Anadys Pharmaceuticals ANA598 update - SVR 12 in Phase II looking good!

SAN DIEGO, July 29 /PRNewswire-FirstCall/ -- Anadys Pharmaceuticals, Inc. (Nasdaq: ANDS) today announced that six of six patients (100%) in the ANA598 200 mg twice daily (bid) arm who were randomized to stop all treatment at Week 24 in an ongoing Phase II trial maintained undetectable levels of virus 12 weeks after stopping treatment, referred to as Sustained Virological Response 12, or SVR12.

The Company also reported that all available patients from the ANA598 200 mg arm who were previously reported to have undetectable levels of virus at Week 24 and continued on pegylated interferon and ribavirin (current standard of care, or SOC) also maintained undetectable levels of virus at Week 36.  In addition, all patients from the ANA598 400 mg arm who were previously reported to have undetectable levels of virus at Week 12 and continued on SOC maintained undetectable levels of virus at Week 24.  ANA598, Anadys' direct-acting antiviral or DAA, is being developed to treat hepatitis C and is in an ongoing Phase II trial in combination with pegylated interferon and ribavirin. 

"The SVR12 data reported today for ANA598 are highly encouraging," said Steve Worland, Ph.D., President and CEO of Anadys. "These data illustrate the potential for HCV patients to be successfully treated with shortened courses of treatment, reflecting the continuing benefit of ANA598 post-therapy. We believe these data, coupled with the excellent barrier to resistance demonstrated in this trial as well as the favorable safety and tolerability, confirm ANA598's position as one of the most attractive agents in Phase II HCV development today." 

The six patients who stopped all treatment at Week 24 were part of an investigation of response-guided treatment duration for ANA598 in which patients who had achieved undetectable levels of virus (<15 IU/mL) at Weeks 4 and 12 were randomized 1:1 to stop all treatment at Week 24 or Week 48. In addition to the six patients who stopped treatment at Week 24, six patients in the 200 mg bid arm are continuing to receive SOC alone through Week 48 for comparison purposes.  Additionally, 14 patients from the ANA598 400 mg bid arm and 4 patients from the control arm (receiving placebo plus SOC) met the stopping criteria and have been randomized to stop all treatment at Week 24 or 48.  The initial post-treatment results from these latter arms are expected later this year for those patients who stopped therapy at Week 24.

Conference Call Webcast and Slides

Anadys will hold a conference call and webcast today, Thursday, July 29, 2010 at 8:30 a.m. Eastern Daylight Time to discuss the post-treatment results from the ongoing Phase II combination study and Anadys' second quarter 2010 financial results. A live webcast of the call, including accompanying slides, will be available online at www.anadyspharma.com.  A telephone replay with slides will also be available approximately one hour after completion of the call.  To access the telephone replay, dial 888-286-8010 (domestic) or 617-801-6888 (international), passcode 28631163.  The webcast and telephone replay will be available through August 12, 2010.

Phase II Combination Study

In the ongoing Phase II study, approximately 90 treatment-naive genotype 1 HCV patients have received ANA598 or placebo in combination with Pegasys (peginterferon alfa-2a) and Copegus® (ribavirin, USP) for 12 weeks at dose levels of 200 mg bid or 400 mg bid, each with a loading dose of 800 mg bid on day one.  After week 12, patients are to continue receiving SOC.  Patients who achieved undetectable levels of virus at weeks 4 and 12 were randomized to stop all treatment at week 24 or 48.  The primary endpoint of the study is the proportion of patients who achieve undetectable levels of virus at week 12 (defined as complete Early Virological Response, or cEVR). Additional endpoints include safety and tolerability as well as the proportion of patients with undetectable levels of virus at week 4 (defined as Rapid Virological Response, or RVR).  Patients will be followed for 24 weeks after stopping therapy to determine the rate of Sustained Virological Response, or SVR.  Approximately 90 patients have been enrolled in this study â?? with approximately 30 patients receiving ANA598 plus SOC at each dose level and 30 patients receiving placebo plus SOC.  The study is being managed by the Duke Clinical Research Institute (DCRI) and is being conducted at a number of clinical sites in the United States.

