Preeclampsia (PE) is a pregnancy-induced hypertensive disorder without an effective treatment. The goal of this project is to produce a novel apheresis therapy for treatment of PE. PE is the leading cause of pregnancy- related mortality and morbidity in the US, affecting over 200,000 pregnant women and newborns annually, at a significant cost to the healthcare system. PE is characterized by an onset of hypertension and proteinuria and can lead to serious complications, including eclampsia (seizure) and HELLP syndrome associated with organ failure and death. Interventions include magnesium sulfate to prevent seizure and antihypertensives to reduce blood pressure, but they do not target the underlying pathogenesis of the disease. One potential cause of PE is an imbalance of angiogenic factors resulting from overexpression of anti-angiogenic factors, soluble VEGF receptor 1 (sVEGFR1) and soluble endoglin (sEng). Excess levels of sVEGFR1 and sEng correlate with disease severity and poor clinical outcome. The product of this SBIR will be an ex vivo immunoadsorption apheresis device (PE Device) to reduce sVEGFR1 and sEng to normal pregnancy levels and prolong pregnancy without adverse maternal or fetal effects. Due to the nature of the high-risk patient population and to increase safety, Aggamin's PE Device therapy is extracorporeal and will not introduce exogenous agents to maternal or fetal circulation. The long term goal is to commercialize PE Device therapy to improve health outcomes by reducing maternal symptoms and extending fetal gestation. Our SBIR Phase I studies showed a scale-down device containing both ?VEGFR1 and ?Eng antibodies removed >90% of sVEGFR1 and sEng from plasma. For SBIR Phase II, we now propose to produce a full-scale prototype PE device capable of reducing sVEGFR1 and sEng efficiently from plasma in vitro and to determine the range of processed blood volumes needed for safe reduction of endogenous sVEGFR1 and sEng in an animal model. After Phase II, Aggamin will initiate cGMP manufacturing of the PE Devices and plan for a clinical trial. PE affects 3-8% of all pregnancies and disease incidence is rising as risk factors such as obesity, diabetes and maternal age at pregnancy increase. PE patients also face lifelong consequences as they are at higher risk for developing cardiovascular diseases and stroke. The market for Aggamin's treatment for severe PE cases is estimated at 25,000 patients annually in the US and 60,000 patients worldwide, and could later include PE cases in which symptoms appear at >34 weeks. The total market for Aggamin's therapeutic product to treat severe PE cases in the U.S. is estimated at $0.5-1.5 billion. Reimbursement rates for adsorption apheresis can be justified by reduction or elimination of NICU costs and improved health outcomes. If proven safe and effective, the PE Device therapy has the potential to alter the clinical practice for the treatment of PE and have a significant impact on maternal and fetal health.
In this SBIR Phase II, Aggamin plans to develop an ex vivo adsorption device (PE Device) to treat preeclampsia patients. Preeclampsia is a pregnancy-induced hypertensive disease associated with high maternal and fetal deaths. There is no effective treatment except for premature delivery which jeopardizes the fetus. Aggamin's PE Device therapy is expected to reverse maternal symptoms, prolong pregnancy and improve maternal and fetal health.