Pharmasset, Inc.
PRINCETON, N.J., Aug. 24, 2011 --
/PRNewswire/ -- Pharmasset, Inc. (Nasdaq: VRUS) has received fast track designation from the U.S. Food and Drug Administration (FDA) for PSI-938 for the treatment of chronic hepatitis C virus (HCV) infection. PSI-938 is an oral guanosine nucleotide analog polymerase inhibitor of HCV.
In March 2011, Pharmasset presented data from the NUCLEAR study demonstrating that PSI-938 has potent antiviral activity and is generally safe and well tolerated, both as monotherapy and in combination with Pharmasset's lead nucleotide analog, PSI-7977. The NUCLEAR study was conducted in treatment naive subjects with genotype 1 HCV who were treated for 14 days with either PSI-938 or a combination of PSI-938 and PSI-7977 with 92% achieving HCV RNA <15IU/mL, the limit of detection, in the combination arms.
Pharmasset plans to initiate QUANTUM, an interferon-free combination trial with PSI-938 and PSI-7977 in the third quarter of 2011.
Under the FDA Modernization Act of 1997, fast track designation may facilitate the development and expedite the review of a drug candidate that is intended for the treatment of a serious and life-threatening condition and demonstrates the potential to address an unmet medical need for such a condition. PSI-938 was granted the fast track designation primarily due to the need for HCV treatments with improved tolerability, safety and efficacy over the existing standard of care for both treatment-naive and treatment-experienced patients.
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 the 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 four 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 in the third quarter of 2011. Mericitabine (RG7128) continues in three Phase 2b trials and one interferon-free trial being conducted through a strategic collaboration with Roche.
ContactRichard E. T. Smith, Ph.D. VP, Investor Relations and Corporate Communicationsrichard.smith@pharmasset.comOffice: +1 (609) 613-4181
Forward-Looking Statements
Pharmasset "Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995: Statements in this press release that are not historical facts are "forward-looking statements," that involve risks, uncertainties, and other important factors, including, without limitation, the risk of cessation or delay of any of the ongoing or planned clinical trials and/or our development of our product candidates, the risk that the results of previously conducted studies involving our product candidates will not be repeated or observed in ongoing or future studies involving our product candidates, the risk that our collaboration with Roche will not continue or will not be successful, and the risk that any one or more of our product candidates will not be successfully developed and commercialized. For a discussion of risks, uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in our Annual Report on Form 10-K for the fiscal year ended September 30, 2010 and our Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission and discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission.
SOURCE Pharmasset, Inc.
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Read more: http://www.heraldonline.com/2011/08/24/3314937/psi-938-receives-fast-track-designation.html
Showing posts with label PSI-938. Show all posts
Showing posts with label PSI-938. Show all posts
Wednesday, August 24, 2011
Wednesday, March 23, 2011
Hepatitis; PSI-938 and PSI-7977 Breaking Down The Media Frenzy
Last week we had a sneak peek at a small study being presented at this months EASL.
According to the recent media frenzy Pharmassets two oral drugs in development "PSI-938 and PSI-7977" showed in early-stage data that 15 out of 16 patients achieved an early/promising antiviral response after 14 days on treatment.
The HCV community, although excited about a regimen of "interferon free" therapy, keep it all in perspective and wait until Pharmasset conducts their phase II study of " interferon-free combinations" with an SVR endpoint, expected in mid-2011. For this community the bottom line is SVR.
You can look at "all" the abstracts that will be presented at the EASL by clicking here
The controversy
The EASL has an embargo in place until the data is presented at the meeting. However, a few investment websites released the data early, breaking the media embargo.
The Study Can Be Found At The EASL Website
"ONCE DAILY DUAL-NUCLEOTIDE COMBINATION OF PSI-938 AND PSI-7977"
You can view the abstract here.
What Study are we talking about, whats the big deal ?
The study included treatment-naïve, non-cirrhotic patients with HCV Genotype 1. The two drugs "PSI-938 AND PSI-7977" were tested in four different cohorts (see below) without using "interferon" over fourteen days. The study was deemed ; NUCLEAR Study .
.
From the Nov "2010" Press Release;
This is the first clinical study combining a purine (PSI-938) and a pyrimidine (PSI-7977) nucleotide analog for HCV, and is designed to evaluate once daily doses of PSI-7977 and PSI-938 in patients with HCV who have not been treated previously.
"We are excited to be initiating this combination study with two proprietary nucleotide analogs for HCV," stated Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "Based on our in vitro data, we believe the combination of two nucleotide analogs could provide potent antiviral activity across multiple HCV genotypes and could also have a higher barrier to resistance compared to other DAA combinations. We believe nucleotide analogs have a number of key attributes that may make them ideal partners for other DAA combinations, in addition to a 'nuc-nuc' combination."
About the Phase 1 Trial - Part 1, Part 2
Part 1 of the Phase 1 multiple ascending dose study of PSI-938, suppression of HCV RNA below the limit of detection (LOD, less then 15 IU/mL) was observed in over half of the patients who received PSI-938 at daily doses of 200 mg or 300 mg for seven days.
Part 2 of the study is designed to evaluate the combination of PSI-938 and PSI-7977.
The primary objective is to assess the safety, tolerability and pharmacokinetics of PSI-938 administered alone for 14 days, and in combination with PSI-7977 for 7 to 14 days.
The secondary objective is to evaluate viral kinetics of HCV RNA during monotherapy (no interferon) and combination nucleotide dosing.