About ANA598

ANA598, a direct-acting antiviral or DAA, is a non-nucleoside inhibitor of the HCV RNA polymerase and is wholly owned by Anadys.  In an ongoing Phase II study in which HCV patients received ANA598 at 200 mg bid or 400 mg bid in combination with interferon and ribavirin for twelve weeks, both dose levels showed comparable cEVR rates of 73-75% and a favorable safety profile.  In a previous Phase I study, ANA598 demonstrated potent antiviral activity, including median end-of-treatment declines in viral load ranging from 2.4 to 2.9 log10 in a three day monotherapy study in treatment-naive genotype 1 patients. ANA598 has also demonstrated a very favorable resistance profile.

Anadys has completed two long-term chronic toxicology studies of ANA598 (26 weeks duration in rats and 39 weeks duration in monkeys). The No Observed Adverse Effect Level, or NOAEL, is 1000 mg/kg, the highest dose tested, in both the rat and monkey.  The completed toxicology studies support the ongoing Phase II clinical study as well as future clinical studies of longer duration.

Anadys has presented in vitro data supporting the use of ANA598 in combination with interferon-alpha as well as with other anti-HCV agents currently in development that act through diverse mechanisms. In particular, data has shown that ANA598 is synergistic in vitro with interferon-alpha as well as representative HCV protease inhibitors, polymerase inhibitors, NS5A inhibitors and cyclophilin inhibitors.  In vitro combination treatment at clinically relevant concentrations of ANA598 with interferon-alpha as well as DAAs from multiple classes results in clearance of HCV RNA from cells rather than selection of resistant isolates.  Furthermore, ANA598 retains full activity in vitro against mutations conferring resistance to protease inhibitors, nucleoside polymerase inhibitors and non-nucleoside polymerase inhibitors that act at binding sites distinct from that of ANA598, while protease and nucleoside polymerase inhibitors retain full activity in vitro against mutations conferring resistance to ANA598.

ANA598 has received Fast Track Status from the FDA for the treatment of chronic hepatitis C.

Pharmasset Initiates Phase 1b Multiple Ascending Dose Clinical Trial of PSI-938 in Patients with Chronic Hepatitis C

-- PSI-938 single ascending dose study in healthy volunteers supports progression to 7 day monotherapy study in HCV infected patients -- PSI-938 was generally safe and well tolerated with no dose-limiting toxicity -- Further results from single ascending and multiple ascending dose trials are expected in the third quarter 2010

PRINCETON, N.J., July 28 /PRNewswire-FirstCall/ -- Pharmasset, Inc. (NASDAQ:VRUS) announced today that safety and pharmacokinetic data from the PSI-352938 ("PSI-938") single ascending dose study support progression to a multiple ascending dose trial with PSI-938, which has initiated dosing. PSI-938 is a guanine nucleotide analog polymerase inhibitor for the treatment of chronic hepatitis C virus (HCV) infection. This study is designed to assess the safety, tolerability and antiviral activity of PSI-938 monotherapy administered over 7 days in HCV-infected individuals.
 

"PSI-938 is the third differentiated nucleoside analog that Pharmasset has advanced into clinical development for HCV," stated Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "As with RG7128 and PSI-7977, PSI-938 demonstrates a high barrier to resistance in vitro; but unlike the cytidine and uridine analogs, PSI-938 retains equivalent potency against the S282T mutant. As the HCV field moves toward IFN-sparing, all-oral DAA combinations, we continue to believe nucleosides could become the backbone of care given these differentiating attributes and have the potential to be combined with all DAA classes."
 

PSI-938 Phase 1 Program Overview
 

The Phase 1 program is investigating the safety, tolerability and pharmacokinetics of PSI-938 in healthy subjects following escalating single doses (Phase 1a), and in patients chronically infected with HCV genotype 1 following repeat dosing for 7 days (Phase 1b). The Phase 1b study will additionally investigate hepatitis C viral dynamics and monitor for the development of drug resistance.
 

Subjects in the Phase 1a single ascending dose study received single doses of PSI-938 ranging from 100 mg to 800 mg or a matching placebo. Preliminary data from the phase 1a single ascending dose study includes:
 

--  No serious adverse events or discontinuations;
  --  No dose-related adverse events or dose-limiting toxicity;
  --  No grade III / IV lab abnormalities;
  --  No clinically significant changes in vital signs or ECGs; and
  --  PK which supports QD dosing.

