Background: RLYB211 is an intravenously administered, investigational, plasma-derived polyclonal anti-Human-Platelet-Antigen-1a (HPA-1a) hyperimmune IgG being developed for the prevention of Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT). FNAIT is a rare condition in which the mother’s immune system attacks the platelets of her fetus, leading to potentially catastrophic fetal and neonatal morbidity and mortality. Fetal-maternal incompatibility in the HPA-1 system is the most common (85-90%) cause of FNAIT. Treatment with RLYB211 is designed to rapidly eliminate fetal HPA-1a positive platelets from a mother’s circulation and prevent maternal alloimmunization, eliminating the risk of FNAIT in the fetus. There are no currently approved treatments for the prevention of FNAIT.

Aims: To determine whether a dose of 1000 IU of anti-HPA-1a antibodies would accelerate the clearance of HPA-1a positive platelets transfused to HPA-1bb (i.e., HPA-1a negative) healthy male volunteers.  

Methods: Following approval by the Paul Ehrlich Institut, Germany and the Ethics Committee, University Hospital Frankfurt, informed consent was obtained from 8 healthy male subjects (HPA-1bb and HLA-A2 negative). Subjects were administered either RLYB211 (n=6)  or placebo (n=2) 60 minutes after administration of 10 X10⁹ HPA-1ab and HLA-A2 positive platelets. The proportion of normalized HLA-A2 positive platelets in circulation following administration of RLYB211 or placebo was determined by flow cytometry.

Results: RLYB211 showed acceptable safety and tolerability with no serious adverse events and minimal adverse events observed. Administration of RLYB211 markedly accelerated the clearance of HPA-1ab positive platelets compared with placebo (half-life of mismatched platelets 0.32 hrs. vs. 65.29 hrs. respectively; p value <0.001).

Rapid and complete clearance of HPA-1ab positive platelets by anti-HPA-1a antibodies compared with placebo in HPA-1bb healthy male subjects

Conclusions: RLYB211 provides proof of concept of the ability of anti HPA-1a antibodies to rapidly and completely clear mismatched HPA-1a positive platelets in HPA-1bb individuals. Administration of anti-HPA-1a antibodies could therefore be a viable treatment for the prevention of FNAIT in mothers at high risk.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/rapid-and-complete-clearance-of-hpa-1a-mismatched-platelets-in-a-human-model-of-fetal-and-neonatal-alloimmune-thrombocytopenia-by-a-hyperimmune-plasma-derived-polyclonal-anti-hpa-1a-antibody/