Preeclampsia (PE) is a pregnancy-induced hypertensive disorder without an effective treatment. The goal of this project is to produce a novel biologic for treatment of 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 and lifelong consequences. 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 manage symptoms but do not target the underlying causes of the disease. One potential cause of PE is hypothesized to be an imbalance of angiogenic factors, specifically antiangiogenic sFlt1 and proangiogenic PlGF. Higher sFlt1:PlGF ratios correlate with increased severity of disease and poor clinical outcome. The product of this SBIR will be recombinant human PlGF1 protein (rhPlGF1) as a parenteral therapy to treat very preterm PE and prolong pregnancy without adverse maternal or fetal effects. The long term goal is to develop and commercialize a therapeutic for PE to improve health outcomes by reducing maternal symptoms and extending fetal gestation toward 36 weeks. For Phase I, we hypothesize the recombinant protein will bind sFlt1 from PE patients and show efficacy in a rat PE model. In phase II, Aggamin will initiate manufacturing and a safety/toxicology study. 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 rate of multiple births increase. The market for Aggamin's treatment for severe PE cases, evident before 34 weeks, is estimated at up to 60,000 patients worldwide, and could later increase to include PE cases where symptoms appear after 34 weeks. Reimbursement rates will be justified for by reducing or eliminating neonatal ICU costs and improving 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 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 drug therapy to restore the angiogenic balance that is disrupted in preeclampsia. This therapy is expected to reverse maternal symptoms and prolong pregnancy toward 36 weeks of gestation, thus enabling safe and full term delivery.