A Phase 1b multiple ascending dose trial has now been initiated in treatment-naïve patients with chronic HCV genotype 1 infection. Subjects will be enrolled at multiple centers in the US and randomized to PSI-938 or placebo. Based upon the results from the first time in human study, the first dose of PSI-938 to be tested will be 100 mg administered once daily. The primary objectives of this study are to assess the safety, tolerability, pharmacokinetics and viral dynamics of PSI-938 after repeat dosing over 7 days.
 

  Results from both studies are expected in the third quarter of 2010.

  Purine and Pyrimidine Analogs

Pharmasset's purine nucleoside/tide analogs share many of the benefits of pyrimidine nucleoside/tide analogs, such as RG7128 and PSI-7977, in that they have demonstrated in vitro activity across multiple HCV genotypes, have a higher barrier to resistance than other classes of HCV small molecules in development, and, in spite of the prodrug technology, have no CYP 3A4 liability and thus a lower risk of drug interactions when combined with other direct acting antivirals targeting HCV. In addition, Pharmasset's purine analogs retain equivalent potency against wild type HCV and virus with the S282T mutation associated with in vitro resistance in other nucleoside/tide analogs in development. Furthermore, the purines are metabolized to the active triphosphate form through a different phosphorylation pathway than the pyrimidine analogs, thus decreasing the risk of competition between the two analogs for conversion to the active triphosphate. Given these characteristics, Pharmasset's purine and pyrimidine analogs have the potential to be combined as part of a future treatment regimen, which will be the focus of upcoming trials.
 

Science Shaping Our World (SHOW): Combating Drug Resistance: Lessons from HIV-1 Protease and Beyond

When: Thursday, July 29, 2010

From: 6:00 PM – 9:00 PM

Where: Microsoft New England Research & Development Center

              1 Memorial Drive             

              Cambridge, MA 02142

              Phone: 857.453.6000

 Evening Speaker: Celia A. Schiffer, Ph.D.

• Dr. Schiffer is a Professor in the Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School where her laboratory primarily studies the molecular basis for drug resistance in HIV and more recently Hepatitis C.  Dr. Schiffer’s research has focused on conceptualizing an interdisciplinary approach toward avoidance of drug resistance and she co-founded the Institute for Drug Resistance. 

July’s SHOW will focus on the development of novel strategies towards addressing drug resistance in diseases such as HIV and Hepatitis C.  As drugs that have worked in the past become less and less effective due to the emergence of drug resistant pathogen variants, how will we combat these new and emerging more lethal strains?  Through her research, Dr. Schiffer has developed a new paradigm for avoiding drug resistance that likely translates to other diseases and is the basis for the design of her novel picomolar HIV-1 protease inhibitors.

These novel inhibitors have been shown to be more potent in viral cultures of wild-type AND drug resistant viruses as compared to current leading commercially available HIV-1 protease inhibitors.  These results strongly support the premise that: through developing strategies to counter the advent of drug resistance early on in the drug design process, inhibitors can be developed that are more robust against drug resistance overall.

Please join us for an excellent evening of science, technology, and networking.  Event sign-in begins at 6:00 PM at the Microsoft New England Research & Development Center. Event pre-registration is free and required for event admittance.  Presentation will begin at 6:30 PM followed by a Q&A session with the speaker.  Following the presentation, you are invited to join us for networking and further discussion with the speaker.  Light food and refreshments will be provided. 

SHOW is brought to you by Munevar & Associates, Inc., a life science technology development and commercialization company with space provided by Microsoft New England Research & Development Center.

http://showjuly2010.eventbrite.com/

National Viral Hepatitis Roundtable reacts to NY Times take on HCV testing in recent article...

