EASL2010

 

HCV Advocate EASL 2010 Coverage

 

·         Pharmasset to Present New Data on RG7128 and PSI-7977 at the EASL Conference

·         Biotech Intermune Reports on Midstage Study Results for Possible Hepatitis C Treatment

·         Merck Demonstrates Continued Commitment to Advancing Hepatitis Therapy at European Association for the Study of the Liver (EASL) 2010 Annual Meeting

·         InterMune Announces Positive Results From Phase 2b Study Of Danoprevir - Update

·         59 Percent of Patients Overall Achieved SVR with Telaprevir-Based Regimens in Study 107 After Not Achieving SVR with at Least One Prior Course of Treatment for Hepatitis C Virus Infection

·         Achillion Presents Data From Studies of ACH-1625 in Hepatitis C at the EASL International Liver Congress

·         Anadys Pharma Says Hepatitis C Combo Treatment Reduces Virus to Undetectable Levels at Week 8 in 72% Patients – Stocks to Watch (Updated)

·         Hepatitis C Virus Polymerase Inhibitor VX-222 Reduced Viral Levels over Three Days in Phase 1b Trial

·         Romark Announces Data From Clinical Trial of Nitazoxanide in Treatment-Naive Patients with Genotype 1 Chronic Hepatitis C

·         Idenix Pharmaceuticals Reports Positive Results With IDX184 From Interim Analysis of Phase IIa Hepatitis C Study

·         GlobeImmune GI-5005 HCV Product Candidate Improves Sustained Virologic Response by 10 Percent, Demonstrating Potential to Be First Therapeutic Vaccine for HCV

·         Positive Interim Data from Idera Pharmaceuticals' Phase 1 Trial of IMO-2125 TLR9 Agonist Presented at 45th EASL

·         SCYNEXIS' SCY-635 Demonstrates Impressive Barrier to Resistance in HCV Treatment

·         Biolex Unveils Interim Results from Empower Locteron Phase 2b Trial

 

Pharmasset to Present New Data on RG7128 and PSI-7977 at the EASL Conference

www.prnewswire.com

 

-- Follow up data from a 28 day trial with RG7128 and standard of care demonstrated an SVR of 65% in HCV genotype 2/3 prior non-responders

 

-- In vitro results demonstrate that a combination of two nucleotide analogs, PSI-7977 and PSI-938, are able to suppress S282T-resistant replicons

PRINCETON, N.J., April 13 /PRNewswire-FirstCall/ -- Pharmasset, Inc. (Nasdaq: VRUS) announces the oral presentation of new sustained virologic response (SVR) follow-up data in hepatitis C virus (HCV) genotype 2 and 3 non-responder patients treated for 28 days with RG7128 in combination with the standard of care (SOC), Pegasys® and Copegus®, and presentation of an in vitro combination study with PSI-7977 and PSI-938.  Both presentations are at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL) in Vienna, Austria (April 14-18, 2010).

On April 15, Edward Gane, M.D., Associate Professor, University of Auckland, and Director, Auckland Clinical Studies Limited, will give an oral presentation entitled "Sustained virologic response (SVR) following RG7128 1500mg BID/PegIFN/RBV for 28 days in HCV Genotype 2/3 prior non-responders" at 5 PM CEST during the hepatitis C drug development session. Data from this trial suggest that the nucleoside RG7128 in combination with SOC is effective in retreatment of HCV genotype 2/3 relapsers/nonresponders and may provide an attractive option for treatment of prior non-responders and treatment-naive patients with HCV genotype 2/3. Larger studies are required to confirm these findings, determine the optimal duration of RG7128 therapy, and evaluate utility in treatment-naive genotype 2/3 patients.

On April 17, Dr Veronique Zennou, a Pharmasset scientist, will present a poster entitled "Combination of two complementary nucleotide analogues PSI-7977 and PSI-938 effectively clears wild type and NS5B S282T HCV replicons – comparison with combinations of other antiviral compounds" (Poster 1034). The data indicate that in vitro combinations of two nucleotides targeting NS5b effectively suppress resistant replicons with no emergence of resistance.  The poster will include comparative data on combinations of other direct acting antivirals (DAA) targeting different HCV proteins.

Biotech Intermune Reports on Midstage Study Results for Possible Hepatitis C Treatment

 

BRISBANE, Calif. (AP) - Biotechnology company InterMune Inc. said Wednesday researchers will add a new drug that promises an increased safety margin to a midstage study of a potential hepatitis C treatment after analyzing preliminary results.

 

The Brisbane, Calif., company said the first part of the study paired the experimental treatment, labeled ITMN-191, with the drugs Pegasys and Copegus. The second part of the study will include those drugs and the virus-fighting drug ritonavir.

 

Using ITMN-191 with ritonavir is an approach that "appears to deliver strong efficacy and offer attractive advantages of dosing convenience and increased safety margin," InterMune Chairman and CEO Dan Welch said in a statement.

 

The second part of the study is expected to start in either the third or fourth quarter.

 

InterMune is partnering with the Swiss drug company Roche to develop ITMN-191, also known as danoprevir. Last fall, InterMune said it was stopping a portion of the midstage study involving 900-milligram doses due to potential liver damage. Other doses in the study continued.

 

Merck Demonstrates Continued Commitment to Advancing Hepatitis Therapy at European Association for the Study of the Liver (EASL) 2010 Annual Meeting

http://www.merck.com

VIENNA, Austria, April 14, 2010 – Merck & Co., Inc., Whitehouse Station, N.J., U.S.A., demonstrated its ongoing commitment to hepatitis therapy at the 45th annual meeting of the European Association for the Study of the Liver (EASL) in Vienna, Austria, presenting data on the company’s comprehensive portfolio of marketed products and investigational direct acting antiviral (DAA) compounds in development for the treatment of chronic hepatitis C. Hepatitis C virus (HCV) infection is a serious, potentially life-threatening disease that affects nearly 4 million people in the United States, 4 million in Europe and approximately 170 million people worldwide. It is the leading cause of cirrhosis and liver cancer, and the primary reason for liver transplants in the United States and Europe.

Merck completed its merger with Schering-Plough Corporation on Nov. 3, 2009, and the company is continuing Schering-Plough’s work in the hepatitis field. For more than 20 years, Schering-Plough has been a leader in the development of innovative therapies that significantly advanced treatment for hepatitis B and C. Merck has been a pioneer in the field through its development of vaccines for the prevention of hepatitis A and B.

“Today, with our combined portfolio, the new Merck is committed to continuing this legacy and to being a leader in the development of vaccines and pharmaceuticals to both prevent and treat viral hepatitis,” said Patrick Bergstedt, senior vice president and general manager, Merck Infectious Diseases. “Our vision in hepatitis C is to continue to be a global leader in the discovery, development, and delivery of therapies that advance patient care, including the development of oral combination therapies.”

Hepatitis C is a key area for current and future investment at Merck. Extensive research efforts are underway to develop differentiated compounds that bring innovation to hepatitis care. These compounds include HCV protease inhibitors and compounds acting through other complementary mechanisms to block HCV replication.

Merck’s HCV portfolio includes:

For more information about Merck data presentations at EASL Vienna 2010, please visit the EASL Web site at: http://www2.kenes.com/liver-congress/Pages/Home.aspx.

For Merck press releases on boceprevir, please visit the Merck newsroom at: http://www.merck.com/newsroom/home.html, search term boceprevir.

