A Single Dose Monoclonal Antibody (mAb) Immunoprophylaxis Strategy to Prevent RSV Disease in All Infants: Results of the First in Infant Study with MEDI8897

BACKGROUND: RSV is the most common cause of lower respiratory tract infection (LRTI) among infants making prevention of RSV disease a public health priority. A significant unmet need exists for RSV prevention in healthy infants. Our goal is to develop a mAb with an extended half-life (t(½)) capable of protecting infants for an entire RSV season by using a single intramuscular (IM) dose. This study was conducted to evaluate the safety profile, pharmacokinetics (PK), RSV neutralizing antibody titers, and anti-drug antibody (ADA) responses for MEDI8897 in healthy preterm infants born between 32 and 35 weeks gestational age. METHODS: Infants were randomized 4:1 to receive a single IM injection of MEDI8897 10mg (n = 8), 25mg (n = 31), 50mg (n = 32) or placebo (n = 18) and followed for 360 days. Enrollment occurred during the 2,015 RSV seasons in the US, South Africa, and Chile. Blood was collected at multiple timepoints. Infants who met criteria for a medically-attended (MA) LRTI had nasal swabs obtained for RSV testing by RT-PCR. RESULTS: A total of 85/89 (95.5%) infants completed the study. Adverse events (AEs) were reported in 17/18 (94.4%) placebo and 66/71 (93.0%) MEDI8897 recipients. Five serious AEs (three LRTIs, two febrile seizures) were reported in three MEDI8897 recipients. No events were consistent with hypersensitivity reactions. The estimated MEDI8897 serum t(½) ranged from 62.5 to 72.9 days. On day 151, 87% of the infants who received the 50mg dose of MEDI8897 had serum concentrations above the target EC(90) level of 6.8 µg/ml, and 93.3% showed a ≥3-fold rise from baseline in serum anti-RSV neutralizing antibody titers. ADA was detected in 28.2% of MEDI8897 recipients, but when present was not associated with any safety findings. ADA was detected at day 361 only in 26.5% of subjects. MA-LRTI was reported in 5 (7%) MEDI8897 recipients through 150 days after dosing. The one subject with an MA-LRTI caused by RSV had received a 10mg dose of MEDI8897. CONCLUSION: In healthy preterm infants, the safety profile of MEDI8897 was favorable. The extended t(½) of MEDI8897 with the corresponding increase in RSV neutralizing antibody levels was confirmed and supports protection from RSV disease during a typical 5-month season with a single 50mg IM dose. This study was sponsored by MedImmune. DISCLOSURES: J. B. Domachowske, Medimmune: Investigator, Research grant; Regeneron: Investigator, Research grant; Pfizer: Investigator, Research grant; Glaxo Smith Kline: Investigator, Research grant; Novavax: Investigator, Research grant; Janssen: Investigator, Research grant; A. Khan, MedImmune: Employee and Shareholder, Salary and stock; M. T. Esser, MedImmune: Employee and Shareholder, Salary and stock; K. M. Jensen, MedImmune: Employee and Shareholder, Salary and stock; T. Takas, MedImmune: Employee and Shareholder, Salary and stock; T. Villafana, MedImmune: Employee and Shareholder, Salary and stock; F. Dubovsky, MedImmune: Employee and Shareholder, Salary and stock; M. P. Griffin, MedImmune: Employee and Shareholder, Salary and stock