Novavax announces final safety, immunogenicity results from H1N1 VLP vaccine at WHO meeting

Novavax, Inc. a clinical-stage biopharmaceutical company, today presented the final safety and immunogenicity results from its 2009 H1N1 virus-like particle (VLP) pandemic influenza vaccine clinical trial in Mexico at the invitation-only 7th World Health Organization Meeting (WHO) on Evaluation of Pandemic Influenza Vaccines in Clinical Trials. The meeting was held at the WHO headquarters in Geneva, Switzerland where Dr. Gregory Glenn, Chief Medical Officer of Novavax, presented the findings at a session entitled: "Pandemic and Potentially Pandemic Vaccines Developed Using New Technologies."  Dr. Glenn's presentation was entitled: "Phase II randomized, double-blind, placebo-controlled trial of a novel (H1N1) influenza VLP vaccine" and is available at www.novavax.com under the Investors/Events tab.

In this randomized, double-blind, placebo-controlled Phase II trial, Novavax's H1N1 VLP vaccine was administered in a single-dose regimen to over 3,000 subjects. The study found that the vaccine exceeded the immunogenicity criteria for seasonal influenza vaccine licensure at all dose levels including the 5mcg dose. Additionally, a single administration of the VLP vaccine induced high levels of hemaglutinin inhibition (HAI) titers in subjects without pre-existing detectable immunity to this pandemic influenza strain. Together, the data indicate that the H1N1 VLP vaccine was well-tolerated and immunogenic.

Dr. Glenn commented:  "This trial was an important milestone for our influenza vaccine program and demonstrated the potential of our recombinant vaccine technology.  The data indicate that our VLP vaccine was well-tolerated and generated robust immunogenicity at all dose levels, including the 5mcg dose. The single-dose seroprotection data in patients who had no pre-existing immunity (seronegatives) achieved protective titers in up to 85% of subjects which indicates that the VLP vaccine will be important in addressing future influenza pandemics.  Novavax VLPs are unique as they are made in a non-egg-based, recombinant manufacturing system that produces particles resembling the influenza virus but which renders them more immunogenic than simple recombinant vaccines."

Methods

This Phase II randomized, double-blind, placebo-controlled trial was conducted at a single study center in Mexico to evaluate the safety, tolerability, and immunogenicity of 3 dose levels (5mcg, 15mcg, and 45mcg HA) of the novel (H1N1) influenza VLP vaccine as compared with a placebo in healthy adults aged 18 to 64 years.  The study was conducted in two parts: Part A was to evaluate the safety and immunogenicity of the H1N1 influenza VLP vaccine over a dose range and to select a dose for an expanded safety evaluation in Part B. In Part A, 1,013 subjects were enrolled (760 active and 253 placebo). Based on an interim safety and immunogenicity analysis, an additional 3,547 (2,535 active and 1,012 placebo) subjects were enrolled in Part B of the study, a safety only study, and received 15mcg of VLP vaccine or placebo as a single injection on Day 1 using a second lot of H1N1 VLP vaccine.

Safety

In Part A, adverse events (AEs) were similar for the placebo group and for the active vaccine groups, except that dose-related local injection site reactions were reported more frequently in the active vaccine groups.  In Part B of the study, the incidence of AEs was consistent with that of Part A and was comparable between the VLP and placebo groups.  The results for the 15mcg vaccine in Part A and Part B of the study demonstrated that the different vaccine lots exhibited comparable safety profiles.  Across all subjects in Part A and Part B, the majority of AEs were of mild or moderate severity and resolved without sequelae and all serious AEs were considered definitely not related to vaccine.

Immunogenicity

In Part A of the study, a single injection of the H1N1 Influenza VLP vaccine at doses of 5mcg, 15mcg, and 45mcg induced immune responses against the H1N1 viral strain that met the Food and Drug Administration (FDA) immunogenicity criteria for licensure of seasonal inactivated influenza vaccines.  A dose-response was observed as measured by the HAI assay.  At Day 14, the rates of seroconversion for the 5mcg, 15mcg, and 45mcg dosage groups were 48.3%, 65.0%, and 74.9%, respectively, as compared to 5.9% for the placebo group.  Similarly, at day 14, the proportion of subjects who achieved an HAI titer greater than or equal to 1:40 (seroprotection) for the 5mcg, 15mcg, and 45mcg dosage groups increased to 81.6%, 90.5%, and 91.6%, respectively.  The second vaccine administration at day 21 did not significantly change the seroconversion and seroprotection rates.

Approximately 40% of all subjects had a baseline HAI titer greater than or equal to 1:40 to H1N1 at day 0, either due to exposure to the ongoing pandemic virus, or past exposure. Therefore, a sub-analysis was performed in subjects who were H1N1 seronegative at baseline.  In this population, the seroconversion rates for the 5mcg, 15mcg and 45mcg groups were, 64%, 79% and 85%, respectively, after the first dose.