Clinical Development of deltaFLU Quadrivalent Live Attenuated Influenza Vaccine (LAIV)
Vivaldi Biosciences AG is developing deltaFLU quadrivalent LAIV with the goal of providing a vaccine with improved safety and greater protection against seasonal influenza for the pediatric population. deltaFLU LAIV is composed of influenza vaccine strains in which the gene encoding influenza nonstructural protein 1 (NS1) has been deleted, generating an advanced LAIV that is safely attenuated and highly immunogenic. A significant advantage and differentiation of deltaFLU technology is that deltaFLU LAIVs are replication-deficient and are not shed by the recipient. The lack of replication and shedding eliminates the risk of unintended transmission. Importantly, deltaFLU LAIVs show cross-reactivity against variant influenza strains in clinical trials, and cross-protection against unmatched strains in animal models. These findings indicate the potential for deltaFLU LAIVs to cross-protect against a broad range of circulating influenza strains.
The expected single-dose regimen for deltaFLU has important advantages in terms of efficacy, patient compliance and convenience, especially in the pediatric population. The pain-free, needle-free mode of administration of deltaFLU LAIVs is expected to be highly acceptable to pediatric patients and their parents. deltaFLU LAIVs are produced in Vero cell culture, an advanced production method with significant advantages in terms of speed, capacity, and reliability versus egg substrate manufacturing of most licensed influenza vaccines.
Vivaldi Biosciences AG is planning a Phase 2 clinical program at leading European medical universities to evaluate safety, efficacy, and effectiveness of deltaFLU quadrivalent LAIV in children and adolescents. A Phase 2a double-blind, dose-ranging, randomized controlled study will be undertaken in adult volunteers to assess safety, tolerability, and immunogenicity of two doses of the quadrivalent candidate, bridging to a Phase 2 study in pediatric subjects. The Phase 2 study will be a double-blind, age de-escalation evaluation of one or two doses of deltaFLU quadrivalent LAIV in subjects 6 months to 11 years of age. This trial is designed to evaluate safety and efficacy, and will provide the basis for a subsequent Phase 3 trial of efficacy and effectiveness in pediatric subjects.
Candidate deltaFLU LAIVs already have performed successfully in four randomized, double-blind, placebo-controlled clinical trials involving a total of 245 adult volunteers and five different influenza strains, including H5N1 ("bird flu"). These studies provide clinical proof of concept, and demonstrate preliminary safety and efficacy. The candidate deltaFLU LAIVs were well-tolerated and induced statistically significant antibody responses. The replication-deficient phenotype of deltaFLU LAIVS also was confirmed in these studies.
Influenza is a severe disease in the pediatric population, and can progress rapidly with serious outcomes, even in children with no underlying risk factors. Children younger than 2 years of age are at the highest risk of influenza and are most likely to develop serious complications, yet this age group has fewer influenza vaccine options than older children.
Vivaldi Biosciences AG, headquartered in Vienna, Austria, is an affiliate of Vivaldi Biosciences Inc. Vivaldi Biosciences AG holds an exclusive worldwide license for development of deltaFLU LAIVs against seasonal influenza for the pediatric population.
deltaFLU Quadrivalent LAIV Target Product Profile
• Broad age range
• Single dose
• Nasal spray administration
• Stable liquid formulation
• Sterile, pre-filled spray device
• Vero cell-based manufacturing