For more information about ongoing boceprevir clinical studies, please visit www.clinicaltrials.gov.

 

InterMune Announces Positive Results From Phase 2b Study Of Danoprevir - Update

http://www.rttnews.com

 

 (RTTNews) -  Biopharmaceutical company InterMune, Inc. (ITMN: News ) on Wednesday announced positive results from Phase 2b study of danoprevir, the hepatitis C virus protease inhibitor. The interim safety analysis conducted on four treatment groups revealed that serious adverse events were generally balanced.

 

In the randomized, partially-blind study, danoprevir was administered for 12 weeks in combination with Pegasys and Copegus, compared to placebo with Pegasys and Copegus for the same duration. Pegasys and Copegus are already approved drugs for the treatment of hepatitis C.

 

InterMune stated that the study was conducted by the Swiss drug company Roche Holding AG in collaboration with InterMune for the development of protease inhibitors. A total of 232 patients were randomized into four treatment groups: 300 mg three times daily, 600 mg twice daily or 900 mg twice daily and placebo.

 

The company said, in the first four weeks, dosing of 300 mg showed rapid virologic response in 73% of patients, while 600 mg and 900 mg indicated rapid virologic response in 86% of patients. Meanwhile, placebo showed rapid virologic response in 7% of patients.

 

For the 12 weeks, dosing of 300 mg, 600 mg, 900 mg and placebo indicated complete early virologic response in 88%, 89%, 92% and 43% of patients respectively.

 

The incidence of treatment-emergent Grade 4 ALT elevations was 0%, 1%, 6% and 0% in the 300 mg, 600 mg, 900 mg and placebo groups, respectively. In the danoprevir treatment groups, serious adverse events occurred generally between six to eight weeks or later and were reversible after discontinuation of danoprevir. Dosing of the 900 mg arm was stopped based on this safety signal.

 

In addition, treatment-emergent Grade 3 or Grade 4 neutropenia was reported in 24%, 25%, 31% and 16% of patients in the 300 mg, 600 mg, 900 mg and placebo groups, respectively. The incidence of rash and anemia was comparable across all treatment groups, including the placebo group.

 

Dan Welch, chairman, chief executive and president of InterMune said, "With Roche, we are now focused on making the critical dose and regimen selection decision for future development plans for ritonavir-boosted danoprevir, an approach that appears to deliver strong efficacy and offer attractive advantages of dosing convenience and increased safety margin."

 

ITMN shares closed Tuesday's regular trading at $48.59, up $0.66 or 1.38% on a volume of 8,986 shares on the Nasdaq.

 

59 Percent of Patients Overall Achieved SVR with Telaprevir-Based Regimens in Study 107 After Not Achieving SVR with at Least One Prior Course of Treatment for Hepatitis C Virus Infection

http://www.businesswire.com/news/home/20100415005890/en

-56% of prior treatment null responder patients achieved SVR with a 48-week telaprevir-based regimen-

-97% of prior treatment relapsers and 55% of prior treatment partial responders achieved SVR with 24-week or 48-week telaprevir-based regimens-

VIENNA--(BUSINESS WIRE)-- In conjunction with an oral presentation at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL) in Vienna, Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that 59 percent of patients overall who received a telaprevir-based combination regimen in Study 107 achieved a sustained viral response (SVR) after failing to achieve SVR with a least one prior course of treatment for hepatitis C virus (HCV) infection. Specifically, 56% of prior treatment null responders (n=27) achieved SVR after treatment with a 48-week telaprevir-based combination regimen, and 97% of prior treatment relapsers (n=29) and 55% of prior treatment partial responders (n=29) achieved SVR after treatment with a 24-week or 48-week telaprevir-based combination regimen. Ten patients (9%, n=117) discontinued all therapy due to adverse events, with rash being the most common reason for discontinuation.

 

Study 107 was an open-label Phase 2 rollover study of patients who did not achieve SVR after receiving pegylated interferon (Peg-IFN) and ribavirin (RBV) in the control arms of the Phase 2 PROVE trials of telaprevir. Telaprevir is an investigational oral HCV protease inhibitor being developed by Vertex in collaboration with Tibotec and Mitsubishi Tanabe Pharma. A Phase 3 registration program for telaprevir is nearing completion, in both treatment-naïve and treatment-failure HCV patients. The Phase 3 REALIZE trial is evaluating a 48-week telaprevir-based treatment regimen in treatment-failure patients, including null responder patients. In the second half of 2010, Vertex plans to submit a New Drug Application to the U.S. Food and Drug Administration (FDA) for telaprevir for both treatment-naïve and treatment-failure patients.

 

“The majority of genotype 1 patients who undergo their first regimen of pegylated-interferon and ribavirin fail to achieve SVR and are left with few options for subsequent re-treatment of their disease," said Thomas Berg, M.D., Medical Development, Hepatology Section, University Clinic, Leipzig, Germany. "Treatment with telaprevir-based regimens in Study 107 resulted in an overall SVR rate of 59 percent across all patients enrolled in the study, with 56 percent of the most difficult-to-treat null responder patients achieving SVR with a 48-week telaprevir-based regimen."

 

"Study 107 provided important insight into the potential future use of telaprevir-based regimens in the treatment of patients who failed to respond to currently approved therapies,” said Robert Kauffman, M.D., Ph.D., Vertex's Senior Vice President, Clinical Development and Chief Medical Officer. “Based on information generated in Study 107, as well as data from the PROVE 3 clinical trial, we believe that a 48-week treatment regimen may increase the likelihood that certain treatment-failure patients are able to achieve SVR. In our Phase 3 REALIZE trial in treatment-failure patients, we are evaluating a 48-week treatment regimen and are currently awaiting final SVR results, which we expect in the third quarter."

 

Study 107 Design and Results

Study 107 was an open-label, Phase 2 rollover study of telaprevir in combination with Peg-IFN and RBV in patients who had previously received treatment with Peg-IFN and RBV in the control arms of either of the PROVE 1, PROVE 2 or PROVE 3 trials, and did not achieve SVR. Patients in Study 107 were well-characterized as null responders, partial responders, relapsers or breakthroughs, based on their antiviral response documented as a result of their participation in the control arms of the PROVE clinical trials.

 

When Study 107 began, all patients were to receive 12 weeks of telaprevir in combination with Peg-IFN and RBV followed by an additional 12 weeks of Peg-IFN and RBV, for a total of 24 weeks of therapy. Stopping rules required any patient who did not achieve HCV RNA of 25 IU/mL or less by week 4 to stop all treatment. In 2008, Study 107 was amended and underwent several changes, most notably to the duration of treatment. The changes to treatment duration in Study 107 were aimed at providing patients with a higher likelihood of achieving SVR. Following the amendments, only patients who did not achieve HCV RNA of 100 IU/mL or less at week 4 were required to stop therapy. In addition, prior treatment null responder patients were to receive a 48-week telaprevir-based treatment regimen. Patients with prior treatment relapse, prior treatment viral breakthrough and prior treatment partial response were eligible to receive a response-guided 24-week telaprevir-based treatment regimen if they achieved undetectable HCV RNA at week 4 and 12, otherwise these patients would receive a 48-week regimen.

 

A total of 117 patients enrolled in Study 107, including 51 patients with prior treatment null response, 29 patients with prior treatment partial response, 8 patients with prior treatment viral breakthrough, and 29 patients with prior treatment relapse.