The Four Cohorts;
Approximately forty patients are expected to be enrolled into four cohorts as follows:
PSI-938 QD administered as monotherapy for 14 days, followed by;
PSI-938 QD for 7 days followed by PSI-938 plus PSI-7977 QD for 7 days and
PSI-7977 QD for 7 days followed by PSI-938 plus PSI-7977 QD for 7 days,
followed by; PSI-938 plus PSI-7977 QD for 14 days
We expect to report preliminary results from Part 2 of this Phase 1 study during the first quarter of calendar year 2011.
The company is expected to initiate a Phase 2 study of PSI-938 in combination with PSI-7977 during mid-2011.
This Phase 2 study proposes to explore durations of PSI-938 and PSI-7977 in "interferon-free combinations" with an SVR endpoint.
.
.
According to the recent media frenzy Pharmassets two oral drugs in development "PSI-938 and PSI-7977" showed in early-stage data that 15 out of 16 patients achieved an early/promising antiviral response after 14 days on treatment.
The HCV community, although excited about a regimen of "interferon free" therapy, keep it all in perspective and wait until Pharmasset conducts their phase II study of " interferon-free combinations" with an SVR endpoint, expected in mid-2011. For this community the bottom line is SVR.
You can look at "all" the abstracts that will be presented at the EASL by clicking here
The controversy
The EASL has an embargo in place until the data is presented at the meeting. However, a few investment websites released the data early, breaking the media embargo.
The Study Can Be Found At The EASL Website
"ONCE DAILY DUAL-NUCLEOTIDE COMBINATION OF PSI-938 AND PSI-7977"
You can view the abstract here.
What Study are we talking about, whats the big deal ?
The study included treatment-naïve, non-cirrhotic patients with HCV Genotype 1. The two drugs "PSI-938 AND PSI-7977" were tested in four different cohorts (see below) without using "interferon" over fourteen days. The study was deemed ; NUCLEAR Study .
.
From the Nov "2010" Press Release;
This is the first clinical study combining a purine (PSI-938) and a pyrimidine (PSI-7977) nucleotide analog for HCV, and is designed to evaluate once daily doses of PSI-7977 and PSI-938 in patients with HCV who have not been treated previously.
"We are excited to be initiating this combination study with two proprietary nucleotide analogs for HCV," stated Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "Based on our in vitro data, we believe the combination of two nucleotide analogs could provide potent antiviral activity across multiple HCV genotypes and could also have a higher barrier to resistance compared to other DAA combinations. We believe nucleotide analogs have a number of key attributes that may make them ideal partners for other DAA combinations, in addition to a 'nuc-nuc' combination."
About the Phase 1 Trial - Part 1, Part 2
Part 1 of the Phase 1 multiple ascending dose study of PSI-938, suppression of HCV RNA below the limit of detection (LOD, less then 15 IU/mL) was observed in over half of the patients who received PSI-938 at daily doses of 200 mg or 300 mg for seven days.
Part 2 of the study is designed to evaluate the combination of PSI-938 and PSI-7977.
The primary objective is to assess the safety, tolerability and pharmacokinetics of PSI-938 administered alone for 14 days, and in combination with PSI-7977 for 7 to 14 days.
The secondary objective is to evaluate viral kinetics of HCV RNA during monotherapy (no interferon) and combination nucleotide dosing.
The Four Cohorts;
Approximately forty patients are expected to be enrolled into four cohorts as follows:
PSI-938 QD administered as monotherapy for 14 days, followed by;
PSI-938 QD for 7 days followed by PSI-938 plus PSI-7977 QD for 7 days and
PSI-7977 QD for 7 days followed by PSI-938 plus PSI-7977 QD for 7 days,
followed by; PSI-938 plus PSI-7977 QD for 14 days
We expect to report preliminary results from Part 2 of this Phase 1 study during the first quarter of calendar year 2011.
From the EASL ; Preliminary results , the public is welcome to view the abstract
The company is expected to initiate a Phase 2 study of PSI-938 in combination with PSI-7977 during mid-2011.
This Phase 2 study proposes to explore durations of PSI-938 and PSI-7977 in "interferon-free combinations" with an SVR endpoint.
.
.
Thursday, January 6, 2011
Hepatitis C Drugs PSI-7977/PSI-938 interim analyses announced Jan 2011
Pharmasset Reports Positive Results from its HCV Clinical Programs
- PSI-7977 400mg QD with pegylated interferon and ribavirin was generally safe and well tolerated while demonstrating potent viral suppression in patients with HCV genotype 2 or 3 over 12 weeks of dosing
- PSI-938 300mg QD monotherapy was generally safe and well tolerated over 14 days of dosing and demonstrated potent antiviral activity and no viral breakthrough
PRINCETON, N.J., Jan. 6, 2011 /PRNewswire/ -- Pharmasset, Inc. (Nasdaq: VRUS), announced today positive data from interim analyses of two of its clinical programs: the HCV genotype 2 or 3 (GT2/3) arm of the PSI-7977 Phase 2b trial and the 14 day PSI-938 monotherapy cohort of the dual nucleotide study.