PR Newswire US - Jul. 22, 2010

WASHINGTON, July 22 /PRNewswire-USNewswire/ -- In response to today's New York Times article, "Hope against Hepatitis C," Andrew Muir, M.D., M.H.S., Director, Gastroenterology/Hepatology Research, Duke Clinical Research Institute and Steering Committee Member of the National Viral Hepatitis Roundtable (NVHR) released the following statement:

"Today's New York Times article details potential promising new drug therapies that could significantly improve the way we treat individuals infected with hepatitis C. Regrettably, the article suggests that expanded screening for hepatitis C may not be warranted. This approach is wrong and contrary to the direction in which we should and must move our health care system, particularly through improved access to care under health care reform. More than 5 million Americans are estimated to be infected with viral hepatitis B or C ?? and most are unaware they are infected as there are often few symptoms. Our health care system misses most infected individuals, who only learn that they have hepatitis C once they have progressed to liver cancer, cirrhosis, or liver failure. At that juncture, treatment options are limited and success rates are lower.

"Precisely because we do not know which individuals with hepatitis C will advance to these terrible diseases, it is critical that our public health infrastructure be modernized to achieve early detection of new infections and also to screen for individuals within specific risk groups, such as baby boomers and disproportionately affected populations. Once individuals are aware of their status, they will be empowered with this information, not only to make treatment choices, but also lifestyle choices to decrease their likelihood of disease progression and not to spread this infectious disease to others. In our current health care system, there are far too few options for diagnosis, care, and treatment. Unless or until the health care system provides access to all persons in need of hepatitis C treatment, it is important for the pharmaceutical industry to provide comprehensive compassionate care programs for those who are un/under insured.

"We can't prevent or treat what we don't know, which is why screening is critical. Access to screening would capture more infected individuals who can respond favorably to early intervention, reduce transmission, avoid needless medical expenses, and ultimately save thousands of lives annually."

NVHR is a coalition of more than 150 public, private, and voluntary organizations dedicated to reducing the incidence of infection, morbidity, and mortality from chronic viral hepatitis that afflicts more than 5 million Americans. www.nvhr.org

SOURCE National Viral Hepatitis Roundtable

NY Times article focuses on emerging treatments for Hepatitis C

Very well done article in the Business section of the NY Times was published today.  Interviewed is Dr. Diane Sylvestre from the OASIS clinic in Oakland, whose patient population consists mainly of current or recovered IV drug users.  I was at the presentation at Vertex she mentions and she makes a very valid point that the drug companies developing antiviral therapies for HCV have largely ignored 'the real face of HCV'. The industry counterpoint is that patients like Dr. Sylvestre's are challenged from a compliance standpoint, therefore not the ideal patient population to do clinical studies in.  A happy medium must be made between industry and treaters like Dr. Sylvestre.

Read the full article here: http://www.nytimes.com/2010/07/22/business/22hepatitis.html?scp=1&sq=%2b%22Centers+for+Disease+Control%22&st=nyt

Here they grow again: Achillion adds NS5A Inhibitor ACH-2928 to growing stable of anti-HCV candidate compounds

Achillion Pharmaceuticals Announces Nomination of NS5A Inhibitor as a Lead Clinical Candidate for Treatmentof HCV

ACH-2928 Demonstrates Excellent Potency Against HCV RNA Replication, Holds Potential for Combination Therapy

NEW HAVEN, Conn., Jul 22, 2010 (GlobeNewswire via COMTEX News Network) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN), a leader in the discovery and development of treatments for the most challenging infectious diseases, today announced the nomination of a lead clinical candidate in its fourth proprietary program against hepatitis C virus (HCV) infection. The candidate, ACH-2928, is an NS5A inhibitor that in preclinical studies has demonstrated excellent potency against HCV RNA replication, as well as good pharmacokinetic and safety profiles.

"The overall profile of ACH-2928 demonstrates that it is highly active and retains potency against HCV genotypes 1a and 1b, as well as across other genotypes. The compound's high potency, in the picomolar range, and its favorable pharmacokinetic properties strongly suggest once-daily dosing," said Milind S. Deshpande, Ph.D., Executive Vice President and Chief Scientific Officer of Achillion. "Importantly, we believe ACH-2928 is highly effective in combination with NS3 protease inhibitors, NS5B polymerase inhibitors, interferon and ribavirin."

Michael D. Kishbauch, Achillion's President and CEO, stated, "The nomination of this novel NS5A clinical candidate is both exciting and significant. The treatment paradigm for HCV is moving toward combination therapies, and we are now poised to pursue our own combination therapies, putting ACH-2928 together with our highly potent protease inhibitors, ACH-1625 and ACH-2684. The development of our fourth proprietary HCV program underscores the depth of our robust drug discovery expertise in this important therapeutic area. We have initiated IND-enabling testing of ACH-2928, and plan to initiate combination treatment in 2011."

