Latest drugs under Clinical Trials(November - 2009 )

Avila Presents Data on Its Novel, Orally-Available Protease Inhibitor, AVL-181, Demonstrating Viral Clearance of Hepatitis C Virus in Preclinical Models

Avila Therapeutics™, Inc., a biotechnology company developing novel covalent drugs that treat diseases through protein silencing, presented results of preclinical studies on its highly selective, small molecule Hepatitis C Virus (HCV) protease inhibitor, AVL-181. Avila showed that AVL-181 promoted complete viral clearance in vitro when used at clinically-relevant concentrations in combination with other HCV therapies. Additionally, using an innovative technology for measuring the extent of covalent bond formation, Avila showed that AVL-181 bonds selectively and irreversibly to HCV protease in vivo in a novel rodent model, thus silencing a key protein necessary for successful viral replication and resulting in a prolonged duration of action in vivo. These new data were presented today at the 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD)

“Potential for Rapid and Prolonged Therapeutic Benefit in HCV through Protein Silencing of NS3 Protease with AVL-181”
* selectively bonds the HCV NS3 protease to completely and irreversibly inactivate proteolytic activity, essentially silencing the HCV protease complex;
* forms a highly specific covalent bond across HCV genotypes and clinically-described drug-resistant mutant proteases;
* inhibits protease activity in cultured replicon cells for >48 hours after very brief exposure and removal of AVL-181;
* demonstrates prolonged pharmacodynamic activity for both wild-type and drug-resistant mutations (e.g. R155K); and;
* results in clearance of HCV RNA from replicon cells in conjunction with a non-nucleoside polymerase inhibitor, contributing to a profile that differentiates AVL-181 from clinically investigated agents.

“AVL-181 Demonstrates Prolonged Inhibition of HCV NS3 Protease Activity In Vivo that Directly Correlates with Prolonged Molecular Target Occupancy”
* potently and irreversibly silences HCV proteases, and that the level of protease inhibition is directly correlated with the extent of target bonding;
* durably inhibits the HCV protease for at least 10 hours in vivo after a single exposure as measured in a novel model in which NS3/4A is expressed in the mouse liver; and
* this duration of action coupled with the low plasma levels of AVL-181 at this late timepoint confirm that the covalent mechanism does not depend on the near-continuous drug exposure such as that required by the reversible HCV protease inhibitors currently in late-stage clinical trials.
Source: http://www.avilatx.com

Sanofi Pasteur Announces Final Results of U.S. Clinical Trials of Influenza A (H1N1) Vaccine in Adults and Children
The data confirm the immunogenicity and safety profile of the vaccine, with no serious vaccine-related adverse events reported during the 42 days of follow-up in the two trials.

The trials confirm that one dose of Influenza A (H1N1) 2009 Monovalent Vaccine induces a robust antibody response in adults -- but two doses of vaccine are needed to assure a robust antibody response in children 9 years of age and younger. The two-dose regimen for these younger children is similar to the recommendations for seasonal influenza immunization in this age group.

About the Trial
The randomized, placebo-controlled, multicenter trials were conducted by Sanofi Pasteur to determine the immunogenicity and safety of the vaccine, given in two doses, with the second dose administered 21 days following the first dose. Immunogenicity was measured at day 21, just prior to administration of the second dose, and again at day 42.

The adult trial was conducted in 849 individuals divided into two age cohorts: 18 through 64 years of age; and 65 years of age and older. Study participants in each age cohort were randomized to four treatment groups. Three groups received a 0.5 mL injection of non-adjuvanted vaccine formulated to contain 7.5, 15 or 30 mcg of hemagglutinin (HA) antigen. The fourth group received a placebo control (ClinicalTrials.gov registration number NCT00953524).

In the pediatric trial, 474 children were enrolled in two age cohorts: 6 months through 35 months of age; and 3 years through 9 years of age. The trial evaluated two vaccine formulations, 7.5 mcg and 15 mcg of HA antigen in each of two cohorts, with a third group receiving a placebo (ClinicalTrials.gov registration number NCT00952419).

At Day 42, 21 days following a second 7.5 mcg dose of Influenza A (H1N1) 2009 Monovalent Vaccine, seroprotection (defined as an antibody titer of 1:40 or greater) was achieved in 92 percent of children 6 months through 35 months of age; and following a second 15 mcg dose of the vaccine, seroprotection was achieved in 99 percent of children 3 through 9 years of age, 99 percent of adults 18 through 64 years of age and in 95 percent of adults age 65 and older.

Sanofi Pasteur previously reported interim data showing that an immune response considered seroprotective was achieved following one 15 mcg dose of the vaccine in 50 percent of children 6 months through 35 months of age, 76 percent of children 3 through 9 years of age, 98 percent of adults 18 through 64 years of age and 92 percent of adults age 65 and older.

A rise in antibody titers lower than 1:40 following vaccination may minimize the occurrence of disease and its consequences but is not considered seroprotective.The data from these clinical trials provide additional information to guide recommendations on the optimal dosage, number of doses and schedule.
No serious vaccine-related adverse events were reported during the trial. Adverse event monitoring will continue for six months after administration of the second vaccine dose. Solicited systemic and local reactions reported were similar to those observed in other studies of seasonal trivalent inactivated influenza vaccine administered to persons in comparable age groups.

About Influenza A (H1N1) 2009 Monovalent Vaccine
The U.S. licensed Influenza A (H1N1) 2009 Monovalent Vaccine manufactured by Sanofi Pasteur is an inactivated influenza virus vaccine indicated for active immunization of persons 6 months of age and older against influenza disease caused by pandemic (H1N1) 2009 virus. Influenza A (H1N1) 2009 Monovalent Vaccine was licensed by the U.S. Food and Drug Administration on September 15 as a monovalent strain change to Sanofi Pasteur's licensed seasonal influenza vaccine.

The Influenza A (H1N1) 2009 Monovalent Vaccine is manufactured by the same process as Sanofi Pasteur's seasonal trivalent influenza virus vaccine licensed in the U.S. Influenza A (H1N1) 2009 Monovalent Vaccine is formulated to contain 15 mcg hemagglutinin (HA) of influenza A/California/07/2009 (H1N1) v-like virus. Influenza A (H1N1) 2009 Monovalent Vaccine is licensed for single-dose presentations in syringes and vials and in multi-dose vials. There is no preservative used in the single-dose presentations. Multi-dose vials contain a preservative.

Safety Information for Influenza A (H1N1) 2009 Monovalent Vaccine
Influenza vaccine should not be administered to anyone with a known severe hypersensitivity to egg proteins, any vaccine component or life-threatening reactions after previous administration of any influenza vaccine. Recurrence of Guillain-Barre syndrome (GBS) has been temporally associated with the administration of influenza vaccine. The decision to give Influenza A (H1N1) 2009 Monovalent Vaccine to individuals who have a prior history of GBS should be based on careful consideration of the potential benefits and risks. Vaccination with Influenza A (H1N1) 2009 Monovalent Vaccine may not protect all individuals.
Video:

http://multivu.prnewswire.com/mnr/sanofi_pasteur/41122/

Source: http://www.sanofipasteur.com/