Inovio Approach for Universal Flu Vaccine
Market Potential
Influenza is one of the most communicable diseases and it typically is most severe in young children and the elderly. Typically, an influenza season strikes both hemispheres each year, resulting in three to five million cases of severe illness and up to 500,000 deaths annually. In addition, pandemics occur every ten to twenty years, with the potential to kill tens of millions of people. The "Spanish Flu" of 1918-1919 resulted in an estimated 50-100 million deaths.
New influenza viruses are constantly produced by mutation or by reassortment, and can develop resistance to standard antiviral drugs. The H5N1 strain has been spreading from Asia despite thoughts that it was under control after outbreaks there in 2004. In 2005, there were reports of H5N1 in wild birds in Europe. In 2006, there were reports of the avian influenza A H5N1 strain in wild birds and poultry in Africa and Asia. Over 200 human cases have been confirmed in Asian countries with an alarmingly high mortality rate of >50%. At this time, no occurrences of man-to-man transmission of H5N1 have been identified. The concern, however, is that through potential reassortment with influenza sub-types that do transf er from man to man that highly pathogenic new strains may emerge.
Product & Indication: VGX-3400X, Avian Influenza
VGX™-3400X is a proprietary, prophylactic DNA vaccine candidate being developed by Inovio. to prevent infection with by avian influenza (H5N1). The vaccine is being delivered using Inovio's CELLECTRA® DNA Delivery System. The plasmid vaccine is delivered into muscle tissue with the assistance of electroporation with the goal of achieving expression of the H5N1 influenza antigen.
Stage of Development
Phase: I
Purpose: Prevention Official Title: Phase I, Open-label, Dose Escalation Study to Evaluate the Safety, Tolerability, and Immunogenicity in Healthy Adults of a DNA Plasmid Vaccine for H5 Avian Influenza (VGX-3400X) Administered by Intramuscular (IM) Injection Followed by Electroporation (EP)
Study Type: Interventional
Study Design: Allocation: Non-Randomized
Study Start Date: June 2010
Status: This study is ongoing, but not recruiting participants. Final data expected Q3 2011.
For more information: www.clinicaltrials.gov Identifier: NCT01142362
Commercialization
Vaccine: Licensed from The University of Pennsylvania.
Delivery technology: owned by Inovio.
License agreement: Financial details undisclosed. VGX™-3400X has been manufactured under cGMP by VGXI, Inc. and has been formulated for Phase I clinical trials.
Product & Indication: INO-3510, Universal Influenza
INO-3510 is a proprietary, prophylactic DNA vaccine candidate being developed by Inovio. The strategy for this vaccine is to combine SynCon® vaccine constructs for Type A influenza sub-types including H1N1, H2N2, H3N2, and/or H5N1. While H5N1 is an influenza sub-type with pandemic potential, the other three are the primary Type A sub-types responsible for seasonal influenza outbreaks. In the future, Inovio will consider adding a Type B influenza construct, Type B being another sub-type responsible for seasonal influenza outbreaks.
The challenge of current influenza vaccines is that their protective capability is substantially limited to protecting against the influenza strains contained in the vaccine: i.e. the circulating strain must match the strain(s) of the vaccine in order for protection to be provided. On an annual basis the influenza vaccine typically consists of two Type A strains and one Type B strain that are determined to be the primary strains of concern for the upcoming influenza season. If the selected strains continue to mutate, by the next flu season the new vaccine may not be able to provide protection against the unmatched strain. While Type B influenza does not typically evolve as quickly, Type A strains can change from season to season.
Inovio’s synthetically created consensus vaccine constructs are based on a set of strains within a sub-type. They do not specifically match one single strain, but substantially match multiple existing as well as newly emergent strains within the sub-type. Inovio has developed individual vaccine constructs for the seasonal sub-types H1N1, H2N2, and H3N2. The company’s clinical strategy is to progress from its first influenza clinical study of VGX-3400X, for H5N1, delivered intramuscularly, to a multi-antigen vaccine. INO-3510 is the first multi-antigen influenza vaccine. It contains H5N1 and H1N1 and will be delivered intradermally using electroporation. This will be Inovio’s first clinical study using intradermal delivery: delivering into skin rather than muscle is believed to be more optimal due to the ability of skin to generate stronger neutralizing antibodies, which are essential for a strong preventive immune response. Following this second influenza clinical study, the next step will be to add further influenza sub-types and to pursue further studies in humans.
Stage of Development
This study is expected to start in Q3 2011 and generate interim data by Q1 2012.
Commercialization
Vaccine: Licensed from The University of Pennsylvania.
Delivery technology: owned by Inovio.
License agreement: Financial details undisclosed. INO-3510 has been manufactured under cGMP by VGXI, Inc. and has been formulated for Phase I clinical trials.
Preclinical Data
Inovio conducted numerous preclinical studies that showed immunogenicity and protection against H1 and H5 viruses in animal models, as reported in the following news releases:
Inovio’s SynCon® Universal Flu Vaccines Provide 100% Protection in Ferrets against Death and Sickness in a Challenge Study with the Pandemic H1N1 Virus
Inovio Biomedical Demonstrates Protective Immune Responses Against Novel H1N1 (2009) Influenza Virus in Ferret ModelInovio Consensus H1N1 DNA Vaccines Show Protective Immune Responses after a Single Shot in Pre-Clinical Animal Study
Inovio Biomedical Universal Influenza Vaccines Demonstrate 100% Protection Against Current Pandemic A/H1N1 Influenza Viruses in Animal StudiesInovio Consensus DNA Vaccine Approach Demonstrates 100% Protection Against Unmatched Flu Virus Strains Currently in Circulation
Inovio Approach for Universal Flu Vaccine
- DNA vaccine targeting variable influenza HA: [H1, H2, H3, and H5 (avian)] along with conserved regions of NA and M2e-NP.
- All constructs are made using SynCon® technology
- Proof of concept studies completed showing immunogenicity and protection against H1 and H5 Viruses in Animal Models.
- Potential for long-term immunity
- Pre-set vaccine regimens for each year
VGX™-3400X Flu Vaccine: Proof of Concept Against Avian Flu (H5N1)
- SynCon® DNA vaccines for avian flu (H5N1) - HA, NA, M1, M2-eNP
- Study Design:
Mice (10/group) immunized with 10 µg DNA at wk 0, 2, 4 and with 25 µg DNA at wk 8
Animals challenged with aerosolized lethal dose of Vietnam strain of avian H5 virus
VGX™-3400X (H5N1) Pre-IND Updates
- Efficacy data in animal models
- Strong neutralizing antibody responses in 5 separate preclinical species
- Strong CD8+ T cell responses
- IND-enabling toxicity testing in animals completed
- cGMP manufacturing of Phase I clinical product
- Conducted at VGXI manufacturing facility in Texas