IXCHIQ® Chikungunya Vaccine, Live (VLA1553)
Valneva SE's IXCHIQ® Chikungunya Vaccine, Live (VLA1553) is a monovalent, single-dose, live-attenuated chikungunya vaccine approved by the U.S. Food and Drug Administration (FDA). IXCHIQ is the most clinically advanced chikungunya vaccine based on an infectious clone (CHIKV LR2006-OPY1) attenuated by deleting a significant gene encoding the non-structural replicase complex protein nsP3 protection against various Chikungunya virus (CHIKV) phylogroups and strains. IXCHIQ is designed for prophylactic, active immunization against CHIKV infections in humans over 1-year-old. Recombumin®, a chemically defined, human and animal origin-free recombinant human albumin, is an enabler for the manufacture and formulation of IXCHIQ.
On November 9, 2023, the U.S. FDA approved Valneva Austria GmbH's IXCHIQ for individuals 18 and older at increased risk of exposure to CHIKV. Continued approval for IXCHIQ indication is contingent upon verification of clinical benefit in confirmatory studies. This indication is approved (STN: 125777) under accelerated approval based on anti-CHIKV neutralizing antibody titers. In addition, the FDA awarded the manufacturer of Ixchiq a tropical disease priority review voucher under a provision included in the Food and Drug Administration Amendments Act of 2007. This provision encourages the development of new drugs and biological products to prevent and treat certain tropical diseases. The FDA approval was based on final pivotal Phase 3 data in 4,115 adults aged 18 years and above reported in March 2022, and the Lancet subsequently published these results in June 2023. Final lot-to-lot consistency results were published in May 2022, and positive twelve-month persistence data in December 2022.
In 2020, VLA1553's complete Phase 1 clinical trial data were published in the peer-reviewed medical journal The Lancet Infectious Diseases. On May 5, 2022, Valneva confirmed that the Coalition for Epidemic Preparedness Innovations (CEPI) funded a phase 3 clinical study. In addition, the Company reported positive topline lot-to-lot manufacturing consistency trial results for VLA1553. In addition, an analysis announced on March 8, 2022, confirmed the very high level of seroprotection, with 98.9% of participants achieving protective levels of 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). In addition, the 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). VLA1553 was also highly immunogenic in elderly study participants (65 years or older), who achieved equally high seroprotection rates and neutralized antibody titers over time as younger adults. In addition, on December 5, 2022, Valneva reported positive antibody persistence data 12 months after vaccination with a single dose of VLA15. No safety concern was identified during follow-up, confirming the safety profile observed in earlier studies.
On June 13, 2023, The Lancet published: Safety and immunogenicity of a single-shot live-attenuated chikungunya vaccine: a double-blind, multicentre, randomized, placebo-controlled, phase 3 trial. VLA1553 demonstrated a high seroresponse rate of 98.9% in participants 28 days after receiving the single administration, and 96% of participants maintained seroresponse six months after vaccination. This article concluded that the strong immune response and the generation of seroprotective titres in almost all vaccinated participants suggest that VLA1553 is an excellent candidate for preventing disease caused by the chikungunya virus.
Valneva and the Butantan Institute in Brazil signed a binding term sheet in May 2020 to develop, manufacture, and market VLA1553. The collaboration is within the $23.4 million funding framework Valneva received from the CEPI in July 2019 to make VLA1553 accessible to Low and Middle-Income Countries. On August 28, 2023, Valneva announced initial safety data generated in the ongoing trial VLA1553-321, Valneva's first clinical trial in an endemic area (Brazil) and with individuals previously infected with CHIKV showed that VLA1553 was generally safe and well tolerated in adolescents aged 12 to 17 years, regardless of previous CHIKV infection.
On November 13, 2023, Valneva reported positive pivotal Phase 3 immunogenicity data in adolescents for VLA1553. These results complement the initial Phase 3 safety data the Company reported for the trial in August 2023. On December 4, 2023, Valneva reported a 97% seroresponse rate 24 months after a single vaccination with IXCHIQ and no safety concerns.
Saint-Herblain, France-based Valneva SE (Nasdaq: VALN; Euronext Paris: VLA) is a specialty vaccine company providing prevention against diseases with significant unmet medical needs. Valneva intends to commercialize Valneva Austria GmbH's IXCHIQ by leveraging its existing manufacturing and commercial operations. In addition, market research indicates that the global vaccine market against Chikungunya will exceed $500 million annually by 2032.
IXCHIQ Vaccine (VLA1553) Availability
On November 27, 2023, Valneva SE announced that the European Medicines Agency (EMA) had performed a technical validation of the Marketing Authorization Application (MAA) for VLA1553 and has determined that all essential regulatory elements required for scientific assessment were included in the application. Previously, the MAA was granted accelerated assessment by the EMA’s Committee for Medicinal Products for Human Use in 2020 and 2023, respectively, based on the vaccine candidate’s “major interest for public health and therapeutic innovation." On October 16, 2020, Valneva announced the EMA granted PRIority MEdicines (PRIME) designation.
The U.S. CDC's Advisory Committee on Immunization Practices (ACIP) is scheduled to meet in February 2024 to vote on the recommended use of IXCHIQ. The U.S. FDA approved IXCHIQ on November 9, 2023. Valneva SE announced on October 25, 2023, the submission of a marketing application to the EMA for approval of VLA1553. EMA's Committee for Medicinal Products for Human Use granted Valneva accelerated assessment for the application based on the vaccine candidate's "major interest for public health and therapeutic innovation." Valneva SE announced on August 29, 2023, that Health Canada has completed screening validation of the Company's regulatory application for marketing approval of VLA1553 in adults and has determined that the New Drug Submission application is sufficiently complete to permit a substantive review. The Company believes the regulatory review could be completed by mid-2024.
On August 18, 2022, Valneva confirmed that it initiated a rolling submission of the BLA to the U.S. FDA. The program previously received FDA Fast Track (2018) and Breakthrough Therapy designations in 2021. The FDA completed a filing review of Valneva's BLA on February 20, 203, and determined that the application was sufficiently complete to permit a substantive review with Priority Classification. On August 14, 2023, Valneva announced that the FDA revised the PDUFA action date for the BLA for VLA1553 to allow sufficient time to align and agree on the phase 4 program necessary under the accelerated approval pathway and the potential award of a priority review voucher in 2023.
IXCHIQ Vaccine U.S. CDC Review
At the U.S. Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) meeting on October 26, 2023, Dr. Beth Bell presented proposed policy options for chikungunya vaccine use among U.S. adults traveling abroad. On June 22, 2023, reviewed the following presentations: ACIP Work Group timeline (tentative); Value of a vaccine to prevent travel-related Chikungunya for U.S. persons. On February 23, 2023, ACIP presentations included: Introduction by Dr. Beth Bell; Global Epidemiology of Chikungunya; Dr. Susan Hills; Chikungunya in U.S. travelers, Ms. Nicole Lindsey; Persistent arthralgia following Chikungunya, Ms. Nicole Lindsey; Workgroup considerations, Ms. Nicole Lindsey. During the ACIP meeting on October 19, 2022, Katrin Dubischar, VP, Program Director Chikungunya Vaccine, delivered VLA1553 Chikungunya Vaccine Candidate Introduction, Evidence Supporting the Serological Endpoint, and Clinical Study Overview.
IXCHIQ Vaccine Indication
IXCHIQ (VLA1553) targets long-term protection against the chikungunya virus in adults following vaccination with a single dose.
IXCHIQ Vaccine Dosage
VLA1553 is administered intramuscularly. At clinical trial centers in Illinois and Alabama, U.S., healthy volunteers aged 18–45 years were randomly assigned (1:1:2) to one of three escalating 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 months 6 or 12 and followed for 28 days after revaccination.
IXCHIQ Vaccine Contraindications
IXCHIQ® should not be given to individuals who have a weakened immune system due to medications used for hematologic and solid tumors, on chemotherapy, history of congenital immunodeficiency, long-term immunosuppressive therapy, or patients with HIV infection who are severely immunocompromised. Individuals with a history of a severe allergic reaction to any vaccine component.
IXCHIQ Vaccine Warnings
Appropriate medical treatment to manage immediate allergic reactions for acute anaphylactic reactions following the administration of IXCHIQ® or any vaccine must be available. Vaccination with IXCHIQ® may cause severe or prolonged chikungunya-like adverse reactions. Severe chikungunya-like adverse reactions that prevented daily activity and/or required medical intervention occurred in 1.6% of 3,082 IXCHIQ® recipients and no placebo recipients. Fourteen IXCHIQ® recipients had prolonged (duration at least 30 days) chikungunyalike adverse reactions.
The most common injection site reaction (>10%) was tenderness (11%), and the most common systemic adverse reactions (>10%) were headache (31%), fatigue (29%), myalgia (24%), arthralgia (17%), fever (13%) and nausea (11%)
IXCHIQ Vaccine Pregnancy
There are no adequate and well-controlled studies of IXCHIQ® in pregnant individuals, and human data available from clinical trials with IXCHIQ® are insufficient to establish the presence or absence of vaccine-associated risk during pregnancy. IXCHIQ® should be administered during pregnancy only after an individual risk-benefit assessment, considering the maternal risk of chikungunya infection and gestational age.
VLA1553 Vaccine Adolescents
The pivotal immunogenicity data on November 13, 2023, showed that a single-dose vaccination with VLA1553 induced a robust immune response in adolescents aged 12 to <18 years, confirming the excellent immunogenicity previously observed in adults. As reported earlier, VLA1553 administered as a single dose was generally well tolerated in adolescents aged 12 to <18 years, irrespective of previous CHIKV infection, and showed a similar safety profile as reported in adults.
Countries in Europe and the Americas confirmed chikungunya virus outbreaks in 2023. In 2022, the Pan American Health Organization / World Health Organization (PAHO/WHO) reported chikungunya incidence in the Americas region above previous years.
Valneva SE Financial News - (VLA)
November 9, 2023 - The Company announced product sales of €106.1 million, an increase of 42.6% compared to the first nine months of 2022.
August 17, 2023 - A new add-on loan facility provides Valneva with immediate access to $50 million, with an additional $50 million available at the Company's discretion until December 31, 2023. The increased funding will further invest in R&D, continued market access preparations, and potential commercialization of Valneva's chikungunya vaccine candidate.
March 23, 2023 - The Company announced financial guidance for 2023: expected total revenues and other income between €220 million and €260 million.
November 10, 2022 - Product sales were €74.4 million (vs. €45.5 million in the first nine months of 2021), driven by the continued recovery of travel vaccine sales and by COVID-19 vaccine sales in Europe.
IXCHIQ Vaccine News
December 4, 2023 - Juan Carlos Jaramillo, M.D., Chief Medical Officer of Valneva, said in a press release, “We are very pleased about these twenty-four-month data which confirm IXCHIQ®‘s ability to induce a robust, long-lasting antibody response in both younger and older adults with a single vaccination."
November 9, 2023 - Peter Marks, M.D., Ph.D., director of the FDA's Center for Biologics Evaluation and Research, stated in a press release, "Today's approval addresses an unmet medical need and is an important advancement in the prevention of a potentially debilitating disease with limited treatment options."
August 28, 2023 - Juan Carlos Jaramillo, M.D., Chief Medical Officer of Valneva, said, "These new safety data in a younger population and individuals previously infected with the chikungunya virus confirm the safety profile we previously observed in adults and the elderly."
August 14, 2023 - Juan Carlos Jaramillo, Chief Medical Officer of Valneva, said, "We appreciate and take pride in the fact that our BLA for VLA1553, if approved, will represent the first vaccine candidate to be approved under the accelerated approval pathway in an outbreak disease, and hence the necessary Phase 4 activities will set a future standard."
June 22, 2023 - The Advisory Committee on Immunization Practices meeting reviewed various presentations.
June 13, 2023 - Juan Carlos Jaramillo, M.D., Chief Medical Officer of Valneva, said, "This publication in the Lancet underlines the strength of VLA1553's scientific approach and is consistent with the quality of our pivotal Phase 3 study."
May 30, 2023 - Juan Carlos Jaramillo, MD, Chief Medical Officer of Valneva, commented, "No vaccine or specific treatments are currently available for this debilitating disease, and we will continue to work diligently to bring VLA1553 to different territories as soon as possible."
April 5, 2023 - Susanne Eder-Lingelbach, Vice President, Clinical Development at Valneva, will review the clinical results of the Company's single-shot chikungunya vaccine candidate.
February 14, 2023 - Valneva SE announced that it completed enrollment and vaccination of its Chikungunya vaccine candidate for a Phase 3 clinical trial in adolescents, VLA1553-321. The first results of the trial are expected in mid-2023.
January 18, 2023 - The peer-reviewed journal Nature Biotechnology published an article: Chikungunya and Lyme vaccines make headway.
October 19, 2022 - The U.S. CDC vaccine committee reviews various presentations, such as OVERVIEW OF CHIKUNGUNYA AND CHIKUNGUNYA VACCINES by Susan Hills, MBBS, MTH CDC Lead, Chikungunya Vaccines Work Group.
May 25, 2022 - Valneva SE announced the successful completion of the lot-to-lot Phase 3 trial of its single-shot chikungunya vaccine candidate, VLA1553. With a 96% seroprotection rate at Day 180, the immunogenicity profile from study VLA1553-301 was also confirmed.
December 21, 2021 - Valneva SE announced positive topline results from the lot-to-lot Phase 3 trial of its single-shot chikungunya vaccine candidate, VLA1553. The VLA1553-302 trial met its primary endpoint, demonstrating that three consecutively manufactured vaccine lots elicited equivalent immune responses measured by neutralizing antibody titer GMT ratios on Day 29 after vaccination.
