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.‘

Review suggests oseltamivir does not reduce risk of hospitalisation for influenza

15th June 2023

Oseltamivir use does not lower the risk of hospitalisation among older and high-risk patients with influzena, according to the findings of a recent systematic review and meta-analysis.

Published in JAMA Internal Medicine, researchers examined whether oseltamivir use in adult and adolescent outpatients with influenza reduced the risk of hospitalisation. They searched for randomised controlled trials that compared oseltamivir against placebo or nonactive controls in outpatients with a confirmed influenza infection. They set the primary outcome of interest as the first hospitalisation but excluded readmissions. In addition, the team also examined a primary safety outcome which was the rate of any adverse event, regardless of grade.

Risk of hospitalisation

A total of 15 eligible trials with 6,295 individuals, of whom 3,443 were assigned to oseltamivir, were included in the final analysis. The participants had a mean age of 45.3 years (53.6% female). Of the 15 studies, 60% were sponsored by Roche, the manufacturer of oseltamivir.

Overall, oseltamivir was not associated with reduced risk of first hospitalisation (Risk Ratio, RR = 0.77, 95% CI 0.47 – 1.27). In addition, the drug failed to reduce hospitalisations among those aged 65 years and older (RR = 0.99, 95% CI 0.19 – 5.13) and in patients considered at greater risk of hospitalisation (RR = 0.90, 95% CI 0.37 – 2.17). 

In terms of the primary safety outcome, patients given oseltamivir experienced significantly more nausea (RR = 1.43, 95% CI 1.13 – 1.82), vomiting (RR = 1.83, 95% CI 1.28 – 2.63) and a composite of gastrointestinal symptoms (RR = 1.21 95% CI 1.02 – 1.45). 

The researchers concluded that oseltamivir use did not reduce the risk of hospitalisation but did lead to an increased risk of adverse gastrointestinal effects. They called for more studies to identify high-risk patients who might benefit from the drug.

Influenza and oseltamivir in context

Oseltamivir is an anti-viral agent used in the management of influenza. However, the benefits of the drug remain unclear. Some evidence demonstrates a clear advantage, whereas another review concluded that the evidence for a clinically significant effects on complications and viral transmission is limited because of a rarity of such events and problems with study design.

During the Covid-19 pandemic, cases of influenza decreased, although it is anticipated that the virus will re-emerge as normalcy returns following the pandemic. Consequently, there is a need to re-evaluate the available treatments for influenza.

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.