Showing posts with label non-nuceloside polymerase inhibitor. Show all posts
Showing posts with label non-nuceloside polymerase inhibitor. Show all posts
Monday, April 23, 2012
Presidio Pharmaceuticals announce new HCV pan-genotypic non-nuc polymerase inhibitor....
Posted on MarketWatch, 4/21/12. Presidio releases pre-clinical profile of it's new novel pan-genotypic non-nuc polymerase inhibitor PPI-393 at EASL. It will be a very competitive environment for HCV drugs just getting started in development given the high bar set with interim SVR data presented for the 2nd generation HCV drugs at EASL. New drugs in development will have to offer a significant advantage in respect to resistance profile, dosing, tolerability and efficacy to compete.
PRESS RELEASE
April 21, 2012, 2:00 a.m. EDT
Presidio Pharmaceuticals Announces a New Clinical Candidate, PPI-383, a Novel Pan-Genotypic Non-Nucleoside Polymerase Inhibitor for HCV
Pre-Clinical Profile to be Presented at the 47th European Association for the Study of the Liver (EASL) Meeting
SAN FRANCISCO, Apr 21, 2012 (BUSINESS WIRE) -- Presidio Pharmaceuticals, Inc. announced today that PPI-383, a novel non-nucleoside polymerase inhibitor to treat hepatitis C virus (HCV), has been nominated for clinical development and will be profiled by Richard Colonno, Ph.D., Chief Scientific Officer, in poster 1173 at the 47th Annual EASL meeting being held in Barcelona, Spain on April 21st, 2012.
PPI-383 is a potent, pan-genotypic inhibitor of HCV discovered at Presidio, which exhibits a favorable pharmacokinetic and safety profile in multiple animal species following oral dosing. PPI-383 binds to the Palm II pocket of the HCV polymerase (NS5B) and possesses excellent biochemical and pharmaceutical properties critical to successful drug development, including a potential for once-daily oral dosing and minimal potential for drug-drug interactions. PPI-383 is currently undergoing further preclinical evaluation to support initiation of clinical studies alone and in combination with PPI-668 next year.
PPI-383, identified through an extensive medicinal chemistry effort, exhibits EC50s of 8.3 and 2.2 nM in HCV 1a and 1b replicon assays, respectively. PPI-383 is also active against other major HCV genotypes (2a, 3a and 4a) in stable replicon cell assays (EC50s of 4.4-11.7 nM). "The selection of PPI-383 underscores Presidio's continued commitment to generate best-in-class compounds for treating HCV," commented Dr. Colonno, who added, "It is an excellent complement to our lead NS5A inhibitor, PPI-668, currently completing Phase 1b clinical studies. We intend to develop oral, combination regimens that possess potent, pan-genotypic activity." The distinct mechanism of action of PPI-383 will potentially allow its use in combination regimens with all other classes of HCV inhibitors.
Poster 1173, entitled "Identification and Characterization of PPI-383, a Next Generation HCV NS5B Non-Nucleoside Inhibitor with Potent Activity Against all Major HCV Genotypes" will be presented by Dr. Colonno on Saturday, April 21st, 2012 at the Centre Convencions Internacional Barcelona (CCIB) from 8:00 AM to 5:00 PM.
About HCV
Chronic hepatitis C is a persistent, potentially progressive inflammatory liver disease caused by chronic infection with the hepatitis C virus (HCV). Worldwide, there are an estimated 130 to 170 million persons with chronic HCV infection, with over 350,000 deaths occurring each year.
The current standard treatment for hepatitis C in the United States, for patients with HCV genotype-1 infection, is combined administration of pegylated-interferon-alfa, ribavirin, and an HCV protease inhibitor. This multi-drug treatment is characterized by incomplete efficacy for HCV genotype-1 patients, variations in efficacy according to patients' underlying human genetic factors, no established efficacy for patients infected with other HCV genotypes, severe side effects in some patients, and dosing inconveniences. In countries where the current HCV protease inhibitors are not yet regulatory-approved, standard treatment is only pegylated-interferon-alfa plus ribavirin, which is less effective.
There is a continuing need for all oral, more consistently effective and better tolerated antiviral combinations for HCV infection, regardless of HCV genotype, patient genetic factors, or disease stage.
About Presidio
Presidio Pharmaceuticals, Inc. is a San Francisco-based clinical stage specialty pharmaceutical company dedicated to the discovery and development of small-molecule antiviral therapeutics. For more information, please visit our website at: www.presidiopharma.com .
SOURCE: Presidio Pharmaceuticals, Inc
Wednesday, June 15, 2011
Vertex licenses early-stage polymerase inhibitors...
