Valneva Successfully Completes Pivotal Phase 3 Trial of Single-Shot Chikungunya Vaccine Candidate

Valneva SE has announced successful completion of the Phase 3 pivotal trial of its single-shot chikungunya vaccine candidate, VLA1553.

The company said that the positive final analysis included six-month follow-up data and confirmed the topline results reported in August 2021. Valneva now expects to commence the pre-submission process with the U.S. Food and Drug Administration (FDA) in the second quarter of 2022.

The VLA1553-301 trial, which enrolled 4,115 adults aged 18 years and above across 44 sites in the U.S., met all primary and secondary endpoints. The final analysis confirmed the very high level of seroprotection, with 98.9% of participants achieving protective levels of chikungunya virus (CHIKV) neutralizing antibodies one month after receiving a single vaccination (263 of 266 subjects from the per-protocol subgroup tested for immunogenicity, 95% CI: 96.7-99.8). The excellent immunogenicity profile was maintained over time, with 96.3% of participants showing protective CHIKV neutralizing antibody titers six months after receiving a single vaccination (233 of 242 subjects from the per-protocol subgroup tested for immunogenicity, 95%CI: 93.1-98.3). The reported levels of seroprotection far exceeded the 70% threshold (for non-acceptance) based on a surrogate of protection agreed with the FDA under the accelerated approval pathway, the company explained.

VLA1553 was also confirmed to be highly immunogenic in elderly study participants (65 years of age or older), who achieved equally high seroprotection rates and neutralizing antibody titers over time as younger adults. A dedicated antibody persistence trial (VLA1553-303) will monitor a subset of participants from study VLA1553-301 for a period of at least five years to confirm the anticipated long-term protection after a single vaccination.

The six-month safety profile was also consistent with previous results across all age groups. VLA1553 was generally well tolerated among the 3,082 subjects evaluated for safety. An independent Data Safety Monitoring Board continuously monitored the study and identified no safety concerns. The majority of solicited adverse events were mild or moderate and resolved within three days. 2.0% of study participants reported severe solicited adverse events, most commonly fever. Approximately 50% of study participants experienced solicited systemic adverse events, most commonly headache, fatigue and myalgia.

Juan Carlos Jaramillo, M.D, Chief Medical Officer of Valneva commented, “These final pivotal Phase 3 results confirm the compelling profile of our single-shot vaccine candidate across all age groups. Delivering these first-ever final Phase 3 results for a chikungunya vaccine candidate means that we are a step closer to addressing a major, growing and unmet public health threat. We would like to thank everyone who participated in the trial and who continued to advance the trial during the pandemic.”

Valneva previously reported positive topline lot-to-lot manufacturing consistency results for VLA1553. This is one of the standard requirements for vaccine licensure, and final lot-to-lot results are expected in the second quarter of 2022. Valneva also recently initiated a Phase 3 trial in adolescents conducted in Brazil by Instituto Butantan to support the label extension in this age group following a potential initial regulatory approval in adults in the U.S[3]. Funded by the Coalition for Epidemic Preparedness Innovations (CEPI), this trial is also expected to support licensure of the vaccine in Brazil, which would be the first potential approval for use in an endemic region.

Valneva’s chikungunya vaccine program was awarded Breakthrough Therapy Designation by the FDA in July 2021. This followed the FDA Fast Track designation and the European Medicines Agency (EMA)’s PRIME designations, which the Company received in December 2018 and in October 2020, respectively. The sponsor of the first chikungunya vaccine approved in the U.S. will be eligible to receive a Priority Review Voucher (PRV).