 

An overall SVR rate of 59 percent and an overall relapse rate of 16 percent were observed in Study 107. Sustained viral response rates for each arm of Study 107 are as follows:

 

SVR in Study 107

 

Treatment Assignment 1:

12 weeks of telaprevir, Peg-IFN & RBV, followed by 12 weeks of only Peg-IFN & RBV

 

Treatment Assignment 2:

12 weeks of telaprevir, Peg-IFN & RBV, followed by 36 weeks of only Peg-IFN & RBV

 

Unassigned:
(2 patients discontinued all therapy prior to week 12 and were thus designated as unassigned)

 

Total:

Overall

SVR Rates

 

60%

(49 of 81)

 

53%

(18 of 34)

 

100%

(2 of 2)

 

59%

(69 of 117)

  • Prior Null Response1

 

17 %

(4 of 24)

 

56%

(15 of 27)

 

-

 

37%

(19 of 51)

  • Prior Partial Response2

 

60%

(15 of 25)

 

0%

(0 of 3)

 

100%

(1 of 1)

 

55%

(16 of 29)

  • Prior Viral Breakthrough3

 

86%

(6 of 7)

 

0%

(0 of 1)

 

-

 

75%

(6 of 8)

  • Prior Relapse4

 

96%

(24 of 25)

 

100%

(3 of 3)

 

100%

(1 of 1)

 

97%

(28 of 29)

1 Defined as patients who achieved a viral load decline of less than 1 log10 at week 4 or 2 log10 or less at week 12 during prior therapy

2 Defined as patients who had a greater than 2 log10 viral decline at week 12 but had detectable HCV RNA at week 24

3 Defined as patients who had undetectable HCV RNA but relapsed before the end of treatment

4 Defined as patients who had undetectable HCV RNA at the end of treatment with Peg-IFN and RBV but subsequently relapsed

 

Study 107 Safety and Tolerability

Adverse events reported in Study 107 were similar to those reported in prior Phase 2 trials of telaprevir. The most common adverse events reported were rash (all types), fatigue, pruritus, and headache. Discontinuation of all therapy due to adverse events occurred in 10 patients (9%; n=117), with rash being the most common reason for discontinuation.

 

About Telaprevir

Telaprevir is an investigational, oral inhibitor of HCV protease, an enzyme essential for viral replication, and is being evaluated as part of a global Phase 3 registration program in more than 2,200 treatment-naïve and treatment-failure patients. Vertex is collaborating with Tibotec and Mitsubishi Tanabe Pharma to develop telaprevir. Vertex retains commercial rights to telaprevir in North America. Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and other countries. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries.

 

1 Institute of Medicine. Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C. Available at: http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx. Accessed March 29, 2010.

2 Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965.

3 Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982.

4 McHutchison JG, Lawitz EJ, Shiffman ML, et al; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593.

5 McHutchison, JG, Manns, MP, Muir, AJ. Retreatment with Telaprevir, Peginterferon, and Ribavirin for Chronic HCV Infection. N Engl J Med 2010; 362(14): 30-41.

6 Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf. Accessed April 2, 2010.

7 Pyenson, B., Fitch, K., Iwasaki, K. Consequences of Hepatitis C Virus (HCV): Costs of a Baby Boomer Epidemic of Liver Disease. Milliman, Inc. This report was commissioned by Vertex Pharmaceuticals, Inc. May, 2009.

8 Davis, G.L., Alter, M. J. , El-Serag, H. Clinical-Liver, Pancreas, and Biliary Tract. Journal of Gastroenterology. 2010;138: 513-521.

9 Veldt, B.J., Heathcote, J., Wedmeyer, H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.

10 Morgan T.R, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).

11 Volk, Michael I., Tocco, Rachel, Saini, Sameer, Lok, Anna S.F. Public Health Impact of Antiviral Therapy for Hepatitis C in the United States. Hepatology.2009;50(6):1750-1755.

 

EASL Webcast

Vertex Pharmaceuticals will host a webcast today, Thursday, April 15, 2010 at 1:45 p.m. ET. This webcast will be broadcast via the Internet at www.vrtx.com. It is suggested that webcast participants go to the web site at least 10 minutes in advance of the call to ensure that they can access the slides. The link to the webcast is available on the “Finances” page under the “Events and Presentations” button. Following the live webcast, an archived version will be available on Vertex's website until 5:00 p.m. ET on April 29, 2010.

 

Source: Vertex Pharmaceuticals Incorporated

 

Achillion Presents Data From Studies of ACH-1625 in Hepatitis C at the EASL International Liver Congress

 

ACH-1625 Achieves Significant Viral Load Reduction and Sustained Viral Suppression With Continued Safety and Tolerability

globenewswire

 

NEW HAVEN, Conn., April 15, 2010 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN - News) today presented data from the Company's ongoing Phase 1 clinical trial of ACH-1625 to treat hepatitis C (HCV) at the European Association for the Study of the Liver's (EASL) International Liver Congress taking place at the Reed Messe Wien Congress Center in Vienna, Austria from April 14-18, 2010.

 

The data were presented by Dr. Elizabeth Olek, Chief Medical Officer of Achillion, on April 15th beginning at 8 a.m. local time in a poster presentation entitled, "Virological Response, Safety, and Pharmacokinetic Profile Following Single- and Multiple-Dose Administration of ACH-0141625 Protease Inhibitor to Healthy Volunteers and HCV Genotype-1 Patients" (Abstract #2012). The data demonstrated that treatment with ACH-1625 achieved a significant reduction in HCV RNA after five-day monotherapy in patients with HCV, showed sustained viral suppression in patients with HCV for at least seven days after dosing was completed, and was generally safe and well tolerated in patients with HCV and in healthy volunteers.

 

ACH-1625 is an inhibitor of HCV NS3 protease that was discovered and is being developed by Achillion.

 

"We are delighted to present this robust data set from our Phase 1 studies of ACH-1625 at this prestigious conference. These data show significant antiviral activity and demonstrate continued suppression of viral load after drug discontinuation while maintaining a safe and tolerable safety profile," said Dr. Olek. "The sustained suppression of viral load is important as it could be a distinguishing feature and competitive advantage for our compound in comparison to other HCV therapeutics in development, given the potential implications for patient compliance and the emergence of resistance."

 

"On the strength of these early data, we have initiated additional dose cohorts under this protocol to explore lower doses as well as a once-daily dose. We have now fully enrolled these additional cohorts and look forward to completing them and reporting results in the coming weeks," added Dr. Olek.

 

In addition to the aforementioned presentation, the following poster presentations highlighting ACH-1625 will be exhibited at the EASL meeting on April 16:

 

1.      "Preclinical Antiviral Activity, Combination and Resistance of ACH-1625, A Potent HCV NS3 Protease Inhibitor" April 16 at 8 a.m. local time, Abstract #492, Presenter: Dr. Mingjun Huang, Executive Director, Virology of Achillion. Dr. Huang will present an analysis of the virology completed to date with ACH-1625 including potency, specificity and resistance profile.

2.      "Characterization of the Hepatoselective Distribution of ACH-1625, a Potent, Clinical Stage HCV NS3 Protease Inhibitor" April 16 at 8 a.m. local time, Abstract #172, Presenter: Dr. Kathe Stauber, Director, Preclinical Candidate Selection of Achillion. Dr. Stauber will present an analysis of the selective liver distribution of ACH-1625 by hepatic uptake transporters, as well as a summary of the pharmacokinetics and metabolic stability of ACH-1625.

