May 12, 2023

expert reaction to Sanofi press release on nirsevimab for RSV in infants, from the HARMONIE study

A Sanofi press release suggests that their antibody treatment, nirsevimab, delivers 83% reduction in RSV infant hospitalizations in a real-world clinical trial setting.

Dr Elizabeth Whittaker, Honorary Clinical Senior Lecturer, Imperial College London; and the local investigator for HARMONIE at Imperial, said:

“The preliminary data from this trial are very exciting and I look forward to seeing the final analyses, including cost effectiveness data.  This could be a real game changer for infant hospitalisations with respiratory infections in the UK.  However, the largest burden of RSV disease is in low and middle income countries and it is essential that we consider equity of access to these novel treatments globally.”

Prof Piero Olliaro, Professor of Infectious Diseases of Poverty, and Director of Science at the ISARIC Global Support Centre (International Severe Acute Respiratory and emerging Infection Consortium); and Pandemic Sciences Institute, University of Oxford, said:

“This looks like a very effective intervention, however, I think the practice of communicating science results via press releases with very scanty information should be changed – particularly if a fuller account is being communicated at the ESPID these days.

“For public health decisions, it is important to know not just by how much an intervention reduces a risk relative to no intervention (called: relative risk reduction (RRR) or risk ratio (RR)) – in the HARMONIE trial 83% reduction of hospitalisation due to RSV with nirsevimab – but also what the actual risk is without and with the intervention so that one can also calculate the absolute risk reduction (ARR, or risk difference (RD)).  With these parameters, one will be able to derive the number needed to treat (NNT), which will tell you how many infants will have to receive nirsevimab for one additional hospitalisation to be avoided.  Without this information, which is not provided in the press release, and without knowing other parameters such as the price of this product, it won’t be possible to know how cost-effective the intervention will be and make informed public health decisions.

“As an example, if we take an earlier nirsevimab trial (MELODY) – Hammit et al, NEJM 2022 – they had 25 medically-attended RSV-associated low respiratory tract infections among 496 infants in the placebo group (5%) versus 12 in 994 on nirsevimab (1.2%) – put differently, out of 1,000 infants in the MELODY trial, 950 will never be hospitalised because of RSV, 50 will be hospitalised if not treated, 12 will still require hospitalisation even if treated.  This means a relative reduction (RR) of 76% (95% confidence interval 53-88%) and an absolute reduction (RD) of 3.8% (from 1.8 to 5.9%) – 38 fewer per 1000 (from 18 to 59).  This translated into a number needed to treat of 26 (from 56 to 17) – one fewer hospitalisation due to RSV every 26 infants receiving nirsevimab (best case 17, worse case 56), from data from the MELODY trial.

“One would need this level of detail for each of the outcomes reported in the HARMONIE trial as well.  So, bottom line, we are eager to see more either through presentation or more definitely a peer review paper.”

Prof Peter Openshaw, Professor of Experimental Medicine, Imperial College London, said:

“This announcement adds to the previous studies published last year showing that a single dose of nirsevimab protects babies against RSV, the major single cause of hospitalisation in this age-group.

“The ‘real world’ data now presented was gathered at a time when RSV was recovering from the dip in case numbers during COVID lockdown, and adds to the evidence that use of long-acting monoclonal antibody may prevent moderate to severe RSV disease after a convenient single dose.  Follow up studies will be needed to determine what happens when older children catch RSV for the first time beyond infancy, the impact of displacing the time of infection on the frequency of later respiratory health (recurrent wheeze and asthma diagnosis) and on the emergence of resistant viral variants.  The cost of nirsevimab will be a critical determinant of how widespread its use can be.”

https://www.sanofi.com/en/media-room/press-releases/2023/2023-05-12-08-50-00-2667568

Declared interests

Dr Elizabeth Whittaker: “I was the local investigator for Harmonie at Imperial.  I was also the local investigator for the MELODY and MEDLEY trials at Imperial which were the previous studies to Harmonie.”

Prof Piero Olliaro: “None.”

Prof Peter Openshaw: “I have been on scientific advisory panels for GSK, Moderna, Janssen, Seqirus and Pfizer on vaccines against respiratory viral infections.”