Kostaive (ARCT-154) / Arcturus Therap, Meiji Seika, CSL Behring - LARVOL DELTA

Alphaviral Genetic Background of Self-Amplifying RNA Influences Protein Expression and Immunogenicity Against SARS-CoV-2 Antigen (ASGCT 2025) - "Clinical trials have shown the dose-sparing capacity of saRNA vectors as evidenced by 6-33 lower dosages of the approved ARCT-154 vaccine compared to Spikevax and Comirnaty messenger RNA vaccines against SARS-Cov-2. Unique alphaviruses can be adapted into saRNA vectors. The genotype of the saRNA vectors influenced the magnitude and duration of expression as well as cellular and humoral immunity against an infectious disease antigen. Disease Focus of Abstract:Vaccines"

Chikungunya • CNS Disorders • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • IFNG

Differential clearance rate of proteins encoded on a self-amplifying mRNA COVID-19 vaccine in muscle and lymph nodes. (PubMed, Biochem Biophys Rep) - "ARCT-154, a recently approved self-amplifying mRNA (saRNA) vaccine for SARS-CoV-2, has shown superior induction and prolonged maintenance of neutralizing antibodies compared to the conventional mRNA vaccine BNT162b2. Data were analyzed using unpaired two-tailed Mann-Whitney U-tests. These data suggest that prolonged expression of spike proteins in lymph nodes may, if not entirely, be responsible for the induction of higher and prolonged levels of neutralizing antibodies by the saRNA vaccine."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Safety profile of self-amplifying mRNA SARS-CoV-2 vaccine ARCT-154 in adults: a pooled phase 1/2/3 randomized clinical study. (PubMed, Expert Rev Vaccines) - "No serious consequences occurred in several pregnancies reported after vaccination, with normal outcomes when followed to term. Data from this large trial suggest that ARCT-154 is safe and well tolerated."

Journal • P1/2 data • Cardiovascular • Fatigue • Infectious Disease • Inflammation • Musculoskeletal Pain • Novel Coronavirus Disease • Pain • Respiratory Diseases

European Commission Approves CSL and Arcturus Therapeutics’ KOSTAIVE, the First Self-amplifying mRNA COVID-19 Vaccine (Businesswire) - "Global biotechnology leader CSL...today announced that the European Commission has granted marketing authorization for KOSTAIVE (ARCT-154), a self-amplifying mRNA COVID-19 vaccine, for individuals 18 years and older. KOSTAIVE is the first sa-mRNA COVID-19 vaccine to receive approval from the European Commission (EC). KOSTAIVE is currently marketed in Japan against COVID-19...The approval is based on positive clinical data from several studies, including an integrated phase 1/2/3 study demonstrating KOSTAIVE’s efficacy and tolerability, and Phase 3 COVID-19 booster trials, which achieved higher immunogenicity results compared to a conventional mRNA COVID-19 vaccine comparator."

EMA approval • Infectious Disease • Novel Coronavirus Disease

Meiji Seika Pharma Receives Approval for Adding Domestic Manufacturing Sites in Japan for KOSTAIVE, a Self-amplifying mRNA Vaccine Against COVID-19 (Businesswire) - "Meiji Seika Pharma...announced today that it has received approval for a partial amendment to the manufacturing and marketing approval of 'KOSTAIVE' for Intramuscular Injection,' a self-amplifying mRNA vaccine for protection against COVID-19, to include domestic manufacturing sites in Japan."

Japan approval • Infectious Disease • Novel Coronavirus Disease

A randomized trial comparing safety, immunogenicity and efficacy of self-amplifying mRNA and adenovirus-vector COVID-19 vaccines. (PubMed, NPJ Vaccines) - "In an exploratory analysis relative vaccine efficacy of ARCT-154 vs. ChAdOx1-S against any COVID-19 from Day 36 to Day 394 was 19.8% (95% CI: 4.0-33.0). Self-amplifying mRNA vaccine offers potential immunological advantages in terms of immunogenicity and efficacy over adenovirus-vector vaccine without compromising safety."