"The nomination of ACH-2928 is further evidence of our expertise in HCV drug discovery and structure-based design. We continue to build discrete intellectual property estates to which we retain all commercial rights," concluded Kishbauch.

Tune in on Tuesday July 27, 2010 to get the scoop on InterMune's HCV portfolio...

InterMune to Release Second Quarter Financial Results on July 27

BRISBANE, Calif., July 20 /PRNewswire-FirstCall/ -- InterMune, Inc. (Nasdaq: ITMN) today announced that it will release second quarter 2010 financial results on Tuesday, July 27, 2010 at 4:00 p.m. Eastern time. A live conference call and webcast will be hosted by InterMune at 4:30 p.m. Eastern time that same day.

To access the live teleconference, dial 888-799-0528 (U.S.) or 973-200-3372 (international), conference ID# 85459924. To access the webcast, please log on to the company's website at www.intermune.com at least 15 minutes prior to the start of the call to ensure adequate time for any software downloads that may be required.

A replay of the webcast and teleconference will be available approximately three hours after the call. The teleconference replay will be available for 10 business days following the call and can be accessed by dialing 800-642-1687 (U.S.) or 706-645-9291 (international), and entering the conference ID# 85459924.

About InterMune

InterMune is a biotechnology company focused on the research, development and commercialization of innovative therapies in pulmonology and hepatology. InterMune has an R&D portfolio addressing idiopathic pulmonary fibrosis (IPF) and hepatitis C virus (HCV) infections. The pulmonology portfolio includes pirfenidone, for which InterMune has completed the Phase 3 CAPACITY program in patients with IPF. A Marketing Authorization Application (MAA) is under review by the European Medicines Agency (EMA). The hepatology portfolio includes the HCV protease inhibitor compound danoprevir (also known as RG7227 and ITMN-191) that entered Phase 2b in August 2009 and a second-generation HCV protease inhibitor research program. For additional information about InterMune and its R&D pipeline, please visit www.intermune.com.

SOURCE InterMune, Inc.

Idenix starts recruiting for drug-drug interaction study evaluating the combination of IDX320 and IDX184 in healthy subjects

Idenix, Inc starts recruiting phase I, double-blind, multiple-dose study to evaluate the pharmacokinetic drug-drug interaction between it's protease inhibitior IDX320 and it's polymerase inhibitor IDX184 in healthy subjects
More info here: http://bit.ly/dlDQdC

Study of VX-985 in Subjects With Chronic Hepatitis C now enrolling....

A Phase 1b study for Vertex's VX-985 protease inhibitor for HCV is now enrolling.  "A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose Study of VX-985 in Subjects With Genotype 1 Chronic Hepatitis C. "

The purpose of this study it to evaluate the safety and tolerability of VX-985 in HCV subjects. This study will also evaluate the antiviral activity and pharmacokinetic profile of VX-985.

More info here: http://www.clinicaltrials.gov/ct2/show/NCT01144936?term=Hepatitis+C&lup_s=07%2F01%2F2010&lup_e=07%2F15%2F2010&rank=36

Pfizer and Samsung Medical Center agree to collaborate on liver cancer research.

Pfizer Inc. and Samsung Medical Center said Wednesday they started a collaboration to do research on liver cancer.

The companies said they formed a partnership in June and will analyze tumors from patients in Korea. They plan to make genetic profiles that could help physicians select which therapy to use on similar patients.
New York-based Pfizer is the world's largest drugmaker in terms of revenue. Its products include the kidney cancer drug Sutent. In April it stopped a late-stage study of Sutent as a treatment for liver cancer because patients were not living as long as people who were on a competing drug, and they were more likely to suffer serious side effects.

Pfizer agreed to invest $300 million in Research and Development in South Korea in 2007, and formed a partnership with the Korea Research Institute of Bioscience and Biotechnology at the time.
Shares of Pfizer fell 9 cents to $14.70 in morning trading.

