Astra and Sanofi’s RSV jab takes a step towards market

A pivotal win puts nirsevimab on track to be filed next year, but the reimbursement hurdle looms.

Several big pharma names are in late-stage development with novel projects designed to prevent respiratory syncytial virus infections, and today Astrazeneca and Sanofi confirmed that they are in pole position. Nirsevimab, a long-acting antibody, succeeded in the pivotal Melody trial, putting the project on track for regulatory filings next year.

Biopharma has struggled for years to come up with something better than Synagis, which is only available to high-risk infants, so this clinical win is notable. But developers are hoping to convince healthcare systems that RSV prevention should be made available to all infants, and winning that argument could be difficult.

This is likely to be especially true in cost-sensitive regions, and of course nirsevimab’s ultimate commercial potential will depend on Astra and Sanofi pitching the right price. It is too early to discuss those details, Tonya Villafana, head of Astra’s global infections franchise, tells Evaluate Vantage, while insisting that the project will prove cost effective for many countries.

“In a normal RSV season paediatric wards are filled with children with this disease,” she says. “We have the first intervention that can be used in a broad infant population. I think countries will look at that and the value it can bring in preventing hospitals being filed up and babies getting quite sick.”

Most RSV hospitalisations occur in otherwise healthy babies; Astra estimates that globally in 2015 there were approximately 30 million cases of acute lower respiratory infections leading to more than three million hospitalisations. Deaths are rare, with an estimated 60,000 in-hospital deaths of children younger than five years in that year.

Ms Villafana rejects the suggestion that nirsevimab could end up being used mainly in regions with loose payer restrictions. “There is a lot of interest [in the project]; we have even talked to the World Health Organization, which sees the value,” she says.

The RSV landscape - on the market and late-stage pipeline
Product Company Description 2026e sales ($m) Current clinical focus 
Synagis Abbvie/Sobi Fusion antibody 410 Indicated for prevention of RSV infections in high-risk infants
Phase 3
SP0232 (nirsevimab) Sanofi/Astrazeneca Fusion antibody 470 Prevention of RSV infections in healthy and high-risk infants
RSVpreF (PF-06928316) Pfizer Vaccine 255 Prevention of RSV infections in the infants of vaccinated mothers
GSK3888550A Glaxosmithkline Vaccine  23 Prevention of RSV infections in the infants of vaccinated mothers
GSK3844766A Glaxosmithkline Recombinant protein, adjuvanted 185 Aresvi 004 (NCT04732871), interim data H2 2022; Aresvi 006 to start in coming months
Source: Evaluate Pharma.    

Another potential challenge could come from vaccines from Glaxosmithline and Pfizer, both of which are in pivotal trials (Glaxo moves up a place in the RSV treatment race, November 26, 2020). Numerous failures in this space means that these projects’ success is far from guaranteed, and both companies will be facing the challenge of running pivotal programmes at a time when social distancing is lowering rates of respiratory infections.

Antibody technology traditionally produces more costly products than vaccine technology, but Ms Villafana insists that nirsevimab will be “very competitive”.

“Countries will have to look at both interventions and determine what would be optimal in various settings. But I would add that we haven’t seen any of these [vaccine] approaches be successful, and they are a way down the line yet,” she says.

First, however, the vaccines will have to shape up to strong efficacy findings from nirsevimab. An earlier phase 2b trial with nirsevimab, which will also be used as part of regulatory filings, generated a 70% reduction in infections (p<0.001) versus placebo.

The Melody trial was designed to find a similar effect size, Ms Villafana says. All Astra has disclosed for now is that this study met its primary endpoint, showing a statistically significant reduction in the rate of medically attended lower respiratory tract infections caused by RSV, compared with placebo.

Melody enrolled healthy infants born at 35 weeks or later entering their first RSV season; the primary efficacy analysis was conducted when only half of the 3,000 targeted infants had been dosed, because Covid-19 was dramatically cutting rates of respiratory infections. A further 1,500 will be enrolled and tracked for safety.

The phase 2b was also conducted in around 1,500 subjects. If the Melody result is as convincing, an early stop will hopefully not prove problematic for regulators.

Passive immunity

Nirsevimab is a fusion antibody designed to have a long half-life, with sufficient duration of effect to protect infants in the first year of life, when they are most vulnerable to respiratory tract infections.

“These children are still exposed to the virus, but they are not getting the same outcome, and it gives them time for their lungs to develop and cope with the disease in the second season,” Ms Villafana says. 

It understandable how this so-called “passive immunity” approach could prove ideal for an illness that poses significantly fewer risks as a child ages. Whether payers around the world agree will depend on the cost, a detail that is still a while away from being revealed.

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