ESPID 2023 – hospitalisation data in tune for Beyfortus

Sanofi and Astrazeneca’s preventative RSV antibody Beyfortus is expected to be one of the biggest launches of the year. But not everything has gone the companies’ way, with the pivotal Melody trial previously failing to show a benefit on hospitalisation rates.

Now the groups have filled in a missing part of the puzzle, today reporting a significant decrease in RSV-related hospitalisations in the European Harmonie trial. This might not make much difference to Beyfortus’s approval prospects – it already has a green light in the EU, and an FDA decision is due in the third quarter. But positive data on this hardest of endpoints could bolster the case for uptake.

Breaking down any resistance will be important as prescribing Beyfortus will take a mindset shift: Sanofi and Astra believe that the antibody, designed to be administered once yearly, should be given to all infants, regardless of risk. The only current preventative option is Astra and Sobi’s Synagis, which is expensive, has a complicated treatment regimen involving five monthly doses, and is reserved for high-risk babies.

Harmonie showed an 83% reduction in its primary endpoint, hospitalisations due to RSV-related lower respiratory tract disease (LRTD), in babies receiving Beyfortus versus no intervention. There was also a 77% decrease in hospitalisations for severe RSV-related LRTD, and a 58% fall in all-cause LRTD hospitalisations.

The data were presented during the annual meeting of the European Society for Paediatric Infectious Diseases (Espid).

Pooled data

This is an improvement over Melody, whose 62% decrease in hospitalisations was not statistically significant. At the time, Sanofi and Astra highlighted a pooled analysis of Melody and the phase 2/3 Medley trial, which found a 77% reduction.

Speaking to Evaluate Vantage under embargo before today's presentation, Natalya Vassilouthis, Sanofi’s Harmonie study lead, stressed that Melody had not been designed around the hospitalisation endpoint, but instead had intended to show a reduction in medically attended RSV – which it did.

She added that the pooled analysis had been prespecified “before Covid ever came along”. The pandemic meant fewer cases of RSV than had been anticipated, hurting the study’s chances of hitting the hospitalisation endpoint.

Harmonie was therefore designed to look specifically at hospitalisations. It also tested Beyfortus “under as close as possible to real world conditions”, Vassilouthis said.

The study enrolled a range of infants ineligible for Synagis, from healthy full-term babies to preterm infants and those with comorbidities. It also tested the administration of Beyfortus in hospital straight after birth, for babies born during the RSV season, and in community settings alongside other routine vaccinations for those born outside the season.

Sanofi and Astra have made much of Beyfortus’s potential to provide protection against RSV regardless of when a baby is born.

With FDA approval widely expected, one question now is whether the Harmonie data will make it onto the US label. Vassilouthis said this would be down to the regulator, but added that Sanofi would provide data on request.

Pricing is another unknown. Sanofi has previously indicated that the antibody’s cost will be more in line with a premium vaccine than Synagis, which comes in at around $6,000.

Competition could be coming from Pfizer’s maternal vaccine candidate Abrysvo, although that project has shown less impressive reductions than Beyfortus on both medically attended RSV infections and hospitalisations.

An FDA approval decision on Abrysvo is expected in August. Which approach is ultimately more commercially successful could come down to various factors, but Sanofi and Astra will hope to make the most of their apparently stronger dataset.