VLA-1553 Chikungunya Vaccine Description
VLA1553 is a monovalent, single dose, live-attenuated vaccine candidate. VLA1553 is based on an infectious clone (CHIKV LR2006-OPY1) attenuated by deleting a major part of the gene encoding the non-structural replicase complex protein nsP3, aiming for protection against various Chikungunya virus outbreak phylogroups and strains.
Valneva SE's VLA1553 is currently the only chikungunya vaccine candidate in clinical development showing fully sustained titers 1-year after a single vaccination. The program was granted Fast Track designation by the U.S. FDA in December 2018.
To make VLA1553 also accessible to Low and Middle-Income Countries, Valneva and the Butantan Institute in Brazil signed a binding term sheet in May 2020 for the development, manufacturing, and marketing of VLA1553. The collaboration will be effective upon the signing of definitive agreements and will fall within the framework of the $23.4 million funding which Valneva received from the Coalition for Epidemic Preparedness Innovations in July 2019.
During the first half of 2020, VLA1553’s complete Phase 1 data were published in the peer-reviewed medical journal The Lancet Infectious Diseases. The Lancet paper provides a detailed analysis of the unique Phase 1 results, which served as a basis for the Company´s End of Phase 2 meeting with the U.S. FDA, and enabled the direct progression into Phase 3 study.
On September 8, 2020, the company announced the initiation of a pivotal Phase 3 clinical trial (VLA1553-301) for its differentiated, single-shot chikungunya vaccine candidate VLA1553a phase 3 study.
This study is a prospective, double-blinded, multicenter, randomized, pivotal Phase 3 study comprising approximately 4,000 participants aged 18 years or above randomized in a 3:1 ratio to the live-attenuated CHIKV vaccine candidate (VLA1553) or placebo. The study will be conducted at multiple sites across the U.S. The final dose of lyophilized VLA1553 or placebo will be administered as a single intramuscular immunization.
The target population segments for this vaccine are travelers, military personnel, and individuals at risk living in endemic regions. To make VLA1553 also accessible to Low and Middle-Income Countries, Valneva and Instituto Butantan in Brazil signed a binding term sheet in May 2020 for the development, manufacturing, and marketing of VLA1553.
Valneva is a specialty vaccine company providing prevention against diseases with major unmet medical needs.
VLA-1553 Chikungunya Vaccine Indication
Chikungunya fever, a disease caused by the chikungunya virus, reemerged and affected over 52,000 people in southern Thailand in 2008 and 2009. This CHIKV strain involved in this outbreak was the East Central South African (ECSA) strain with the E1-A226V mutation.
Chikungunya disease, which results in incapacitating arthralgia, has been reported worldwide. Chikungunya virus, a Togaviridae virus, is a mosquito-borne alphavirus that circulates predominantly in tropical and subtropical regions, potentially affecting over 1 billion people. Recently, an outbreak began in the western hemisphere.
The VLA1553 vaccine candidate is designed for prophylactic, active, single-dose immunization against Chikungunya in humans over 1-year-old. The vaccine targets long-lasting protection and an anticipated safety profile similar to licensed vaccines for active immunization in adults and children.
The Chikungunya virus causes clinical illness in 72-92 percent of infected humans around 4 to 7 days after an infected mosquito bite. Complications resulting from the disease include visual, neurological, heart, and gastrointestinal manifestations; fatalities have been reported (case fatality rates of 0.1% to 4.9% from epidemics) in elderly patients at higher risk.
VLA-1553 Chikungunya Vaccine Dosage
VLA1553 is administered intramuscularly. At professional clinical trial centers in Illinois and Alabama, USA, healthy volunteers aged 18–45 years were randomly assigned (1:1:2) to one of three escalating dose groups (low dose 3·2 × 10 3 per 0·1 mL; medium dose 3·2 × 10 4 per 1 mL; or high dose 3·2 × 10 5 50% tissue culture infection dose per 1 mL) and received a single-shot immunization on day 0. Individuals in all groups were revaccinated with the highest dose on either month 6 or 12 and followed up for 28 days after revaccination.
