A Phase 1b PK/PD Study to Demonstrate Antigen Elimination With RLYB212, a Monoclonal Anti-HPA-1a Antibody for FNAIT Prevention
A Phase 1b PK/PD Study to Demonstrate Antigen Elimination With RLYB212, a Monoclonal Anti-HPA-1a Antibody for FNAIT Prevention

A Phase 1b PK/PD Study to Demonstrate Antigen Elimination With RLYB212, a Monoclonal Anti-HPA-1a Antibody for FNAIT Prevention

Thromb Haemost. 2024 Aug 21. doi: 10.1055/a-2398-9344. Online ahead of print.

ABSTRACT

BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare bleeding disorder of the fetus/newborn caused by development of maternal alloantibodies against fetal human platelet antigens (HPAs), predominantly HPA-1a. Currently there are no treatments available to prevent maternal alloimmunization to HPAs or FNAIT.

METHODS: This proof-of-concept study (EudraCT Number: 2021-005380-49) was designed to assess the ability of subcutaneous (SC) RLYB212, a monoclonal anti-HPA-1a antibody, to eliminate HPA-1a positive platelets in an antigen challenge model of a 30 mL fetal-maternal hemorrhage. Subjects were randomized to receive a single SC dose of RLYB212 or placebo on day 1 in a single-blinded manner, followed by transfusion of 10 × 10^9 HPA-1a positive platelets on day 8.

RESULTS: Four subjects received 0.09 mg SC RLYB212, 5 received 0.29 mg SC RLYB212, and 2 received placebo. RLYB212 achieved rapid elimination of HPA-1a positive platelets in a concentration-dependent manner, with concentrations as low as 3.57 ng/mL meeting the prespecified proof-of-concept criterion of ≥90% reduction in platelet elimination half-life vs placebo. Following HPA-1a positive platelet transfusion, a rapid decline was observed in the concentration of RLYB212 over a period of 2 to 24 hours, corresponding to the time needed for RLYB212 to bind to ~10% of HPA-1a on cell surfaces. RLYB212 was well tolerated with no reports of drug-related adverse events.

CONCLUSION: The data from this study are consistent with preclinical efficacy data and support the potential use of RLYB212 as a prophylactic treatment for FNAIT that prevents maternal HPA-1a alloimmunization during at-risk pregnancies.

PMID:39168139 | DOI:10.1055/a-2398-9344