EASL presentation on HCV-796

[chcnme]

For those following or interested in HCV-796  (polymerase inhibitor)  here's what they presented at the EASL.

ViroPharma Announces Presentation of Additional HCV-796 Data at Meeting of The European Association for the Study of the Liver      

(continued next post)

[chcnme]

ViroPharma Announces Presentation of Additional HCV-796 Data at Meeting of The European Association for the Study of the Liver

13 Apr 2007 Phase 1b Combination Data Highlight Favorable Tolerability and Additive Antiviral Activity of HCV-796


EXTON, PA, USA | Apr 13, 2007 | ViroPharma Incorporated (Nasdaq: VPHM) today announced additional data from a Phase 1b study of HCV- 796, a unique, orally dosed hepatitis C virus (HCV) polymerase inhibitor at the 42nd Annual Meeting of the European Association for the Study of the Liver (EASL). This meeting is being held in Barcelona, Spain. These data on the antiviral activity and tolerability of twice daily HCV-796 in combination with pegylated interferon alfa-2b (peg-IFN) elaborate on previously presented data. HCV-796 is currently undergoing Phase 2 evaluation and is being co-developed with Wyeth Pharmaceuticals, a division of Wyeth (NYSE: WYE).

These Phase 1b combination data demonstrate the additive antiviral effects of HCV-796 across multiple genotypes of hepatitis C virus, in treatment-naïve adult subjects with chronic hepatitis C infection. HCV-796 dosed twice daily plus peg-IFN displays clinical antiviral activity that is greater than that of HCV-796 or peg-IFN alone across all dose cohorts and tested HCV genotypes. Final safety and tolerability data show that HCV-796 is generally well tolerated when added to peg-IFN. Adverse events were generally consistent with known effects of interferons. No dose-limiting toxicities were observed across the range of HCV-796 study doses.

"In this Phase 1b study, HCV-796 provided added antiviral activity to that of pegylated interferon across multiple HCV genotypes and did so largely without altering interferon's tolerability profile," commented Colin Broom, ViroPharma's chief scientific officer. "The adverse events observed in patients on combination therapy were typical of those seen in patients on pegylated interferon alone. The antiviral activity of HCV-796, its strong tolerability profile, and its lack of dose limiting toxicities encourage us as we proceed expeditiously through our ongoing Phase 2 program."

Phase 1b Clinical Trial Design

This 14 day randomized, double-blind, placebo-controlled, sequential-group study of ascending multiple doses enrolled subjects with chronic HCV infection who were naive to treatment. Subjects were enrolled in sequential, ascending dose cohorts with a target of 16 subjects (12 subjects receiving HCV-796 BID and 4 receiving placebo in each cohort). The first cohorts assessed the effect of HCV-796 as monotherapy compared to placebo (data from which were released on November 10, 2005). Subsequent cohorts were comprised of subjects who received peg-IFN (PEG-Intron; 1.5 ug/kg/dose) on days -1 and 7 in combination with either placebo or HCV-796 (100 mg, 250 mg, 500 mg or 1000 mg) every 12 hours, from days 1 to 14.

Antiviral Activity Results

Data are available through treatment day 14 from subjects in four combination treatment groups (n= 10 to 12 subjects per group) and on 19 subjects who received peg-IFN alone.

-- For genotype 1, mean reduction from baseline ranged from 1.5 to 2.3 log10 on day 7 and from 2.6 to 3.2 log10 on day 14 in the combination therapy groups compared to 0.9 log10 on day 7 and 1.3 log10 on day 14 for peg-IFN alone.

-- For non-genotype 1, mean reduction from baseline ranged from 2.8 to 3.5 log10 on day 7 and from 3.5 to 4.8 log10 on day 14 in the combination therapy groups compared to 1.5 log10 on day 7 and 2.6 log10 on day 14 for peg-IFN alone.

-- Viral reduction greater or equal to 2.0 log10 at day 14 was achieved in 70 to 92 percent of subjects in all combination groups compared to 40 percent on peg-IFN alone.

-- At day 14, 30 to 33 percent of patients in the combination groups receiving greater than or equal to 250 mg BID of HCV-796 achieved viral levels below the quantification limit of 50 IU/mL HCV RNA.

Safety and Tolerability Results

A safety review of HCV-796 in combination with peg-IFN has been completed. Combination therapy including HCV-796 was found to be generally well tolerated. The observed safety profile supports the evaluation of HCV-796 in studies of longer duration.

-- Adverse events across all dose cohorts were generally mild to moderate in severity and were characteristic of the known side effects of interferons.

-- Adverse events that occurred at a frequency of greater than 15 percent across all dose cohorts of HCV-796 plus peg-IFN and peg-IFN alone included headache, chills, myalgias, fever, pain, arthralgia and rash.

-- There were two reports of serious adverse events: one in the placebo arm (pneumonia), and one in the 1000 mg combination cohort (seizure and rhabdomyolysis in a subject receiving high dose methadone chronically).

-- The rate of discontinuation due to adverse events was low across the study. No patient discontinued due to adverse events in the 100, 250, or 500 mg dose cohorts. In the peg-IFN alone group, one patient discontinued due to hypertension; of those that received 1000 mg HCV-796 plus peg-IFN, three patients discontinued due to either vasovagal syncope after a blood draw, rash, or seizure and rhabdomyolysis (in a subject receiving high dose methadone chronically).

-- No dose-limiting toxicities were identified across the range of study doses.

Genetic Sequencing

NS5B sequencing was performed on 36 subjects (11 on peg-IFN alone; 25 HCV- 796 and peg-IFN). Consistent with data from the Phase 1b study of HCV-796 as monotherapy, the only variant of importance detected in patients receiving HCV-796 was a C316Y variant known to have reduced susceptibility to HCV-796. Baseline sequencing did not find any variation from wild type at this position. The C316Y variant was observed in 7 (28 percent) of patients on HCV- 796 plus peg-IFN, occurring less frequently than previously seen in patients receiving HCV-796 as monotherapy, and was not clearly associated with virologic response pattern. The clinical implication of this mutation, if any, will be evaluated in ongoing and future long-term studies.

About Hepatitis C

Hepatitis C is a blood-borne virus recognized as a major cause of chronic hepatitis worldwide. The World Health Organization estimates that 170 million persons worldwide are chronically infected with HCV, and three to four million persons are newly infected globally each year. According to the U.S. Centers for Disease Control and Prevention (CDC), about four million people in the U.S., or 1.8 percent of the population, are infected with HCV.

Currently, there is no specific antiviral agent directed against HCV that is commercially available, and no vaccine for prevention of HCV infection. Several interferon (IFN) products are available worldwide, but there are substantial limitations to the use of these products when given as monotherapy or in conjunction with ribavirin in the treatment of chronic HCV infection. In addition to the relatively poor treatment response in patients infected with genotype 1 HCV, the most common strain in the U.S., Western Europe and Japan, the considerable side effects frequently associated with the use of IFN can lead to discontinuation of therapy in approximately 20 percent of patients.

About ViroPharma Incorporated

ViroPharma Incorporated is committed to the development and commercialization of products that address serious diseases treated by physician specialists and in hospital settings. ViroPharma commercializes Vancocin(R), approved for oral administration for treatment of antibiotic- associated pseudomembranous colitis caused by Clostridium difficile and enterocolitis caused by Staphylococcus aureus, including methicillin-resistant strains (for prescribing information, please download the package insert at http://www.viropharma.com/docs/pulvules_pi.pdf ). ViroPharma currently focuses its drug development activities in viral diseases including cytomegalovirus (CMV) and hepatitis C (HCV). For more information on ViroPharma, visit the company's website at http://www.viropharma.com .

Certain statements in this press release contain forward-looking statements that involve a number of risks and uncertainties. .including those relating to the company's progress of its HCV clinical development program as well as its ability to develop an effective small molecule antiviral treatment for HCV disease. Our actual results could differ materially from those results expressed in, or implied by, these forward-looking statements.. Conducting clinical trials for investigational pharmaceutical products is subject to risks and uncertainties. Further testing such as the ongoing Phase 2 clinical studies of HCV-796 with pegylated interferon, may not support any or all of the statements in this press release. There can be no assurance that ViroPharma's additional HCV studies will yield positive results, or that ViroPharma will be successful in gaining regulatory approval of any of its HCV product candidates. These factors, and other factors, including, but not limited to those described in ViroPharma's quarterly report on Form 10-K for the year ended December 31, 2006 filed with the Securities and Exchange Commission, could cause future results to differ materially from the expectations expressed in this press release. The forward-looking statements contained in this press release may become outdated over time. ViroPharma does not assume any responsibility for updating any forward-looking statements.

SOURCE: ViroPharma Incorporated

[chcnme]

For those interested in the trials with HCV 796 see:

SOURCE:  
http://clinicaltrials.gov/ct/show/NCT00367887?order=1

A Study Evaluating the Safety and Clinical Activity of HCV-796 in Treatment-Naive and Non-Responder Subjects

This study is currently recruiting patients.

