Oct 18 2012
Novavax, Inc. today reported positive top-line results from two Phase 1 clinical trials of its A/H5N1 avian influenza vaccine candidate administered alone or with either one of two undisclosed adjuvants.
The trials' primary objectives of demonstrating the safety and immunogenicity of varying dose-levels of the vaccine, with and without adjuvant, and the demonstration of statistically significant adjuvant effects on the immune responses were achieved. The vaccine safety was acceptable with no vaccine-related serious adverse events observed.
Stanley C. Erck, President and CEO of Novavax, stated, "The data from these trials represent a landmark event in the history of Novavax. We have demonstrated that Novavax can produce antigens from avian influenza strains that are as, or more, immunogenic than any other described in published results to date. Importantly, as we accelerate our development activities, these results give us tremendous flexibility for pursuing pandemic vaccine products, including vaccines directed at population segments that are sensitive to adjuvant use."
The two randomized, observer-blind, dose-ranging, placebo-controlled Phase 1 trials were conducted under the company's contract with the U.S. Department of Health and Human Services' Biomedical Advanced Research and Development Authority (BARDA). The primary objectives of the two trials were to demonstrate the safety and immunogenicity of Novavax' VLP-based H5N1 vaccine candidate at varying dose-levels, with and without an adjuvant, using identical clinical study designs but with a different adjuvant in each study. A total of 666 healthy adults 18 to 49 years old were enrolled in the two trials. Each subject received intramuscular injections of vaccine or placebo at day 0 and day 21, and will be followed for 13 months following the first dose. The current data relate to safety and immune responses over the first 42 days.
- 88 to 100% of subjects receiving adjuvanted vaccine at all dose levels demonstrated serum HAI titers =40, a seroprotection level believed to be associated with reduced risk of disease.
- 86 to 100% of subjects receiving adjuvanted vaccine at all dose levels demonstrated seroconversion rates with either a four-fold rise in HAI titer or a titer of =1:40 from a negative baseline.
- Immune responses would fulfill U.S. Food and Drug Administration (FDA) Center for Biologics Evaluation and Research (CBER) seroprotection and seroconversion criteria for accelerated approval at the lower bound of the 95% confidence level.
- When tested against another avian A/H5N1 virus different from that in the vaccine, up to 80% of subjects receiving adjuvanted vaccine developed HAI titers =40 against the drifted virus.
The adjuvanted vaccines induced strong immunogenicity at all antigen doses tested, including the lowest (3.75 µg) dose, based on hemagglutination inhibition assay (HAI) responses against the vaccine virus at day 42.
Notably, in both trials the unadjuvanted vaccine elicited HAI titers = 40 in >82% of subjects at a dose of 45 µg, which would fulfill CBER criteria for accelerated approval. The unadjuvanted vaccine also elicited HAI titers =40 in more than 52% of subjects against the drifted virus.
Gregory Glenn, M.D., Novavax' Senior Vice President and Chief Medical Officer, stated, "We have reviewed the preliminary top-line results of these trials and believe that achieving similar immune responses to our vaccine in future clinical trials, regardless of which of the two adjuvants is used, if any, would meet the immunogenicity criteria for accelerated approval of a pandemic influenza vaccine set by CBER. These data would also fulfill immunogenicity criteria set forth by the European Medicines Agency." Dr. Glenn added, "The response measured to the drift variant antigen is especially encouraging as the data suggest that our vaccine can be protective when the vaccine strain did not perfectly match a pandemic virus strain, which is an important consideration in the emergent response to a pandemic. We believe that with the results from these trials we have sufficient data to advance our avian influenza vaccine program into later-stage clinical testing."
Source: http://www.novavax.com