Synopsis of the GI-5005 study presented at AASLD 2010. Overall, the numbers for GI-5005 aren't extraordinary, but certainly worth further studies. The true benefit for this vaccine may be how it appears to illicit a T-cell response in patients carrying the T allele of the IL28 gene, which didn't occur when the same patients were given standard of care
By: DIANA MAHONEY, Internal Medicine News Digital Network
12/01/10
BOSTON – A therapeutic vaccine against the hepatitis C virus was associated with a significantly higher sustained virologic response rate when added to standard-of-care treatment, and the findings justify further development of the vaccine, Dr. Paul Pockros reported at the annual meeting of the American Association for the Study of Liver Diseases.
In the proof-of-concept trial, 133 patients infected with hepatitis C virus (HCV) genotype 1 were randomized to either triple therapy comprising the experimental GI-5005 vaccine, which is designed to elicit a T-cell response specific to HCV, along with pegylated interferon alfa-2b plus ribavirin (P/R), or the standard P/R therapy alone.
The primary outcome measure was sustained virologic response (SVR), defined as undetectable HCV RNA at 6 months after treatment, said Dr. Pockros of the Scripps Clinic in La Jolla, Calif.
The 68 patients in the experimental group initially received monotherapy with the vaccine, consisting of five weekly injections followed by two monthly injections for a 12-week lead-in period, before progressing to the standard-of-care P/R treatment and once-monthly injections. The 65 patients in the control group received standard-of-care P/R treatment alone.
In both groups, the treatment duration was 48 weeks for treatment-naive patients and 72 weeks for those who had a poor or partial response to prior P/R treatment, said Dr. Pockros. Patients in whom prior P/R therapy induced no notable decrease in HCV viral load, as well as those in whom prior treatment initially resulted in undetectable HCV RNA followed by a viral rebound, were excluded from the analysis.
Among the study’s treatment-naive patients, 58% of those who received the vaccine achieved SVR, compared with 48% of those who received P/R alone. Among the prior poor and partial responders, the respective SVR rates in the vaccine and control groups were 17% and 5%, Dr. Pockros reported.
"There was a slight benefit in the treatment-naive and nonresponders, [but] this was numerical only and was not statistically significant," he said. However, the overall benefit in the vaccine vs. control groups was statistically significant, with respective SVR rates of 47% and 35%, he noted.
The vaccine strategy appears to be safe. "The most common associated adverse events were mild, transient injection-site reactions," said Dr. Pockros. Additionally, he stated, "the discontinuation rates due to adverse events were comparable [13%] in both the triple-therapy and standard-of-care arms."
Of particular interest, Dr. Pockros noted, was the T-cell response in a subgroup of difficult-to-treat patients receiving the vaccine. Previous studies have suggested that patients carrying the T allele of the IL28 gene are at high risk of treatment failure with the standard interferon-based therapy. The T-cell response in vaccine-treated patients, as measured by interferon-gamma enzyme-linked ImmunoSpot assay, "mimicked what we saw with a virologic response," he said.
"Four of five T/T allele patients had a T-cell response – one did not actually get treated – but none of the patients who received standard of care had a T-cell response."
This finding is consistent with the hypothesis that the GI-5005 vaccine corrects a fundamental deficit in cellular immunity in IL28B T/T genotype patients, he said. Although the findings need to be confirmed in additional studies with larger patient populations, the vaccine will likely be genotype specific, he noted.
Because the immune response is similar to that observed in HCV-infected patients who are able to clear the virus without treatment, future studies will evaluate the efficacy of monotherapy with the vaccine in genotype-specific patients, Dr. Pockros said.
The proof-of-concept study was funded by GlobeImmune, manufacturer of the vaccine. Dr. Pockros disclosed financial relationships with GlobeImmune, Genentech, Vertex, Merck, Gilead, Abbott, Pfizer, Phenomix, Tibotec, Pharmasset, 3RT, Novartis, Johnson & Johnson, Achillon, Regulus, Debio, Zymogenetics, and Human Genome Sciences.
Wednesday, December 1, 2010
Tuesday, November 30, 2010
Caleco Pharma Corp amends IP patents for compounds to treat HCV...
