibitor

This randomized, parallel-arm, double-blind, placebo-controlled proof-of-concept trial evaluated the safety, tolerability, antiviral activity and pharmacokinetics of IDX320 in treatment-naive HCV genotype 1-infected patients. Thirty patients were randomized equally and received placebo, 50, 100, 200 or 400 mg of IDX320 orally once-a-day for three days. One cohort of eight patients was randomized to receive 200 mg IDX320 BID or placebo. At Day 3, mean (+/- standard deviation) viral load reductions were 0.1 (+/- 0.15) logs for placebo (n=5), 2.6 (+/-0.49) logs for 50 mg IDX320 QD (n=5), 3.1 (+/- 0.29) logs for 100 mg QD (n=6), 3.1 (+/- 0.41) logs for 200 mg QD (n=6) and 3.3 (+/- 0.28) logs for 400 mg QD (n=7). At daily doses of placebo, 50, 100, 200, and 400 mg, 0%, 20%, 67%, 67% and 86%, respectively, of patients achieved greater than or equal to 3 log reduction in HCV RNA at the end of treatment. In the 200 mg IDX 320 BID cohort at Day 3, mean (+/- standard deviation) viral load reductions were 3.8 (+/- 0.52) logs and all patients (100%) achieved greater than or equal to 3 log reduction in HCV RNA. In the 3-day proof-of-concept study, IDX320 was generally safe, well tolerated, and demonstrated potent, dose-related HCV antiviral activity.

Phase I: IDX375, an HCV non-nucleoside polymerase inhibitor
Idenix has an ongoing Phase I clinical trial in healthy volunteers evaluating single doses of the free acid form of IDX375 ranging from 200 to 1200 mg per day. Overall, IDX375 achieved pharmacologically relevant drug exposure and was well tolerated for doses up to 1200 mg for one day in healthy subjects. In the fourth quarter of 2010, Idenix plans to initiate a 3-day proof-of-concept trial in treatment-naive genotype 1 HCV-infected patients.

Conference Call Information
Idenix will hold a conference call today at 8:30 a.m. ET. To access the call please dial (800) 471-3635 U.S./Canada or (706) 758-9475 International and enter passcode 99538089. A replay of the conference call and webcast will be available until September 21, 2010. To access the replay, please dial (800) 642-1687 U.S./Canada or (706) 645-9291 International and enter the passcode 99538089.
About HCV

Inhibitex completes phase 1a trial of nucleotide polymerase inhibitor INX-189

Proof-of-Concept Trial in Patients with Chronic Hepatitis C Planned for Q4 2010

ATLANTA--(BUSINESS WIRE)--Sep 1, 2010 - Inhibitex, Inc. (Nasdaq: INHX), announced today that it has successfully completed a Phase1a, first-in-man, single ascending dose trial of INX-189, its nucleotide polymerase inhibitor in development for the treatment of chronic hepatitis C (HCV) infections. In this trial, 42 healthy volunteers received either a single oral dose of INX-189, ranging from 3 mg to 100 mg, or placebo. The Company plans to present detailed results from this trial during a future scientific meeting. Preliminary data from the trial are as follows:

• INX-189 was generally well tolerated at all dose levels;
• No drug-related serious adverse events;
• No dose-related trends in frequency or type of adverse events; adverse events occurring in more than one subject were headache and nasal congestion;
• No grade II or higher laboratory abnormality adverse events or clinically significant changes in ECGs; and
• Pharmacokinetic data supports INX-189's potential for once daily (QD) dosing.

“We are encouraged with the initial safety and pharmacokinetic profile of INX-189 in this first-in-man trial,” stated Dr. Joseph Patti, Senior Vice President and Chief Scientific Officer of Inhibitex, Inc. “Based upon the pharmacokinetics observed in this study, we continue to believe that INX-189 has the potential to demonstrate antiviral activity with a low once-daily dose, and we look forward to assessing its ability to reduce HCV RNA viral loads in patients with chronic hepatitis C in a Phase 1b multiple ascending dose trial we plan to start in the fourth quarter.”

About Inhibitex

Inhibitex, Inc., headquartered in Alpharetta, Georgia, is a biopharmaceutical company focused on developing products to prevent and treat serious infectious diseases. The Company's pipeline includes FV-100, which is in Phase II clinical development for the treatment of shingles, and INX-189, a nucleotide polymerase inhibitor in development for the treatment of chronic hepatitis C infections. The Company also has additional HCV nucleotide polymerase inhibitors in preclinical development and has licensed the use of its proprietary MSCRAMM^® protein platform to Pfizer for the development of staphylococcal vaccines. For additional information about the Company, please visit www.inhibitex.com.