Interesting licensing deal between Vertex and Alios BioPharma for two preclinical HCV polymerase inhibitors. With so many promising HCV compounds in the later stages of development and only so many of the lucrative insured baby boomer Tx naive population to go around, you have to wonder about this deal... Unless Vertex is laying down the foundation for an HCV resistance arms race similar to what we've experienced in the HIV therapeutic category. Could Vertex ultimately cash in on a problem they helped create with Telaprevir resistance? i
Vertex licenses Hep C candidates in milestone-heavy deal
Vertex Pharmaceuticals Inc. of Cambridge and Alios BioPharma Inc. of South San Francisco, Calif., have announced a deal under which Vertex will license two Alios compounds designed to be inhibitors of the hepatitis C virus polymerase enzyme.
With the deal, Vertex said it has multiple opportunities to develop new, all-oral combination regimens for chronic hepatitis C. Vertex expects the nucleotide drug candidates, ALS-2200 and ALS-2158, wto enter clinical development later this year.
In return for Vertex gaining worldwide rights to the hepatitis C drug candidates, Alios gets a $60 million upfront payment and research and development costs of ALS-2200 and ALS-2158 covered by Vertex. The Cambridge pharmaceutical firm could pay up to $715 million in R&D milestone payments if both drugs are approved, and up to $750 million more if both drug candidates then meet sales milestones.
The announcement came just weeks after Vertex won approval from the U.S. Food and Drug Administration for its hepatitis C drug, Incivek.
“The recent approval of Incivek was a milestone in hepatitis C care, and today’s announcement underscores our long-term commitment to further improving the treatment of this disease with new combinations of medicines,” said Peter Mueller, Ph.D., chief scientific officer and executive vice resident of global research and development at Vertex in a press release. “Alios has discovered anti-HCV nucleotides that have the potential to be leading agents in hepatitis C. Based on impressive in vitro data, we look forward to evaluating ALS-2200 and ALS-2158 together and in combination with our approved and investigational hepatitis C medicines with the goal of creating a highly potent all-oral regimen in the years ahead.”
Approval of Incivek also spurred Vertex to sign a lease for a new headquarters in Boston’s waterfront innovation district.
Vertex licenses Hep C candidates in milestone-heavy deal
Vertex Pharmaceuticals Inc. of Cambridge and Alios BioPharma Inc. of South San Francisco, Calif., have announced a deal under which Vertex will license two Alios compounds designed to be inhibitors of the hepatitis C virus polymerase enzyme.
With the deal, Vertex said it has multiple opportunities to develop new, all-oral combination regimens for chronic hepatitis C. Vertex expects the nucleotide drug candidates, ALS-2200 and ALS-2158, wto enter clinical development later this year.
In return for Vertex gaining worldwide rights to the hepatitis C drug candidates, Alios gets a $60 million upfront payment and research and development costs of ALS-2200 and ALS-2158 covered by Vertex. The Cambridge pharmaceutical firm could pay up to $715 million in R&D milestone payments if both drugs are approved, and up to $750 million more if both drug candidates then meet sales milestones.
The announcement came just weeks after Vertex won approval from the U.S. Food and Drug Administration for its hepatitis C drug, Incivek.
“The recent approval of Incivek was a milestone in hepatitis C care, and today’s announcement underscores our long-term commitment to further improving the treatment of this disease with new combinations of medicines,” said Peter Mueller, Ph.D., chief scientific officer and executive vice resident of global research and development at Vertex in a press release. “Alios has discovered anti-HCV nucleotides that have the potential to be leading agents in hepatitis C. Based on impressive in vitro data, we look forward to evaluating ALS-2200 and ALS-2158 together and in combination with our approved and investigational hepatitis C medicines with the goal of creating a highly potent all-oral regimen in the years ahead.”
Approval of Incivek also spurred Vertex to sign a lease for a new headquarters in Boston’s waterfront innovation district.
Wednesday, January 5, 2011
Anadys Pharmaceuticals intiates Phase IIb study of HCV Polymerase Inhibitor ANA598
Anadys getting it's non-nuc to Phase IIb, that's a pretty big hurdle for this company. If this gets to Phase III, they will have done what many drug developers previously have not. The Phase II graveyard for the DAA's is huge. Interesting that no week 4 (RVR) timepoint is mentioned for this protocol - Chris
SAN DIEGO, January 4, 2011 --Anadys Pharmaceuticals, Inc. (Nasdaq: ANDS) announced today that it has initiated the planned Phase IIb study of ANA598 in combination with pegylated interferon and ribavirin. The protocol for the study has been cleared by the United States Food and Drug Administration (FDA) and Health Canada. Patient screening has begun and patient dosing is expected to commence within the next several weeks. In the study ANA598 will be tested in both treatment-naïve patients and treatment-experienced patients who failed a prior course of therapy with interferon and ribavirin. ANA598 is the Company’s direct-acting antiviral, or DAA, being developed for the treatment of hepatitis C.
“We are excited to initiate this Phase IIb study of ANA598,” said James L. Freddo, M.D., Anadys’ Senior Vice President, Drug Development and Chief Medical Officer. “By establishing safety and efficacy in a greater number of patients, including those who have failed prior HCV treatment, we hope to position ANA598 as a highly attractive HCV agent ready for Phase III development.”