LONG VALLEY, NEW JERSEY--(Marketwire - 11/30/10) - Caleco Pharma Corp. (www.calecopharmacorp.com), a diversified healthcare company with biopharmaceutical and consumer health product development programs that develop products derived from natural sources such as plant extracts, today reports that it has amended its intellectual property (IP) filing with the European Patent Office in The Hague to further secure and strengthen Caleco's anti-viral pipeline.
In response to the EU Patent Office's Examination Report, Caleco reports that the company's European Patent Application number 08725530.3 is amended with regard to compositions comprising derivatives and derivative combinations of Lamiridosin and Iridoid for treatment of Hepatitis C. The molecular specifications required in these amendments resulted in the exclusion of certain derivative claims. However, these claims will not be abandoned, but instead, these claims will be pursued through one or more divisional applications.
John Boschert, Caleco's CEO, said, "By amending our filing we are seeking to solidify our intellectual property position in the billion dollar Hepatitis C and anti-viral marketplace. We plan to continue to pursue a broader pipeline of semi-synthetic derivatives that will be prepared for further testing in 2011. The Hepatitis C patient population remains greatly underserved by existing treatment options and we are eager to move these compounds into the next stage of development."
About Caleco Pharma Corp.
Caleco is focused on the ongoing research and development of its pipeline of over-the-counter and prescription medications including its proprietary antiviral and "Liver Health" OTC formulations. In addition Caleco is developing Dermatological Products based on the active ingredients found in its proprietary formulation. Caleco's intellectual property covering the Liver Health formulations and derivatives consists of patent applications in the United States, Europe and Canada and four European Drug Master File applications.
Caleco's shares are traded in the United States on the OTC Bulletin Board (OTC.BB:CAEH - News) and in Germany on the Frankfurt Stock Exchange (Frankfurt:T3R - News)(WKN: A0N9Y0).
In response to the EU Patent Office's Examination Report, Caleco reports that the company's European Patent Application number 08725530.3 is amended with regard to compositions comprising derivatives and derivative combinations of Lamiridosin and Iridoid for treatment of Hepatitis C. The molecular specifications required in these amendments resulted in the exclusion of certain derivative claims. However, these claims will not be abandoned, but instead, these claims will be pursued through one or more divisional applications.
John Boschert, Caleco's CEO, said, "By amending our filing we are seeking to solidify our intellectual property position in the billion dollar Hepatitis C and anti-viral marketplace. We plan to continue to pursue a broader pipeline of semi-synthetic derivatives that will be prepared for further testing in 2011. The Hepatitis C patient population remains greatly underserved by existing treatment options and we are eager to move these compounds into the next stage of development."
About Caleco Pharma Corp.
Caleco is focused on the ongoing research and development of its pipeline of over-the-counter and prescription medications including its proprietary antiviral and "Liver Health" OTC formulations. In addition Caleco is developing Dermatological Products based on the active ingredients found in its proprietary formulation. Caleco's intellectual property covering the Liver Health formulations and derivatives consists of patent applications in the United States, Europe and Canada and four European Drug Master File applications.
Caleco's shares are traded in the United States on the OTC Bulletin Board (OTC.BB:CAEH - News) and in Germany on the Frankfurt Stock Exchange (Frankfurt:T3R - News)(WKN: A0N9Y0).
Pharmasset Initiates Dosing in a Combination Study of PSI-7977 and PSI-938 for Chronic Hepatitis C...
First study to look at a combination of of a purine and a pyrimidine nucleotide analog (PSI-938 and PSI-7977 respectively). Pharmasset believes the combination of two 'nucs' has a potential higher barrier to resistance, making it attractive to use in combo with other STAT-C/DAA drugs. The company plans a Phase II trail looking at the combination without interferon mid-2011 - Chris
- 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, <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.
- 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, <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.
