CHIKV-VLP Chikungunya Vaccine 2024
Bavarian Nordic A/S chikungunya adjuvanted CHIKV-VLP vaccine candidate (PXVX0317) is a single dose aluminum hydroxide-adjuvanted chikungunya virus-like particle vaccine (VLP) with a multi-protein structure that mimics the organization and conformation of naturally occurring viruses without the viral genome, promoting a more robust immune response and increased antibody production. Studies have shown that VLP vaccines are highly immunogenic, have a proven safety record, and typically elicit high titer-neutralizing antibodies needed to protect against the chikungunya virus (CHIKV). The CHIKV VLP vaccine candidate is licensed from the U.S. National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH).
The Lancet Infectious Diseases published a research article on June 13, 2022: Safety and immunogenicity of PXVX0317, an aluminum hydroxide-adjuvanted chikungunya virus-like particle vaccine: a randomized, double-blind, parallel-group, phase 2 trial. On June 21, 2022, Emergent announced the CHIKV VLP vaccine candidate was found in a phase 2 study to be well tolerated and induce a robust and durable serum-neutralizing antibody immune response against the Chikungunya virus for up to two years. And on November 1, 2022, the Company announced results from a Phase 2 study that demonstrated the CHIKV VLP vaccine candidate was well-tolerated and immunogenic in alphavirus vaccine-naïve participants and participants previously vaccinated against the Venezuelan equine encephalitis virus.
On June 20, 2023, the Company announced phase 3 study results: 413 participants were enrolled and randomized 1:1 to receive either a single intramuscular injection of CHIKV VLP or a placebo. The initial results up to Day 22 post-vaccination showed that CHIKV VLP was immunogenic in healthy adults ≥65 years of age, as demonstrated by a strong induction of CHIKV neutralizing antibodies in 87% of vaccinees with neutralizing antibody titres exceeding the threshold agreed with authorities as a marker of seroprotection, thus meeting the primary endpoints of the study. Notably, most subjects (82%) were also observed seroprotective neutralizing antibodies at Day 15 post the single vaccination, demonstrating a fast onset of protection for the VLP-based CHIKV vaccine candidate.
On August 6, 2023, Bavarian Nordic announced positive topline results from a Phase 3 clinical trial (NCT05072080); PXVX0317 met all the co-primary endpoints and was shown to be highly immunogenic in the majority of subjects 22 days post a single vaccination, and fast and durable response was confirmed with high levels of immunity at both two weeks and six months post a single immunization.
Bavarian Nordic is a fully integrated vaccine company focused on developing, manufacturing, and commercializing life-saving vaccines, with various office locations, including Denmark. For 2024, Bavarian Nordic expects revenue of DKK 5,000-5,300 million and EBITDA of DKK 1,100-1,350 million. Gaithersburg, Maryland-based Emergent BioSolutions sold this vaccine to Bavarian Nordic A/S on May 15, 2023.
CHIKV-VLP Vaccine Pending Approvals
The CHKV-VLA vaccine candidate received the U.S. Food and Drug Administration (FDA) Fast Track designation in May 2018. The FDA posted the Briefing Document on November 8, 2019. The European Medicines Agency (EMA) granted PRIME designation in January 2020 (EMEA-002656-PIP01-19). The Company stated results from phase 3 studies were the basis for submitting a Biologics License Application (BLA) to the FDA and a Marketing Authorization Application (MAA) to the EMA in 2024. Bavarian Nordic confirmed plans to submit its MAA for CHIKV VLP to the EMA during H1 2024.
CHIKV-VLP Vaccine Indication
The CHIKV-VLP vaccine candidate is indicated to prevent infections of the chikungunya virus. The Chikungunya virus is spread to people through infected mosquitoes. Symptoms lasting 3-4 weeks include high-grade fever, joint pain, headache, muscle pain, joint swelling, or rash, while chronic arthritis occurs in a minority of patients.
CHIKV-VLP Vaccine Dosage
In clinical trials, the CHIKV-VLP vaccine candidate is administered as a 40 µg dose muscular injection.
CHIKV-VLP Vaccine Side Effects
The most common solicited adverse event in a phase 2 study was pain at the injection site, reported in 12 (23%) of 53 participants who received the unadjuvanted vaccine (group 1) and 111 (31%) of 356 who received the adjuvanted vaccine. No vaccine-related serious adverse events were reported.
Chikungunya Cases
Since 2014, the U.S. CDC has reported chikungunya virus disease cases among U.S. travelers returning from affected countries in the Americas, and local transmission was identified in Florida, Puerto Rico, and the U.S. Virgin Islands, According to the U.S. CDC, Chikungunya outbreaks have occurred in North and South America, Africa, Asia, Europe, and the Indian and Pacific Oceans and can be found in over 70 countries. An updated map is posted at this CDC link. In addition, various countries worldwide have confirmed chikungunya virus outbreaks in 2023.
CHIKV-VLP Vaccine News
February 23, 2024 - "We are pleased to receive the accelerated assessment in recognition of our chikungunya vaccine candidate and our efforts to bring this novel product to the market. With this, we can accelerate the approval and launch timelines for the vaccine in Europe. As part of our global strategy, we also plan to submit our biologics license application (BLA) for the vaccine candidate to the U.S. Food and Drug Administration later this year," said Paul Chaplin, President and CEO of Bavarian Nordic.
August 6, 2023 - Paul Chaplin, President and CEO of Bavarian Nordic, stated in a press release,""With a fast and durable response, our vaccine can be the best in class to prevent chikungunya infections in adolescents to elderly adults. Chikungunya, which can often result in severe and incapacitating disease, affects large parts of the world. With international travel rising again, our CHIKV vaccine offers a significant opportunity to address this large unmet medical need""
June 20, 2023 - The Company announced data from the second pivotal Phase 3 study in people aged 12 to 64, expected in the third quarter of 2023.
