A Phase 1b study for Vertex's VX-985 protease inhibitor for HCV is now enrolling. "A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose Study of VX-985 in Subjects With Genotype 1 Chronic Hepatitis C. "
The purpose of this study it to evaluate the safety and tolerability of VX-985 in HCV subjects. This study will also evaluate the antiviral activity and pharmacokinetic profile of VX-985.
More info here: http://www.clinicaltrials.gov/ct2/show/NCT01144936?term=Hepatitis+C&lup_s=07%2F01%2F2010&lup_e=07%2F15%2F2010&rank=36
Thursday, July 15, 2010
Pfizer and Samsung Medical Center agree to collaborate on liver cancer research.
Pfizer Inc. and Samsung Medical Center said Wednesday they started a collaboration to do research on liver cancer.
The companies said they formed a partnership in June and will analyze tumors from patients in Korea. They plan to make genetic profiles that could help physicians select which therapy to use on similar patients.
New York-based Pfizer is the world's largest drugmaker in terms of revenue. Its products include the kidney cancer drug Sutent. In April it stopped a late-stage study of Sutent as a treatment for liver cancer because patients were not living as long as people who were on a competing drug, and they were more likely to suffer serious side effects.
Pfizer agreed to invest $300 million in Research and Development in South Korea in 2007, and formed a partnership with the Korea Research Institute of Bioscience and Biotechnology at the time.
Shares of Pfizer fell 9 cents to $14.70 in morning trading.
The companies said they formed a partnership in June and will analyze tumors from patients in Korea. They plan to make genetic profiles that could help physicians select which therapy to use on similar patients.
New York-based Pfizer is the world's largest drugmaker in terms of revenue. Its products include the kidney cancer drug Sutent. In April it stopped a late-stage study of Sutent as a treatment for liver cancer because patients were not living as long as people who were on a competing drug, and they were more likely to suffer serious side effects.
Pfizer agreed to invest $300 million in Research and Development in South Korea in 2007, and formed a partnership with the Korea Research Institute of Bioscience and Biotechnology at the time.
Shares of Pfizer fell 9 cents to $14.70 in morning trading.
Tuesday, July 13, 2010
Everything you wanted to know about BMS-790052 resistance and pharmacokinetics, but were afraid to ask.
The ubiquitous Jules Levin posts slides giving a resistance overview of the highly touted BMS-790052 compound presented at the recent HCV Drug Resistance New Compounds Workshop in Boston, MA. See it all here: http://www.natap.org/2010/HCVresist/HCVresist_07.htm
So far, this is what we know:
* Once-daily NS5A Inhibitor
* Used in combo with P/R, there is an additive effect. Looks to be a good candidate for combination therapy as well - when used in combo with BMS NS5B inhibitor, BMS NS3 inhibitor and an unnamed nuc, there are both additive and synergistic effects.
* Blocks multiple stages of viral replication - inactivation of NS5A appears to take out a whole communication network between NS5A's, as they communicate with each other in a replication network.
* Nice correlation between in vitro and in vivo resistance. No surprises.
* Is there pre-existing resistance? Yep. Like the linear NS3 PIs, it appears that G1a virus are inherently more resistant to BMS-790052 than G1b. BMS suggests that "NS5A baseline sequences may provide useful information for predicting resistance emergence".
* Another big question for BMS-790052, as is for the other drugs in development, is drug interactions. As we've seen in HIV antiretroviral therapy, drug interactions are extremely important to know to prevent adverse events and fluctuations in pharmacokinetics that may compromise efficacy and lead to emergence of resistant virus.
So far, this is what we know:
* Once-daily NS5A Inhibitor
* Used in combo with P/R, there is an additive effect. Looks to be a good candidate for combination therapy as well - when used in combo with BMS NS5B inhibitor, BMS NS3 inhibitor and an unnamed nuc, there are both additive and synergistic effects.
* Blocks multiple stages of viral replication - inactivation of NS5A appears to take out a whole communication network between NS5A's, as they communicate with each other in a replication network.
* Nice correlation between in vitro and in vivo resistance. No surprises.
* Is there pre-existing resistance? Yep. Like the linear NS3 PIs, it appears that G1a virus are inherently more resistant to BMS-790052 than G1b. BMS suggests that "NS5A baseline sequences may provide useful information for predicting resistance emergence".
* Another big question for BMS-790052, as is for the other drugs in development, is drug interactions. As we've seen in HIV antiretroviral therapy, drug interactions are extremely important to know to prevent adverse events and fluctuations in pharmacokinetics that may compromise efficacy and lead to emergence of resistant virus.
Monday, July 12, 2010
ZymoGenetics Financial results Conference Call on August 3, 2010.