 

"We are very pleased to have this body of scientific and clinical data on ACH-1625 presented at this year's EASL meeting, as it continues to underscore the potential of ACH-1625 as a powerful protease inhibitor for the treatment of HCV," commented Michael D. Kishbauch, Chief Executive Officer of Achillion. "We look forward to advancing the development of this promising therapeutic, which R&D Directions magazine recently ranked among its 'Top 100' investigational drugs."

 

Poster Presentations

Copies of the EASL poster presentations will be available beginning Friday, April 16, 2010 on Achillion's website at www.achillion.com on the "Achillion Today" page.

 

Proof-of-Concept Study Results

In Phase 1a safety studies with ACH-1625, subjects in the single ascending dose (SAD) segment of the study received doses ranging from 50mg to 2000mg. Subjects in the Phase 1a multiple ascending dose (MAD) segment of the study received five days of ACH-1625 up to a maximal dose of 2000mg per day. Preliminary data from the SAD and MAD trial segments demonstrated ACH-1625 was well tolerated at all doses and there were no serious adverse events, and no clinically significant changes in vital signs, electrocardiograms or laboratory evaluations. All reported adverse events were classified as mild or moderate, were transient and showed no apparent dose relationship.

 

In December 2009, Achillion announced proof-of-concept data from the first dosing cohort in the Phase 1b study. Subjects in this cohort of HCV-infected patients received doses of 600mg twice-daily (n=9, randomized to 6 active drug, 3 placebo). Preliminary results showed that a mean reduction in viral load of 3.94 log10 was achieved in the treatment group, as compared to a mean reduction of 0.22 log10 in the placebo group. All subjects in the treatment group had viral load decline between 3.0 and 4.5 log10, and two subjects reached undetectable levels of HCV RNA. Safety results from this dosing group were similar to those observed in the Phase 1a segment of the trial. There were no serious adverse events, and no clinically significant changes in vital signs, electrocardiograms or laboratory evaluations. All reported adverse events were classified as mild or moderate, were transient and showed no apparent dose relationship. Furthermore, all patients had viral loads that remained suppressed for at least seven days after dosing was completed, maintaining a mean reduction of more than 2.0 log10 from baseline through day 12, the last day of viral load measurement in the study.

 

In January 2010, Achillion announced results from the second dosing cohort in the Phase 1b study. HCV-infected subjects in this cohort (n=9, randomized to 6 active drug, 3 placebo) received doses of 500mg of ACH-1625 twice-daily. Preliminary results showed that a mean reduction in viral load of 4.25 log10 was achieved in the treatment group, as compared to a mean reduction of 0.29 log10 in the placebo group. Safety results from this dosing group were similar to those observed in both the Phase 1a segment of the trial and in the first cohort of HCV-infected subjects. Sustained viral suppression was also similar to the first cohort of HCV-infected subjects, with patients maintaining a mean reduction of more than 3.0 log10 from baseline through day 12, seven days after dosing was completed and the last day of viral load measurement in the study.

 

About ACH-1625

ACH-1625 is an HCV protease inhibitor designed and synthesized based on crystal structures of enzyme/inhibitor complex. ACH-1625 is an open chain, non-covalent, reversible inhibitor of NS3 protease. In preclinical studies, ACH-1625 demonstrated high potency, unique pharmacokinetic properties and an excellent safety profile at high drug exposures. With its rapid and extensive partitioning to the liver, as well as high liver/plasma ratios demonstrated in preclinical studies, Achillion believes that ACH-1625 has the potential for once-daily dosing. ACH-1625 has shown low single-digit nanomolar potency that is specific to HCV. It is equipotent against HCV genotypes 1a and 1b at IC50~1nM.

 

About Achillion

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

ACHN-G

 

Anadys Pharma Says Hepatitis C Combo Treatment Reduces Virus to Undetectable Levels at Week 8 in 72% Patients – Stocks to Watch (Updated)

http://www.rttnews.com

 

(RTTNews) -  Anadys Pharmaceuticals, Inc. (ANDS: News ) said that 72% of hepatitis C patients receiving its experimental drug in combination with the current standard of care or SOC achieved undetectable levels of virus at week eight compared to 38% of patients receiving placebo plus SOC.

 

The results were derived from an ongoing mid-stage study, in which the patients received either the drug candidate – ANA598 400 mg twice daily dose plus SOC or ANA598 200 mg twice daily dose plus SOC or placebo plus SOC.

 

ANA598 is wholly owned by Anadys, which has completed three Phase I clinical studies of the drug demonstrating potent antiviral activity and good tolerability.

 

The preliminary analysis of results through eight weeks also showed that ANA598 400 mg twice daily dose plus SOC was well tolerated, with an adverse event profile comparable to SOC alone, the company noted, adding that at 200 mg twice daily dose of the drug, no patient experienced viral breakthrough, which is an increase in viral load while on antiviral treatment.

 

 

Through eight weeks, 32% of patients receiving ANA598 400 mg twice daily plus SOC developed rash, compared to 21% of patients at week four and 41% at week 12 for patients who received ANA598 200 mg twice daily plus SOC, Anadys said in a statement.

 

The company believes that the clinical profile to date establishes ANA598 as an attractive agent to advance into Phase IIb development.

 

Hepatitis C Virus Polymerase Inhibitor VX-222 Reduced Viral Levels over Three Days in Phase 1b Trial

http://www.marketwatch.com

 

--VX-222 was well-tolerated across all four dose groups through three days of dosing, with all adverse events being mild to moderate in severity-

 

VIENNA, Austria, Apr 15, 2010 (BUSINESS WIRE) -- ---Greater than 3 log10 reduction in HCV RNA observed across all four VX-222 dose groups-

 

---Results support previously announced Phase 2 proof-of-concept clinical trial evaluating VX-222 in combination with Vertex's lead HCV protease inhibitor telaprevir-

 

In conjunction with an oral presentation at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL) in Vienna, Vertex Pharmaceuticals Incorporated /quotes/comstock/15*!vrtx/quotes/nls/vrtx (VRTX 39.66, -0.33, -0.83%) today announced results from a Phase 1b clinical trial of the investigational oral hepatitis C virus (HCV) polymerase inhibitor, VX-222. In the trial, treatment with VX-222 for three days was well-tolerated, with all adverse events being mild to moderate in severity. Dosing with VX-222 for three days resulted in a greater than 3 log10 reduction in HCV RNA across all four of the VX-222 dosing groups. No serious adverse events or treatment discontinuations were reported in the Phase 1b trial. The results from this trial support the Phase 2 proof-of-concept clinical trial of VX-222 dosed in combination with Vertex's lead investigational HCV protease inhibitor telaprevir, which is expected to complete enrollment in the second quarter of 2010. Vertex retains worldwide rights to VX-222.

 

"In this Phase 1b clinical trial, treatment with VX-222 for three days resulted in a reduction in viral load across all the dose groups studied," said Maribel Rodriguez-Torres, M.D., Medical Director of Fundacion de Investigacion de Diego in Puerto Rico. "This trial was designed primarily to gain important safety and viral kinetic information to enable the continued development of VX-222 as part of novel HCV combination regimens. I am pleased that additional development efforts for VX-222 are advancing, including the first trial to evaluate a two-drug regimen of VX-222 dosed in combination with the HCV protease inhibitor telaprevir."