Everything you wanted to know about BMS-790052 resistance and pharmacokinetics, but were afraid to ask.

The ubiquitous Jules Levin posts slides giving a resistance overview of the highly touted BMS-790052 compound presented at the recent HCV Drug Resistance New Compounds Workshop in Boston, MA. See it all here: http://www.natap.org/2010/HCVresist/HCVresist_07.htm

So far, this is what we know:

* Once-daily NS5A Inhibitor
* Used in combo with P/R, there is an additive effect. Looks to be a good candidate for combination therapy as well - when used in combo with BMS NS5B inhibitor, BMS NS3 inhibitor and an unnamed nuc, there are both additive and synergistic effects.
* Blocks multiple stages of viral replication - inactivation of NS5A appears to take out a whole communication network between NS5A's, as they communicate with each other in a replication network.
* Nice correlation between in vitro and in vivo resistance. No surprises.
* Is there pre-existing resistance? Yep. Like the linear NS3 PIs, it appears that G1a virus are inherently more resistant to BMS-790052 than G1b. BMS suggests that "NS5A baseline sequences may provide useful information for predicting resistance emergence".
* Another big question for BMS-790052, as is for the other drugs in development, is drug interactions. As we've seen in HIV antiretroviral therapy, drug interactions are extremely important to know to prevent adverse events and fluctuations in pharmacokinetics that may compromise efficacy and lead to emergence of resistant virus.

ZymoGenetics Financial results Conference Call on August 3, 2010.

ZymoGenetics to Host Conference Call and Webcast on August 3, 2010 to Discuss Second Quarter 2010 Financial Results

SEATTLE--(BUSINESS WIRE)--Jul 12, 2010 - ZymoGenetics, Inc. (NASDAQ: ZGEN) announced today that it will report second quarter financial results on Tuesday, August 3, 2010 after market close. Following the announcement, members of the company's senior management will discuss the results and provide a corporate update.

Conference Call and Webcast Information

ZymoGenetics Second Quarter 2010 Financial Results Conference Call will be held on August 3, 2010 at 4:30 p.m. Eastern Time and may be accessed at www.zymogenetics.com or by dialing (877) 407-0778 (International: 201-689-8565). Participants should dial in to the call approximately 10 minutes prior to the scheduled start time to register. A live audio webcast and slide presentation can be accessed by going to: www.zymogenetics.com. The webcast will be archived for 60 days.

For replay, please visit www.zymogenetics.com or use the following information:

• U.S. callers: (877) 660-6853
• International callers: (201) 612-7415

Replay passcode account #: 286

Conference ID #: 353663

Medivir / Tibotec announce impressive 24-week EOT and interim SVR4 and SVR 12 Phase 2b data on TMC435 HCV protease inhibitor

Potent and consistent antiviral efficacy was demonstrated at 24-week end-of-treatment and in interim SVR4 and SVR12 results. There were no clinically relevant differences between TMC435 treatment groups and placebo for adverse events.

12-Jul-10 Medivir announced today 24-week end-of-treatment interim results from the 5-arm phase 2b response guided PILLAR study in 386 treatment-naïve patients with hepatitis C virus (HCV) genotype-1 (TMC435-C205).

TMC435 is a protease inhibitor jointly developed by Medivir and Tibotec Pharmaceuticals, dosed as one pill once daily (q.d.) to treat hepatitis C virus infections (HCV).

In the PILLAR study, 75mg or 150mg TMC435 was given for either 12 weeks or 24 weeks in combination with 24 weeks of ribavirin and pegIFNalpha-2A, the current standard of care (SOC). Patients stopped all treatment at week 24 when HCV RNA levels at week 4 were < 25 log10 IU/mL detectable or undetectable and HCV RNA levels at week 12, week 16 and week 20 were < 25 log10 IU/mL undetectable. Patients who did not meet the above response-guided criteria continued with SOC until week 48. The results showed that in the TMC435 treatment groups  83% of patients were able to stop all therapy at Week 24. 

Potent and consistent antiviral efficacy was demonstrated at 24-week end-of-treatment and in interim SVR4 and SVR12 rates with no major differences between TMC435 doses or length of triple therapy. 92% of patients taking TMC435 and Peg-IFN/RBV (SoC) achieved undetectable HCV RNA levels at week 4 and 92% at week 12 after cessation of treatment, i.e. SVR4 and SVR12. SVR4 and SVR12 data were available for 82% and 42% of the TMC435-treated patients respectively who had stopped all therapy before or at Week 24 and had completed the follow-up visits. Both the viral breakthrough rate (4.9%) and relapse rate (1.6%) were low in the TMC435 treatment groups.

TMC435 was generally safe and well tolerated with no relevant differences in adverse events (AEs) between placebo and TMC435 treatment groups. Most AEs were mild to moderate in severity and the discontinuation rate due to AEs was low and not different from placebo.

When looking at particular adverse events of interest, the incidence of rash, pruritis, GI side effects and anemia were similar in TMC435 groups and placebo and were generally mild to moderate in nature. Use of erythropoetin-stimulating agents (ESAs) was not allowed during the trial.

In laboratory parameters, there were no clinically relevant differences between any TMC435 groups and placebo except for mild bilirubin elevations. Significant decreases in transaminases (ALT and AST) were observed in all treatment groups.

Further safety and efficacy data will be presented at future scientific meetings later in 2010.

"We are extremely encouraged and excited by the efficacy and safety demonstrating that TMC435 is truly a second-generation HCV protease inhibitor," stated Bertil Samuelsson, CSO of Medivir. "We also are looking forward to the top-line data coming up from the phase 2b trial C206 (ASPIRE) in treatment-experienced patients later this year as well as start of phase 3 clinical trials in treatment-naïve patients early next year.”

Frequency of Undetectable* HCV RNA Levels During and After Treatment
[Removed graphics] See PDF for table

About TMC435 clinical trial programs
TMC435 is a protease inhibitor jointly developed by Medivir and Tibotec Pharmaceuticals to treat hepatitis C virus infections (HCV).

TMC435 is currently being developed in three phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215) in G1 treatment-naïve and in G1 patients that failed previous IFN-based treatment. Safety and efficacy data from the phase 2b trials will be presented at scientific meetings later in 2010.

TMC435-C205 is a global phase 2b study in 386 genotype-1 treatment-naïve patients. It is a once daily treatment of TMC435 with different doses and durations given in addition to standard of care treatment, consisting of ribavirin and pegIFNalpha-2A.

TMC435-C215 is a Japan phase 2b study in 92 genotype-1 treatment-naïve patients. It is a once daily treatment of TMC435 with different doses and durations given in addition to standard of care treatment, consisting of ribavirin and pegIFNalpha-2A.

TMC435-C206 is a global phase 2b study in 463 genotype-1 treatment-experienced patients. It is a once daily treatment of TMC435 in with different doses of given in addition to standard of care treatment, consisting of ribavirin and pegIFNalpha-2A. 

AIDS vaccine development takes a step forward?

July 09--An effective vaccine against the AIDS virus may have moved one step closer to reality, researchers said Thursday.

Federal researchers have identified a pair of naturally occurring antibodies that are able to kill more than 90 percent of all strains of the AIDS virus, a finding they say could lead to the development of new treatments for HIV infections and to the production of the first successful vaccine against the virus.

HIV, the virus that causes AIDS, is notoriously mutable, changing the composition of proteins on its surface with ease to escape pressure from the immune system. This enables it to continue infecting cells even after the appearance of antibodies targeting it -- and to avoid the relatively ineffective vaccines developed so far.

Hundreds of variants of the virus are now in circulation around the world, and the identification of so-called broadly neutralizing antibodies that can block the bulk of them has been the holy grail of HIV researchers.

To date, however, the best antibodies -- immune system proteins that fight infections -- that researchers have found block only 30 percent to 40 percent of all HIV strains. The identification of antibodies that can block more than 90 percent of strains could lead to what some researchers are dubbing a renaissance in AIDS prevention and treatment.

The key to the new antibodies is that they bind to a site on the virus surface that rarely mutates.

"I am more optimistic about an AIDS vaccine at this point in time than I have been probably in the last 10 years," Dr. Gary Nabel of the National Institute of Allergy and Infectious Diseases told Reuters. He led the research reported Thursday in the online edition of the journal Science.

