IXCHIQ® Chikungunya Vaccine, Live (VLA1553) Clinical Trials, Dosage, Indication, Side Effects
Valneva SE's IXCHIQ® Chikungunya Vaccine, Live (VLA1553) is a monovalent, single-dose, live-attenuated chikungunya vaccine that was approved by the U.S. Food and Drug Administration (FDA, STN: 125777) on November 9, 2023. IXCHIQ® is the first and only vaccine approved to address chikungunya virus (CHIKV) infections in adults at increased risk of exposure to the mosquito-transmitted disease. On November 9, 2023, the FDA approved Valneva Austria GmbH's IXCHIQ for individuals 18 and older at increased risk of exposure to CHIKV. This indication is approved under FDA-accelerated approval based on anti-CHIKV neutralizing antibody titers. In addition, the FDA awarded Valneva a tropical disease priority review voucher under a provision included in the FDA Amendments Act of 2007. The vaccine program previously received FDA Fast Track (2018) and Breakthrough Therapy designations in 2021.
IXCHIQ is 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.
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. On June 13, 2023, The Lancet published the 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 zero response rate of 98.9% in participants 28 days after receiving the single administration, and 96% of participants maintained zero response six months after vaccination.
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. As of March 2024, the Company estimates that the travel market opportunity for chikungunya vaccines could be valued between €300 million to €400 million based on the number of travelers to endemic regions and their anticipated vaccine adoption. In addition, market research indicates that the global vaccine market against Chikungunya will exceed $500 million annually by 2032.
On April 3, 2024, Valneva announced it won the Best Prophylactic Vaccine at the Vaccine Industry Excellence Awards 2024. On April 5, 2024, the CDC issued an updated Level 2 Travel Health Advisory regarding Timor-Leste's current chikungunya outbreak. The CDC confirmed chikungunya vaccination is recommended for adults traveling to a destination with a current chikungunya outbreak.
Saint-Herblain, France-based Valneva SE (Nasdaq: VALN; Euronext Paris: VLA) is a specialty vaccine company that provides prevention against diseases with significant unmet medical needs. Valneva’s commercial portfolio is composed of three travel vaccines: IXIARO®/JESPECT®, DUKORAL®, and IXCHIQ®. The Company also distributes certain third-party products in countries where it operates its own marketing and sales infrastructure. The Company's 2023 Sustainability Report includes activities during 2023 and prospective priorities and is by French Decree No. 2017-1265 of August 9, 2017.
IXCHIQ Vaccine Sales
Valneva SE reported on May 7, 2024, that IXCHIQ produced initial sales of €0.2 million in the first quarter of 2024.
IXCHIQ Vaccine Review By U.S. CDC Advisory Committee on Immunization Practices
On February 28, 2024, the U.S. CDC Advisory Committee on Immunization Practices (ACIP) reviewed the following presentation: Key points from FDA licensure and package insert; Review of proposed policy options for chikungunya vaccine use among U.S. adults traveling abroad; Review of proposed policy options for chikungunya vaccine use among laboratory workers; Vaccine use among pregnant and breastfeeding women. On February 29, 2024, Valneva SE announced that the ACIP voted to recommend the use of IXCHIQ® for the prevention of disease caused by CHIKV.
Dr. Beth Bell presented proposed policy options for chikungunya vaccine use among U.S. adults traveling abroad at the ACIP meeting on October 26, 2023. On June 22, 2023, the ACIP 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 Recommended Use
The U.S. FDA published full prescribing information in 2023 at this link. The U.S. CDC published recommendations for using the chikungunya vaccine among travelers: ACIP recommends the chikungunya vaccine for persons aged ≥18 years traveling to a country or territory with a chikungunya outbreak. In addition, the chikungunya vaccine may be considered for those traveling to a country or territory without an outbreak but with evidence of chikungunya virus transmission among humans within the last five years. Persons aged >65 years, particularly those with underlying medical conditions, are likely to have at least moderate exposure* to mosquitoes OR Persons staying for a cumulative period of 6 months or more. Moderate exposure could include travelers with at least two weeks (cumulative) of exposure to mosquitoes in indoor or outdoor settings.