VLA-1553 Chikungunya Vaccine Updates
- September 8, 2020 - Valneva SE announced the initiation of a pivotal Phase 3 clinical trial for its differentiated, single-shot chikungunya vaccine candidate VLA1553, the first chikungunya vaccine Biologics License Application to be approved in the U.S. will be eligible to receive a Priority Review Voucher.
- August 4, 2020 - Valneva announced it is currently advancing all necessary activities, including with its Contract Research Organization, and intends to initiate the pivotal Phase 3 study in the fourth quarter of 2020, as planned.
- June 1, 2020 - A new study published in The Lancet found the live-attenuated CHIKV vaccine was well tolerated and highly immunogenic in an adult population and could be an effective intervention for prophylaxis of chikungunya disease worldwide.
- May 7, 2020 - Valneva Reports Q1 Results and Updates 2020 Guidance. Valneva is currently advancing all activities, including its Contract Research Organization (CRO), to allow Phase 3 initiation as soon as the COVID-19 situation permits. As previously announced, the Company’s assumption is that it may start Phase 3 clinical studies in the fourth quarter of this year, which is three months later than originally planned.
- May 5, 2020 - Valneva SE and Instituto Butantan announced the signing of a binding term sheet for the development, manufacturing, and marketing of Valneva’s single-shot chikungunya vaccine, VLA1553, in Low and Middle-Income Countries (LMICs). Valneva held its End of Phase 2 meeting with the U.S. Food and Drug Administration (FDA) in February 2020 and is now preparing to initiate Phase 3 clinical studies in the U.S. later in 2020.
- March 25, 2020 – Valneva SE announced that it has successfully completed an End-of-Phase 2 meeting with the U.S. FDA and agreed on the clinical development plan towards licensure for its unique, single-shot chikungunya vaccine VLA1553.
- January 24, 2020 - The Company’s assumption is that it may start Phase 3 in the fourth quarter of 2020, representing approximately a delay of 3 to 6 months compared to its original plans.
- January 7, 2020 – An End Of Phase 2 meeting has been scheduled with the U.S. Food and Drug Administration on February 24, 2020, for the chikungunya vaccine candidate VLA1553.
- November 18, 2019 - Final Phase 1 results up to Month 13 confirm the excellent immunogenicity and safety profile for VLA1553, its single-shot vaccine candidate. The final results showed an excellent immunogenicity profile in all vaccinated dose groups after a single vaccination, with a 100 percent seroconversion achieved at Day 14 after a single vaccination, in all dose groups, and titers were sustained at 100 percent at Month 12.
- December 21, 2018: VLA1553 was granted Fast Track designation by the US Food and Drug Administration (FDA).
VLA-1553 Chikungunya Vaccine Clinical Trials
Clinical Trial NCT03382964: A Phase 1 Study to Assess the Safety and Immunogenicity of a Chikungunya Virus Vaccine Candidate (VLA1553) in Healthy Volunteers. On May 22, 2019: Phase 1 unblinded results up to month 7 showed excellent immunogenicity and safety profile confirming Valneva's unique, single-shot vaccine candidate. These results strongly support further development acceleration. Then on June 1, 2020, The Lancet published a summary of this phase 1 study.
On March 25, 2020, Valneva announced that it has successfully completed an End-of-Phase 2 meeting with the U.S. FDA.
Clinical Trial: VLA1553-301: This is a prospective, double-blinded, multicenter, randomized, pivotal Phase 3 study comprising approximately 4,000 participants aged 18 years or above randomized in a 3:1 ratio to the live-attenuated CHIKV vaccine candidate (VLA1553) or placebo. The study will be conducted at multiple sites across the U.S. The final dose of lyophilized VLA1553 or placebo will be administered as a single intramuscular immunization.