Nabel and his colleagues isolated the antibodies from the blood of a 60-year-old African American gay man. Using newly developed imaging and analytical techniques, they found that the two antibodies, called VRC01 and VRC02, bind to a spike on the surface of the virus. This spike interacts with a receptor called the CD4 binding site on the surface of human cells, and when an antibody binds to it, the virus cannot enter a cell.

Because the virus must use CD4 to enter cells, it cannot tolerate mutations in the spike. The composition of the spike is thus pretty much constant in all variants of HIV in circulation.

"The antibodies attach to a virtually unchanging part of the virus, and this explains why they can neutralize such an extraordinary range of HIV strains," Dr. John R. Mascola of the infectious diseases institute, a coauthor, said in a statement.

With the antibodies in hand, the team was able to determine precisely how the HIV spike and the antibodies interact. They were then able to produce a synthetic version of the spike that could elicit the production of similar blocking antibodies in animal cells.

They are now testing the synthetic spike as a possible vaccine in animals and hope to expand to human testing in the relatively near future. The antibodies can also be reproduced by biotechnology and used as a treatment for someone who is already infected.

Researchers, who are already testing the antibodies in infected animals, hope that at the very least the antibodies will provide synergistic effects when used in conjunction with antiviral drugs.

Other researchers, such as Dennis Burton of the Scripps Research Institute in La Jolla, have also discovered broadly neutralizing antibodies, although most of the discoveries have not yet been published. Fortuitously, Mascola has found, antibodies discovered by Burton block viral variants that are not blocked by the antibodies reported Thursday.

Researchers thus hope that incorporating synthetic chemicals that stimulate production of several different antibodies might provide nearly complete protection against HIV.

Expanded label for Infergen - too little too late?

New Labeling Provides Alternative for Hepatitis C Patients Who Need Retreatment

WARRENDALE, Pa.--(BUSINESS WIRE)--Three Rivers Pharmaceuticals, LLC, today received expanded labeling from the U.S. Food and Drug Administration (FDA) to include daily use of INFERGEN (Consensus Interferon) in combination with ribavirin (RBV) for retreatment of chronic hepatitis C patients. The expanded labeling targets hepatitis C patients who need retreatment. In the clinical trial leading to the expanded labeling, the primary endpoint of increased sustained virological response (SVR) was achieved demonstrating that INFERGEN provides a second chance for patients to clear their hepatitis C virus.


“Approximately 50 percent of patients with chronic hepatitis C do not respond to their initial course of therapy,” stated Dr. Bruce Bacon, the lead investigator for the registration trial. “The FDA’s recognition of this expanded label allows patients failing therapy a safe and efficacious retreatment strategy. The results from this study legitimize how we properly treat these patients helping them to achieve SVR.”

The data reported and published in Hepatology (2009) from the U.S.-based, randomized, DIRECT clinical trial (Daily-Dose Consensus Interferon and Ribavirin: Efficacy of Combined Therapy) led to the approval of the expanded label. Results from the DIRECT trial had shown that the use of INFERGEN and RBV is a safe and effective retreatment strategy for patients failing initial therapy with PEG-IFN/RBV. This was especially apparent with interferon-sensitive patients with lower baseline fibrosis scores. In fact, up to 38 percent of non-cirrhotic patients (in the 15mcg arm) who were sensitive to Peg-IFN/RBV and who did not modify their INFERGEN and RBV dosages achieved an SVR. Additionally, patients with cirrhosis were less likely to benefit from retreatment with INFERGEN and RBV unless they displayed previous interferon sensitivity or at least 1-log₁₀ drop in viral levels on prior therapy.

“The expanded labeling for INFERGEN is a significant step forward for retreatment of hepatitis C patients who deserve a second chance to overcome their HCV,” stated Patrick Kerrish, R.Ph, M.B.A., President of Three Rivers Pharmaceuticals, LLC. “Our hope is that INFERGEN will become the standard of care for the retreatment of chronic hepatitis C patients.”

Three Rivers Pharmaceuticals, LLC is expanding its INFERGEN and hepatitis C education efforts via physician outreach and online patient support programs. An instructional video and guide about proper at-home injections of INFERGEN, tips for patient compliance, access to reimbursement specialists and a hotline staffed by nurse counselors are available at www.infergen.com.