Single-dose RSV immunoprophylaxis safe, effective in preterm infants

Issue: November 2017

SAN DIEGO — A 50-mg dose of MEDI8897, a single-dose monoclonal antibody immunoprophylaxis designed to prevent respiratory syncytial virus, was found to be safe and effective in healthy preterm infants, supporting protection within the standard 5-month season, according to research presented at IDWeek 2017.

“At the present time, RSV prophylaxis is only routinely available for premature infants born at less than 29 weeks gestational age,” Joseph B. Domachowske, MD, from the department of pediatrics at SUNY Upstate Medical University, said in an interview with Infectious Diseases in Children.

“The dilemma is that all premature infant groups have higher hospitalization rates than term infants do, and we know that approximately 2% of all term newborns require hospitalization for an RSV-related illness,” he added. “This is especially problematic for babies during their first 3 months of life.”

To evaluate the safety and efficacy of MEDI8897 (AstraZeneca), including pharmacokinetics, RSV-neutralizing antibody titers and anti-drug antibody responses, the researchers conducted a study that included healthy preterm infants born at 32 to 35 weeks’ gestational age.

Infants were randomly assigned to receive either 10 mg (n=8), 25 mg (n=31), 50 mg (n=32) or a placebo n = 18) as an intramuscular injection in a single dose. Each infant was evaluated over the following 360 days. All infants were selected for this study from the United States, South Africa and Chile in the 2015 RSV season, and blood was collected from these infants at several times during the study. Nasal swabs were also tested for RSV through RT-PCR if infants had medically attended lower respiratory tract infection.

Of the 89 infants enrolled in the study, 95.5% completed their treatment. Adverse events were fairly common, with 94.4% of placebo recipients experiencing at least one, alongside 93% of those administered MEDI8897. Lower respiratory tract infections (n=3) and febrile seizures (n=2) were experienced by 3 MEDI8897 recipients. All adverse events were unrelated to hypersensitivity reactions.

The half-life of the drug varied, with a range of 62.5 days to 72.9 days. Infants who received 50 mg of MEDI8897 had observable serum concentrations above the target EC90 level of 6.8 µg/mL (87%), and a threefold or higher increase from baseline for serum anti-RSV neutralizing antibody titers was observed in 93.3% of infants at day 151. The researchers noted the presence of anti-drug antibodies in 28.2% of drug recipients; however, no safety findings were related to the presence of these antibodies. These same antibodies were observed in 26.5% of infants at 361 days.

Additionally, only 7% of infants receiving MEDI8897 reported medically attended lower respiratory tract infections after 150 days. One medically attended lower tract infection was observed as a result of RSV. This infection was acquired after receiving a 10-mg dose.

“My prediction is that MEDI8897 will be highly effective at preventing RSV disease among premature and term infants alike, and if so, can be implemented as a single dose for all infants as they enter their first RSV season,” Domachowske said. “If we can achieve high coverage rates at reasonable costs, this strategy has the potential to completely change the landscape of RSV disease.”–by Katherine Bortz

Reference:

Domachowske JB, et al. 1001. A single dose monoclonal antibody (mAb) immunoprophylaxis strategy to prevent RSV disease in all infants: Results of the First in Infant Study with MEDI8897. Presented at: IDWeek 2017; Oct. 4-8; San Diego.

Disclosure: Domachowske received research grants from and is an investigator for Medimmune, Regeneron, Pfizer, GlaxoSmithKline, Novavax and Janssen. Khan, Esser, Jensen, Takas, Villafana, Dubovsky and Griffin are employees and shareholders at Medimmune and report collection of salary and stock.