Phase IIb Protocol Design
In the study, approximately 200 chronically infected genotype 1 hepatitis C patients are expected to receive ANA598 200 mg twice a day (bid) in combination with Pegasys® (peginterferon alfa2a) and Copegus® (ribavirin, USP) (a current standard of care, or SOC) with a loading dose of 800 mg bid on day 1, while approximately 66 patients are to receive placebo and SOC. Enrollment is expected to include approximately equal numbers of treatment-naïve patients and patients who have failed a prior course of SOC, including difficult to treat prior null-responders. The primary endpoint of the study is Sustained Virological Response 24 weeks after patients conclude all treatment, known as SVR24. Anadys is conducting the study at sites within and outside the United States.
Naïve Arm
Approximately 100 treatment-naïve HCV patients are expected to receive ANA598 in combination with SOC and 33 treatment-naïve HCV patients are to receive placebo plus SOC. Treatment duration for naïve patients will be response-guided; patients who achieve undetectable levels of virus at Week 8 and maintain undetectable levels of virus will be scheduled to conclude all treatment at Week 28. For naïve patients with detectable virus at Week 8 dosing with ANA598, or placebo, and SOC is planned to continue through Week 48. The Company expects to receive Week 8 antiviral response data by the end of the second quarter of 2011, Week 12 antiviral response data in the third quarter of 2011 and Week 24 antiviral response data in the fourth quarter of 2011.
Treatment-Experienced Arm, Including Prior Null Responders
Approximately 80 patients who were partial responders during, or relapsers after, a prior course of therapy with SOC alone are expected to receive ANA598 in combination with SOC, and 33 corresponding patients are to receive placebo plus SOC. Additionally, approximately 28 prior null responder patients are to receive ANA598 in combination with SOC. All treatment-experienced patients who receive ANA598 are scheduled to receive triple combination therapy for 48 weeks. For the treatment-experienced patients, the Company expects to receive Week 12 antiviral response data in the third quarter of 2011 and Week 24 antiviral response data in the fourth quarter of 2011.
SAN DIEGO, January 4, 2011 --Anadys Pharmaceuticals, Inc. (Nasdaq: ANDS) announced today that it has initiated the planned Phase IIb study of ANA598 in combination with pegylated interferon and ribavirin. The protocol for the study has been cleared by the United States Food and Drug Administration (FDA) and Health Canada. Patient screening has begun and patient dosing is expected to commence within the next several weeks. In the study ANA598 will be tested in both treatment-naïve patients and treatment-experienced patients who failed a prior course of therapy with interferon and ribavirin. ANA598 is the Company’s direct-acting antiviral, or DAA, being developed for the treatment of hepatitis C.
“We are excited to initiate this Phase IIb study of ANA598,” said James L. Freddo, M.D., Anadys’ Senior Vice President, Drug Development and Chief Medical Officer. “By establishing safety and efficacy in a greater number of patients, including those who have failed prior HCV treatment, we hope to position ANA598 as a highly attractive HCV agent ready for Phase III development.”
Phase IIb Protocol Design
In the study, approximately 200 chronically infected genotype 1 hepatitis C patients are expected to receive ANA598 200 mg twice a day (bid) in combination with Pegasys® (peginterferon alfa2a) and Copegus® (ribavirin, USP) (a current standard of care, or SOC) with a loading dose of 800 mg bid on day 1, while approximately 66 patients are to receive placebo and SOC. Enrollment is expected to include approximately equal numbers of treatment-naïve patients and patients who have failed a prior course of SOC, including difficult to treat prior null-responders. The primary endpoint of the study is Sustained Virological Response 24 weeks after patients conclude all treatment, known as SVR24. Anadys is conducting the study at sites within and outside the United States.
Naïve Arm
Approximately 100 treatment-naïve HCV patients are expected to receive ANA598 in combination with SOC and 33 treatment-naïve HCV patients are to receive placebo plus SOC. Treatment duration for naïve patients will be response-guided; patients who achieve undetectable levels of virus at Week 8 and maintain undetectable levels of virus will be scheduled to conclude all treatment at Week 28. For naïve patients with detectable virus at Week 8 dosing with ANA598, or placebo, and SOC is planned to continue through Week 48. The Company expects to receive Week 8 antiviral response data by the end of the second quarter of 2011, Week 12 antiviral response data in the third quarter of 2011 and Week 24 antiviral response data in the fourth quarter of 2011.
Treatment-Experienced Arm, Including Prior Null Responders
Approximately 80 patients who were partial responders during, or relapsers after, a prior course of therapy with SOC alone are expected to receive ANA598 in combination with SOC, and 33 corresponding patients are to receive placebo plus SOC. Additionally, approximately 28 prior null responder patients are to receive ANA598 in combination with SOC. All treatment-experienced patients who receive ANA598 are scheduled to receive triple combination therapy for 48 weeks. For the treatment-experienced patients, the Company expects to receive Week 12 antiviral response data in the third quarter of 2011 and Week 24 antiviral response data in the fourth quarter of 2011.
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