ZymoGenetics to Host Conference Call and Webcast on August 3, 2010 to Discuss Second Quarter 2010 Financial Results
Conference Call and Webcast Information
ZymoGenetics Second Quarter 2010 Financial Results Conference Call will be held on August 3, 2010 at 4:30 p.m. Eastern Time and may be accessed at www.zymogenetics.com or by dialing (877) 407-0778 (International: 201-689-8565). Participants should dial in to the call approximately 10 minutes prior to the scheduled start time to register. A live audio webcast and slide presentation can be accessed by going to: www.zymogenetics.com. The webcast will be archived for 60 days.
For replay, please visit www.zymogenetics.com or use the following information:
- U.S. callers: (877) 660-6853
- International callers: (201) 612-7415
Replay passcode account #: 286
Conference ID #: 353663
Medivir / Tibotec announce impressive 24-week EOT and interim SVR4 and SVR 12 Phase 2b data on TMC435 HCV protease inhibitor
Potent and consistent antiviral efficacy was demonstrated at 24-week end-of-treatment and in interim SVR4 and SVR12 results. There were no clinically relevant differences between TMC435 treatment groups and placebo for adverse events.
12-Jul-10 Medivir announced today 24-week end-of-treatment interim results from the 5-arm phase 2b response guided PILLAR study in 386 treatment-naïve patients with hepatitis C virus (HCV) genotype-1 (TMC435-C205).
TMC435 is a protease inhibitor jointly developed by Medivir and Tibotec Pharmaceuticals, dosed as one pill once daily (q.d.) to treat hepatitis C virus infections (HCV).
In the PILLAR study, 75mg or 150mg TMC435 was given for either 12 weeks or 24 weeks in combination with 24 weeks of ribavirin and pegIFNalpha-2A, the current standard of care (SOC). Patients stopped all treatment at week 24 when HCV RNA levels at week 4 were < 25 log10 IU/mL detectable or undetectable and HCV RNA levels at week 12, week 16 and week 20 were < 25 log10 IU/mL undetectable. Patients who did not meet the above response-guided criteria continued with SOC until week 48. The results showed that in the TMC435 treatment groups 83% of patients were able to stop all therapy at Week 24.
Potent and consistent antiviral efficacy was demonstrated at 24-week end-of-treatment and in interim SVR4 and SVR12 rates with no major differences between TMC435 doses or length of triple therapy. 92% of patients taking TMC435 and Peg-IFN/RBV (SoC) achieved undetectable HCV RNA levels at week 4 and 92% at week 12 after cessation of treatment, i.e. SVR4 and SVR12. SVR4 and SVR12 data were available for 82% and 42% of the TMC435-treated patients respectively who had stopped all therapy before or at Week 24 and had completed the follow-up visits. Both the viral breakthrough rate (4.9%) and relapse rate (1.6%) were low in the TMC435 treatment groups.
TMC435 was generally safe and well tolerated with no relevant differences in adverse events (AEs) between placebo and TMC435 treatment groups. Most AEs were mild to moderate in severity and the discontinuation rate due to AEs was low and not different from placebo.
When looking at particular adverse events of interest, the incidence of rash, pruritis, GI side effects and anemia were similar in TMC435 groups and placebo and were generally mild to moderate in nature. Use of erythropoetin-stimulating agents (ESAs) was not allowed during the trial.
In laboratory parameters, there were no clinically relevant differences between any TMC435 groups and placebo except for mild bilirubin elevations. Significant decreases in transaminases (ALT and AST) were observed in all treatment groups.
Further safety and efficacy data will be presented at future scientific meetings later in 2010.
"We are extremely encouraged and excited by the efficacy and safety demonstrating that TMC435 is truly a second-generation HCV protease inhibitor," stated Bertil Samuelsson, CSO of Medivir. "We also are looking forward to the top-line data coming up from the phase 2b trial C206 (ASPIRE) in treatment-experienced patients later this year as well as start of phase 3 clinical trials in treatment-naïve patients early next year.”
Frequency of Undetectable* HCV RNA Levels During and After Treatment
[Removed graphics] See PDF for table
About TMC435 clinical trial programs
TMC435 is a protease inhibitor jointly developed by Medivir and Tibotec Pharmaceuticals to treat hepatitis C virus infections (HCV).
TMC435 is currently being developed in three phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215) in G1 treatment-naïve and in G1 patients that failed previous IFN-based treatment. Safety and efficacy data from the phase 2b trials will be presented at scientific meetings later in 2010.
TMC435-C205 is a global phase 2b study in 386 genotype-1 treatment-naïve patients. It is a once daily treatment of TMC435 with different doses and durations given in addition to standard of care treatment, consisting of ribavirin and pegIFNalpha-2A.
TMC435-C215 is a Japan phase 2b study in 92 genotype-1 treatment-naïve patients. It is a once daily treatment of TMC435 with different doses and durations given in addition to standard of care treatment, consisting of ribavirin and pegIFNalpha-2A.
