Nirsevimab data leave the door open for Pfizer

A lack of impact on hospitalisations could hit Astra and Sanofi’s plans for broad use.

Astrazeneca and Sanofi hope that their antibody nirsevimab could become the first product approved for the prevention of respiratory syncytial virus in all infants, not just those at a high risk of complications. Full data from the Melody trial, published in the New England Journal of Medicine today, suggest that the project could well get the nod – but uptake might be a different story.

This is because nirsevimab was shown to prevent medically attended RSV compared with placebo, but had no impact on hospitalisation rates, and the latter is surely the main measure of interest for healthcare providers. The expense of giving an antibody with limited benefit to all infants looks hard to justify.

Results were also published today on nirsevimab in infants at high risk of severe RSV infection. The phase 2/3 Medley trial found similar rates of adverse events with nirsevimab and the currently approved high-risk RSV antibody Synagis.

Nirsevimab, a long-acting antibody, could have a convenience advantage over the incumbent: the former is given via a single dose, while Synagis has a complicated treatment regimen involving five monthly doses.

Astra and Sanofi could also gain an edge in the high-risk space if they compete on cost. Astra previously told Evaluate Vantage that if nirsevimab was approved its price tag would be “very competitive” (Astra and Sanofi’s RSV jab takes a step towards market, April 26, 2021).

However, the broad infant population is the big prize, and here vaccines, which might be cheaper, could soon be coming. Glaxosmithkline recently halted enrolment into studies of its maternal RSV candidate – an upgrade from an earlier “pause” – but Pfizer’s RSVpreF, which now has breakthrough therapy status, is set to yield data from a phase 3 trial in pregnant women this half.

Late-stage infant RSV pipeline 
Project Company Description Details 
Fusion antibody Filed in EU & accepted under accelerated assessment
Pfizer Protein subunit vaccine Data from maternal protection trial due H1 2022
Glaxosmithkline Protein subunit vaccine, unadjuvanted Trials halted; Grace maternal protection trial was due to read out H2 2022
Merck & Co Fusion antibody MK-1654-007 in high-risk infants; ph2/3 MK-1654-004 in healthy infants, data due 2022*
Johnson & Johnson Oral RSV F-protein fusion inhibitor Daisy trial in hospitalised children started late 2021
*Leerink estimate. Source: Evaluate Pharma, & company statements.

Virtually all children get an RSV infection before the age of two, but most of the time this merely causes a mild illness. RSV is more dangerous in premature infants and those with weakened immune systems or some pre-existing diseases.

The economic case for broad use of a preventative antibody always looked on shaky ground given the low risk of hospitalisation or death in the healthy infant population. And the results from Melody merely reinforce these concerns.

The trial, in healthy late preterm and term infants, met its primary endpoint, the incidence of medically attended RSV, with nirsevimab showing 75% efficacy versus placebo. The rate of hospitalisations was a secondary endpoint, and here there was no statistically significant difference with nirsevimab versus placebo.

Astra pointed to a prespecified pooled analysis of Melody and Medley, which did find a benefit on hospitalisations: there were nine admissions with nirsevimab versus 21 with placebo, giving efficacy of 77% and a p value of less than 0.001.

Regulatory submissions have already begun, and approvals look likely to follow, but there is a bigger question mark around nirsevimab’s commercial prospects. Sellside consensus compiled by Evaluate Pharma currently forecasts sales of $700m in 2026.

Pfizer’s maternal RSV vaccine now has a bar to clear.

Data from the Melody trial of nirsevimab in healthy late preterm & term infants
  Nirsevimab Placebo Efficacy
Cases of medically-attended RSV 12 25 74.5%, p<0.001
Hospitalisation for RSV 6 8 62.1%, p=0.07
Serious adverse events 6.8% 7.3% -
Source: NEJM.

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