901. MEDI8897 Prevents Serious RSV Disease in Healthy Preterm Infants

BACKGROUND: RSV is the principal cause of lower respiratory tract infection (LRTI) among infants, and a significant unmet need exists for RSV prevention in healthy infants. We have developed a highly potent, extended half-life monoclonal antibody (mAb), to protect infants for an entire RSV season using a single IM dose. Here we report the efficacy, safety, pharmacokinetics, and anti-drug antibody (ADA) responses for MEDI8897 in palivizumab-ineligible preterm infants born between 29 and 35 weeks gestation. METHODS: A total of 1,453 Infants were randomized 2:1 to receive a single 50 mg IM injection of MEDI8897 (n = 969) or placebo (n = 484) and followed for 360 days. Enrollment occurred just prior to the 2016 and 2017 RSV seasons in 23 northern and southern hemisphere countries. Blood was collected periodically. Infants with a medically attended (MA) LRTI (outpatient or inpatient) had nasal swabs obtained for central RSV testing by RT-PCR. Predefined clinical criteria were used for the case definition. RESULTS: A total of 1,417 (97.5%) subjects completed the 150-day efficacy follow-up period and 1,367 (94.1%) completed the study. In the MEDI8897 group, a 70.1% (95% CI: 52.3%, 81.2%; P < 0.0001) reduction in the incidence of medically attended RSV LRTI and a 78.4% (95% CI: 51.9%, 90.3%; P = 0.0002) reduction in the incidence of RSV LRTI hospitalization was achieved. These efficacy results were consistent when analyzed by hemisphere, RSV subtype, and subject demographics. Similar proportions of adverse events (86.8% placebo; 86.2% MEDI8897) and serious adverse events (16.9% placebo; 11.2% MEDI8897) were reported in study subjects. There were no significant hypersensitivity reactions with similar proportions reported for both groups (0.6% placebo; 0.5% MEDI8897). The incidence of ADA detected any time post baseline was low (3.8% placebo; 5.6% MEDI8897) with no impact on PK or safety. The occurrence of non-RSV LRTIs was similar for both groups indicating no replacement by other pathogens. CONCLUSION: In this large randomized study of RSV prophylaxis in healthy preterm infants, MEDI8897 immunoprophylaxis provided a significant reduction in RSV MA-LRTI and hospitalization. These results have promising implications for the future of RSV prophylaxis for all infants. This study was funded by AstraZeneca and sanofi pasteur. DISCLOSURES: All Authors: No reported Disclosures.