New single-dose RSV immunoprophylaxis safe, effective in preterm infants
A single, 50-mg dose of MEDI8897, a monoclonal antibody immunoprophylaxis designed to prevent respiratory syncytial virus, was safe and effective in healthy preterm infants, supporting protection within the standard 5-month season, according to research presented at IDWeek.
“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, professor of pediatrics and microbiology and immunology at SUNY Upstate Medical University, told Infectious Disease News.
“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.”
The researchers evaluated the safety and efficacy of MEDI8897 (AstraZeneca) in healthy preterm infants born at 32 to 35 weeks’ gestational age in the United States, South Africa and Chile during the 2015 RSV season. 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. The researchers collected blood samples several times throughout the study, and infants with medically attended lower respiratory tract infection (LRTI) had nasal swabs tested for RSV using RT-PCR.
Of the 89 infants enrolled in the study, 95.5% completed their treatment. Adverse events were reported in 94.4% of placebo recipients and 93% of those administered MEDI8897. Five serious adverse events — three LRTIs and two febrile seizures — were reported in three infants who received MEDI8897. No adverse events were related to hypersensitivity reactions, the researchers said.
The half-life of the drug varied, with a range of 62.5 days to 72.9 days. At day 151, 87% of infants who received 50 mg of MEDI8897 had observable serum concentrations above the target EC90 level of 6.8 µg/mL, and 93.3% had a threefold or higher increase from baseline in serum anti-RSV neutralizing antibody titers. The researchers noted the presence of anti-drug antibodies in 28.2% of MEDI8897 recipients. However, the researchers said 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 LRTIs after 150 days. One medically attended LRTI 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
- Domachowske JB, et al. Abstract 1001. IDWeek; Oct. 4-8; San Diego.
Disclosures: Domachowske reports receiving research grants from and being an investigator for Medimmune, Regeneron, Pfizer, GlaxoSmithKline, Novavax and Janssen. Please see the study for all other authors’ relevant financial disclosures.