In short
Bretovameran is the active substance in the Comirnaty JN.1 COVID-19 mRNA vaccine, an authorised medicine in the European Union. It is being studied in five clinical trials covering COVID-19 infection, healthy volunteers, immunocompromised patients, and a rare bone disorder called fibrodysplasia ossificans progressiva. The trials range from Phase 1/2 to Phase 4 and include between 10 and 4,000 participants.
Key points
- Bretovameran is the active substance in the Comirnaty JN.1 COVID-19 mRNA vaccine, authorised in the EU.
- It is classified as a nucleic acid substance and is given as a dispersion for injection, mainly by intramuscular injection.
- Five clinical trials are listed, covering COVID-19 infection, healthy volunteers, immunocompromised patients, and fibrodysplasia ossificans progressiva.
- The largest trial enrolled 4,000 participants and is a Phase 3 study comparing several COVID-19 vaccines.
- Two trials are completed; three are authorised but not yet reported as completed.
- One trial studies an intradermal injection of Comirnaty JN.1 in patients with a rare bone disorder.
What is bretovameran?
Bretovameran is a nucleic acid substance and the active ingredient in the Comirnaty JN.1 COVID-19 mRNA vaccine. It is authorised as a medicine in the European Union under the name Comirnaty JN.1, with authorisation records held by BioNTech Manufacturing GmbH. The product is also referred to as Comirnaty JN.1 30 micrograms/dose dispersion for injection COVID-19 mRNA Vaccine, and it appears in both vial and pre-filled syringe presentations. Bretovameran is an mRNA vaccine encoding the spike protein of the SARS-CoV-2 JN.1 variant, and it is classified under ATC code J07BN01, which covers COVID-19 mRNA vaccines.
How does bretovameran work?
Bretovameran is an mRNA vaccine. The mRNA carries instructions for cells to produce the SARS-CoV-2 spike protein, which triggers an immune response. The immune system then recognises the spike protein and produces antibodies and immune cells that can respond to the virus. In the clinical trials listed here, bretovameran is used as the test substance in three trials, where the main measures include antibody levels against the prevailing virus variant, neutralising antibody titres, and spike-protein-specific binding IgG antibodies.
Which conditions is it used or studied for?
- COVID-19 infection — bretovameran is studied as a vaccine to generate immune responses against SARS-CoV-2, including in a large Phase 3 trial with 4,000 participants.
- Healthy volunteers — a Phase 1/2 trial compares a booster dose of an intranasal COVID-19 vaccine with a booster dose of Comirnaty JN.1 in 238 healthy adults.
- Immunocompromised patients — a Phase 3 cohort study follows nursing home residents, dialysis patients, and kidney and lung transplant patients to assess antibody levels over time.
- Fibrodysplasia ossificans progressiva (FOP) — a rare bone disorder where bretovameran is given intradermally to assess safety and immune response in 10 patients.
How is bretovameran given?
Bretovameran is supplied as a dispersion for injection. The authorised presentations are for intramuscular injection, including vials and pre-filled syringes. In the clinical trials, the substance is also being studied by intradermal injection in patients with fibrodysplasia ossificans progressiva. The authorised product information lists presentations such as Comirnaty JN.1 30 micrograms/dose dispersion for injection in vials of 1 dose, 6 doses, or 10 doses, and in pre-filled syringes of 1 dose.
What do the clinical trials show?
Five clinical trials involving bretovameran are listed in the registries. The largest is a Phase 3 trial with 4,000 participants that compares immune responses after vaccination with several COVID-19 vaccine products, including Comirnaty JN.1, Spikevax, and Nuvaxovid. Two trials are completed: the 4,000-participant Phase 3 study and a small Phase 3 study in 20 healthy adults that measured innate immune responses before, 6 hours after, and 24 hours after vaccination with Comirnaty JN.1. Three trials are authorised but not yet completed: a Phase 1/2 study in 238 healthy adults, a Phase 3 cohort study in 360 immunocompromised patients, and a Phase 3 study in 10 patients with FOP.
The trials measure different things. The large Phase 3 study looks at the proportion of seropositive participants with antibody levels above a target level six months after two doses. The Phase 1/2 study measures safety outcomes such as immediate adverse events, local and systemic reactions, and serious adverse events, as well as mucosal immune responses in the nose. The cohort study assesses binding and neutralising antibodies against the predominant SARS-CoV-2 variant three times a year. The FOP study measures safety events including flare-ups, fever, fatigue, and joint pain, and also measures neutralising antibody titres and spike-protein-specific IgG antibodies.
What side effects are known?
The supplementary source provided does not contain a list of side effects for bretovameran. The clinical trial records describe safety outcomes being measured, such as immediate adverse events, solicited local and systemic reactions, serious adverse events, and adverse events of special interest, but they do not report the results of those measurements.