TMC435-C206 is a global phase 2b study in 463 genotype-1 treatment-experienced patients. It is a once daily treatment of TMC435 in with different doses of given in addition to standard of care treatment, consisting of ribavirin and pegIFNalpha-2A.
12-Jul-10 Medivir announced today 24-week end-of-treatment interim results from the 5-arm phase 2b response guided PILLAR study in 386 treatment-naïve patients with hepatitis C virus (HCV) genotype-1 (TMC435-C205).
TMC435 is a protease inhibitor jointly developed by Medivir and Tibotec Pharmaceuticals, dosed as one pill once daily (q.d.) to treat hepatitis C virus infections (HCV).
In the PILLAR study, 75mg or 150mg TMC435 was given for either 12 weeks or 24 weeks in combination with 24 weeks of ribavirin and pegIFNalpha-2A, the current standard of care (SOC). Patients stopped all treatment at week 24 when HCV RNA levels at week 4 were < 25 log10 IU/mL detectable or undetectable and HCV RNA levels at week 12, week 16 and week 20 were < 25 log10 IU/mL undetectable. Patients who did not meet the above response-guided criteria continued with SOC until week 48. The results showed that in the TMC435 treatment groups 83% of patients were able to stop all therapy at Week 24.
Potent and consistent antiviral efficacy was demonstrated at 24-week end-of-treatment and in interim SVR4 and SVR12 rates with no major differences between TMC435 doses or length of triple therapy. 92% of patients taking TMC435 and Peg-IFN/RBV (SoC) achieved undetectable HCV RNA levels at week 4 and 92% at week 12 after cessation of treatment, i.e. SVR4 and SVR12. SVR4 and SVR12 data were available for 82% and 42% of the TMC435-treated patients respectively who had stopped all therapy before or at Week 24 and had completed the follow-up visits. Both the viral breakthrough rate (4.9%) and relapse rate (1.6%) were low in the TMC435 treatment groups.
TMC435 was generally safe and well tolerated with no relevant differences in adverse events (AEs) between placebo and TMC435 treatment groups. Most AEs were mild to moderate in severity and the discontinuation rate due to AEs was low and not different from placebo.
When looking at particular adverse events of interest, the incidence of rash, pruritis, GI side effects and anemia were similar in TMC435 groups and placebo and were generally mild to moderate in nature. Use of erythropoetin-stimulating agents (ESAs) was not allowed during the trial.
In laboratory parameters, there were no clinically relevant differences between any TMC435 groups and placebo except for mild bilirubin elevations. Significant decreases in transaminases (ALT and AST) were observed in all treatment groups.
Further safety and efficacy data will be presented at future scientific meetings later in 2010.
"We are extremely encouraged and excited by the efficacy and safety demonstrating that TMC435 is truly a second-generation HCV protease inhibitor," stated Bertil Samuelsson, CSO of Medivir. "We also are looking forward to the top-line data coming up from the phase 2b trial C206 (ASPIRE) in treatment-experienced patients later this year as well as start of phase 3 clinical trials in treatment-naïve patients early next year.”
Frequency of Undetectable* HCV RNA Levels During and After Treatment
[Removed graphics] See PDF for table
About TMC435 clinical trial programs
TMC435 is a protease inhibitor jointly developed by Medivir and Tibotec Pharmaceuticals to treat hepatitis C virus infections (HCV).
TMC435 is currently being developed in three phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215) in G1 treatment-naïve and in G1 patients that failed previous IFN-based treatment. Safety and efficacy data from the phase 2b trials will be presented at scientific meetings later in 2010.
TMC435-C205 is a global phase 2b study in 386 genotype-1 treatment-naïve patients. It is a once daily treatment of TMC435 with different doses and durations given in addition to standard of care treatment, consisting of ribavirin and pegIFNalpha-2A.
TMC435-C215 is a Japan phase 2b study in 92 genotype-1 treatment-naïve patients. It is a once daily treatment of TMC435 with different doses and durations given in addition to standard of care treatment, consisting of ribavirin and pegIFNalpha-2A.
TMC435-C206 is a global phase 2b study in 463 genotype-1 treatment-experienced patients. It is a once daily treatment of TMC435 in with different doses of given in addition to standard of care treatment, consisting of ribavirin and pegIFNalpha-2A.
Saturday, July 10, 2010
AIDS vaccine development takes a step forward?
July 09--An effective vaccine against the AIDS virus may have moved one step closer to reality, researchers said Thursday.
Federal researchers have identified a pair of naturally occurring antibodies that are able to kill more than 90 percent of all strains of the AIDS virus, a finding they say could lead to the development of new treatments for HIV infections and to the production of the first successful vaccine against the virus.
