IXCHIQ® Chikungunya Vaccine, Live (VLA1553) Clinical Trials, Dosage, Efficacy, Indication, Side Effects

Valneva SE's IXCHIQ® Chikungunya Vaccine, Live (VLA1553) is a monovalent, single-dose, live-attenuated vaccine. IXCHIQ® is the first vaccine approved to address chikungunya virus (CHIKV) infections in adults at increased risk of exposure to the mosquito-transmitted disease. IXCHIQ was approved by the U.S. Food and Drug Administration (FDA, STN: 125777) on November 9, 2023. This indication was approved under FDA-accelerated approval based on anti-CHIKV neutralizing antibody titers. IXCHIQ achieves target immunogenicity with a single dose. The FDA previously awarded Valneva a tropical disease priority review voucher under a provision in the FDA Amendments Act of 2007. The IXCHIQ vaccine program 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.

The U.S. Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) approved recommendations for using IXCHIQ in travelers and laboratory workers in February 2024. On October 23, 2024, the ACIP reviewed an IXCHIQ update - Long-term persistence clinical trial is ongoing; High seroresponse rate (97%) at 2 years; Monitoring continuing through 10 years to determine if booster dose needed in future.

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 and reported positive topline lot-to-lot manufacturing consistency trial results for VLA1553. 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. 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. VLA1553 was also highly immunogenic in elderly study participants (65+), 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-masked, multicentre, randomized, placebo-controlled, phase 3 trial. VLA1553 demonstrated a high 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. On May 13, 2024, an analysis of study VLA1553-321 Day 180 results confirmed the initial positive Immunogenicity and safety data Valneva reported previously and are intended to support filing for potential label extension for use in adolescents aged 12 to 17 years.

On September 4, 2024, The Lancet published results from a CEPI and EU Horizon 2020-funded phase 3 study conducted in Brazil. The study concluded that VLA1553 was generally safe and induced seroprotective titers in almost all vaccinated adolescents, with favorable safety data in seropositive adolescents at baseline. The data support using VLA1553 to prevent diseases caused by the chikungunya virus among adolescents and in endemic areas. 

Valneva and the Butantan Institute in Brazil signed a 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.

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. On April 3, 2024, Valneva announced it won the Best Prophylactic Vaccine at the Vaccine Industry Excellence Awards 2024. Valneva won Breakthrough of the Year on June 14, 2024, for its chikungunya vaccine at the 2024 European Mediscience Awards.

IXCHIQ Vaccine Efficacy

The Lancet Infectious Disease published results from a phase 3b study that concluded that after a single VLA1553 vaccination, chikungunya virus-neutralizing antibodies were above the threshold considered to be protective persisted for up to two years, and there were no long-term serious adverse events related to vaccination. Health Canada's label extension application on September 18, 2024, included IXCHIQ®'s antibody persistence data, which showed that the vaccine's immune response was sustained for 24 months by 97% of participants and was equally durable in younger and older adults. The Company expects to publish 36 months of persistence data later in 2024.

IXCHIQ Vaccine Efficacy Against Alphaviruses

Alphaviruses are vector-borne, medically relevant, positive-stranded RNA viruses that cause human disease worldwide. A study published on August 7, 2024, characterized nAbs against CHIKV strains. IXCHIQ elicited 100% seroconversion to each virus, except for RRV at 83.3% seroconversion of vaccinees, and cross-neutralizing antibody potency decreased with increasing genetic distance from CHIKV. These data suggest that IXCHIQ efficiently and potently elicits cross-nAb breadth that extends to related alphaviruses similar to natural CHIKV infection. The journal Science Translational Medicine published a Research Article, Vol 15, Issue 696, on May 17, 2023, which found MAbs with the greatest passive protective efficacy in a mouse model of CHIKV also protected against related arthritogenic alphaviruses.

IXCHIQ Vaccine Availability

As of November 2024, IXCHIQ was available for adults in the U.S., Canada, Europe, and the Virgin Islands. On May 31, 2024, the EMA, then the European Commission (EMA/271910/2024), recommended As of November 2024, Brazil's Health Regulatory Agency (Anvisa) is reviewing IXCHIQ's marketing application. The U.S. Defense Health Agency – Immunization Healthcare Division (DHA-IHD) recently published chikungunya and vaccines guidance, authorizing IXCHIQ® as a U.S. Department of Defense CHIKV countermeasure. 

To make the vaccine more accessible to Low- and Middle-Income Countries, 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 U.S. CDC Reviews

On June 26, 2024, the U.S. CDC Advisory Committee on Immunization Practices (ACIP) reviewed the following IXCHIQ and chikungunya virus presentations. On February 28, 2024, the ACIP reviewed Key points from FDA licensure and package insert, a review of proposed policy options for chikungunya vaccine use among U.S. adults traveling abroad, a review of proposed policy options for chikungunya vaccine use among laboratory workers, and 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. VLA1553 is an efficient and safe intervention that offers high seroprotection against chikungunya virus infection, a virus likely to spread globally with an urgent demand for long-lasting prophylaxis.