Pipeline Update and 2011 Highlights
PSI-7977
In August 2010, we began dosing of PSI-7977 in combination with pegylated interferon and ribavirin (Peg-IFN/RBV) in a Phase 2b study. This study is evaluating PSI-7977 200mg QD, 400mg QD, or placebo in combination with Peg-IFN/RBV in approximately 125 treatment-naive patients with HCV genotype 1 (GT1), and PSI-7977 400mg QD with Peg-IFN/RBV in an open-label arm in patients with HCV GT2 or GT3. HCV GT1 patients receive an RVR-directed regimen of 12 weeks of PSI-7977/Peg-IFN/RBV followed by 12 or 36 weeks of Peg-IFN/RBV. The HCV GT2/3 patients receive 12 weeks of PSI-7977/Peg-IFN/RBV with no additional therapy. The primary goal of the study is to assess the safety and tolerability of PSI-7977 in combination with Peg-IFN/RBV for 12 weeks. The primary efficacy endpoint of the study is the proportion of patients who achieve SVR12 and SVR24, defined as HCV RNA below the limit of detection (<15 IU/ml) 12 and 24 weeks, respectively, after the discontinuation of all therapy. Enrollment of this Phase 2b trial has been completed.
Twenty five treatment-naive patients with HCV GT2/3 patients were enrolled in the open label arm. 24/25 patients completed 12 weeks of PSI-7977 400mg QD with Peg-IFN/RBV; one patient was lost to follow-up after the first visit. A preliminary analysis of all data available at the end of 12 weeks of dosing revealed no serious adverse events and no discontinuations due to adverse events. The most commonly reported adverse events (AEs) overall were nausea, headache, chills, and fatigue; AEs were consistent in severity and frequency to historical Peg-IFN/RBV treatment. There were no clinically significant, treatment-emergent trends in any clinical laboratory parameters.
PSI-7977 with Peg-IFN/RBV resulted in rapid viral suppression, with all HCV GT2 or 3 patients (n=24) achieving both a rapid virologic response (RVR) and remaining below the limit of detection through the end of treatment at week 12 (EOT). No patient exhibited viral breakthrough. These HCV GT2 or 3 patients are now being monitored for an additional 24 weeks to assess SVR at 12 weeks (SVR12) and 24 weeks (SVR24) after the discontinuation of therapy. Initial data have been submitted for presentation at an upcoming major scientific conference scheduled to take place during the first half of 2011.
In addition to the ongoing Phase 2b dose-ranging study, we recently announced the initiation of an exploratory Phase 2 study of PSI-7977 and RBV with 0-12 weeks of interferon in patients with HCV GT2 or GT3. During the second quarter of 2011, we also expect to initiate a 24-week Phase 2b study of PSI-7977 with Peg-IFN/RBV.
PSI-938
In late November 2010, we initiated Part 2 of a Phase 1 study that includes the first combination of a purine (PSI-938) and a pyrimidine (PSI-7977) nucleotide analog for the treatment of HCV. The cohorts within Part 2 are evaluating PSI-938 300mg QD as monotherapy and in combination with PSI-7977 400mg QD. The primary objective is to assess the safety, tolerability and pharmacokinetics of PSI-938 alone and in combination with PSI-7977. The secondary objective of Part 2 is to evaluate the short-term change in HCV RNA.
Preliminary results with PSI-938 300mg QD administered as monotherapy for 14 days demonstrate:
PSI-938 was generally safe and well tolerated over 14 days
There were no serious adverse events, and no dose modifications or discontinuations
There were no clinically significant, treatment-emergent trends in any clinical laboratory parameters
PSI-938 demonstrated potent antiviral activity with a median HCV RNA change from baseline of 5.23 log10 IU/mL in the 8 patients receiving 300mg QD monotherapy for 14 days. HCV RNA declined rapidly and consistently throughout the 14 day dosing period, with no viral breakthrough noted. In the 8 subjects who received PSI-938 300mg QD monotherapy for 14 days, half (4 of 8) of the subjects achieved HCV RNA below the limit of detection (15 IU/mL), and 5 of 8 patients achieved HCV RNA below the limit of quantification (43 IU/mL). The median baseline HCV RNA in patients enrolled in Part 2 was approximately 1 log10 higher than in the Part 1 multiple ascending dose trial (6.95 log10 IU/mL versus 5.92 log10 IU/mL), allowing for a full assessment of the antiviral activity of the nucleotide analog.
Patients are now being enrolled in the second and third cohorts. Patients will receive monotherapy with either PSI-938 or PSI-7977 for days 1-7, followed by the combination of PSI-938 plus PSI-7977 for days 8-14. Following availability of data from these initial combination cohorts, the fourth and final cohort will receive both PSI-938 and PSI-7977 for 14 days. We anticipate reporting further data from this study during this quarter. In addition, we plan on initiating a Phase 2 study of PSI-938 in combination with PSI-7977 during mid-2011. This Phase 2 study will explore multiple treatment durations of PSI-938 and PSI-7977 with an SVR endpoint.
"We are encouraged by the initial results generated with PSI-7977 in combination with Peg-IFN/RBV over 12 weeks and with PSI-938 monotherapy over 14 days," stated Michelle Berrey, MD, MPH, Chief Medical Officer. "Both programs are progressing on schedule and we anticipate reporting further efficacy, safety and resistance data throughout 2011. We are excited to be moving PSI-938 into the combination phase of this study with PSI-7977, as this may provide a preliminary proof-of-concept for an all oral, nucleotide combination regimen."