Journal • Infectious Disease • Novel Coronavirus Disease

Addressing Vaccine Hesitancy and misinformation amidst Japan's self-amplifying mRNA COVID-19 Vaccine Rollout. (PubMed, QJM) - "Notably, this program includes the world's first self-amplifying mRNA COVID-19 vaccine, zapomeran (Kostaive®, Meiji Seika Pharma Co., Ltd) approved on November 28, 2023...Japan's history has experienced vaccine hesitancies in human papillomavirus and diphtheria-tetanus-pertussis vaccination cases. To prevent a public health crisis, it is crucial that governmental bodies and academic groups actively counter misinformation, advocating for evidence-based understanding and encouraging vaccination among those most at risk."

Journal • Infectious Disease • Novel Coronavirus Disease • Oncology • Pertussis • Respiratory Diseases • Tetanus

Immunogenicity of a booster dose of a bivalent (Asp614Gly and omicron BA.4/5 variant) self-amplifying mRNA SARS-CoV-2 booster vaccine versus the BNT162b2 omicron BA.4/5 mRNA vaccine: a randomised phase 3 trial. (PubMed, Lancet Infect Dis) - "Boosting mRNA-immunised adults with ARCT-2301 induced superior immunogenicity compared with Comirnaty BA.4-5 against both Wuhan-Hu-1 and omicron BA.4/5 variant COVID-19, and elicited a higher response against omicron XBB.1.5. Both vaccines had similar tolerability profiles. Self-amplifying mRNA vaccines could provide a substantial contribution to pandemic preparedness and response, inducing robust immune responses with a lower dose of mRNA to allow wider and more equitable distribution."

Journal • P3 data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Modelling the Relative Vaccine Efficacy of ARCT-154, a Self-Amplifying mRNA COVID-19 Vaccine, versus BNT162b2 Using Immunogenicity Data. (PubMed, Vaccines (Basel)) - "Sensitivity analysis showed that varying the threshold titer for 50% protection against severe disease up to 10% of convalescent sera revealed incremental benefits of ARCT-154 over BNT162b2, with an rVE of up to 28.0% against Omicron BA.4/5 in adults aged ≥60 year. Overall, the results of this study indicate that ARCT-154 elicits broader and more durable immunogenicity against SARS-CoV-2, translating to enhanced disease protection, particularly for older adults against Omicron BA.4/5."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

12-month persistence of immune responses to self-amplifying mRNA COVID-19 vaccines: ARCT-154 versus BNT162b2 vaccine. (PubMed, Lancet Infect Dis) - No abstract available

Journal • Infectious Disease • Novel Coronavirus Disease

Modelling the relative vaccine effectiveness of ARCT-154 versus BNT162b2 in younger and older adults (ISIRV-OPTIONS XII 2024) - No abstract available

Clinical

Modelling the relative vaccine effectiveness of ARCT-154 versus BNT162b2 using immunogenicity data (ISIRV-OPTIONS XII 2024) - No abstract available

Modelling the Relative Vaccine Effectiveness of ARCT-154 versus BNT162b2 in Younger and Older Adults (IDWeek 2024) - No abstract available

Clinical • Infectious Disease • Novel Coronavirus Disease

Modelling the Relative Vaccine Effectiveness of ARCT-154 versus BNT162b2 using Immunogenicity Data (IDWeek 2024) - No abstract available

Infectious Disease • Novel Coronavirus Disease

Delivery vehicle and route of administration influences self-amplifying RNA biodistribution, expression kinetics, and reactogenicity. (PubMed, J Control Release) - "The approval of saRNA-based vaccines, such as the ARCT-154 for COVID-19 in Japan, underscores its potential for diverse therapeutic applications, including vaccine development, cancer immunotherapy, and gene therapy...Additionally, our research unveiled distinct biodistribution profiles and inflammatory responses contingent upon the chosen delivery formulation and route. This research illuminates the intricate dynamics governing saRNA delivery, biodistribution and reactogenicity, offering essential insights for optimizing therapeutic strategies and advancing the clinical and commercial viability of saRNA technologies."

