INHA-21

Staphylococci, especially coagulase negative staphylococci (CONS), are responsible for over 75 % of late-onset infections in very low birth weight infants. These infections cause increased length of hospital stay, need for antibiotics, and cost of medical care. Several drug companies have developed and evaluated hyperimmune polyclonal and monoclonal antibodies for the prevention of neonatal staphylococcal infection including 1) Altastaph by North American Biologics Inc., 2) Veronate by Inhibitex Inc., and 3) Pagibaximab by Biosynexus Inc, and Glaxo Smith Kline Inc. We will review the development and status of these potential products. Altastaph is a S. aureus serotype 5 and 8 vaccine induced hyperimmune polyclonal antibody whose development has been placed on hold due to its failure to demonstrate any trend toward efficacy in a recently completed Phase II study. Veronate is a polyclonal antibody obtained by plasmapheresis from donors with high titers of MSCRAMM (microbial surface components recognizing adhesion matrix molecules) activity against CONS whose development has been placed on hold due to its failure to demonstrate effectiveness in a recently completed Phase III study. Pagibaximab is a humanized mouse chimeric monoclonal antibody (previously known as BSYX-A110) directed against lipoteichoic acid (LTA), a major cell wall component of gram-positive bacteria, that has recently completed a Phase II study suggesting efficacy and is being developed further for clinical investigation.

INH-A21 is an experimental human immune globulin for intravenous infusion (IGIV) derived from donors specifically selected for elevated levels of antibodies against the Staphylococcal fibrinogen-binding proteins, serine aspartate dipeptide repeat G and clumping factor A. Phase II results demonstrated that infusions of INH-A21 were well tolerated and there were no trends for increasing adverse events, or the common morbidities associated with prematurity. Enrollment has been completed in (but no results have been released from) a Phase III human trial testing INH-A21 as a prophylactic agent against staphylococcal infection in very low birth weight infants (500-1250 g).