S-268019 / Shionogi - LARVOL DELTA

Longitudinal analysis of immune responses to SARS-CoV-2 recombinant vaccine S-268019-b in phase 1/2 prime-boost study. (PubMed, Front Immunol) - "The expansion of B- and T-cell repertoires and presence of cross-reactive NAbs targeting conserved epitopes within the receptor-binding domain following a booster accounted for the broad-spectrum neutralizing activity. These findings highlight the potential of S-268019-b to provide broad and robust protection against a range of SARS-CoV-2 variants, addressing a critical challenge in the ongoing fight against coronavirus disease 2019 (COVID-19)."

Clinical • Journal • P1/2 data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A-910823, a squalene-based emulsion adjuvant, enhances robust and broad immune responses of quadrivalent influenza vaccine in ferrets. (PubMed, Vaccine) - "It effectively enhances the humoral and cellular immunity of S-268019-b, a recombinant COVID-19 vaccine; however, the adjuvant effects of A-910823 on other vaccines, including influenza vaccine, have not been evaluated...Of note, QIV combined with A-910823 caused only minor detectable side effects, whereas a significant increase in fever was observed after two doses of mRNA-LNP in ferrets. This study provides information on the effectiveness and safety of A-910823-adjuvanted QIV and suggests the usefulness of the ferret model for evaluating vaccine-induced reactogenicity."

Journal • Infectious Disease • Influenza • Novel Coronavirus Disease • Respiratory Diseases

A SARS-CoV-2 recombinant spike protein vaccine (S-268019-b) for COVID-19 prevention during the Omicron-dominant period: A phase 3, randomised, placebo-controlled clinical trial. (PubMed, Vaccine) - P3 | "S-268019-b demonstrated immunogenicity and was well-tolerated. ClinicalTrials.gov identifier: NCT05212948."

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

A phase 3 randomized controlled trial of a COVID-19 recombinant vaccine S-268019-b versus ChAdOx1 nCoV-19 in Japanese adults. (PubMed, Sci Rep) - "No serious treatment-related adverse serious TRAEs events were reported in the two groups. S-268019-b was more immunogenic than ChAdOx1 nCoV-19 vaccine and was well tolerated (jRCT2051210151)."

Clinical • Journal • P3 data • P3 data • Fatigue • Infectious Disease • Musculoskeletal Pain • Novel Coronavirus Disease • Pain • Respiratory Diseases

Safety and immunogenicity of a booster dose of S-268019-b: Interim findings of a Phase 3, open-label clinical study in Japan. (PubMed, Vaccine X) - "We performed an interim analysis of an open-label, Phase 3 study data until Day 29 following S-268019-b booster in Japanese adults (aged 20-64 years) who had completed primary vaccination with mRNA-1273 and in Japanese elderly (aged ≥ 65 years) who had completed primary vaccination with mRNA-1273 or BNT162b2. Reactogenicity was mild in most participants; no serious treatment-related adverse events were noted. S-268019-b enhanced SARS-CoV-2 neutralizing antibodies, immunoglobulin G antibodies, and predominant T-helper 1-mediated immune reaction in all cohorts, regardless of age, in Japanese participants with prior vaccination with mRNA vaccines."

Journal • P3 data • P3 data: top line • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Study of S-268019 for the Prevention of COVID-19 (clinicaltrials.gov) - P3 | N=9902 | Completed | Sponsor: Shionogi | Active, not recruiting ➔ Completed | N=54915 ➔ 9902

Enrollment change • Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Study of S-268019 for the Prevention of COVID-19 (clinicaltrials.gov) - P3 | N=54915 | Active, not recruiting | Sponsor: Shionogi | Trial completion date: Dec 2023 ➔ Jul 2023 | Trial primary completion date: Mar 2023 ➔ Dec 2022

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

A-910823, a squalene-based emulsion adjuvant, induces T follicular helper cells and humoral immune responses via α-tocopherol component. (PubMed, Front Immunol) - "A-910823 is a squalene-based emulsion adjuvant used for S-268019-b, a novel vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is currently in clinical development...The findings also emphasize that α-tocopherol drives the potent Tfh-inducing adjuvant function of A-910823. Overall, our data provide key information that may inform the future production of improved adjuvants."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Results from a preclinical study in rodents and a Phase 1/2, randomized, double-blind, placebo-controlled, parallel-group study of COVID-19 vaccine S-268019-a in Japanese adults. (PubMed, Vaccine) - "The S-268019-a vaccine was not sufficiently immunogenic in Japanese adults despite robust immunogenicity and efficacy in mice. Our results exemplify the innate challenges in translating preclinical data in animals to clinical trials, and highlight the need for continued research to overcome such barriers. (jRCT2051200092)."