Calendar Year 2011 Anticipated Milestones:
-- Pharmasset expects to report SVR12 data from its ongoing phase 2b trial with PSI-7977 in HCV genotype 2/3 patients in the second quarter of 2011
-- Pharmasset expects to report the 12 week interim analysis from its PSI-7977 Phase 2b genotype 1 arms in the second quarter of 2011
-- Pharmasset expects to initiate a 24 week Phase 2b trial with PSI-7977 in the second quarter of 2011
-- Pharmasset expects to initiate a Phase 2 study with PSI-7977 and PSI-938 in mid-2011
-- Pharmasset plans to file an IND for PSI-661 in the first quarter of 2011 and to initiate a phase 1 trial in the second quarter of 2011
-- Roche expects to initiate INFORM-SVR with RG7128 and RG7227 in the first quarter of 2011
-- Roche expects to initiate a phase 2 study with RG7128 in HCV genotype 2/3 patients in the first half of 2011
-- Roche expects to initiate a phase 3 program with RG7128 in 2011
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 on the development of oral therapeutics for the treatment of hepatitis C virus (HCV). Our research and development efforts focus on nucleoside/tide analogs, a class of compounds which act as alternative substrates for the viral polymerase, thus inhibiting viral replication. We currently have four clinical-stage product candidates. RG7128, a cytosine nucleoside analog for chronic HCV infection, is in two Phase 2b clinical studies in combination with Pegasys® plus Copegus® and is also in the INFORM studies, the first series of studies designed to assess the potential of combinations of small molecules without Pegasys® and Copegus® to treat chronic HCV. These clinical studies are being conducted through a strategic collaboration with Roche. Our other clinical stage HCV candidates include PSI-7977, an unpartnered uracil nucleotide analog that is in two Phase 2b studies in patients with HCV genotypes 1, 2, or 3, and PSI-938, an unpartnered guanine nucleotide analog which has completed a 14-day monotherapy study and has recently initiated a 14-day combination study with PSI-7977. We also have in our pipeline an additional purine nucleotide analog, PSI-661, in advanced preclinical development.
Pegasys(R) and Copegus(R) are registered trademarks of Roche.
Contact
Richard E. T. Smith, Ph.D.
VP, Investor Relations and Corporate Communications
Office +1 (609) 613-4181
Forward-Looking Statements
Pharmasset "Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995: Statements in this press release that are not historical facts are "forward-looking statements," that involve risks, uncertainties, and other important factors, including, without limitation, the risk of cessation or delay of any of the ongoing or planned clinical trials and/or our development of our product candidates, the risk that the results of previously conducted studies involving our product candidates will not be repeated or observed in ongoing or future studies involving our product candidates, the risk that our collaboration with Roche will not continue or will not be successful, and the risk that any one or more of our product candidates will not be successfully developed and commercialized. For a discussion of risks, uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in our Annual Report on Form 10-K for the fiscal year ended September 30, 2010 filed with the Securities and Exchange Commission and discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission.
SOURCE Pharmasset, Inc.
News Provided by Acquire Media
Related Links
Pharmasset to Present at the 29th Annual J.P. Morgan Healthcare Conference
Jan 4, 2011
Pharmasset Initiates Exploratory Interferon Sparing Clinical Trial of PSI-7977 for Chronic Hepatitis C
Dec 14, 2010
RELATED NEWS
Pharmasset Reports Positive Data From Two HCV Clinical Programs - Quick Facts
BASi Enters Into Preferred Provider Agreement With Pharmasset - Quick Facts
Pharmasset To Present At Deutsche Bank Conference; Webcast At 2:05 PM ET
Pharmasset Starts Dosing In An Exploratory Study Of PSI-7977 For Chronic HCV
Pharmasset Starts Dosing In Part 2 Of A Phase 1 Study - Quick Facts
Tuesday, November 30, 2010
Hepatitis C: PSI-7977 and PSI-938 Pharmasset Initiates Dosing
Pharmasset Initiates Dosing in a Combination Study of PSI-7977 and PSI-938 for Chronic Hepatitis C
- Phase 1 combination study of a pyrimidine (PSI-7977) and purine (PSI-938) nucleotide analog in patients with chronic hepatitis C- Interim data expected in first quarter of 2011
PRINCETON, N.J., Nov. 30, 2010 /PRNewswire-FirstCall/ -- Pharmasset, Inc. (Nasdaq: VRUS) announced today that dosing has begun in Part 2 of a Phase 1 study. This is the first clinical study combining a purine (PSI-938) and a pyrimidine (PSI-7977) nucleotide analog for HCV, and is designed to evaluate once daily doses of PSI-7977 and PSI-938 in patients with HCV who have not been treated previously.
"We are excited to be initiating this combination study with two proprietary nucleotide analogs for HCV," stated Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "Based on our in vitro data, we believe the combination of two nucleotide analogs could provide potent antiviral activity across multiple HCV genotypes and could also have a higher barrier to resistance compared to other DAA combinations. We believe nucleotide analogs have a number of key attributes that may make them ideal partners for other DAA combinations, in addition to a 'nuc-nuc' combination."
.
About the Phase 1 Trial
In Part 1 of the Phase 1 multiple ascending dose study of PSI-938, suppression of HCV RNA below the limit of detection (LOD, less then 15 IU/mL) was observed in over half of the patients who received PSI-938 at daily doses of 200 mg or 300 mg for seven days. Part 2 of the study is designed to evaluate the combination of PSI-938 and PSI-7977. The primary objective is to assess the safety, tolerability and pharmacokinetics of PSI-938 administered alone for 14 days, and in combination with PSI-7977 for 7 to 14 days. The secondary objective is to evaluate viral kinetics of HCV RNA during monotherapy and combination nucleotide dosing.
Approximately forty patients are expected to be enrolled into four cohorts as follows:
.
PSI-938 QD administered as monotherapy for 14 days, followed by;
.