Sunday, November 28, 2010
Avilla Therapeutics publishes paper on a new class of highly selective, irreversible HCV protease inhibitors
Publication in Nature Chemical Biology demonstrates that irreversible covalent inhibition can increase selectivity, potency and duration of action, broadens applications for targeted covalent drugs to the protease gene family
WALTHAM, MA – November 28, 2010 – Avila Therapeutics™, Inc., a biotechnology company developing novel targeted covalent drugs, has published research in Nature Chemical Biology demonstrating the first-ever selective irreversible inhibition of a viral protease using a targeted covalent drug. In the paper titled "Selective Irreversible Inhibition of a Protease by Targeting a Non-Catalytic Cysteine", Avila used its proprietary Avilomics™ platform to design covalent irreversible protease inhibitors that are highly selective, potent and with superior duration of action as compared to conventional protease inhibitors.
Importantly, the published research demonstrates that covalent drugs can be designed and targeted to irreversibly and covalently bond to molecular domains specific to proteases. This is the first report of the irreversible covalent approach being successfully extended to proteases, a very broad class of proteins that includes many important potential drug targets.
"This research elevates covalent drug design to a fundamentally new level," said Simon Campbell, PhD, CBE, FMedSci, FRS, a renowned scientist and former Senior Vice President for Worldwide Drug Discovery and Medicinal R&D Europe of Pfizer. "By creating extremely selective protease inhibitors with their platform, Avila is showing the remarkable therapeutic potential of irreversible covalent drugs to address a broad spectrum of drug targets."
"This publication showcases the creation of a whole new class of small molecule drugs," said Juswinder Singh, PhD, Chief Scientific Officer of Avila and a co-author of the paper. "This approach can make a difference to patients living with HCV infection, and we expect to make an impact in other important areas such as cancer and inflammatory disease."
In order to maximize selectivity and minimize off-target effects, the irreversible covalent inhibitors of HCV protease were designed to covalently target a unique structure in the HCV protease not found in human proteases. Key findings include:
* A representative irreversible covalent inhibitor designed, by Avila, was shown to inhibit the HCV protease (also known as "NS3") in cells at a concentration of 6 nM .
* Specific covalent bond formation between the drug and target protease was demonstrated through use of mass spectrometry and also x-ray crystallography.
* Very high selectivity of the Avila compounds was demonstrated by showing no notable inhibition of a panel of human proteases in biochemical assays with additional specificity demonstrated in cellular assays; this was contrasted experimentally with Telaprevir, an HCV protease inhibitor in late-stage clinical testing which demonstrated off-target biochemical activity against several human targets.
Avila has subsequently optimized additional drug candidates, yielding current development candidates, AVL-181 and AVL-192, which have excellent pharmacokinetics and bind potently to wild- type HCV protease as well as multiple genotypes and mutant forms of HCV protease.
###
About Avila Therapeutics™, Inc.
Avila focuses on design and development of targeted covalent drugs to achieve best-in class outcomes that cannot be achieved through traditional chemistries. This approach is called "protein silencing". The company's product pipeline has been built using its proprietary Avilomics™ platform and is currently focused on viral infection, cancer and autoimmune disease. Avila is funded by leading venture capital firms: Abingworth, Advent Venture Partners, Atlas Venture, Novartis Option Fund, and Polaris Venture Partners. For additional information, please visit http://www.avilatx.com
WALTHAM, MA – November 28, 2010 – Avila Therapeutics™, Inc., a biotechnology company developing novel targeted covalent drugs, has published research in Nature Chemical Biology demonstrating the first-ever selective irreversible inhibition of a viral protease using a targeted covalent drug. In the paper titled "Selective Irreversible Inhibition of a Protease by Targeting a Non-Catalytic Cysteine", Avila used its proprietary Avilomics™ platform to design covalent irreversible protease inhibitors that are highly selective, potent and with superior duration of action as compared to conventional protease inhibitors.
Importantly, the published research demonstrates that covalent drugs can be designed and targeted to irreversibly and covalently bond to molecular domains specific to proteases. This is the first report of the irreversible covalent approach being successfully extended to proteases, a very broad class of proteins that includes many important potential drug targets.
"This research elevates covalent drug design to a fundamentally new level," said Simon Campbell, PhD, CBE, FMedSci, FRS, a renowned scientist and former Senior Vice President for Worldwide Drug Discovery and Medicinal R&D Europe of Pfizer. "By creating extremely selective protease inhibitors with their platform, Avila is showing the remarkable therapeutic potential of irreversible covalent drugs to address a broad spectrum of drug targets."
"This publication showcases the creation of a whole new class of small molecule drugs," said Juswinder Singh, PhD, Chief Scientific Officer of Avila and a co-author of the paper. "This approach can make a difference to patients living with HCV infection, and we expect to make an impact in other important areas such as cancer and inflammatory disease."
In order to maximize selectivity and minimize off-target effects, the irreversible covalent inhibitors of HCV protease were designed to covalently target a unique structure in the HCV protease not found in human proteases. Key findings include:
* A representative irreversible covalent inhibitor designed, by Avila, was shown to inhibit the HCV protease (also known as "NS3") in cells at a concentration of 6 nM .
* Specific covalent bond formation between the drug and target protease was demonstrated through use of mass spectrometry and also x-ray crystallography.
* Very high selectivity of the Avila compounds was demonstrated by showing no notable inhibition of a panel of human proteases in biochemical assays with additional specificity demonstrated in cellular assays; this was contrasted experimentally with Telaprevir, an HCV protease inhibitor in late-stage clinical testing which demonstrated off-target biochemical activity against several human targets.
Avila has subsequently optimized additional drug candidates, yielding current development candidates, AVL-181 and AVL-192, which have excellent pharmacokinetics and bind potently to wild- type HCV protease as well as multiple genotypes and mutant forms of HCV protease.
###
About Avila Therapeutics™, Inc.
Avila focuses on design and development of targeted covalent drugs to achieve best-in class outcomes that cannot be achieved through traditional chemistries. This approach is called "protein silencing". The company's product pipeline has been built using its proprietary Avilomics™ platform and is currently focused on viral infection, cancer and autoimmune disease. Avila is funded by leading venture capital firms: Abingworth, Advent Venture Partners, Atlas Venture, Novartis Option Fund, and Polaris Venture Partners. For additional information, please visit http://www.avilatx.com
Friday, November 26, 2010
Clinical Care Options AASLD 2010 Highlights slide deck ready for download...
Robert G. Gish, MD, and Stephen A. Harrison, MD, FACP, review the most clinically relevant data from this important annual meeting. Registration required. You can download them here.
Tuesday, November 23, 2010
Roche severs HCV treatment collaboration and license agreement between with Ligand Pharma...
Drug giant Roche terminates it's treatment collaboration and license agreement with Ligand Pharma. Ligand gets a good deal, with non-exclusive, worldwide, royalty-bearing license under specified Roche patents to develop, make and sell related compounds and products, subject to royalty payments on net sales. Roche, on the other hand, is prohibited for ten years following the termination from developing or commercializing related compounds. Maybe the InterMune deal was enough? Nah. Has to be some other reason.
Tue, Nov 23 2010
* Says received a notice from Roche unit on Nov 19
* Roche prohibited to develop related compounds for 10 yrs
* Shares down 1 pct after-the-bell
Nov 23 (Reuters) - Ligand Pharmaceuticals Inc (LGNDD.O: Quote, Profile, Research) said Swiss drugmaker Roche Holding AG (ROG.VX: Quote, Profile, Research) was exercising its right to terminate the collaboration and license agreement between the two companies on developing hepatitis C treatment.
The collaboration and license agreement with Roche began in 2008 to develop new treatments for hepatitis C viral infection using liver-targeting technology.
In April, Ligand received $6.5 million milestone payment from Roche.
As per the agreement, Ligand will receive a non-exclusive, worldwide, royalty-bearing license under specified Roche patents to develop, make and sell related compounds and products, subject to royalty payments on net sales.
Roche will be prohibited for ten years following the termination from developing or commercializing related compounds, Ligand said in a regulatory filing.
Ligand said it received a notice from Roche units last Friday regarding the termination.
Ligand's shares, which have lost about 18 percent since the company got Japanese marketing nod for its blood clotting treatment earlier this month, were trading down about 1 percent at $8.16 Tuesday after-the-bell.