IO biomarker • Journal • Gene Therapies • Infectious Disease • Inflammation • Novel Coronavirus Disease • Oncology

A Trial Evaluating the Safety and Immunogenicity of 3 COVID-19 SARS-CoV-2 RNA Vaccines in Healthy Adults (clinicaltrials.gov) - P1/2 | N=72 | Completed | Sponsor: Arcturus Therapeutics, Inc. | Recruiting ➔ Completed | Trial completion date: Mar 2023 ➔ Dec 2023 | Trial primary completion date: Mar 2023 ➔ Dec 2023

Trial completion • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Safety, immunogenicity and efficacy of the self-amplifying mRNA ARCT-154 COVID-19 vaccine: pooled phase 1, 2, 3a and 3b randomized, controlled trials. (PubMed, Nat Commun) - P2/3 | "Efficacy of ARCT-154 was 56.6% (95% CI: 48.7- 63.3) against any COVID-19, and 95.3% (80.5-98.9) against severe COVID-19. ARCT-154 vaccination is well tolerated, immunogenic and efficacious, particularly against severe COVID-19 disease."

Clinical • Journal • P1 data • P2 data • P3 data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Self-amplifying RNA COVID-19 vaccine. (PubMed, Cell) - "In November 2023, Japan's Ministry of Health, Labour and Welfare granted regulatory approval of ARCT-154, a self-amplifying RNA COVID-19 vaccine developed by Arcturus Therapeutics. Clinical trials showed comparable safety and efficacy using a lower dose compared to the mRNA vaccine BNT162b2. To view this Bench-to-Bedside, open or download the PDF."

Journal • Infectious Disease • Novel Coronavirus Disease

Safety of a self-amplifying mRNA COVID-19 vaccine, ARCT-154 (ECCMID 2024) - No abstract available

Clinical • Infectious Disease • Novel Coronavirus Disease

Persistence of immune responses of a self-amplifying RNA COVID-19 vaccine (ARCT-154) versus BNT162b2. (PubMed, Lancet Infect Dis) - No abstract available

Journal • Infectious Disease • Novel Coronavirus Disease

Immunogenicity and safety of a booster dose of a self-amplifying RNA COVID-19 vaccine (ARCT-154) versus BNT162b2 mRNA COVID-19 vaccine: a double-blind, multicentre, randomised, controlled, phase 3, non-inferiority trial. (PubMed, Lancet Infect Dis) - "In adults who had previously received three doses of an mRNA COVID-19 vaccine, immune responses 28 days after an ARCT-154 booster dose were non-inferior to those observed after a BNT162b2 booster dose for the Wuhan-Hu-1 strain of SARS-CoV-2 and superior for the Omicron BA.4/5 variant. Increased immune responses at 28 days might provide increased likelihood of protection against these strains during this period and could also result in longer duration of protection. Further studies will assess the immunogenicity induced against more recent SARS-CoV-2 variants."

Head-to-Head • Journal • P3 data • Cardiovascular • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pain • Respiratory Diseases

The ARCT-154 Self-Amplifying RNA Vaccine Efficacy Study (ARCT-154-01) (clinicaltrials.gov) - P2/3 | N=19467 | Completed | Sponsor: Vinbiocare Biotechnology Joint Stock Company | Active, not recruiting ➔ Completed | Trial completion date: Aug 2023 ➔ Jan 2023

Trial completion • Trial completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Vaccination of non-human primates with self-amplifying mRNA vaccines reveal two distinct immunotypes across major SARS-CoV-2 variants. (IMMUNOLOGY 2022) - P1/2 | "Arcturus Therapeutics has developed two low-dose, self-amplifying mRNA vaccines, ARCT-154 and ARCT-165, that elicits robust neutralizing antibodies in non-human primates (NHPs) as a primary vaccination series and as a booster vaccination to Comirnaty® in humans. However, in the context of a booster dose in humans (NCT05037097), ARCT-154 provides robust humoral responses across all variants tested. Next generation self-amplifying mRNA vaccines may provide better coverage and at booster doses that are 6-10 times lower than those of currently authorized mRNA vaccines."

Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

The ARCT-154 Self-Amplifying RNA Vaccine Efficacy Study (ARCT-154-01) (clinicaltrials.gov) - P2/3; N=19400; Active, not recruiting; Sponsor: Vinbiocare Biotechnology Joint Stock Company; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases