PSI-7977 + BMS-790052 Trial for Hepatitis C (an all-oral antiviral regimen)

[Guest guest]

http://www.hivandhepatitis.com/hep_c/news/2011/0603_2011_a.html

PSI-7977 + BMS-790052 Trial for Hepatitis C

SUMMARY

Pharmasset announced the start of a Phase 2a study of an all-oral antiviral

regimen of HCV polymerase inhibitor PSI-7977 plus NS5A replication complex

inhibitor BMS-790052.

The advent of direct-acting antiviral agents that target different steps of the

hepatitis C virus (HCV) lifecycle is expected to revolutionize chronic hepatitis

C treatment.

The first 2 such drugs approved by the U.S. Food and Drug Administration -- the

HCV protease inhibitors boceprevir (Victrelis) and telaprevir (Incivek) -- are

indicated for use in combination with current standard therapy consisting of

pegylated interferon plus ribavirin. But hepatitis C patients and clinicians are

eagerly awaiting all-oral regimens that will avoid injected interferon and its

difficult side effects.

Pharmasset, Inc. announced last week that it will test a variety of 24-week

regimens of PSI-7977 plus Bristol-Myers Squibb's BMS-790052. As reported at this

year's EASL meeting in April, PSI-7977 worked well both with standard therapy

and in an all-oral regimen with PSI-938. A combination of BMS-790052 plus

BMS-650032 produced high response rates in prior non-responders.

The new Phase 2a trial will enroll treatment-naive patients with both

hard-to-treat HCV genotype 1 and genotypes 2 or 3. Some participants will have a

1-week PSI-7977 monotherapy lead-in period before adding BMS-790052. Other arms

will start the 2 experimental drugs plus ribavirin at the same time.

Below is an edited excerpt from a recent Pharmasset press release describing the

trial.

All-Oral Combination Study with PSI-7977 for

HCV Genotypes 1, 2 and 3 Initiated

Princeton, N.J. -- May 26, 2011 -- Pharmasset, Inc. (Nasdaq: VRUS) announced

today the initiation of a Phase 2a trial investigating the combination of

Pharmasset's PSI-7977, a nucleotide polymerase inhibitor, and BMS-790052,

Bristol-Myers Squibb Company's (NYSE: BMY) NS5A replication complex inhibitor,

for the treatment of chronic hepatitis C (HCV). This trial is the result of a

clinical collaboration agreement between Pharmasset and Bristol-Myers Squibb

announced in January 2011.

" We are happy to announce the initiation of this important combination trial, "

stated Symonds, Pharmasset's Senior Vice President of Clinical

Pharmacology and Translational Medicine. " Recent data from Bristol-Myers

Squibb's combination study demonstrated that individuals with HCV can be cured

without the traditional interferon and ribavirin, but only if two potent DAAs

are used and drug resistance is avoided. We believe Pharmasset's nucleotide

analogs have demonstrated potent antiviral activity and a high barrier to

resistance and therefore have the potential to be the future backbone of

interferon-free treatment. "

About the Trial

This Phase 2a trial is planned to enroll approximately 84 patients with chronic

HCV genotypes 1, 2 or 3 who have not been treated previously. The primary

endpoint of the trial is sustained virologic response (SVR). The trial will be

conducted in the U.S. Subjects will be randomized equally across each of the

following arms:

PSI-7977 400mg QD for 7 days, then add BMS-790052 60mg QD for further 23 weeks

in genotype 1 subjects;

PSI-7977 400mg QD for 7 days, then add BMS-790052 60mg QD for further 23 weeks

in genotype 2 or 3 subjects;

PSI-7977 400mg QD and BMS-790052 60mg QD for 24 weeks in genotype 1 subjects;

PSI-7977 400mg QD and BMS-790052 60mg QD for 24 weeks in genotype 2 or 3

subjects;

PSI-7977 400mg QD, BMS-790052 60mg QD and ribavirin for 24 weeks in genotype 1

subjects;

PSI-7977 400mg QD, BMS-790052 60mg QD and ribavirin for 24 weeks in genotype 2

or 3 subjects.

Additional details can be found at www.clinicaltrials.gov.

About Pharmasset

Pharmasset is a clinical-stage pharmaceutical company committed to discovering,

developing, and commercializing novel drugs to treat viral infections.

Pharmasset's primary focus is development of oral therapeutics for the treatment

of hepatitis C virus (HCV) infection. Our research and development efforts are

focused on nucleoside/tide analogs, a class of compounds which act as

alternative substrates for the viral polymerase, thus inhibiting viral

replication. We currently have three clinical-stage product candidates advancing

in trials in various populations. Our pyrimidine, PSI-7977, an unpartnered

uracil nucleotide analog, is currently under study in three Phase 2b trials in

patients with HCV genotypes 1 through 6, including abbreviated duration

interferon and interferon-free regimens. Our purine, PSI-938, an unpartnered

guanosine nucleotide analog, recently reported safety and efficacy data from

14-days of monotherapy as well as 14 days in combination with the pyrimidine,

PSI-7977. An SVR-endpoint study of the purine-pyrimidine combination is

anticipated to begin third quarter 2011. Mericitabine (RG7128) continues in two

Phase 2b trials and one interferon-free trial conducted through a strategic

collaboration with Roche.

For more information, see www.pharmasset.com.

6/3/11

Source

Pharmasset, Inc. All-Oral Combination Study with PSI-7977 for HCV Genotypes 1, 2

and 3 Initiated. Press release. May 26, 2011.