 

"These early safety and efficacy results support the evaluation of VX-222 as part of novel combination regimens for the treatment of HCV, including the first Phase 2 proof-of-concept clinical trial evaluating multiple telaprevir/VX-222-based combination regimens," said Robert Kauffman, M.D., Ph.D., Senior Vice President, Clinical Development and Chief Medical Officer of Vertex Pharmaceuticals. "With VX-222, we believe we have a unique opportunity to broaden our commitment to improving patient care in hepatitis C and to strengthen our leadership position in the development of novel specifically targeted antiviral therapies for the treatment of hepatitis C."

 

Trial Design

The clinical results announced today are from the Phase 1b viral kinetic portion (Part A) of a two-part Phase 1b/2a clinical trial of VX-222. This double-blind, randomized placebo-controlled, dose-ranging Phase Ib clinical trial was designed to evaluate the safety, tolerability, pharmacokinetics and effect on viral kinetics of four doses of VX-222, including doses of 250 mg every 12 hours (BID), 500 mg BID, 750 mg BID, and 1,500 mg once a day (QD), or placebo. In the trial, VX-222 was administered as monotherapy for three days. Patients then had the option to receive treatment with pegylated interferon (Peg-IFN) and ribavirin (RBV) for up to 48 weeks.

 

Thirty-two treatment-naive patients with chronic genotype 1 HCV infection were enrolled in the trial, including six patients in each dose group who received 250 mg of VX-222 BID, 500 mg of VX-222 BID, 750 mg of VX-222 BID, and 1,500 mg of VX-222 QD. Two patients received placebo in each of the four dosing groups, for a total of eight patients who received placebo. Part A of the trial was conducted at 10 centers in the United States, Canada and Argentina. Of the patients enrolled in the trial, 24 patients had genotype 1a HCV infection and eight patients had genotype 1b HCV infection. Six of the patients enrolled in the trial were African American, 25 were Caucasian and one was American Indian/Alaskan.

 

Viral Kinetic Results

Treatment with VX-222 resulted in mean reductions in plasma HCV RNA of greater than 3 log10 across the four VX-222 dose groups. Additionally, an increasing dose response was observed across the four dose groups, with the results in the 500 mg, 750 mg and 1,500 mg dose groups being very similar. The mean HCV RNA decline achieved after three days of dosing with 250 mg BID, 500 mg BID, and 750 mg BID of VX-222 was 3.1 log10 (range: 2.0 to 4.2), 3.4 log10 (range: 3.2 to 3.6), and 3.2 log10 (range: 2.3 to 3.8), respectively. The mean HCV RNA decline achieved after three days of dosing with 1,500 mg QD of VX-222 was 3.4 log10 (range: 3.1 to 3.9). In the patients receiving placebo, no notable decline in HCV RNA was observed. Similar viral declines were observed for patients infected with genotype 1a and 1b.

 

The results of Part A of this trial are consistent with the findings from a previously conducted three-day, five-patient viral kinetic study of VX-222 dosed as 750 mg BID. Part B of the study will evaluate 12 weeks of VX-222 dosed in combination with pegylated-interferon and ribavirin in treatment-naive HCV patients. Part B of this trial is expected to begin enrolling patients in the second quarter.

 

Safety and Tolerability Results

Safety and tolerability information collected for Part A of this trial remains blinded and thus the safety information provided today includes pooled data for patients after administration of placebo or VX-222. Placebo or VX-222 were well-tolerated across all four dose groups, no severe or serious adverse events were reported and no treatment discontinuations occurred. All adverse events reported after administration of placebo or VX-222 were mild or moderate in severity. The most frequently reported adverse events occurring in at least two patients per dose group were diarrhea, headache, nausea, asthenia and fever.

 

VX-222 Clinical Development Plans

Data from this Phase 1b clinical trial support the clinical evaluation of VX-222 as part of novel regimens for the treatment of HCV infection and provided information for VX-222 dose selection. In addition, Vertex recently completed a Phase 1 study of telaprevir and VX-222 designed to evaluate the safety, tolerability and drug-drug interaction of telaprevir and VX-222 in 20 healthy volunteers, which also supports the evaluation of telaprevir-VX-222-based combination regimens.

 

In March 2010, Vertex announced plans to initiate the first clinical trial evaluating VX-222 dosed in combination with the investigational HCV protease inhibitor telaprevir. The trial will evaluate the safety and sustained viral response rates with multiple 12-week response-guided regimens of telaprevir/VX-222-based combination therapy, including two-drug regimens of telaprevir and VX-222. Vertex expects to complete enrollment in this trial in the second quarter of 2010 and expects interim clinical data from this trial in the second half of 2010.

 

About VX-222 and Telaprevir

VX-222 is a small molecule non-nucleoside inhibitor of HCV NS5B polymerase. Vertex obtained VX-222 as part of its acquisition of ViroChem Pharma Inc. in March 2009. Vertex retains worldwide rights to VX-222.

 

Telaprevir is an investigational oral inhibitor of HCV protease, an enzyme essential for viral replication, and is being evaluated as part of a global Phase 3 registration program in more than 2,200 treatment-naive and treatment-failure patients. Vertex is collaborating with Tibotec and Mitsubishi Tanabe Pharma to develop telaprevir. Vertex retains commercial rights to telaprevir in North America. Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and other countries. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries.

 

Romark Announces Data From Clinical Trial of Nitazoxanide in Treatment-Naive Patients with Genotype 1 Chronic Hepatitis C

 

Study Presented at the International Liver Congress(TM) Shows Improvement in Virologic Response Rates 12 Weeks after End of Treatment and Favorable Safety Profile

 

TAMPA, Fla., April 15 /PRNewswire/ -- Romark Laboratories announced results from its STEALTH C-3 clinical trial, a phase 2 clinical study of nitazoxanide in treatment-naive patients with genotype 1 chronic hepatitis C.  Study results were presented as a late breaking communication at the International Liver Congress™ 2010, the 45th Annual Meeting of the European Association for the Study of the Liver (EASL) in Vienna, Austria.

 

The study was a randomized, double-blind, placebo controlled trial conducted at thirteen centers in the United States in patients with genotype 1 chronic hepatitis C, 35% of whom had advanced stage 3 or 4 fibrosis.  A sustained virologic response (undetectable HCV RNA) twelve weeks after the end of treatment (SVR12) occurred in 44% of patients treated with nitazoxanide (500 mg twice daily) plus standard therapy (Pegasys® and Copegus®, F. Hoffman LaRoche) for 48 weeks versus 32% of patients treated with placebo plus standard therapy. SVR12 rates were consistently higher in subsets of patients with high baseline viral load (41% vs. 29%) and in African Americans (38% vs. 20%).  Safety analyses showed no adverse events attributable to nitazoxanide, with the exception of mild to moderate intermittent diarrhea and discolored urine. Final results of this study will be presented at a late breaking forum of the American Gastroenterological Association Institute during Digestive Disease Week in May of this year.

 

Results of the STEALTH C-3 study are consistent with previously reported data from studies of nitazoxanide plus Pegasys® and Copegus® in treatment-naive patients with genotype 4 chronic hepatitis C.(1,2,3)  The STEALTH C-3 study is the first trial of nitazoxanide in treatment-naïve patients with genotype 1 chronic hepatitis C.

 

"We are pleased to achieve these results in a population representative of the broad range of hepatitis C patients in the United States, including 35% with advanced fibrosis," said Jean-Francois Rossignol, M.D., Ph.D., Chairman and Chief Science Officer of Romark and inventor of the drug.  "We plan to initiate phase 3 clinical trials of nitazoxanide using our 675 mg controlled release tablets in combination with peginterferon with or without ribavirin later this year.  The 675 mg controlled release tablets deliver a higher dose of nitazoxanide with a better pharmacokinetic profile.  Additional clinical trials using the 675 mg controlled release tablets in genotype 1 and 4 patients are underway and include reduction of the duration of peginterferon to 24 weeks with and without ribavirin.  We also plan to investigate combinations with direct acting antiviral drugs.  Because of its novel mechanism and very  favorable safety profile, we expect nitazoxanide to play an important role in a broad range of patients with chronic hepatitis C."

 

Nitazoxanide is the first of a new class of broad spectrum antiviral drugs called the thiazolides.(3,4,5)  It is a potent inhibitor of hepatitis C virus in replicon studies,(4) and studies have shown that it does not induce viral mutations that confer drug resistance.(5)  Nitazoxanide is synergistic with interferon and direct acting antivirals.(4,6)  In patients with chronic hepatitis C, the addition of nitazoxanide has not resulted in an increase in the toxicity associated with peginterferon and ribavirin. Studies in patients with genotype 4 chronic hepatitis C suggest that nitazoxanide can be used to replace ribavirin.(1,2)   The AIDS Clinical Trials Group (ACTG) in the United States is studying nitazoxanide plus peginterferon and ribavirin for treating chronic hepatitis C in patients coinfected with HIV.

 

"Patients with chronic hepatitis C are diverse in many respects with patient and virus characteristics that affect treatment outcomes (HCV genotype, viral load, stage of liver disease, IL28B genotype, race, body weight, coinfection with HIV or hepatitis B virus, and ability to tolerate treatment)," said Emmet B. Keeffe, Chief Medical Officer of Romark Laboratories.   "The trend in therapy of chronic hepatitis C has been toward individualized therapy with combinations of antiviral drugs.  There is a need for a new class of safe drugs with novel mechanism that can be used in combination with current standard therapy or with other new classes of drugs to improve treatment outcomes.  We believe nitazoxanide can play an important role in these combinations."

 

Another communication of late-breaking data related to use of nitazoxanide plus standard therapy in patients with genotype 1 chronic hepatitis C who previously failed to respond to peginterferon plus ribavirin is scheduled for Saturday, April 17.  In keeping with the embargo policy of the conference, the title and authors of the abstract on the nonresponder study are as follows:

 

Title: Phase 2  Randomized, Double-Blind, Placebo-Controlled Study of Nitazoxanide with Peginterferon Alfa-2a and Ribavirin in Nonresponders with Chronic HCV Genotype 1: Final Report

 

Authors: M.L. Shiffman,(1) A. Ahmed,(2) I.M. Jacobson,(3) R.E. Pruitt,(4) E.B. Keeffe,(2,5) and STEALTH C-2 Investigators. (1)Liver Institute of Virginia, Bon Secours Health System, Newport News, VA, USA  (2)Stanford University Medical Center, Stanford, CA, USA  (3)Weill Cornell Medical College, New York, NY, USA, (4)Nashville GI Specialists, Nashville, TN, USA  and (5)Romark Institute for Medical Research, Tampa, FL, USA

 

SOURCE Romark Laboratories, L.C.

 

Idenix Pharmaceuticals Reports Positive Results With IDX184 From Interim Analysis of Phase IIa Hepatitis C Study

www.prnewswire.com

 

-- IDX184 50 and 100 mg cohorts in combination with pegylated interferon and ribavirin (PegIFN/RBV) demonstrated a favorable safety profile and potent antiviral activity at 14 days

-- Fifty percent of subjects receiving a total daily dose of 100 mg IDX184 achieved undetectable virus levels by Day 14

-- Study continuing with enrollment of 150 mg cohort

 

CAMBRIDGE, Mass., April 15 /PRNewswire-FirstCall/ -- Idenix Pharmaceuticals, Inc. (Nasdaq:IDIX - News), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today announced interim data from a 14-day, phase IIa clinical trial evaluating IDX184, a novel liver-targeted nucleotide prodrug of 2'-methyl guanosine monophosphate, in HCV-infected patients. Data are being presented at the 45th annual meeting of the European Association for the Study of the Liver being held in Vienna, Austria. 

 

The phase IIa clinical trial, initiated in the fourth quarter of 2009, is a randomized, double-blind, placebo-controlled, sequential dose-escalation study evaluating the safety, tolerability, pharmacokinetics and antiviral activity of IDX184 in combination with PegIFN/RBV in treatment-naive HCV genotype 1-infected patients. Patients receive a daily dose of IDX184 or placebo, plus pegIFN/RBV for 14 days and then continue on PegIFN/RBV for an additional 14 days. The study is evaluating four dosing regimens of IDX184 ranging from 50 to 200 mg per day. In the 100 mg and 200 mg cohorts, once daily (QD) and twice daily (BID) regimens are compared. Each cohort includes 20 patients randomized 4:1, IDX184:placebo.

 

In the data presented today, IDX184 demonstrated potent dose-dependent antiviral activity when combined with PegIFN/RBV. At Day 14, mean (+/- standard deviation) viral load reductions were 1.2 (+/- 1.1), 2.7 (+/- 1.3), 4.0 (+/- 1.7) and 4.2 (+/- 1.9) log(10) IU/mL in the placebo (n=8), 50 mg IDX184 QD (n=16), 50 mg IDX184 BID (n=8) and 100 mg IDX184 QD (n=8) cohorts, respectively. Half of the subjects receiving a total daily dose of 100 mg IDX184 achieved undetectable virus levels (< 15 IU/mL) by Day 14. Liver injury parameters (ALT and AST) improved (normalized) with all doses of IDX184. Antiviral activity and safety parameters measured after a total daily dose of 100 mg IDX184 did not differ between a QD or BID dosing regimen. 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. No virologic breakthrough was observed during treatment with IDX184 in combination with PegIFN/RBV.

 

"We are very encouraged by these interim data for IDX184 combined with pegylated interferon and ribavirin as the viral load reductions for the 100 mg cohorts are on par with the first-generation nucleoside in development but at a fraction of the dose," said Douglas Mayers, M.D., Idenix's executive vice president and chief medical officer. "We are currently enrolling the 150 mg once-daily dose cohort and look forward to reporting full data later this year. We believe that with the favorable antiviral activity, safety and resistance profile seen to date, IDX184 could be a potential component of future direct-acting antiviral combination regimens."

 

"With a high barrier to resistance and broad genotypic coverage, nucleosides and/or nucleotides could become an important part of future combination therapy for hepatitis C patients," said Dr. Fred Poordad, a principal investigator in the study, Chief of Hepatology at the Liver Disease and Transplant Center at Cedars-Sinai Medical Center in Los Angeles. "The interim 50 and 100 mg cohort data for IDX184 in combination with pegylated interferon and ribavirin have been promising and we look forward to the continued clinical development of this drug candidate."

 

About IDX184

IDX184 is a novel, liver-targeted nucleotide prodrug of 2'-methyl guanosine, which includes Idenix's proprietary liver-targeting technology. This technology enables the delivery of nucleoside monophosphate to the liver, leading to the formation of high levels of nucleoside triphosphate, potentially maximizing drug efficacy and limiting systemic side effects with low, once-daily dosing.

 

GlobeImmune GI-5005 HCV Product Candidate Improves Sustained Virologic Response by 10 Percent, Demonstrating Potential to Be First Therapeutic Vaccine for HCV

 

Final Phase 2b Data for GI-5005 in Treatment-Naive Patients Presented at 45th Annual Meeting of the European Association for the Study of the Liver

 

LOUISVILLE, CO--(Marketwire - April 15, 2010) -  GlobeImmune, Inc. today announced final Phase 2b data for GI-5005, the Company's investigational Tarmogen® product candidate, demonstrating its potential to be the first successful therapeutic vaccine for chronic hepatitis C virus (HCV) infection. The data show that GI-5005 increased the sustained virologic response (SVR) in genotype 1 interferon-naïve patients to 58 percent when used in combination with standard of care (SOC), pegylated interferon-a2a plus ribavirin, versus 48 percent for patients receiving SOC alone. The study also demonstrated that adding GI-5005 to SOC results in an improvement in normalization of alanine aminotransferase (ALT) levels and suggests an improvement in liver biopsies, both markers used to assess liver damage.

 

Ira M. Jacobson, M.D., the Vincent Astor Distinguished Professor of Medicine at NewYork-Presbyterian/Weill Cornell Medical Center, and John G. McHutchison, M.D., Associate Director of the Duke Clinical Research Institute at Duke University Medical Center, presented the data today at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL).

 

"This is the first clinical study to demonstrate that a therapeutic vaccine can be used for patients with chronic hepatitis C infection," said Dr. Jacobson. "With its novel mode of action and apparent safety profile, the GI-5005 therapeutic vaccine could have an important impact on the treatment of this disease."

 

The Phase 2b study compared GI-5005 plus SOC versus SOC alone in 140 patients with chronic genotype 1 hepatitis C infection who were either treatment naïve or prior non-responders to SOC. On an intent-to-treat basis (patients having received at least one dose of combination therapy), treatment naïve patients receiving GI-5005 plus SOC as a triple therapy had an SVR rate of 58 percent, compared to an SVR rate of 48 percent in treatment naïve patients receiving SOC alone, a relative improvement of 21 percent. GI-5005 triple therapy demonstrated a 67 percent relative improvement in the proportion of patients achieving normalization of ALT levels on therapy. ALT is a marker of liver injury that is used to follow liver function in HCV patients. In addition, a trend toward an improvement in biopsy necroinflammatory scores was seen with a 39 percent relative improvement compared to those receiving SOC alone. The most common adverse events associated with GI-5005 were injection site reactions that were generally mild and transient in nature. Importantly, GI-5005 did not increase the discontinuation rates due to adverse events when added to standard of care [GI-5005 + SOC - 13.2 percent vs. SOC alone - 12.3 percent].

 

"These data show that adding GI-5005 to standard of care may give patients a clinically important advantage without added toxicity," said David Apelian, M.D., Ph.D., Chief Medical Officer at GlobeImmune. "We believe that this is an important medical breakthrough in the treatment of hepatitis C, and it may have implications for the development of treatments for other chronic viral infections."

 

Pharmacogenomic data demonstrating a correlation between GI-5005 treatment effect and polymorphisms in the human IL-28 B gene will also be presented at the EASL meeting on Saturday, April 17 by Dr. McHutchison.

 

Tarmogens are whole, heat-killed recombinant S. cerevisiae yeast that are engineered to express one or more disease-related proteins. GlobeImmune's GI-5005 Tarmogen is a therapeutic vaccine product candidate that contains conserved HCV structural proteins and is designed to generate an HCV specific T-cell response.

 

About GlobeImmune

GlobeImmune, Inc. is a private company developing active immunotherapies called Tarmogens for the treatment of cancer and infectious diseases. Tarmogens generate activated killer T cells that locate and eliminate cancer cells and/or virally-infected cells. The Company's lead product candidate, GI-5005, is a Tarmogen being developed for the treatment of chronic hepatitis C infection (HCV). GI-5005 is designed to complement both the current standard of care and emerging novel therapies for HCV. The Company's lead oncology program, GI-4000, targets cancers caused by mutated versions of the Ras oncoprotein. GI-4000 is being investigated in clinical trials for the treatment of pancreas cancer as well as other cancers that contain mutated Ras, including non-small cell lung cancer and colorectal cancer. In May 2009, the Company announced a global partnership with Celgene focused on the discovery, development and commercialization of multiple product candidates for the treatment of cancer.

 

For additional information, please visit the company's Web site at www.globeimmune.com.

 

Positive Interim Data from Idera Pharmaceuticals' Phase 1 Trial of IMO-2125 TLR9 Agonist Presented at 45th EASL

http://www.news-medical.net

 

Idera Pharmaceuticals, Inc. (Nasdaq: IDRA) announced today that positive interim data from a Phase 1 clinical trial of IMO-2125, a Toll-like Receptor 9 (TLR9) agonist, in null responder patients with chronic hepatitis C virus (HCV) infection were presented at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL). The oral presentation, entitled "A Phase 1, Multi-Center, Randomized, Placebo-controlled, Dose-escalation Study of IMO-2125, a TLR9 Agonist, in Hepatitis C Non-responders", was made by John McHutchison, M.D., Associate Director, Duke Clinical Research Institute and Director, Gastroenterology and Hepatology Research, Duke University Medical Center, Principal Investigator for the trial. The presentation provided additional detail from the trial regarding the interim data that was announced in December 2009.

 

 “New therapeutic approaches, including novel classes of immune modulators, are needed for the null responder HCV patient population, who show no benefit from standard of care therapy.”

 

In this trial, null responder HCV patients received IMO-2125 or placebo treatment once per week for four weeks. IMO-2125 was well tolerated by all patients receiving IMO-2125 through the first four dose levels. These patients showed dose-dependent increases in endogenous interferon-alpha and other anti-viral proteins. In addition, serum concentrations of induced interferon-alpha correlated with decreases in HCV viral load, and six of the eight null responder HCV patients who received IMO-2125 at 0.32 mg/kg/week showed maximum viral load reductions ranging from 1.0 to 3.5 logs at least once during the treatment period.

 

"In this interim report from a Phase 1 study, the results seen in patients receiving IMO-2125 are encouraging and warrant further study," said Dr. McHutchison. "New therapeutic approaches, including novel classes of immune modulators, are needed for the null responder HCV patient population, who show no benefit from standard of care therapy."

 

"Results from this first-in-man trial confirm the intended mechanism of action of IMO-2125. Based on these data, we have extended the trial to a fifth dose level and are evaluating dosage and treatment schedules in preparation for a planned Phase 2 trial in combination with ribavirin in the null responder HCV patient population," said Robert Arbeit, M.D., Vice President of Clinical Development at Idera. "In parallel we are conducting a Phase 1 clinical trial of IMO-2125 in combination with ribavirin in treatment-naïve HCV patients."

 

"We are encouraged with the results to date, which show that IMO-2125 induction of endogenous interferon-alpha and other cytokines correlates with anti-viral activity in this difficult-to-treat patient population," said Sudhir Agrawal, D.Phil., Chief Executive Officer and Chief Scientific Officer at Idera. "IMO-2125 was designed based on our expertise in nucleic acid chemistry and our application of structure-activity relationship studies to the creation of TLR-targeted therapeutics."

 

The presentation includes results at four dose levels of IMO-2125, 0.04, 0.08, 0.16, and 0.32 mg/kg, administered by weekly subcutaneous injection.

 

Source Idera Pharmaceuticals, Inc.

 

SCYNEXIS' SCY-635 Demonstrates Impressive Barrier to Resistance in HCV Treatment

http://finance.yahoo.com

 

--Candidate requires virus to develop multiple mutations to establish resistance--

 

--Results presented in an oral presentation at EASL--

 

RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)--Drug discovery company SCYNEXIS, Inc. today presented data supporting an impressive resistance profile for SCY-635—a novel, oral cyclophilin inhibitor being studied for the treatment of hepatitis C virus (HCV) infection. In the study, SCYNEXIS demonstrated that the hepatitis C virus required multiple mutations across two separate proteins in order to establish resistance to SCY-635. The majority of HCV drugs on the market and in development require only one targeted viral mutation to establish resistance. The results were presented in an oral session entitled, “Resistance Selection Following 15 Days of Monotherapy with SCY-635 a Non-immunosuppressive Cyclophilin Inhibitor with Potent Anti-HCV Activity,” at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL) in Vienna, Austria.

 

“These latest findings greatly strengthen the promise of SCY-635 as an important new drug candidate for the treatment of HCV,” said Sam Hopkins, PhD, Chief Scientific Officer of SCYNEXIS. “Over the year, we have established that single-agent treatment with SCY-635 yields a clinically meaningful reduction in viral load while exhibiting a very favorable safety profile. We have shown that SCY-635 exhibits additive to synergistic antiviral activity when combined with both approved and leading investigational agents and now we have demonstrated that SCY-635 appears to present the hepatitis C virus with a much a higher barrier to resistance than current therapies in development.”

 

Previous Phase 1b studies demonstrated that single-agent SCY-635 was associated with a clinically meaningful decline in plasma viremia (group mean maximum decrease of 2.3 log10) and that the mean maximal decline was observed on the last day of the study, day 15, suggesting a high barrier to the development of viral resistance. For the resistance studies presented at EASL, SCYNEXIS conducted an in-depth analysis of samples of plasma virus from individuals who participated in the Phase 1b study to assess the extent to which prolonged SCY-635 monotherapy treatment is associated with markers of drug resistance.

 

Participants had either received placebo (n=3) or 900 milligrams daily of SCY-635 (n=6). Samples were obtained at three time points during the study—day 1 (immediately before treatment), day 15 (the final day of treatment) and day 22 (follow-up seven days after completing treatment). HCV-specific RNA was extracted from patient plasma and RT-PCR was performed using specific primers to amplify the NS5A and NS5B genetic regions, which encode key viral replication proteins. Both strands of the resulting PCR products were sequenced and sequences obtained on days 15 and 22 were compared against day 1 sequence data to assess for the emergence of resistance mutations. No treatment-associated mutations in NS5A were detected in any samples. Two subjects experienced treatment-associated mutations in NS5B, but neither patient showed evidence of virologic break-through during treatment. These data are consistent with previous in vitro studies which also indicate that multiple mutations in NS5A and NS5B are required to confer high level resistance to SCY-635.

 

“There is a significant need for more effective treatments for HCV that work for a broader patient population and help overcome resistance issues,” said Yves J. Ribeill, PhD, President and Chief Executive Officer of SCYNEXIS. “We become more confident every day that SCY-635 could play an important role in establishing a new standard of care for a wider spectrum of HCV patients and look forward to continuing studies to this end. SCYNEXIS will initiate a Phase 2a study of SCY-635 in treatment naïve genotype 1 HCV patients in combination with the standard of care in the second quarter of 2010 and we anticipate top-line results from this study by year-end.”

 

About SCY-635 and SCYNEXIS’ Cyclophilin Inhibitor Platform

SCY-635 represents a new class of therapeutic agents for the treatment of HCV infection. SCY-635 is the first candidate in a novel class of non-immunosuppressive cyclophilin inhibitors owned by SCYNEXIS. Cyclophilins are a family of enzymatic proteins that assist in the folding and transport of other proteins synthesized within a cell. Scientists at SCYNEXIS have synthesized derivatives of Cyclosporine A in which cyclophilin binding activity (which mediates anti-HCV activity) is separated from calcineurin binding activity (which mediates immunosuppression). A growing body of scientific evidence indicates that non-immunosuppressive analogs of Cyclosporine A may have applications in multiple therapeutic areas. Cyclophilins play a central role in the pathophysiology of chronic viral infection, neuro- and cardio- degenerative diseases. Cyclophilin inhibition therefore represents an attractive target for drug discovery and development.

 

Biolex Unveils Interim Results from Empower Locteron Phase 2b Trial

http://clinicaltrials.pharmaceutical-business-review.com

 

Biolex, a biopharmaceutical company, has presented interim results from Empower, a prospectively designed analysis of results from two Phase 2b trials of Locteron, at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL) in Vienna, Austria.

 

Locteron, a controlled-release interferon alpha 2b, is designed to improve patient care by providing a more convenient once-every-two week dosing schedule and by reducing the flu-like symptoms associated with pegylated interferons, the current standard of care.

 

In the Empower study, the 480ug dose of Locteron demonstrated viral kinetics and response rates that were comparable to the PEG-Intron control while also achieving a 57% reduction in flu-like adverse events.

 

The objective of the Empower study was to test the hypothesis that the 480ug dose of Locteron dosed once every two weeks reduces flu-like symptoms but retains equivalent efficacy compared to PEG-Intron (1.5ug/kg, administered every week).

 

Reportedly, the 133 patients in the Empower study were enrolled in two contributing Phase 2b trials: Select-2 and 480 Study.

 

All patients were treatment-naive-genotype-1 subjects with chronic hepatitis C, and all patients were also treated with weight-based ribavirin. A total of 30 sites participated in the two trials (14 sites in the US, 11 in Europe, and five in Israel). All patients in Empower have completed at least six weeks of study, and over 80% of the patients have completed 12 weeks of study.

 

Through six weeks of treatment, Locteron 480ug administered once every two weeks demonstrated reductions in viral loads (mean changes in HCV RNA from baseline) that were somewhat more rapid than that achieved with PEG-Intron administered once per week.

 

Rates of undetectable HCV RNA achieved after six weeks of treatment were 31% for Locteron 480ug and 19% for PEG-Intron. The currently available results after 12 weeks of treatment (a number of patients have not yet reached the 12-week time point) suggest comparable reductions in mean HCV RNA and rates of undetectable HCV RNA for Locteron 480ug and PEG-Intron.

 

Walker Long, chief medical officer and vice president of drug development at Biolex Therapeutics, said: "The Empower study allows us to focus on the activity associated with one specific dose of Locteron and test our hypothesis that equivalent efficacy can be achieved while greatly reducing flu-like adverse events.

 

"These results exceed our expectations. We believe that the importance of reducing flu-like adverse events will grow with the advent of direct-acting antivirals and the shortening of therapy, due to the prevalence of these side effects during the first three months of treatment."