HIV, the virus that causes AIDS, is notoriously mutable, changing the composition of proteins on its surface with ease to escape pressure from the immune system. This enables it to continue infecting cells even after the appearance of antibodies targeting it -- and to avoid the relatively ineffective vaccines developed so far.
Hundreds of variants of the virus are now in circulation around the world, and the identification of so-called broadly neutralizing antibodies that can block the bulk of them has been the holy grail of HIV researchers.
To date, however, the best antibodies -- immune system proteins that fight infections -- that researchers have found block only 30 percent to 40 percent of all HIV strains. The identification of antibodies that can block more than 90 percent of strains could lead to what some researchers are dubbing a renaissance in AIDS prevention and treatment.
The key to the new antibodies is that they bind to a site on the virus surface that rarely mutates.
"I am more optimistic about an AIDS vaccine at this point in time than I have been probably in the last 10 years," Dr. Gary Nabel of the National Institute of Allergy and Infectious Diseases told Reuters. He led the research reported Thursday in the online edition of the journal Science.
Nabel and his colleagues isolated the antibodies from the blood of a 60-year-old African American gay man. Using newly developed imaging and analytical techniques, they found that the two antibodies, called VRC01 and VRC02, bind to a spike on the surface of the virus. This spike interacts with a receptor called the CD4 binding site on the surface of human cells, and when an antibody binds to it, the virus cannot enter a cell.
Because the virus must use CD4 to enter cells, it cannot tolerate mutations in the spike. The composition of the spike is thus pretty much constant in all variants of HIV in circulation.
"The antibodies attach to a virtually unchanging part of the virus, and this explains why they can neutralize such an extraordinary range of HIV strains," Dr. John R. Mascola of the infectious diseases institute, a coauthor, said in a statement.
With the antibodies in hand, the team was able to determine precisely how the HIV spike and the antibodies interact. They were then able to produce a synthetic version of the spike that could elicit the production of similar blocking antibodies in animal cells.
They are now testing the synthetic spike as a possible vaccine in animals and hope to expand to human testing in the relatively near future. The antibodies can also be reproduced by biotechnology and used as a treatment for someone who is already infected.
Researchers, who are already testing the antibodies in infected animals, hope that at the very least the antibodies will provide synergistic effects when used in conjunction with antiviral drugs.
Other researchers, such as Dennis Burton of the Scripps Research Institute in La Jolla, have also discovered broadly neutralizing antibodies, although most of the discoveries have not yet been published. Fortuitously, Mascola has found, antibodies discovered by Burton block viral variants that are not blocked by the antibodies reported Thursday.
Researchers thus hope that incorporating synthetic chemicals that stimulate production of several different antibodies might provide nearly complete protection against HIV.
Tuesday, July 6, 2010
Expanded label for Infergen - too little too late?
New Labeling Provides Alternative for Hepatitis C Patients Who Need Retreatment
“Approximately 50 percent of patients with chronic hepatitis C do not respond to their initial course of therapy,” stated Dr. Bruce Bacon, the lead investigator for the registration trial. “The FDA’s recognition of this expanded label allows patients failing therapy a safe and efficacious retreatment strategy. The results from this study legitimize how we properly treat these patients helping them to achieve SVR.”
The data reported and published in Hepatology (2009) from the U.S.-based, randomized, DIRECT clinical trial (Daily-Dose Consensus Interferon and Ribavirin: Efficacy of Combined Therapy) led to the approval of the expanded label. Results from the DIRECT trial had shown that the use of INFERGEN and RBV is a safe and effective retreatment strategy for patients failing initial therapy with PEG-IFN/RBV. This was especially apparent with interferon-sensitive patients with lower baseline fibrosis scores. In fact, up to 38 percent of non-cirrhotic patients (in the 15mcg arm) who were sensitive to Peg-IFN/RBV and who did not modify their INFERGEN and RBV dosages achieved an SVR. Additionally, patients with cirrhosis were less likely to benefit from retreatment with INFERGEN and RBV unless they displayed previous interferon sensitivity or at least 1-log10 drop in viral levels on prior therapy.
“The expanded labeling for INFERGEN is a significant step forward for retreatment of hepatitis C patients who deserve a second chance to overcome their HCV,” stated Patrick Kerrish, R.Ph, M.B.A., President of Three Rivers Pharmaceuticals, LLC. “Our hope is that INFERGEN will become the standard of care for the retreatment of chronic hepatitis C patients.”
Three Rivers Pharmaceuticals, LLC is expanding its INFERGEN and hepatitis C education efforts via physician outreach and online patient support programs. An instructional video and guide about proper at-home injections of INFERGEN, tips for patient compliance, access to reimbursement specialists and a hotline staffed by nurse counselors are available at www.infergen.com.
Subscribe to:
Posts (Atom)
Posts