[Guest guest]

http://www.hivandhepatitis.com/hep_c/news/2011/0603_2011_a.html

PSI-7977 + BMS-790052 Trial for Hepatitis C

SUMMARY

Pharmasset announced the start of a Phase 2a study of an all-oral antiviral

regimen of HCV polymerase inhibitor PSI-7977 plus NS5A replication complex

inhibitor BMS-790052.

The advent of direct-acting antiviral agents that target different steps of the

hepatitis C virus (HCV) lifecycle is expected to revolutionize chronic hepatitis

C treatment.

The first 2 such drugs approved by the U.S. Food and Drug Administration -- the

HCV protease inhibitors boceprevir (Victrelis) and telaprevir (Incivek) -- are

indicated for use in combination with current standard therapy consisting of

pegylated interferon plus ribavirin. But hepatitis C patients and clinicians are

eagerly awaiting all-oral regimens that will avoid injected interferon and its

difficult side effects.

Pharmasset, Inc. announced last week that it will test a variety of 24-week

regimens of PSI-7977 plus Bristol-Myers Squibb's BMS-790052. As reported at this

year's EASL meeting in April, PSI-7977 worked well both with standard therapy

and in an all-oral regimen with PSI-938. A combination of BMS-790052 plus

BMS-650032 produced high response rates in prior non-responders.

The new Phase 2a trial will enroll treatment-naive patients with both

hard-to-treat HCV genotype 1 and genotypes 2 or 3. Some participants will have a

1-week PSI-7977 monotherapy lead-in period before adding BMS-790052. Other arms

will start the 2 experimental drugs plus ribavirin at the same time.

Below is an edited excerpt from a recent Pharmasset press release describing the

trial.

All-Oral Combination Study with PSI-7977 for

HCV Genotypes 1, 2 and 3 Initiated

Princeton, N.J. -- May 26, 2011 -- Pharmasset, Inc. (Nasdaq: VRUS) announced

today the initiation of a Phase 2a trial investigating the combination of

Pharmasset's PSI-7977, a nucleotide polymerase inhibitor, and BMS-790052,

Bristol-Myers Squibb Company's (NYSE: BMY) NS5A replication complex inhibitor,

for the treatment of chronic hepatitis C (HCV). This trial is the result of a

clinical collaboration agreement between Pharmasset and Bristol-Myers Squibb

announced in January 2011.

" We are happy to announce the initiation of this important combination trial, "

stated Symonds, Pharmasset's Senior Vice President of Clinical

Pharmacology and Translational Medicine. " Recent data from Bristol-Myers

Squibb's combination study demonstrated that individuals with HCV can be cured

without the traditional interferon and ribavirin, but only if two potent DAAs

are used and drug resistance is avoided. We believe Pharmasset's nucleotide

analogs have demonstrated potent antiviral activity and a high barrier to

resistance and therefore have the potential to be the future backbone of

interferon-free treatment. "

About the Trial

This Phase 2a trial is planned to enroll approximately 84 patients with chronic

HCV genotypes 1, 2 or 3 who have not been treated previously. The primary

endpoint of the trial is sustained virologic response (SVR). The trial will be

conducted in the U.S. Subjects will be randomized equally across each of the

following arms:

PSI-7977 400mg QD for 7 days, then add BMS-790052 60mg QD for further 23 weeks

in genotype 1 subjects;

PSI-7977 400mg QD for 7 days, then add BMS-790052 60mg QD for further 23 weeks

in genotype 2 or 3 subjects;

PSI-7977 400mg QD and BMS-790052 60mg QD for 24 weeks in genotype 1 subjects;

PSI-7977 400mg QD and BMS-790052 60mg QD for 24 weeks in genotype 2 or 3

subjects;

PSI-7977 400mg QD, BMS-790052 60mg QD and ribavirin for 24 weeks in genotype 1

subjects;

PSI-7977 400mg QD, BMS-790052 60mg QD and ribavirin for 24 weeks in genotype 2

or 3 subjects.

Additional details can be found at www.clinicaltrials.gov.

About Pharmasset

Pharmasset is a clinical-stage pharmaceutical company committed to discovering,

developing, and commercializing novel drugs to treat viral infections.

Pharmasset's primary focus is development of oral therapeutics for the treatment

of hepatitis C virus (HCV) infection. Our research and development efforts are

focused on nucleoside/tide analogs, a class of compounds which act as

alternative substrates for the viral polymerase, thus inhibiting viral

replication. We currently have three clinical-stage product candidates advancing

in trials in various populations. Our pyrimidine, PSI-7977, an unpartnered

uracil nucleotide analog, is currently under study in three Phase 2b trials in

patients with HCV genotypes 1 through 6, including abbreviated duration

interferon and interferon-free regimens. Our purine, PSI-938, an unpartnered

guanosine nucleotide analog, recently reported safety and efficacy data from

14-days of monotherapy as well as 14 days in combination with the pyrimidine,

PSI-7977. An SVR-endpoint study of the purine-pyrimidine combination is

anticipated to begin third quarter 2011. Mericitabine (RG7128) continues in two

Phase 2b trials and one interferon-free trial conducted through a strategic

collaboration with Roche.

For more information, see www.pharmasset.com.

6/3/11

Source

Pharmasset, Inc. All-Oral Combination Study with PSI-7977 for HCV Genotypes 1, 2

and 3 Initiated. Press release. May 26, 2011.