Preeclampsia (PE) is a pregnancy-induced hypertensive disorder without an effective treatment. The goal of this project is to produce a novel and safe therapy for PE. PE is the leading cause of pregnancy-related morbidity and mortality in the US, affecting over 200,000 pregnant women and newborns annually, at a significant cost to the healthcare system. PE is characterized by the onset of hypertension and proteinuria and can lead to more serious complications, such as seizure (eclampsia) and HELLP syndrome associated with systemic organ failure and death. Current interventions to treat PE include magnesium sulfate as an anticonvulsant and antihypertensive drugs, which can sometimes manage symptoms but do not target the underlying causes of the disease. Antiangiogenic factors, soluble VEGF Receptor 1 (sVEGFR1) and soluble Endoglin (sEng), are elevated in PE patients and are associated with adverse clinical outcomes. Aggamin proposes to develop a novel immunoadsorption therapy to remove excess levels of antiangiogenic factors sVEGFR1 and sEng from PE patients. Due to the nature of the high-risk patient population and safety requirements, this therapy is an extracorporeal treatment similar to dialysis. The long term goal is to develop and commercialize a therapeutic device for PE to improve health outcomes by reducing maternal symptoms and extending fetal gestation to 36 weeks. For Phase I, we hypothesize that a scaled-down cartridge packed with aVEGFR1 and aEng antibodies can remove sVEGFR1 and sEng protein from blood, using conditions that mimic clinical apheresis treatment. In Phase II, Aggamin will initiate cGMP manufacturing, produce a prototype device and conduct studies in a baboon PE model for efficacy and safety. PE affects 3-8% of all pregnancies and disease incidence is rising as risk factors such as obesity, diabetes, women's age at pregnancy and the rate of multiple births increase. The market for Aggamin's treatment for severe PE cases, evident before 34 weeks, is estimated at up to 25,000 patients in the US, and could later increase to include PE cases where symptoms appear after 34 weeks. Reimbursement rates for adsorption apheresis range from $5-10,000 and could be justified for PE patients by reducing or eliminating ICU costs and improved health outcomes for the newborn and mother. The total market for Aggamin's therapeutic product to treat severe early-onset PE cases in the US is estimated at $0.5-1.5 billion.
Public Health Relevance Statement: Public Health Relevance: Preeclampsia is a serious disorder of pregnancy associated with high maternal and fetal morbidity and mortality. Currently, there is no therapy to treat preeclampsia except for premature delivery, which poses a significant risk to the fetus. The proposed work is to develop a novel ex vivo therapy for preeclampsia that targets the underlying causes of preeclampsia by removing excess levels of antiangiogenic factors from preeclampsia patients. This therapy is expected to reverse the adverse maternal symptoms and prolong pregnancy to 36 weeks of gestation, thus enabling safe and full term delivery.
NIH Spending Category: Biotechnology; Cardiovascular; Contraception/Reproduction; Hypertension; Pediatric; Perinatal Period - Conditions Originating in Perinatal Period
Project Terms: Adsorption; Affect; Angiogenesis Inhibitors; Animals; Antibodies; Anticonvulsants; Antihypertensive Agents; Biotechnology; Blood; Blood Component Removal; Blood Proteins; Cerebral hemisphere hemorrhage; Cessation of life; Clinical; commercial application; commercialization; Communities; cost; Cyclic GMP; Devices; Diabetes Mellitus; Dialysis procedure; Disease; early onset; Eclampsia; Edema; effective therapy; Effectiveness; Endoglin; fetal; Fetus; Future; Goals; Health; Healthcare Systems; HELLP Syndrome; high risk; Human; Hypertension; improved; Incidence; Innovative Therapy; Intervention; Ischemia; Lead; Life; Magnesium Sulfate; Marketing; Maternal Age; medically underserved; Modeling; Monoclonal Antibodies; Morbidity - disease rate; Mortality Vital Statistics; Mothers; Multiple Birth Offspring; Nature; neonate; Newborn Infant; novel; Obesity; Organ failure; Outcome; Papio; patient population; patient safety; Patients; Phase; Physiology; Placenta; Placental Growth Factor; Plasma; Pre-Eclampsia; Pregnancy; pregnancy disorder; Pregnancy Rate; Pregnant Women; Premature Birth; Prolonged Pregnancy; Proteinuria; prototype; public health relevance; Recombinants; Relative (related person); Risk; Risk Factors; Safety; Seizures; Small Business Innovation Research Grant; stable cell line; Staging; standard of care; Symptoms; System; Therapeutic; Time; Vascular Diseases; Vascular Endothelial Growth Factor Receptor; Woman; Work