PSI-938 QD for 7 days followed by PSI-938 plus PSI-7977 QD for 7 days and
.
PSI-7977 QD for 7 days followed by PSI-938 plus PSI-7977 QD for 7 days,
.
followed by; PSI-938 plus PSI-7977 QD for 14 days
. ..
We expect to report preliminary results from Part 2 of this Phase 1 study during the first quarter of calendar year 2011. We also expect to initiate a Phase 2 study of PSI-938 in combination with PSI-7977 during mid-2011. This Phase 2 study proposes to explore durations of PSI-938 and PSI-7977 in interferon-free combinations with an SVR endpoint.
.
We expect to report preliminary results from Part 2 of this Phase 1 study during the first quarter of calendar year 2011. We also expect to initiate a Phase 2 study of PSI-938 in combination with PSI-7977 during mid-2011. This Phase 2 study proposes to explore durations of PSI-938 and PSI-7977 in interferon-free combinations with an SVR endpoint.
.
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 on the development of oral therapeutics for the treatment of hepatitis C virus (HCV). Our research and development efforts focus on nucleoside/tide analogs, a class of compounds which act as alternative substrates for the viral polymerase, thus inhibiting viral replication. We currently have four clinical-stage product candidates. RG7128, a cytosine nucleoside analog for chronic HCV infection, is in two Phase 2b clinical studies in combination with Pegasys(R) plus Copegus(R) and is also in the INFORM studies, the first series of studies designed to assess the potential of combinations of small molecules without Pegasys(R) and Copegus(R) to treat chronic HCV. These clinical studies are being conducted through a strategic collaboration with Roche. Our other clinical stage HCV candidates include PSI-7977, an unpartnered uracil nucleotide analog that has recently initiated dosing in a Phase 2b study in patients with HCV genotypes 1, 2, or 3, and PSI-938, an unpartnered guanosine nucleotide analog which recently completed a 7-day monotherapy study. We also have in our pipeline an additional purine nucleotide analog, PSI-661, in advanced preclinical development.
.
Pharmasset is a clinical-stage pharmaceutical company committed to discovering, developing, and commercializing novel drugs to treat viral infections. Pharmasset's primary focus is on the development of oral therapeutics for the treatment of hepatitis C virus (HCV). Our research and development efforts focus on nucleoside/tide analogs, a class of compounds which act as alternative substrates for the viral polymerase, thus inhibiting viral replication. We currently have four clinical-stage product candidates. RG7128, a cytosine nucleoside analog for chronic HCV infection, is in two Phase 2b clinical studies in combination with Pegasys(R) plus Copegus(R) and is also in the INFORM studies, the first series of studies designed to assess the potential of combinations of small molecules without Pegasys(R) and Copegus(R) to treat chronic HCV. These clinical studies are being conducted through a strategic collaboration with Roche. Our other clinical stage HCV candidates include PSI-7977, an unpartnered uracil nucleotide analog that has recently initiated dosing in a Phase 2b study in patients with HCV genotypes 1, 2, or 3, and PSI-938, an unpartnered guanosine nucleotide analog which recently completed a 7-day monotherapy study. We also have in our pipeline an additional purine nucleotide analog, PSI-661, in advanced preclinical development.
.
Pegasys(R) and Copegus(R) are registered trademarks of Roche.
Contact
Richard E. T. Smith, Ph.D.
VP, Investor Relations and Corporate Communications
Office +1 (609) 613-4181
Forward-Looking Statements
Pharmasset "Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995: Statements in this press release that are not historical facts are "forward-looking statements," that involve risks, uncertainties, and other important factors, including, without limitation, the risk of cessation or delay of any of the ongoing or planned clinical trials and/or our development of our product candidates, the risk that the results of previously conducted studies involving our product candidates will not be repeated or observed in ongoing or future studies involving our product candidates, the risk that our collaboration with Roche will not continue or will not be successful, and the risk that any one or more of our product candidates will not be successfully developed and commercialized. For a discussion of risks, uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in our Annual Report on Form 10-K for the fiscal year ended September 30, 2010 filed with the Securities and Exchange Commission and discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission.
Contact
Richard E. T. Smith, Ph.D.
VP, Investor Relations and Corporate Communications
Office +1 (609) 613-4181
Forward-Looking Statements
Pharmasset "Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995: Statements in this press release that are not historical facts are "forward-looking statements," that involve risks, uncertainties, and other important factors, including, without limitation, the risk of cessation or delay of any of the ongoing or planned clinical trials and/or our development of our product candidates, the risk that the results of previously conducted studies involving our product candidates will not be repeated or observed in ongoing or future studies involving our product candidates, the risk that our collaboration with Roche will not continue or will not be successful, and the risk that any one or more of our product candidates will not be successfully developed and commercialized. For a discussion of risks, uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in our Annual Report on Form 10-K for the fiscal year ended September 30, 2010 filed with the Securities and Exchange Commission and discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission.
RELATED LINKShttp://www.pharmasset.com/
Sunday, November 7, 2010
Hepatitis C Drugs: R7128 with the protease inhibitor R7227
Wednesday, November 3, 2010
Pharmasset Riding High on Nucs
Pharmasset is a biotech company focused on the development of HCV therapeutics. It has multiple drugs in development, all based on its core strength in RNA nucleoside analog chemistry.
The current standard of care for HCV is a combination of pegylated alpha interferon (IFN-α) and ribavirin taken for 48 weeks depending on patient response. Unfortunately, only 55% of patients on this regimen achieve a sustained virologic response (SVR), where levels of HCV RNA remain undetectable six months after treatment has stopped.