Clinical • Journal • P1/2 data • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Immune response and protective efficacy of the SARS-CoV-2 recombinant spike protein vaccine S-268019-b in mice. (PubMed, Sci Rep) - "This led to the formation of germinal centers and the induction of memory B cells, antibody-secreting cells, and memory T cells. These findings provide fundamental property of S-268019-b, especially importance of A-910823 to elicit humoral and cellular immune responses."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Homologous and heterologous booster vaccinations of S-268019-b, a recombinant S protein-based vaccine with a squalene-based adjuvant, enhance neutralization breadth against SARS-CoV-2 Omicron subvariants in cynomolgus macaques. (PubMed, Vaccine) - "Additionally, expansion of Omicron-specific B cells was confirmed after boosting with S-268019-b. These results indicate that a booster dose of S-268019-b with the adjuvant enhances the neutralization breadth."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Study of S-268019 for the Prevention of COVID-19 (clinicaltrials.gov) - P3 | N=54915 | Active, not recruiting | Sponsor: Shionogi | Recruiting ➔ Active, not recruiting

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

Immunogenicity and safety of booster dose of S-268019-b or BNT162b2 in Japanese participants: An interim report of phase 2/3, randomized, observer-blinded, noninferiority study. (PubMed, Vaccine) - "No serious adverse events were reported. In conclusion, S-268019-b was safe and showed robust immunogenicity as a booster, supporting its use as COVID-19 booster vaccine."

Head-to-Head • Journal • P2/3 data • Fatigue • Infectious Disease • Musculoskeletal Pain • Novel Coronavirus Disease • Pain • Respiratory Diseases

Immunogenicity and protective efficacy of SARS-CoV-2 recombinant S-protein vaccine S-268019-b in cynomolgus monkeys. (PubMed, Vaccine) - "Pathological analysis revealed no detectable vaccine-dependent enhancement of disease in the lungs of challenged vaccinated monkeys. The current findings provide fundamental information regarding vaccine doses for human trials and support the development of S-268019-b as a safe and effective vaccine for controlling the current pandemic, as well as general protection against SARS-CoV-2 moving forward."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Phase 1/2 clinical trial of COVID-19 vaccine in Japanese participants: A report of interim findings. (PubMed, Vaccine) - "Based on the interim analysis, the S-268019-b vaccine is safe, produces neutralizing antibodies titer comparable with that in convalescent serum from COVID-19-recovered patients. However, further evaluation of the vaccine in a large clinical trial is warranted."

Journal • P1/2 data • Infectious Disease • Novel Coronavirus Disease • CD4 • IFNG • IL2 • IL4

A Phase 3 Study of S-268019 for the Prevention of COVID-19 (clinicaltrials.gov) - P3 | N=54915 | Recruiting | Sponsor: Shionogi

New P3 trial • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • PCR

Japan drugmaker Shionogi aims to launch coronavirus vaccine in 2021 (The Mainichi) - "Japanese pharmaceutical company Shionogi & Co. said Friday it aims to launch a vaccine for the novel coronavirus as early as fall next year, as it is preparing to begin clinical trials by the end of the year....Chugai Pharmaceutical Co., said Friday it has begun joint research on an antibody to fight COVID-19 with Singapore's Agency for Science, Technology and Research. The study will focus on a potential therapeutic antibody discovered earlier by a research team at the agency....The government is also expected to approve the anti-flu drug Avigan...later in the month to be used for novel coronavirus patients." "

Japanese regulatory • Launch Japan • New trial • Infectious Disease • Novel Coronavirus Disease