IXCHIQ Vaccine Pediatric
On January 10, 2024, Valneva announced that the first participant had been vaccinated in a Phase 2 clinical trial evaluating the safety and Immunogenicity in children of two different dose levels of Valneva's single-shot chikungunya vaccine. On December 4, 2023, Valneva reported a 97% seroresponse rate 24 months after a single vaccination with IXCHIQ and no safety concerns. On November 13, 2023, Valneva reported positive pivotal Phase 3 immunogenicity data in adolescents. 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. These results complement the initial Phase 3 safety data the Company reported for the trial in August 2023.
IXCHIQ Vaccine Availability
As of May 2024, IXCHIQ was available in the USA, and three marketing applications are under review by the European Medicines Agency, Health Canada, and the Brazilian Health Regulatory Agency (Anvisa), with potential approvals in 2024. On November 27, 2023, Valneva SE announced that the 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.
To make the vaccine more accessible to Low- and Middle-Income Countries (LMIC), Valneva and Instituto Butantan in Brazil signed an agreement in January 2021 to develop, manufacture, and market VLA1553. The collaboration falls within the framework of the agreement signed between CEPI and Valneva in July 2019, which provides funding of up to $23.4 million with support from the European Union's Horizon 2020 program.
IXCHIQ Vaccine Indication
IXCHIQ (VLA1553) targets long-term protection against the chikungunya virus in adults following a sinvaccination dose. However, vaccination with IXCHIQ may not protect all individuals.
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, says the FDA. 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 And Lactation
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. Human data are not available to assess the impact of IXCHIQ on milk production, its presence in breast milk, or its effects on the breastfed child. A developmental study was conducted in female rats IXCHIQ® should be administered during pregnancy only after an individual risk-benefit assessment, considering the maternal risk of chikungunya infection and gestational age. Vertical transmission of wild-type CHIKV to neonates from pregnant individuals with viremia at delivery is common and can cause severe, potentially fatal CHIKV disease in neonates.
IXCHIQ Immunocompromised Individuals
Due to disease or medical therapy, IXCHIQ should not be administered to immunodeficient or immunosuppressed individuals.
IXCHIQ Vaccine Coadministration
The Company has not disclosed coadministration information.
Chikungunya Outbreaks
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)
May 7, 2024—Peter Bühler, Valneva’s Chief Financial Officer, commented, “The first quarter performance has been in line with our expectations. We are aiming to capitalize further on the travel industry recovery during the rest of the year, including ramping up sales for IXCHIQ® to support our commercial sales growth while executing on our key R&D milestones."
March 20, 2024 - Valneva SE announced total revenues in 2023 of €153.7 million, including €144.6 million in product sales. 2024 total revenues are now expected to reach between €170 million and €190 million compared to €153.7 million in 2023, driven by continued sales growth of the Company's proprietary travel vaccines and the launch-year sales of IXCHIQ®.
IXCHIQ Vaccine News
May 7, 2024 - Valneva has focused on launching its single-dose chikungunya vaccine in the U.S. and recorded initial sales of €0.2 million in the first quarter.
March 20, 2024 - Peter Bühler, Valneva's Chief Financial Officer, commented, "Our objective for 2024 is to continue capitalizing on the travel industry recovery to generate further commercial growth and successfully launch our chikungunya vaccine IXCHIQ®. With the recent successful sale of our PRV and loan repayment extension, we have entered 2024 in a solid financial position to support our near- and mid-term commercial and R&D objectives."
January 10, 2024 - Juan Carlos Jaramillo, M.D., Chief Medical Officer of Valneva, said, "This pediatric clinical trial is significant. Given the significant threat that Chikungunya poses to individuals living in or traveling to endemic areas, it is crucial to make the vaccine accessible to all age groups."
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."
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.
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 to develop, manufacture, and market 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.
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.
A clinical study in adolescents, VLA1553-321, is ongoing. Additionally, the Company initiated a Phase 2 pediatric trial, VLA1553-221, in children aged 1 to 11 years, in January 2024. This is designed to support a Phase 3 pivotal pediatric study and potentially extend the label to this age group following initial regulatory approvals in adults and possibly in adolescents.
Phase 2 Trial VLA1553-221 is a multicenter, randomized, observer-blinded, dose-response Phase 2 clinical trial in approximately 300 healthy children aged one to eleven years. The trial will be performed at three sites in the Dominican Republic and potentially Honduras. The primary and secondary objectives of the trial are to evaluate the safety and Immunogenicity of two different dose levels of Valneva's single-shot chikungunya vaccine. Additional information, including a detailed description of the trial design, eligibility criteria, and investigator sites, is available at ClinicalTrials.gov (Identifier: NCT06106581).
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 in 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.