Verified by Wyeth April 2007

Sponsored by: Wyeth
Information provided by: Wyeth
ClinicalTrials.gov Identifier: NCT00367887


Purpose

This is a phase 2, randomized, open-label study comparing the safety, antiviral activity, and pharmacokinetics of HCV-796 administered in combination with peginterferon alfa 2B (Peg-Intron) plus concomitant Rebetol vs. Peg-Intron plus Rebetol in Hepatitis C Virus (HCV) genotype

1-infected subjects who are either naive to treatment or who have previously failed treatment (non-responders).


Hepatitis C
Drug: HCV 796
Phase II

Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Official Title: A Phase 2, Randomized, Open-Label Study of the Safety, Antiviral Activity, and Pharmacokinetics of HCV-796 Administered in Combination With Peginterferon Alfa 2B (Peg-Intron) Plus Ribavirin (Rebetol) Versus Peg-Intron Plus Rebetol in Subjects With Hepatitis C Virus Genotype 1 Infection

Further study details as provided by Wyeth:
Primary Outcomes: Hepatitis C Virus (HCV) RNA concentrations in the blood.
Expected Total Enrollment:  267
Study start: September 2006;  Expected completion: October 2008


Eligibility

Ages Eligible for Study:  18 Years   -   65 Years,  Genders Eligible for Study:  Both
Criteria
Major Criteria for Inclusion:

Infection with HCV genotype 1
HCV- infected subjects naive to treatment
HCV-infected non-responder subjects
Major Criteria for Exclusion:

Women who are pregnant or breastfeeding
ALT > or = 3X the upper limit of normal
AST > or = 5X the upper limit of normal
Location and Contact Information

Please refer to this study by ClinicalTrials.gov identifier  NCT00367887

Trial Manager       ***@****


United States, Alabama
      Birmingham,  Alabama,  35235,  United States; Recruiting

United States, California
      San Diego,  California,  92123,  United States; Recruiting

      San Francisco,  California,  94115,  United States; Recruiting

      San Diego,  California,  92161,  United States; Recruiting

      Los Angeles,  California,  90033,  United States; Recruiting

      Long Beach,  California,  90882,  United States; Recruiting

      La Jolla,  California,  92037,  United States; Recruiting

      Los Angeles,  California,  90048,  United States; Not yet recruiting

      Pasadena,  California,  91105,  United States; Recruiting

      San Francisco,  California,  94121,  United States; Recruiting

      Anaheim,  California,  92801,  United States; Recruiting

United States, Colorado
      Denver,  Colorado,  80262,  United States; Recruiting

United States, District of Columbia
      Washington,  District of Columbia,  20010,  United States; Recruiting

United States, Florida
      Gainesville,  Florida,  32610,  United States; Recruiting

      Miami,  Florida,  33136,  United States; Recruiting

United States, Georgia
      Atlanta,  Georgia,  30309,  United States; Recruiting

United States, Illinois
      Chicago,  Illinois,  60637,  United States; Recruiting

United States, Kentucky
      Louisville,  Kentucky,  40202,  United States; Recruiting

United States, Louisiana
      New Orleans,  Louisiana,  70115,  United States; Recruiting

United States, Maryland
      Baltimore,  Maryland,  21287,  United States; Not yet recruiting

United States, Massachusetts
      Boston,  Massachusetts,  02215,  United States; Recruiting

      Worcester,  Massachusetts,  01655,  United States; Recruiting

United States, Michigan
      Detroit,  Michigan,  48202,  United States; Recruiting

United States, Minnesota
      Plymouth,  Minnesota,  55446,  United States; Recruiting

United States, Missouri
      St. Louis,  Missouri,  63104,  United States; Recruiting

United States, New Mexico
      Albuquerque,  New Mexico,  87131,  United States; Recruiting

United States, New York
      Bronx,  New York,  10468,  United States; Recruiting

      New York,  New York,  10032,  United States; Recruiting

      New York,  New York,  10021,  United States; Recruiting

      New York,  New York,  10029,  United States; Recruiting

      Bronx,  New York,  10461,  United States; Recruiting

United States, North Carolina
      Chapel Hill,  North Carolina,  27514,  United States; Recruiting

      Durham,  North Carolina,  27710,  United States; Recruiting

United States, Ohio
      Cleveland,  Ohio,  44195,  United States; Recruiting

      Cincinnati,  Ohio,  45219,  United States; Recruiting

United States, Pennsylvania
      Philadelphia,  Pennsylvania,  19141,  United States; Recruiting

United States, Texas
      Houston,  Texas,  77030,  United States; Not yet recruiting

      Houston,  Texas,  77030,  United States; Recruiting

United States, Virginia
      Richmond,  Virginia,  23249,  United States; Recruiting

      Fairfax,  Virginia,  22031,  United States; Recruiting

      Annandale,  Virginia,  22003,  United States; Recruiting

United States, Washington
      Seattle,  Washington,  98195,  United States; Terminated

United States, West Virginia
      Morgantown,  West Virginia,  26506,  United States; Not yet recruiting

Puerto Rico
      Santurce,  00909,  Puerto Rico; Recruiting


Study chairs or principal investigators

Medical Monitor,  Study Director,  Wyeth Research    
More Information

Study ID Numbers:  3173A1-200
Last Updated:  April 11, 2007
Record first received:  August 21, 2006
ClinicalTrials.gov Identifier:  NCT00367887
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on April 13, 2007
=================================

SOURCE:  

http://clinicaltrials.gov/ct/show/NCT00367887?order=1

[foofighter]

Does this info have anyone else interested in participating in the trial?