July 7, 2021 - Valneva SE announced that the U.S. FDA had awarded Breakthrough Therapy Designation for VLA1553.
January 25, 2021 - Valneva SE and Instituto Butantan signed definitive agreements for developing, manufacturing, and marketing Valneva's single-shot chikungunya vaccine, VLA1553, in Low and Middle-Income Countries.
October 16, 2020 - Valneva SE announced that the European Medicines Agency had granted PRIority MEdicines designation for VLA1553.
June 1, 2020 - A new study published in The Lancet found that the live-attenuated CHIKV vaccine was well tolerated and highly immunogenic in adults. It could be an effective intervention for preventing chikungunya disease worldwide.
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. After a single vaccination, the final results showed an excellent immunogenicity profile in all vaccinated dose groups. In addition, 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 - the U.S. Food and Drug Administration granted VLA1553 Fast Track designation.
VLA-1553 Clinical Trials
Valneva continues to test the VLA1553 Chikungunya Vaccine in various clinical trials.
The VLA1553-321 study in Brazil, posted on August 28, 2023, is a prospective, double-blinded, multicenter, randomized, placebo-controlled, pivotal Phase 3 trial conducted in 754 adolescents aged 12 to 17 years old in Brazil. The VLA1553-321 clinical trial was initiated in January 2022, and Valneva reported enrollment and vaccination completion in February 2023. VLA1553 or placebo was administered as a single intramuscular immunization to randomized participants into two study groups at a 2:1 ratio. The primary objective is to evaluate the immunogenicity and safety of the adult dose of VLA1553 28 days following a single vaccination. Secondary objectives of the trial include assessment of safety and immunogenicity up to twelve months following a single immunization with VLA1553. The study will also provide safety and immunogenicity data in participants previously exposed to Chikungunya.
On June 13, 2023, the phase 3 study results were published: Between Sept 17, 2020, and April 10, 2021, 6,100 people were screened for eligibility. One thousand nine hundred seventy-two people were excluded, and 4128 participants were enrolled and randomized (3093 to VLA1553 and 1035 to placebo). 358 participants in the VLA1553 group and 133 in the placebo group discontinued before the trial ended. The per-protocol population for immunogenicity analysis comprised 362 participants (266 in the VLA1553 group and 96 in the placebo group). After a single vaccination, VLA1553 induced seroprotective chikungunya virus neutralizing antibody levels in 263 (98·9%) of 266 participants in the VLA1553 group (95% CI 96·7–99·8; p<0·0001) 28 days post-vaccination, independent of age. VLA1553 was generally safe with an adverse event profile similar to other licensed vaccines and equally well tolerated in younger and older adults. Serious adverse events were reported in 46 (1·5%) of 3082 participants exposed to VLA1553 and eight (0·8%) of 1033 participants in the placebo arm. Only two serious adverse events related to VLA1553 treatment (one mild myalgia and one syndrome of inappropriate antidiuretic hormone secretion) were considered. Both participants recovered fully.
On December 5, 2022, the Company announced the antibody persistence trial enrolled 363 healthy adult participants and followed them from month six after vaccination to month twelve. 99% of participants retained neutralizing antibody titers above the seroresponse threshold of 150 12 months after the single-dose vaccination. These antibody levels confirm the antibody persistence profile observed in an earlier study. In addition, the antibody persistence was similar in older adults aged ≥65 years, who retained neutralizing antibody titers comparable to younger adults throughout the follow-up. These results follow the completion of the pivotal study VLA1553-301, for which a seroresponse rate of 96% was reported six months after vaccination.
VLA1553-301 Phase 3 trial was initiated in September 2020. It is a prospective, double-blinded, multicenter, randomized, pivotal Phase 3 trial evaluating 4,115 participants aged 18 years or above. Lyophilized VLA1553 or placebo was administered as a single intramuscular immunization. The trial's primary objective was to assess the immunogenicity and safety of VLA1553 at one month following a single vaccination.
Conducted in Brazil by Instituto Butantan, VLA1553-321 is a double-blinded, multicenter, randomized, and placebo-controlled Phase 3 trial. Seven hundred fifty0 adolescents aged 12 to 1s will be randomized at a 2:1 ratio to receive either VLA1553 or a placebo. The trial's primary objective is to evaluate safety and immunogenicity following a single vaccination with VLA1553. Participants will be assessed after 28 days and followed up to twelve months. The study will also provide safety and immunogenicity data in participants previously exposed to Chikungunya.