Both Vertex and Merck intend on launching new HCV treatments in 2011 based on a new class of compounds known as NS3 protease inhibitors (PI). These drugs herald a new breed of targeted medicines- sometimes called direct acting antivirals (DAA). The advantage is a significantly higher cure rate and shorter duration of treatment. However, these drugs are susceptible to viral resistance and require concurrent use with both interferon and ribavirin.
A second type of compound focuses on inhibition of the NS5B polymerase. Of these there are two classes, non-nucleoside polymerase inhibitors (non-nucs), and nucleoside polymerase inhibitors (nucs). Both have been shown to be effective in combination with interferon + ribavirin, but non-nucs, like protease inhibitors, are also prone to mutation driven resistance. On the other hand, nucleoside polymerase inhibitors have a high barrier to resistance.
In studies shown by Roche, no resistance was observed in cultures treated with R7128, its nucleoside polymerase inhibitor licensed from Pharmasset, for two weeks as monotherapy. Cultures treated with non-nucs or protease inhibitors all developed resistance. R7128 was also shown to reduce the formation of resistant colonies when added to either a non-nuc or PI. These studies show the flexibility of nucs in combination treatment.
The race is on to develop the next generation of HCV treatments even before the first generation has been approved. Side effects of interferon + ribavirin therapy include fatigue, flu-like symptoms, rash, and nausea. The goal for drug developers is a treatment that can dispense with these two drugs. Heavy viral loads and high mutation rates preclude the use of monotherapies, hence, multi-drug cocktails is the next best thing.
At least seven companies are pursuing the development of drug combos for HCV. Nearly all consist of a protease inhibitor combined with a compound of a different class. Additive or synergistic effects and non-overlapping resistance profiles drive the combo selection.
Pharmasset’s lead compound is currently in multiple Phase II trials. Results from the 12 week R7128 treatment portion of a 48 week triple combo PROPEL trial with interferon + ribavirin trial have been released showing high rapid virologic responses and a low rate of adverse events. Full SVR data will be available in 2011. A longer trial involving 24 weeks of dosing called JUMP-C is now dosing. Phase III studies are expected to begin in 2011 as well, with an NDA filing anticipated in 2013.
Roche is conducting a combination trial of R7128 with the protease inhibitor R7227 from Intermune. Results from a 14 day INFORM-1 trial showed the drugs were safe when administered together and resulted in a sustained viral load reduction. Continuing studies will add the drug Ritonavir to boost R7227 without increasing side effects.
The balance of Pharmasset’s HCV pipeline consists of PSI-7977, which is enrolling patients in Phase IIb and PSI-938, which has completed Phase 1b. The company is planning studies combining these two nucs; initial data should be available Q1 next year. Phase II combo studies are expected to begin around the second or third quarter of 2011.
Nucleoside polymerase inhibitors look to have significant potential in HCV therapy, with possible advantages over protease inhibitors and non-nucs. Pharmasset is the leader in nuc development. A bet on Pharmasset is a bet on the entire compound class.
Author is Long RHHBY.PK, VRUS, MRK
Pharmasset Riding High on Nucs
Pharmasset is a biotech company focused on the development of HCV therapeutics. It has multiple drugs in development, all based on its core strength in RNA nucleoside analog chemistry.
The current standard of care for HCV is a combination of pegylated alpha interferon (IFN-α) and ribavirin taken for 48 weeks depending on patient response. Unfortunately, only 55% of patients on this regimen achieve a sustained virologic response (SVR), where levels of HCV RNA remain undetectable six months after treatment has stopped.
Both Vertex and Merck intend on launching new HCV treatments in 2011 based on a new class of compounds known as NS3 protease inhibitors (PI). These drugs herald a new breed of targeted medicines- sometimes called direct acting antivirals (DAA). The advantage is a significantly higher cure rate and shorter duration of treatment. However, these drugs are susceptible to viral resistance and require concurrent use with both interferon and ribavirin.
A second type of compound focuses on inhibition of the NS5B polymerase. Of these there are two classes, non-nucleoside polymerase inhibitors (non-nucs), and nucleoside polymerase inhibitors (nucs). Both have been shown to be effective in combination with interferon + ribavirin, but non-nucs, like protease inhibitors, are also prone to mutation driven resistance. On the other hand, nucleoside polymerase inhibitors have a high barrier to resistance.
In studies shown by Roche, no resistance was observed in cultures treated with R7128, its nucleoside polymerase inhibitor licensed from Pharmasset, for two weeks as monotherapy. Cultures treated with non-nucs or protease inhibitors all developed resistance. R7128 was also shown to reduce the formation of resistant colonies when added to either a non-nuc or PI. These studies show the flexibility of nucs in combination treatment.
The race is on to develop the next generation of HCV treatments even before the first generation has been approved. Side effects of interferon + ribavirin therapy include fatigue, flu-like symptoms, rash, and nausea. The goal for drug developers is a treatment that can dispense with these two drugs. Heavy viral loads and high mutation rates preclude the use of monotherapies, hence, multi-drug cocktails is the next best thing.
At least seven companies are pursuing the development of drug combos for HCV. Nearly all consist of a protease inhibitor combined with a compound of a different class. Additive or synergistic effects and non-overlapping resistance profiles drive the combo selection.