IXCHIQ Vaccine Recommended Use U.S. CDC

The U.S. FDA published complete prescribing information in 2023 at this link. The U.S. CDC published recommendations for using the chikungunya vaccine among adult 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. On April 5, 2024, the CDC issued an updated Level 2 Travel Health Advisory regarding Timor-Leste's chikungunya outbreak, confirming chikungunya vaccination is recommended for adults traveling to a destination with a current chikungunya outbreak.

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 doses 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 Indication

The U.S. CDC says vaccination is recommended for adults aged 18 years and older traveling to a country with a chikungunya outbreak. Over 50 million North Americans, including approximately 7 million Canadians, travel to countries where Chikungunya is endemic. Chikungunya outbreaks continue to occur, with changing epidemiology. Awareness about Chikunguny among at-risk travelers and healthcare professionals can result in underdiagnosis and underreporting. While mortality due to CHIKV infection is low, the morbidity and overall burden of the disease are high. After the acute disease phase, chronic sequelae, including persistent arthralgia, are common, with around 40% of people infected with CHIKV developing chronic post-CHIK arthritis, which may last for months or years.

XCHIQ targets long-term protection against the chikungunya virus in adults following vaccination. However, vaccination with IXCHIQ may not protect all individuals. 

On September 18, 2024, Valneva submitted Label Extension Applications for IXCHIQ to EMA and Health Canada to adolescents aged 12 to 17. The Canadian label extension application also includes two-year antibody persistence data, a key differentiator for IXCHIQ® that was already included in the initial EMA filing. Valneva expects to submit data to the U.S. FDA in 2024 to support potential label extensions in the U.S.

IXCHIQ Vaccine Dosage

VLA1553 is administered intramuscularly with a single dose. 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

On October 14, 2024, a study concluded, 'A single dose of VLA1553 presented with an excellent local tolerability profile and overall safety in line with that expected for a live-attenuated vaccine.' 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. In general, vaccination should be deferred until after delivery. However, if pregnant women choose to be vaccinated, out of caution, vaccination should generally be avoided during the 1st trimester (until 14 weeks gestation) and after the 36th week of gestation. 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 women with viremia at delivery is standard and can cause severe, potentially fatal CHIKV disease in neonates. 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.

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.

IXCHIQ Vaccination for Laboratory Staff

According to the CDC, chikungunya vaccination is recommended for laboratory workers with potential exposure to the chikungunya virus. Transmission through the aerosol and percutaneous routes of the chikungunya virus has been documented in the laboratory setting, and transmission through accidental mucosal exposure is possible. Laboratory work with the chikungunya virus is generally restricted to biosafety level-3 (BSL-3) facilities and practices.

Chikungunya Outbreaks

Countries in Europe and the Region of the Americas confirmed chikungunya virus outbreaks in 2024 and 2023.

Valneva SE Agreements with CEPI

The Coalition for Epidemic Preparedness Innovations (CEPI) and Valneva SE announced on July 22, 2024, that they have expanded their partnership to support broader access to IXCHIQ® in Low—and Middle-Income countries (LMICs), as well as post-marketing trials and potential label extensions in children, adolescents, and pregnant women. CEPI will provide Valneva up to U.S. $41.3 million of additional funding over the next five years, with support from the European Union's (EU) Horizon Europe program. An earlier CEPI agreement awarded Valneva U.S. $24.6 million in CEPI-EU funding to develop, manufacture, and market its single-shot vaccine in certain LMICs affected by Chikungunya.

Valneva SE Financial News

On November 7, 2024, Valneva announced total revenues of €116.6 million, including product sales of €112.5 million and IXCHIQ initial sales of €1.8 million in the first nine months of 2024. Operating profit was €34.2 million, compared to an operating loss of €57.2 million in the first nine months of 2023.

Valneva SE presented a financial overview on October 10, 2024. The Company estimates that the travel market opportunity for IXCHIQ® sales may exceed €100 million in year 3 of launch, even assuming competitive product entry. Seperately market research indicates that the global vaccine market against ChikChikungunyal exceed $500 million annually by 2032.

IXCHIQ Vaccine News 2024

November 7, 2024 - Peter Bühler, Valneva’s Chief Financial Officer, commented, “Our objective is to become sustainably profitable in 2027."

September 4, 2024 - The Lancet published a Comment - An effective chikungunya vaccine would reduce the burden of acute infections and mitigate the substantial loss of economic productivity in working-age adults.

July 22, 2024—Thomas Lingelbach, Chief Executive Officer of Valneva, said, "We are extremely pleased to strengthen our partnership with CEPI." Valneva will receive up to $41.3 million from CEPI and the European Union to expand access to the chikungunya vaccine, IXCHIQ®.

July 1, 2024 - Dr. Richard Hatchett, Chief Executive Officer of the Coalition for Epidemic Preparedness Innovations, commented, "Supported by CEPI and EU funding, IXCHIQ is the world's first vaccine offering protection against the debilitating CHIKV." 

May 21, 2024 – Valneva SE announced the appointment of Dr. Hanneke Schuitemaker, Ph.D., as Chief Scientific Officer and Executive Committee member, effective June 3, 2024.

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 ChikChikungunyaes 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. IXCHIQ®'s final pivotal Phase 3 data were published in The Lancet in June 2023.

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 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 ChikChikungunya 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.