Valneva SE (“Valneva” or “the Company”), a biotech company developing and commercializing vaccines for infectious diseases with major unmet medical needs, today announced positive Phase 1 interim results for its Chikungunya vaccine candidate, VLA1553.
The primary objective of VLA1553-101 Phase 1 study was to assess the overall safety and immunogenicity profile 28 days after a single vaccination across three dose levels. The interim results showed an excellent immunogenicity profile after a single vaccination with a 100% seroconversion rate achieved at Day 28 in a pooled analysis3 of all vaccinated groups. Results also showed 96.5% of subjects achieved at least a 16-fold increase in antibody titres and a high geometric mean titre, fully supporting VLA1553’s differentiated target product profile. The pooled safety profile of all groups was considered acceptable and supports further development. No serious adverse events nor adverse events of special interest were reported up to Day 28 and the local tolerability was considered excellent. Systemic adverse events included short-term fever, headache and fatigue. As with other live-attenuated vaccines, transient cases of reduced levels of neutrophils, lymphocytes or leucocytes without clinical symptoms were observed in the pooled analysis.
Wolfgang Bender, M.D., Ph.D., Chief Medical Officer of Valneva commented, “These results mark an important milestone towards our goal of developing a single-shot vaccine against Chikungunya. We are making every commitment to advance our vaccine quickly so that we can address this serious threat to public health. Phase 1 revaccination data post month six is expected by mid-year and will be key to define development acceleration options. The recent award of FDA Fast Track designation will allow us to work closely with the FDA on this development strategy.”
Valneva is committed to advance its Chikungunya vaccine candidate as quickly as possible into pivotal trials, after dialogue and alignment with the authorities. The Company expects unblinded safety and immunogenicity data at dose group level by mid-2019 including additional information on whether subjects are protected from Chikungunya viremia. This may allow Valneva to determine the final dose for development.
About The Phase 1 Clinical Study VLA1553-101
This study is a randomized, observer-blinded, multicenter, dose-escalation Phase 1 clinical study investigating three dose levels of VLA1553 after a single immunization. The study enrolled 120 healthy volunteers, 18 to 45 years of age, in the United States. Subjects were randomized in three different study groups to receive one of three dose levels (30 subjects in the low and medium and 60 subjects in the high dose group).
The protocol includes a re-vaccination at Month 6 or Month 12 to confirm that a single vaccination will be sufficient to induce high titer neutralizing antibodies and protect subjects from Chikungunya viremia (intrinsic viral challenge). Study participants will be followed up until 13 months after initial vaccination. The interim results included blinded, pooled safety and immunogenicity data up to Day 28. It did not provide group specific information or formal primary endpoint read-out. An independent Drug Safety Monitoring Board (DSMB) continuously oversees the study and reviews data.
Additional information, including a detailed description of the study design, eligibility criteria and investigator sites, is available at ClinicalTrials.gov (NCT03382964).
Chikungunya is a mosquito-borne viral disease caused by the Chikungunya virus (CHIKV), a Togaviridae virus, transmitted by Aedes mosquitoes. Clinical symptoms include acute onset of fever, debilitating joint and muscle pain, headache, nausea and rash, potentially developing into long-term, serious health impairments. Chikungunya virus causes clinical illness in 72-92% 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. Chikungunya outbreaks have been reported in Asia, Africa, the Americas and recently (2017) in Europe. As of 2017, there have been more than one million reported cases in the Americas and the economic impact is considered to be significant (e.g. Colombia outbreak 2014: $73.6m). The medical and economic burden is expected to grow as the CHIKV primary mosquito vectors continue to further spread geographically. There are no preventive vaccines or effective treatments available and, as such, Chikungunya is considered to be a major public health threat.
VLA1553 is a monovalent, single dose, live-attenuated vaccine candidate for protection against Chikungunya and was granted Fast Track designation by the U.S. Food and Drug Administration (FDA) in December 2018. The vaccine candidate is designed for prophylactic, active, single-dose immunization against Chikungunya in humans over one year old. The vaccine aims for long-lasting protection and an anticipated safety profile similar to licensed vaccines for active immunization in adults and children. The target population segments are travelers, military personnel and individuals at risk living in endemic regions.
The global market for vaccines against Chikungunya is estimated at up to €500 million annually. 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. In pre-clinical development, a single-vaccine shot was shown to be highly immunogenic in vaccinated Non-Human Primates (NHP) (cynomolgus macaques) and showed no signs of viremia after challenge. In NHPs, VLA1553 induced a strong, long lasting (more than 300 days) neutralizing antibody response comparable to wild-type CHIKV infections combined with a good safety profile.
About Valneva SE
Valneva is a biotech company developing and commercializing vaccines for infectious diseases with major unmet needs. Valneva’s portfolio includes two commercial vaccines for travelers: IXIARO®/JESPECT® indicated for the prevention of Japanese encephalitis and DUKORAL® indicated for the prevention of cholera and, in some countries, prevention of diarrhea caused by ETEC. The Company has various vaccines in development including a unique vaccine against Lyme disease. Valneva has operations in Austria, Sweden, the United Kingdom, France, Canada and the US with over 450 employees. More information is available at www.valneva.com.