EC approves CSL and Arcturus Therapeutics’ KOSTAIVE mRNA COVID-19 vaccine

The European Commission (EC) has officially granted COVID-19 vaccine approval for KOSTAIVE, the first self-amplifying mRNA vaccine for COVID-19, developed by CSL and Arcturus Therapeutics. The approval follows a positive opinion issued by the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) on December 12, 2024. This milestone makes KOSTAIVE the first self-amplifying mRNA vaccine authorized in the European Union, covering all 27 member states as well as the European Economic Area (EEA).

KOSTAIVE, also known as ARCT-154, had already been introduced in Japan, where it has been marketed as a next-generation COVID-19 vaccine designed to provide superior immune response and long-term protection against multiple SARS-CoV-2 variants. The latest approval paves the way for broader adoption of self-amplifying mRNA vaccines, which are emerging as a key advancement in global vaccination strategies.

How Does the Self-Amplifying mRNA Technology Enhance Vaccine Efficacy?

Unlike conventional mRNA vaccines, self-amplifying mRNA vaccines are designed to enhance immune response by allowing the body to produce additional copies of the mRNA after injection. This technology significantly reduces the required dose while delivering a superior immune response and extended antibody persistence. KOSTAIVE’s ability to generate sustained immunity for up to 12 months post-vaccination sets it apart from standard mRNA vaccines, which typically require more frequent booster doses.

CSL’s Senior Vice President of the Vaccines Innovation Unit, Jonathan Edelman, emphasized the vaccine’s significance in addressing the evolving nature of COVID-19. He stated that CSL remains committed to optimizing KOSTAIVE’s formulation to enhance its effectiveness for both healthcare providers and patients. With COVID-19 continuing to pose a global health risk, particularly with emerging variants, CSL and Arcturus are focused on ensuring that this innovative self-amplifying mRNA vaccine is made widely available in Europe as soon as possible.

What Do Clinical Trials Reveal About KOSTAIVE’s Effectiveness?

KOSTAIVE’s approval is supported by strong clinical data from multiple studies, including an integrated Phase 1/2/3 trial and Phase 3 booster trials. These trials demonstrated that the self-amplifying mRNA vaccine outperformed conventional mRNA vaccines in terms of superior immune response, particularly against Omicron BA.4-5 and other SARS-CoV-2 variants.

A pivotal 12-month follow-up analysis confirmed that a booster dose of KOSTAIVE induced significantly higher levels of neutralizing antibodies compared to Comirnaty, a widely used mRNA COVID-19 vaccine. The study, conducted in Japan, found that KOSTAIVE recipients had nearly twice the antibody levels at the one-year mark, reinforcing its potential for long-term protection.

Joseph Payne, CEO of Arcturus Therapeutics, highlighted the breakthrough nature of self-amplifying mRNA vaccines, stating that KOSTAIVE’s extended durability makes it a promising tool for global pandemic preparedness. He emphasized that sustained protection is critical in mitigating the impact of COVID-19 and reducing the frequency of booster doses required to maintain immunity.

How Does KOSTAIVE Compare to Conventional mRNA Vaccines?

The self-amplifying mRNA vaccine platform has demonstrated significant advantages over traditional mRNA vaccines, particularly in its ability to provide long-lasting immunity at a fraction of the dosage. In a head-to-head clinical trial, KOSTAIVE maintained a superior immune response against key variants, including Delta, Omicron BA.2, and XBB.1.5.6, with a dose that was only one-sixth of its comparator, Comirnaty.

These findings were presented at the OPTIONS XII Conference for Influenza Control, further underscoring the vaccine’s potential in global immunization efforts. The durability of the self-amplifying mRNA vaccine response suggests that it may offer a more efficient and sustainable solution for COVID-19 protection, reducing the need for frequent re-vaccination.

Dr. Edelman reiterated the importance of these findings, stating that KOSTAIVE’s extended efficacy reinforces its role as a next-generation COVID-19 vaccine capable of providing strong, long-term protection at lower doses compared to standard mRNA platforms.

What Do the Latest Bivalent Vaccine Trials Indicate?

In addition to KOSTAIVE, CSL and Arcturus have been developing a bivalent self-amplifying mRNA vaccine, ARCT-2301, based on the same advanced platform. Recent clinical trials in Japan compared ARCT-2301 to Comirnaty Original/BA.4-5, with results revealing a superior immune response that persisted for at least six months.

The study, which involved 930 participants who had previously received three to five doses of an mRNA COVID-19 vaccine, demonstrated that ARCT-2301 generated significantly higher neutralizing antibody levels against multiple variants. At six months post-vaccination, the immune response was nearly twice as strong as that of the comparator vaccine, reinforcing the potential of self-amplifying mRNA vaccines to offer sustained protection.

Igor Smolenov, Chief Development Officer of Arcturus Therapeutics, noted that the continued emergence of new COVID-19 variants highlights the urgency of developing vaccines with longer-lasting immunity. He emphasized that self-amplifying mRNA vaccines could play a vital role in future pandemic preparedness by reducing the need for frequent booster shots and enhancing population-wide protection.

What Does This Approval Mean for Future COVID-19 Vaccination Strategies?

The European Commission’s COVID-19 vaccine approval for KOSTAIVE represents a crucial step in advancing global immunization efforts. With traditional mRNA vaccines requiring multiple boosters to sustain protection, the approval of a self-amplifying mRNA vaccine introduces a promising alternative that could redefine long-term vaccination strategies.

With distribution expected to begin in Europe soon, CSL and Arcturus are prioritizing production and logistics to ensure broad access to this next-generation COVID-19 vaccine. As additional clinical trials continue to support the effectiveness of self-amplifying mRNA vaccines, regulatory bodies worldwide may look to adopt similar solutions for long-term pandemic preparedness.

KOSTAIVE’s approval underscores the growing recognition of self-amplifying mRNA vaccines as a transformative advancement in vaccine technology. With its ability to elicit a superior immune response at lower doses, this breakthrough may serve as a model for future mRNA-based immunization programs.

A Game-Changer in the Fight Against COVID-19

The approval of KOSTAIVE by the European Commission signals a major turning point in COVID-19 vaccination. As the first self-amplifying mRNA vaccine to receive regulatory clearance in Europe, KOSTAIVE sets a new benchmark for long-lasting and effective protection. With strong clinical evidence supporting its superior immune response, this next-generation vaccine has the potential to reshape the landscape of pandemic preparedness worldwide.