Infants Receiving a Single Dose of Nirsevimab to Prevent RSV Do Not Have Evidence of Enhanced Disease in Their Second RSV Season

Design

Follow-up study for the phase 3, randomized, double-blind, placebo-controlled MELODY trial

N= 3,012

Objective

To evaluate the theoretical risk of antibody-dependent enhancement (ADE) of infection and whether prophylaxis with nirsevimab results in a shift of the burden of disease to the second year of life

Study Groups

Nirsevimab (n= 2,009)

Placebo (n= 1,003)

Inclusion Criteria

Healthy infants born at ≥35 weeks 0 days gestational age

Exclusion Criteria

Met criteria to receive palivizumab; fever or acute illness within 7 days before randomization; respiratory syncytial virus (RSV) infection before or at the time of randomization

Methods

Patients were randomized in the MELODY trial 2:1 to a single intramuscular dose of nirsevimab (50 mg for infants <5 kg; 100 mg for infants ≥5 kg) or placebo at the beginning of their first RSV season, with no nirsevimab dose given prior to the start of the second season. Due to the COVID-19 pandemic's potential influence on RSV circulation, all RSV infection cases were reported, including those occurring between seasons.

Duration

Between July 23, 2019 and October 22, 2021

Follow-up: up to 511 days

Outcome Measures

Disease events due to RSV

Baseline Characteristics

Nirsevimab

(n= 2,009)

Placebo

(n= 1,003)

Age, months

Female

White

Results

First RSV Season (Through 151 Days Post-dose)

Second RSV Season (362-511 Days Post-dose)

Nirsevimab

(n= 2,009)

Placebo

(n= 1,003)

Nirsevimab

(n= 1,944)

Placebo

(n= 967)

Events due to RSV

Medically attended RSV LRTI

Medically attended RSV LRTI with hospitalization

Medically attended RSV LRTI (very severe)

Medically attended RSV-associated LRTI on any test result

Hospitalization for any respiratory illness due to RSV on any test result

1.2%

0.4%

0.3%

1.7%

0.7%

5.4%

2.0%

1.7%

7.5%

2.6%

1.0%

0.2%

0.2%

1.8%

0.5%

1.0%

0.3%

0.3%

2.1%

0.6%

Events of any cause (inclusive of RSV)

Medically attended LRTI of any cause

Hospitalization for any respiratory illness of any cause

8.6%

2.2%

13.9%

3.7%

6.9%

1.1%

7.3%

1.1%

Abbreviations: ITT, intent-to-treat; LRTI, lower respiratory tract infection

Data provided for ITT population; disease events are classified under per-protocol definition of medically attended RSV LRTI. In the second season, the number of ITT participants who were followed up for ≥362 days post-dose was used as the denominator for calculation of incidence.

The incidence of RSV-associated respiratory disease between Seasons 1 and 2 (152-361 days post-dose) were similar between nirsevimab and placebo across case definitions of disease.

Adverse Events

Not disclosed

Study Author Conclusions

In conclusion, these data do not indicate an increase in the incidence or severity of events of RSV LRTI in the second year of life among infants administered nirsevimab prior to their first RSV season. Although ADE is a theoretical concern of RSV prevention approaches, there was no evidence of such an effect in infants who received nirsevimab.

InpharmD Researcher Critique

Data particularly from 2020-2021 included in the analysis may be limited due to nonpharmacologic interventions during the start of the COVID-19 pandemic, and follow-up data on the enrolled cohorts may further become limited as patients age, due to the lower likelihood of RSV LRTI, and subsequently, hospitalization.