High-dose influenza vaccine candidate deemed safe and effective

2nd August 2023

OVX836 is a universal influenza A vaccine which appears to be safe and has previously shown a preliminary signal of protection against influenza symptoms.

Now, in a study published in The Lancet Infectious Diseases, researchers sought to explore the safety and potential efficacy of higher doses of OVX836. This is a recombinant protein-based vaccine which targets the highly conserved influenza nucleoprotein (NP) and therefore potentially confers broad-spectrum protection against influenza.

Influenza viruses are associated with over five million hospitalisations every year across the world. Moreover, anti-viral agents such as oseltamivir do not appear to reduce influenza-related hospitalisations, highlighting the need for effective vaccinations.

OVX836 safety and efficacy

In the trial, a total of 137 healthy adults aged 18-55 years were randomly assigned to receive one single intramuscular administration of OVX836 influenza vaccine at three doses (180 μg, 300 μg or 480 μg) or placebo.

OVX836 had a favourable safety profile up to 480 μg without reaching the maximum tolerated dose and showed a good safety profile at all doses with only mild local and systemic reactogenicity.

Seven days after vaccination, there were no significant differences observed between the doses. Dose-dependent and poly-functional nucleoprotein-specific CD4 T-cell responses were observed, and CD8 T-cell responses were elicited at 300 μg and 480 μg.

In a planned further exploratory endpoint, the study also evaluated the protection level of the vaccine against RT-PCR-confirmed influenza A. During the influenza season, there were four RT-PCR-confirmed influenza A cases in the placebo group but only two in the OVX836 group. This resulted in an observed level of protection of 84% (95% CI 17–97) for OVX836 at the time of maximum exposure to influenza.

Study lead investigator Dr Paul Griffin said: ‘By combining OVX836 with the current standard of care, we expect to bring much-needed and critical additional protection against seasonal influenza, especially for high-risk populations, including the elderly.‘

Alexandre Le Vert, CEO and co-founder of the vaccine manufacturer Osivax, added: ‘The initiation of our multicenter Phase 2a trial marks an important milestone for Osivax as we continue optimising the development of OVX836 in combination with conventional influenza vaccines within a larger and more diverse population. We are eager to build upon the promising initial data from our previous study in an effort to provide improved and broad-spectrum protection, especially for at-risk populations.‘

Influenza vaccine approved for treatment and prevention in children aged one year and above

25th January 2023

Xofluza (baloxavir) has been approved in the EU for uncomplicated influenza and post-exposure prophylaxis for children aged one and older.

Roche’s Xofluza (baloxavir) is now approved for use for the treatment of both uncomplicated influenza and post-exposure prophylaxis of influenza in children from one year of age, the company has announced.

The human influenza viruses are known to cause regular epidemics creating a huge public health burden. Although influenza vaccines are available, there are also three classes of anti-viral agents that have also been used. The M2 proton channel blockers such as amantadine, neuraminidase inhibitors (e.g. oseltamivir) and finally, polymerase inhibitors like favipiravir, for example.

The influenza virus polymerase complex has become seen as a possible target for anti-viral agents and comprises three subunits: polymerase basic protein 1, polymerase basic protein 2 (PB2) and finally polymerase acidic protein (PA). These three subunits are highly conserved and PB2 is known to bind with the cap of the host cellular pre-messenger RNA and is subsequently cleaved by a cap-dependent endonuclease in the PA subunit. Xofluza contains the pro-drug baloxavir marboxil and inhibits the endonuclease activity of the polymerase acid protein.

Studies to date have shown that in adults, xofluza reduces the median time to the resolution of influenza symptoms by as much as 28 hours compared to placebo and the drug was originally indicated for use in patients from 12 years of age. The updated indication was based on the findings from two studies.

Xofluza studies in patients under 12 years of age

The first study, MiniSTONE-2 enrolled children between the ages of one and 12 years with a clinical diagnosis of influenza. Participants were randomised 2:1 to either a single dose of oral baloxavir or oseltamivir twice a day for five days. The results showed that Xofluza reduced the median time to symptom resolution to 138.1 hours compared to 150 hours with oseltamivir.

The second trial examined the post-exposure prophylactic efficacy of xofluza and found that the risk of influzena was lower with baloxavir compared to placebo (adjusted risk ratio = 0.43, 95% CI 0.32 – 0.58).

Another clinical trial has been designed to assess the safety and efficacy of baloxavir in healthy patients from birth to less than one year of age with influenza-like symptoms.

The updated information from the EMA can be found here.