I go for my trial screening exam tomorrow.  I somehow missed that Phase 1 didn't include Riba (or didn't remember). And adding the Riba might really kick it into high gear. Or cause problems, I guess.

So, even though it was a small group it looks pretty good, right? What do you think Jim? Of the three that dropped out on the combination therapy, the side effects didn't seem too scary (except for the methadone guy). Scary enough if it happens to you I know.

[chcnme]

Hi foo.  I have heard from some (or read notes) where some are interested, though I don't think the word is out as much about 796 as VX  (understandably), and VX is what everyone has been eyeing.  Personally, based on what I've read - I think the 796 looks like a great trial for someone to shoot for if they want to be treated with "newer drugs".   Doc said that unlike VX-950 it would allow people such as myself who had just had a few weeks of prior treatment to get in.   He said it would be given with SOC  (PegIntron and Riba) for 48 weeks.  

I recall reading  (can't tell you where from what source I read it)   that one day HCV treatment will most likely consist of a protease inhibitor and a polymerase inhibitor  (and I recall it was thought the two might be VX-950 and HCV 796).  That sparked my interest even moreso in the 796.  

It's got pretty good looking data, don't you think?  If I weren't so concerned about the fact that no rescue drugs will be allowed  (probably)  I'd be real excited about the chance.  For someone who's never treated or who's had only a few weeks and doesn't have concerns about neutropenia, reduction of dose, or other health issues, or for nonresponders, I think it's a great chance if someone can get in it.  If my doc at Duke thinks it's the next best "newer drug" as far as a trial,  then it's a good one,  I think.   My hepatologist locally is concerned about the rescue drug issue  (trials usually don't allow them.)  Doc at Duke said that was to be seen and that I would be told about whether they're allowed or not and when they're allowed when they (the research coordinator)  calls me.   THe clinical trials site has just recently updated many of the sites to "now recruiting" (they had mostly been listed as "not recruiting yet" -- for months).  And so...it looks like they're starting up and getting into gear.  Ask your doc if you're interested!  Best of luck.  

[coeric]

for what it's worth,  Dr. E at the university of colorado characterized this drug as "very promising."  and is currently enrolling subjects. two weeks ago my alt was 400 so i  don't  qualify.  

[chcnme]

DA**!  I am so sorry about the 400 something enzymes :(  Hang in there.  Let us know how you're doing.  

[willing]

thanks for posting - if anyone has a link to Wyeth's '05 monotheraphy results it would be interesting to compare those with the combo ones. The combined polymerase/protease inhibitor strategy is one I'm betting on as well. The escape mutations required for the virus to survive each inhibitor are independent so the effects should multiply: if 10 % of the virus can evolve to the C316F/Y or S365T/A mutations required to replicate in the presence of 796 and 10% can evolve to the corresponding 750 escape mutations combo tx should only leave 1% to ifn's general purpose antiviral effect. I assume it won't be too much longer before some specialist/research-lab that has access to both drugs can post results.

[jmjm530]

http://www.hivandhepatitis.com/2006icr/ddw/docs/053006_c.html

[Willy50]

http://www.marketwatch.com/News/Story/Story.aspx?guid=%7b26632261-E630-4A66-9A16-371F06B1B3E5%7d&siteid=yhoo&dist=yhoo

SGP's (PI) + a polymerase inhibitor= possible new TX

TVR (PI) VX-950 is also expected to be combined with another polymerase inhibitor at some point in the future.  IF they are in partnership with SGP could that prevent combining these 2 compounds? (TVR and HCV-796 )

Some folks think the new inhibitirs will be the wave of the future; no more shots.  No more interferon.

best,
Willy

[chcnme]

Good question, Willie  (thanks for the link on that).  I think a poly and prot inhib will be the treatment one day, for sure - hopefully without INF (probably for sure, too.)  I wonder which two it'll be (another wait and see, definitely for sure :)

And thanks, Willing  - great observation.  

[Forseegood]

Just wanted to say, it's always good to see you here, I'd be interested in hearing your observations, once all this data comes in on a few of these new meds...hope youre well and thriving...