Tue, Nov 23 2010
* Says received a notice from Roche unit on Nov 19
* Roche prohibited to develop related compounds for 10 yrs
* Shares down 1 pct after-the-bell
Nov 23 (Reuters) - Ligand Pharmaceuticals Inc (LGNDD.O: Quote, Profile, Research) said Swiss drugmaker Roche Holding AG (ROG.VX: Quote, Profile, Research) was exercising its right to terminate the collaboration and license agreement between the two companies on developing hepatitis C treatment.
The collaboration and license agreement with Roche began in 2008 to develop new treatments for hepatitis C viral infection using liver-targeting technology.
In April, Ligand received $6.5 million milestone payment from Roche.
As per the agreement, Ligand will receive a non-exclusive, worldwide, royalty-bearing license under specified Roche patents to develop, make and sell related compounds and products, subject to royalty payments on net sales.
Roche will be prohibited for ten years following the termination from developing or commercializing related compounds, Ligand said in a regulatory filing.
Ligand said it received a notice from Roche units last Friday regarding the termination.
Ligand's shares, which have lost about 18 percent since the company got Japanese marketing nod for its blood clotting treatment earlier this month, were trading down about 1 percent at $8.16 Tuesday after-the-bell.
Roche severs HCV treatment collaboration and license agreement between with Ligand Pharma...
Drug giant Roche terminates it's treatment collaboration and license agreement with Ligand Pharma. Ligand gets a good deal, with non-exclusive, worldwide, royalty-bearing license under specified Roche patents to develop, make and sell related compounds and products, subject to royalty payments on net sales. Roche, on the other hand, is prohibited for ten years following the termination from developing or commercializing related compounds. Maybe the InterMune deal was enough? Nah. Has to be some other reason.
Tue, Nov 23 2010
* Says received a notice from Roche unit on Nov 19
* Roche prohibited to develop related compounds for 10 yrs
* Shares down 1 pct after-the-bell
Nov 23 (Reuters) - Ligand Pharmaceuticals Inc (LGNDD.O: Quote, Profile, Research) said Swiss drugmaker Roche Holding AG (ROG.VX: Quote, Profile, Research) was exercising its right to terminate the collaboration and license agreement between the two companies on developing hepatitis C treatment.
The collaboration and license agreement with Roche began in 2008 to develop new treatments for hepatitis C viral infection using liver-targeting technology.
In April, Ligand received $6.5 million milestone payment from Roche.
As per the agreement, Ligand will receive a non-exclusive, worldwide, royalty-bearing license under specified Roche patents to develop, make and sell related compounds and products, subject to royalty payments on net sales.
Roche will be prohibited for ten years following the termination from developing or commercializing related compounds, Ligand said in a regulatory filing.
Ligand said it received a notice from Roche units last Friday regarding the termination.
Ligand's shares, which have lost about 18 percent since the company got Japanese marketing nod for its blood clotting treatment earlier this month, were trading down about 1 percent at $8.16 Tuesday after-the-bell.
Tue, Nov 23 2010
* Says received a notice from Roche unit on Nov 19
* Roche prohibited to develop related compounds for 10 yrs
* Shares down 1 pct after-the-bell
Nov 23 (Reuters) - Ligand Pharmaceuticals Inc (LGNDD.O: Quote, Profile, Research) said Swiss drugmaker Roche Holding AG (ROG.VX: Quote, Profile, Research) was exercising its right to terminate the collaboration and license agreement between the two companies on developing hepatitis C treatment.
The collaboration and license agreement with Roche began in 2008 to develop new treatments for hepatitis C viral infection using liver-targeting technology.
In April, Ligand received $6.5 million milestone payment from Roche.
As per the agreement, Ligand will receive a non-exclusive, worldwide, royalty-bearing license under specified Roche patents to develop, make and sell related compounds and products, subject to royalty payments on net sales.
Roche will be prohibited for ten years following the termination from developing or commercializing related compounds, Ligand said in a regulatory filing.
Ligand said it received a notice from Roche units last Friday regarding the termination.
Ligand's shares, which have lost about 18 percent since the company got Japanese marketing nod for its blood clotting treatment earlier this month, were trading down about 1 percent at $8.16 Tuesday after-the-bell.
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