May 15, 2023 - Bavarian Nordic acquired the rights to the development-stage chikungunya vaccine candidate CHIKV VLP. Bavarian Nordic also acquired manufacturing facilities in Bern, Switzerland, and development facilities in San Diego, California.
November 14, 2022 - Chris Cabell, M.D., chief medical officer and SVP clinical development at Emergent BioSolutions, stated in a press release,""We look forward to combining our product development expertise with the capabilities of the Armed Forces Research Institute of Medical Sciences in chikungunya epidemiology and field studies, and of our academic partners in infectious disease modeling and efficacy trial design, to find ways to address chikungunya disease, a public health threat for which no vaccine or treatment exists""
November 1, 2022 - Emergent BioSolutions Inc. announced results from a Phase 2 study evaluating the safety and immunogenicity of the CHIKV VLP vaccine candidate in prior recipients of other investigational alphavirus vaccines. The study demonstrated that the CHIKV VLP vaccine candidate was well-tolerated and immunogenic in alphavirus vaccine-naïve participants and participants previously vaccinated against the Venezuelan equine encephalitis virus.
May 26, 2021 - Emergent BioSolutions Inc. announced two-year persistence data from its Phase 2 clinical study. Two years post-vaccination, SNA responses were 19 times higher than pre-vaccination titers following a single adjuvanted 40 µg dose of the CHIKV VLP vaccine, supporting the persistence of the immune response. All subjects in the single-dose regimen remained seropositive at their one-year and two-year visits. The vaccine candidate was well-tolerated, and no significant vaccine-related safety concerns were identified.
April 17, 2020 - The U.S. NIH announced,''After analyzing the results, the researchers concluded that the vaccine was safe and well-tolerated. None of the volunteers experienced serious adverse effects related to the vaccine. In addition, the volunteers who received the vaccine developed an immune response to the chikungunya virus that remained strong for th weeks of the study.
January 13, 2020 - Emergent BioSolutions Inc. announced that it had received an agreement from the European Medicines Agency to pursue its proposed development plan for its chikungunya virus virus-like particle (CHIKV VLP) vaccine candidate.
April 26, 2019 - Study published by PLOS: Vaccination with a chikungunya virus-like particle vaccine exacerbates disease in aged mice. Conclusions: Unadjuvanted CHIK VLP vaccination elicits immune responses that protect 100% of adult mice against CHIKV infection. However, an improved vaccine/adjuvant combination is still necessary to enhance the protective immunity against CHIKV in the aged.
August 25, 2014 - The U.S. NIH issued a press statement:"The candidate vaccine prompted a robust immunological response in recipients and was very well tolerated."
January 28, 2021 - A VLP vaccine for the epidemic Chikungunya virus protects non-human primates against infection.
CHIKV-VLP Clinical TrialsEmergent'ss CHIKV-VLP vaccine candidate, a single-dose, 40 μg injection of adjuvanted, is being investigated in phase 3 clinical trials (clinicaltrials.gov i identifiers NCT05072080 and NCT05349617).
According to a study presented in October 2023, the researchers assessed anti-CHIKV serum-neutralizing antibody titers at designated time points throughout the study. They determined the seroresponse rate (SRR) in the two cohorts. In total, 3,254 participants were enrolled in the adult/adolescent trial, of whom 2,790 received a dose of CHIKV VLP, and 464 received a placebo. The data showed an SRR of 98% on day 22 for the vaccine and 1% for placebo. A rapid antibody response was also observed in the vaccine group, with an SRR of 47% on day 8 and 97% on day 15. These responses were""durable"" through day 183, when the SRR was 86%. For the older adult trial, 413 participants were enrolled — 206 received CHIKV VLP, and 207 received a placebo. On day 22, the SRR was 87% for vaccine recipients and 1% for placebo recipients. By day 15, a rapid antibody response was also observed in the CHIKV VLP group, with an SRR of 82%. Additional data from the study showed that the vaccine had a favorable safety profile, with most adverse events being mild to moderate, the most common of which were myalgia, fatigue, and headache.
On November 14, 2022, the Company announced a planned post-approval multicenter Phase 3b clinical study will evaluate the vaccine candidate's efficacy in preventing CHIKV disease and assess the utility of a model-guided disease surveillance framework to optimize the execution of a field efficacy trial using CHIKV as a model emerging pathogen.
On Nov. 1, 2022, the Company reported a Phase 2 parallel group- a gender-matched, open-label study evaluating the safety and immunogenicity of an adjuvanted CHIKV VLP vaccine candidate in prior recipients of experimental alphavirus vaccines in comparison to a cohort of alphavirus vaccine-naïve individuals, enrolled 60 healthy adults at two U.S. sites. The vaccine candidate was well-tolerated, with no notable difference in the incidence of adverse events between the groups. The majority of solicited adverse events were mild or moderate. The most common adverse event was local injection site pain. The seroconversion rate 21 days post-vaccination was 100% in both groups. A higher percentage of prior alphavirus vaccine candidate recipients rose four-fold on study day eight, tightening the alphavirus vaccine-naïve group.
The randomized, double-blind, parallel-group, phase 2 study was conducted at three U.S. sites with 445 participants. Eligible participants were healthy CHIKV-naïve adults aged 18–45 years. The primary endpoint was the geometric mean titer of the anti-CHIKV neutralizing antibody on day 57 (28 days after the last vaccination). Safety was also assessed.
