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 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.
VLA-1553 Chikungunya Vaccine History
The vaccine 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 to develop, manufacture, and market VLA1553. The collaboration will be effective upon the signing of definitive agreements. It will fall within the $23.4 million funding framework that 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.
Thomas Lingelbach, Valneva's CEO, commented in a press statement issued on January 25, 2021, “Chikungunya outbreaks have impacted over 120 countries and affected millions, yet no vaccine or treatment is currently available to prevent this debilitating disease. We look forward to working with Instituto Butantan to help address this urgent public health need and speed up the development of a chikungunya vaccine in LMICs, which are high outbreak risk areas.”
Saint-Herblain, France-based Valneva is a specialty vaccine company providing prevention against diseases with major unmet medical needs.
VLA-1553 Chikungunya Vaccine Indication
This vaccine's target population segments 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.
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. A Togaviridae virus is a mosquito-borne alphavirus circulating predominantly in tropical and subtropical regions, potentially affecting over 1 billion people. Recently, an outbreak began in the western hemisphere.
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
February 25, 2021 - Valneva Reports FY 2020 Results and Major Corporate Achievements: Only Phase 3 chikungunya vaccine program to date worldwide; Potentially eligible for Priority Review Voucher – for the first company to receive Biologics License Application approval. Thomas Lingelbach, Chief Executive Officer, commented, “With over €200 million of cash, Valneva is in a strong position to continue to focus on execution of our key programs which could result in an even greater transformation in 2021 and beyond.”
February 22, 2021 - Valneva SE announced that it had initiated the clinical lot-to-lot consistency Phase 3 study for its single-shot chikungunya vaccine candidate, VLA1553. This study aims to show the manufacturing consistency of the vaccine by demonstrating that three consecutively manufactured lots elicit equivalent immune responses measured by neutralizing antibody titers on Day 29 after vaccination. This study will run parallel to the ongoing, pivotal Phase 3 study, VLA1553-301, which includes the determination of seroprotection based on an immunological surrogate.
January 25, 2021 - Valneva SE and Instituto Butantan announced the signing of definitive agreements for the development, manufacturing, and marketing of Valneva’s single-shot chikungunya vaccine, VLA1553, in Low and Middle-Income Countries (LMICs). This finalization follows the signing of a binding term sheet in May 2020. The collaboration falls within the framework of the $23.4 million funding agreement Valneva signed with the Coalition for Epidemic Preparedness Innovations in July 2019.
November 3, 2020 - 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 to develop, manufacture, and market VLA1553. The collaboration will be effective upon the signing of definitive agreements. It will fall within the $23.4 million funding framework that Valneva received from the Coalition for Epidemic Preparedness Innovations in July 2019.
October 16, 2020 - Valneva SE announced that the European Medicines Agency (EMA) has granted PRIority MEdicines designation for its single-shot Phase 3 chikungunya vaccine candidate VLA1553. This new designation from the EMA complements the Fast Track designation received by the U.S. FDA in December 2018.
September 30, 2020 - Health officials in Chad have reported an outbreak of chikungunya. The Abéché health district (Ouaddaï Region) is reporting the most cases; the health districts of Biltine (Wadi Fira Region) and Abdi (Ouaddaï Region) are also reporting cases.
September 30, 2020 - Chikungunya is an ongoing risk in many parts of Africa, and there is currently an outbreak in Ethiopia. Travelers should protect themselves by preventing mosquito bites.
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. would 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 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 assumes that it may start Phase 3 clinical studies in the fourth quarter of this year, 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 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 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 assumes that it may start Phase 3 in the fourth quarter of 2020, representing approximately a 3 to 6 months delay compared to its original plans.
January 7, 2020 – An End Of Phase 2 meeting was 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. A 100 percent seroconversion was achieved on 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.
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 August 29, 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. On June 1, 2020, The Lancet published a summary of this phase 1 study. On March 25, 2020, Valneva announced that it had completed an End-of-Phase 2 meeting with the U.S. FDA.
Clinical Trial NCT04546724: 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. Last updated on December 19, 2020. Estimated Study Completion Date: July 2021.
Clinical Trial NCT04650399: The VLA1553-302 clinical lot-to-lot consistency Phase 3 study is a prospective, multicenter, randomized, pivotal Phase 3 study comprising approximately 400 participants 18 to 45 years. Lyophilized VLA1553 will be administered as a single intramuscular immunization. The equivalence of immune responses will be determined based on neutralizing antibody titers. The study's primary objective is to evaluate a pair-wise comparison of the 95% CI on the ratio of GMTs on Day 29 after vaccination in the three vaccine lots. The two-sided 95% CI on the GMT ratio should be within 0.67 and 1.5. Study volunteers will be followed for six months, and overall, the study is expected to last approximately eight months. Last Update Posted: December 2, 2020.