RLYB212
RLYB212
- Stage
- Phase 2
- Indication
- Prevention of HPA-1a alloimmunization in pregnant women at higher risk of HPA-1a alloimmunization and Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT)
- Approach
- Monoclonal anti-HPA-1a antibody
- Mode of Administration
- Subcutaneous injection
Fetal and Neonatal Alloimmune Thrombocytopenia
Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT) is a potentially life-threatening rare disease that can cause uncontrolled bleeding in fetuses and newborns. FNAIT can arise during pregnancy due to an immune incompatibility between a pregnant woman and her fetus in a specific platelet antigen called human platelet antigen 1, or HPA-1.
There are two predominant forms of HPA-1, known as HPA-1a and HPA-1b, which are expressed on the surface of platelets. Individuals who are homozygous for HPA-1b, meaning that they have two copies of the HPA-1b allele and no copies of the HPA-1a allele, are also known as HPA-1a negative. Upon exposure to the HPA-1a antigen, these individuals can develop antibodies to that antigen in a process known as alloimmunization. In HPA-1a-negative pregnant women bearing a HPA-1a-positive fetus, alloimmunization can occur upon mixing of fetal blood with maternal blood. When alloimmunization occurs in a pregnant woman, the anti-HPA-1a antibodies that develop in the woman can cross the placenta and destroy platelets in the fetus. The destruction of platelets in the fetus can result in severely low platelet counts, or thrombocytopenia, and potentially lead to devastating consequences including miscarriage, stillbirth, death of the newborn, or severe lifelong neurological disability in those babies who survive. There is currently no approved therapy for the prevention or prenatal treatment of FNAIT.
RLYB212
RLYB212 is designed to rapidly eliminate HPA-1a positive fetal platelets from an pregnant woman’s circulation, thereby preventing maternal HPA-1a alloimmunization. Prevention of maternal alloimmunization eliminates the risk of FNAIT in the fetus.
Journal Publications
- Moc Willeford et al. (2024). Informing pregnancy dose via target-mediated drug disposition modeling and simulations for a recombinant human monoclonal antibody. Clinical Pharmacology and Therapeutics: Pharmacometrics & Systems Pharmacology, 13 (11): 2002 – 2015. https://doi.org/10.1002/
psp4.13250 - Geisen et al. (2023). An HPA-1a–positive platelet–depleting agent for prevention of fetal and neonatal alloimmune thrombocytopenia: a randomized, single-blind, placebo–controlled, single-center, phase 1/2 proof-of-concept study. Journal of Thrombosis and Haemostasis, 21(4):, 838–849. https://doi.org/10.1016/j.jtha.2022.11.041
- Geisen et al. (2023). An HPA-1a–positive platelet–depleting agent for prevention of fetal and neonatal alloimmune thrombocytopenia: a randomized, single-blind, placebo–controlled, single-center, phase 1/2 proof-of-concept study. Journal of Thrombosis and Haemostasis, 21(4), 838–849. https://doi.org/10.1016/j.jtha.2022.11.041
- Zhi et al. (2022). Prophylactic Administration of HPA-1a–Specific Antibodies Prevents Fetal/Neonatal Alloimmune Thrombocytopenia in Mice. Blood, 140(20), 2146–2153. https://doi.org/10.1182/blood.2022015666
- Semple, J.W., & Kapur, R. (2022). Protecting the Fetus from FNAIT. Blood, 140(20), 2097–2099. https://doi.org/10.1182/blood.2022017937
Scientific Presentations
- Zhi et al. (2024). Prophylactic Administration of HPA-1a-Specific Antibody RLYB212 Safely Prevents Fetal/Neonatal Alloimmune Thrombocytopenia in Pregnant Mice. 66th American Society of Hematology Meeting & Exposition (December 2024)
- Hayward et al. (2024). Quantifying the proportion of women at risk of an FNAIT pregnancy in diverse populations in the United States. 2024 American Society of Human Genetics (ASHG) Annual Meeting (November 2024)
- Hayward et al. (2024). Quantifying the proportion of women at risk of an FNAIT pregnancy in diverse populations in the United States. 2024 NORD Breakthrough Summit Annual Meeting (October 2024)
- Margulis et al. (2024). Fetal and Neonatal Alloimmune Thrombocytopenia: A Systematic Literature Review and Meta-analysis of Adverse Pregnancy-Related Outcomes to Support the Development of a Novel Prophylactic Therapeutic. 2024 Academy of Managed Care Pharmacy (AMCP) Annual Meeting (April 2024)
- Vander Haar et al. (2023). Identifying Pregnancies at Higher Risk for HPA-1a Alloimmunization and Fetal/Neonatal Alloimmune Thrombocytopenia (FNAIT): An International, Prospective, Natural History Study. 65th American Society of Hematology (ASH) Annual Meeting (December 2023)
- Geisen et al. (2023). Dose-Dependent Elimination of HPA-1a Platelets by Subcutaneous RLYB212, a Monoclonal Antibody to Prevent Fetal and Neonatal Alloimmune Thrombocytopenia. 31st Congress of the International Society of Thrombosis and Haemostasis (ISTH) (June 2023)
- Geisen et al. (2021). 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. XXIX Congress of the International Society on Thrombosis and Haemostasis (ISTH) (July 2021)