Pharmasset’s lead compound is currently in multiple Phase II trials. Results from the 12 week R7128 treatment portion of a 48 week triple combo PROPEL trial with interferon + ribavirin trial have been released showing high rapid virologic responses and a low rate of adverse events. Full SVR data will be available in 2011. A longer trial involving 24 weeks of dosing called JUMP-C is now dosing. Phase III studies are expected to begin in 2011 as well, with an NDA filing anticipated in 2013.
Roche is conducting a combination trial of R7128 with the protease inhibitor R7227 from Intermune. Results from a 14 day INFORM-1 trial showed the drugs were safe when administered together and resulted in a sustained viral load reduction. Continuing studies will add the drug Ritonavir to boost R7227 without increasing side effects.
The balance of Pharmasset’s HCV pipeline consists of PSI-7977, which is enrolling patients in Phase IIb and PSI-938, which has completed Phase 1b. The company is planning studies combining these two nucs; initial data should be available Q1 next year. Phase II combo studies are expected to begin around the second or third quarter of 2011.
Nucleoside polymerase inhibitors look to have significant potential in HCV therapy, with possible advantages over protease inhibitors and non-nucs. Pharmasset is the leader in nuc development. A bet on Pharmasset is a bet on the entire compound class.
Author is Long RHHBY.PK, VRUS, MRK
Thursday, October 28, 2010
Pharmasset Positive Preliminary Data with PSI-938 /Treatment of Hepatitis C
Pharmasset Reports Positive Preliminary Antiviral Data with PSI-938 for the Treatment of Hepatitis C
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-- PSI-938 achieves a median 3.94 to 4.64 log10 reduction in HCV RNA after 7 days of monotherapy -- No early discontinuations or serious adverse events reported -- Initiating nucleotide combination trial later this quarter -- Conference call at 8:00 AM ET today
Administered as Monotherapy for 7 Days
LOQ = limit of quantification (<43 IU/mL)
PSI-938 demonstrated potent antiviral activity with a mean
HCV RNA change from baseline of 4.31 log10 IU/mL, 4.64 log10 IU/mL, 3.94 log10 IU/mL and 4.59 log10 IU/mL in patients receiving 100 mg QD, 200 mg QD, 300 mg QD and 100 mg BID for seven days, respectively. HCV RNA declined consistently throughout the 7-day dosing period, with no viral breakthrough. For the 16 subjects who received PSI-938 200 mg QD or 300 mg QD for 7 days, more than half (9 of 16) of the subjects on PSI-938 monotherapy achieved HCV RNA below the limit of detection (15 IU/mL) and 11 out of 16 patients achieved HCV RNA below the limit of quantification (43 IU/mL).
Contact
Richard E. T. Smith, Ph.D. VP, Investor Relations and Corporate Communications
Office: +1 (609) 613-4181
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-- PSI-938 achieves a median 3.94 to 4.64 log10 reduction in HCV RNA after 7 days of monotherapy -- No early discontinuations or serious adverse events reported -- Initiating nucleotide combination trial later this quarter -- Conference call at 8:00 AM ET today
PRINCETON, N.J., Oct 28, 2010 /PRNewswire via COMTEX News Network/ -- Pharmasset, Inc. (Nasdaq: VRUS) reported positive preliminary results today from its phase I monotherapy trial of PSI-352938 ("PSI-938") for the treatment of chronic hepatitis C (HCV). PSI-938 is a guanosine nucleotide analog polymerase inhibitor in development for the treatment of chronic HCV infection.
PSI-938 Phase 1 Multiple Ascending Dose Study Overview
In August 2010, Pharmasset initiated a phase 1 multiple ascending dose study with PSI-938 administered once daily (QD) or twice daily (BID) for 7 days. The trial was conducted at two US centers as a blinded, randomized, and placebo-controlled study in 40 patients chronically infected with HCV genotype 1. The primary objective was to assess the safety, tolerability, and pharmacokinetics of PSI-938 administered over 7 days. The secondary objective was to assess antiviral activity by measuring the change in HCV RNA. Patients were randomized within each cohort to receive either PSI-938 (8 patients per cohort) or placebo (2 patients per cohort). Four dose cohorts of PSI-938 (100 mg QD, 200 mg QD, 300 mg QD and 100 mg BID) have been completed.
PSI-938 Antiviral Activity Summary
Preliminary Antiviral Response Observed
Following PSI-938
Administered as Monotherapy for 7 Days
Dose n Median Change in Range Number of Subjects
HCV RNA at Day 8 with HCV RNA
(log10 IU/mL) (log10 IU/mL) lt;LOD <LOQ
100 mg QD 8 -4.31 -2.66 to -5.12 1 3
200 mg QD 8 -4.64 -3.49 to -5.35 5 7
300 mg QD 8 -3.94 -3.43 to -5.29 4 4
100 mg BID 8 -4.59 -3.94 to -5.08 2 3
Placebo 8 -0.05 +0.17 to -0.29 0 0
------- --- ----- -------------- --- ---
LOD = limit of detection (<15 IU/mL)
LOQ = limit of quantification (<43 IU/mL)
PSI-938 demonstrated potent antiviral activity with a mean
HCV RNA change from baseline of 4.31 log10 IU/mL, 4.64 log10 IU/mL, 3.94 log10 IU/mL and 4.59 log10 IU/mL in patients receiving 100 mg QD, 200 mg QD, 300 mg QD and 100 mg BID for seven days, respectively. HCV RNA declined consistently throughout the 7-day dosing period, with no viral breakthrough. For the 16 subjects who received PSI-938 200 mg QD or 300 mg QD for 7 days, more than half (9 of 16) of the subjects on PSI-938 monotherapy achieved HCV RNA below the limit of detection (15 IU/mL) and 11 out of 16 patients achieved HCV RNA below the limit of quantification (43 IU/mL).
PSI-938 Pharmacokinetic and Safety Summary
Pharmacokinetics parameters were similar between healthy subjects in the single ascending dose study and HCV infected patients in the seven-day multiple ascending dose study. PSI-938 at all doses provided good systemic exposure and continue to support once-daily administration.
PSI-938 was generally safe and well tolerated across all doses studied to date with no serious adverse events and no discontinuations. There were no dose-related trends in adverse events through the dose escalations, no grade 4 treatment emergent laboratory changes, and no trends in clinical laboratory abnormalities.
PSI-938 SAD and preclinical data
The Phase 1a single ascending dose study conducted earlier this year assessed single doses of PSI-938 ranging from 100 mg to 1600 mg or matching placebo in healthy male and female volunteers. No dose-limiting toxicity was identified. Safety and pharmacokinetic data supported progression of PSI-938 to the 7-day monotherapy trial. Full data from the SAD trial will be presented at the upcoming AASLD Annual Liver Meeting in Boston, MA, October 29-November 3, 2010 (poster #1890).
Preclinically, both PSI-938 and Pharmasset's other guanosine analog, PSI-661, which is in late preclinical development, have demonstrated similar potency against wild-type HCV or HCV with the S282T mutation, which can be selected by RG7128 and PSI-7977 in vitro. Although the S282T has not been detected in treatment-naive individuals with HCV, nor selected in clinical trials with any of Pharmasset's nucleoside/tide analogs, the potential for interferon-sparing regimens may increase the focus on antivirals with complementary resistance profiles.
"We are very encouraged by the preliminary efficacy and safety data with PSI-938, our purine nucleotide analog for HCV," said Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "These data provide the first confirmatory evidence that a nucleoside/tide analog can exhibit substantial early antiviral activity in monotherapy as has been observed with compounds in other DAA classes. Unlike other classes of DAAs to date, our nucleotide analogs also provide a higher barrier to resistance and clinically-validated antiviral activity across a broad range of HCV genotypes, characteristics not yet demonstrated with other classes of DAA. We continue to believe that nucleoside/tide analogs will become the backbone of HCV therapy. In addition, similar to HIV, the combination of two complementary nucleoside/tide analogs could provide a differentiated therapy for HCV patients in the
future."
PSI-938 and PSI-7977 Combination Study
In this quarter, Pharmasset plans to initiate a short-term study to assess the combination of PSI-938 and PSI-7977. The trial will be conducted in the US, as a blinded, randomized, placebo-controlled study in approximately 50 patients chronically infected with HCV genotype 1. The primary objective will be to assess the safety, tolerability, and pharmacokinetics of PSI-938 and PSI-7977 alone and in combination. Preliminary results are expected in the first half of 2011.
Conference Call and Webcast
Members of Pharmasset's management team will host a conference call today, October 28, 2010, at 8:00 a.m. ET to discuss the preliminary results of the multiple ascending dose trial with PSI-938. Investors may listen to the webcast of the conference call live on the "Events & Presentations" section of Pharmasset's website, http://www.pharmasset.com/. Alternatively, investors may listen to the call by dialing 877-771-7028 from locations in the U.S. and 973-200-3092 from outside the U.S. The webcast replay will be available for at least 72 hours following the call.
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 on the development of oral therapeutics for the treatment of hepatitis C virus (HCV). Our research and development efforts focus on nucleoside/tide analogs, a class of compounds which act as alternative substrates for the viral polymerase, thus inhibiting viral replication. We currently have four clinical-stage product candidates. RG7128, a cytosine nucleoside analog for chronic HCV infection, is in two Phase 2b clinical studies in combination with Pegasys(R) plus Copegus(R) and is also in the INFORM studies, the first series of studies designed to assess the potential of combinations of small molecules without Pegasys(R) and Copegus(R) to treat chronic HCV. These clinical studies are being conducted
through a strategic collaboration with Roche. Our other clinical stage HCV candidates include PSI-7977, an unpartnered uracil nucleotide analog presently in a Phase 2b study, and PSI-938, an unpartnered guanosine nucleotide analog in Phase 1. We also have in our pipeline an additional purine nucleotide analog, PSI-661, in advanced preclinical development. Racivir, for the treatment of HIV, has completed a Phase 2 clinical study.
Pegasys(R) and Copegus(R) are registered trademarks of Roche.
Contact
Richard E. T. Smith, Ph.D. VP, Investor Relations and Corporate Communications
Office: +1 (609) 613-4181
Forward-Looking Statements
Pharmasset "Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995: Statements in this press release that are not historical facts are "forward-looking statements," that involve risks, uncertainties, and other important factors, including, without limitation, the risk of cessation or delay of any of the ongoing or planned clinical trials and/or our development of our product candidates, the risk that the results of previously conducted studies involving our product candidates will not be repeated or observed in ongoing or future studies involving our product candidates, the risk that our collaboration with Roche will not continue or will not be successful, and the risk that any one or more of our product candidates will not be successfully developed and commercialized. For a discussion of risks, uncertainties, and other important factors, any of
which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in our Annual Report on Form 10-K for the fiscal year ended September 30, 2009 and our Quarterly Reports on Form 10-Q for the periods ended December 31, 2009, March 31, 2010 and June 30, 2010 filed with the Securities and Exchange Commission and discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission.
SOURCE Pharmasset, Inc.
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