What is preeclampsia?
Preeclampsia is a potentially life-threatening disease of pregnancy with serious complications for both mothers and babies. Despite decades of research, there is no effective treatment except to deliver the baby. Globally preeclampsia affects 2-8% of pregnancies and results in nearly 50,000 maternal deaths, making it the second most frequent cause of obstetrical death after hemorrhage. Tragically, 500,000 babies die before birth, or in the first few weeks afterwards. In the US there are about 200,000 cases of preeclampsia annually. Preeclampsia disproportionately affects women of color, those who have diabetes, hypertension, or high BMI, those who have undergone IVF and those of lower socio-economic status.
What are the risks?
Preeclampsia occurring before the 34th week of pregnancy (there are about 25,000 such cases in the US annually) involves an impossible trade-off between the best interests of the mother and the best interests of the baby. In mothers the combination of elevated blood pressure and blood vessel dysfunction can cause severe complications including stroke and damage to the kidneys, liver and lungs. For babies, the risks include growth restriction, premature delivery, and even death.
Delivery before 34 weeks, while effective in relieving preeclampsia symptoms in the mother, can lead to lengthy NICU stays for the baby as complications such as breathing difficulties, brain hemorrhage and intestinal damage are managed. Longer-term neurodevelopmental issues are also associated with premature birth. Therefore, a key goal of managing the disease is to extend the pregnancy to at least 34 weeks (“every day counts”) while protecting the mother from harm.
Unmet needs and key disease drivers
Current treatment includes supportive care and medications to manage seizure risk and high blood pressure in the mother. Unfortunately, common classes of medications that are used to manage high blood pressure (ACE inhibitors and ARBs) cannot be safely used in pregnant women due to safety concerns for the baby, thus limiting the treatment options. Elevated blood pressure is one symptom of preeclampsia but a new treatment needs to address the underlying cause of the disease which is dysfunction of the blood vessel lining. A protein called sFlt1 has been identified as a central driver for preeclampsia. There is a very strong scientific rationale linking elevated circulating levels of sFlt1 to blood vessel dysfunction in preeclampsia including studies in animals, human clinical studies and the relationship of elevated levels to preeclampsia symptoms. In preeclampsia, sFlt1 is produced in excessive amounts by the placenta, goes into the mother’s blood circulation and damages her blood vessels, leading to organ damage.
Our approach
Avilar’s solution for preeclampsia is to selectively bind sFlt1 and remove it from circulation using a pathway in the human body naturally used for recycling proteins. The drug is designed not to cross the placental barrier and therefore avoids entering the baby’s circulation. Initial laboratory data show that it will act rapidly to lower sFlt1 and importantly can be adjusted to the needs of each mother and baby to maximize the benefit for both. As a result of lowering sFlt1, damage to the mother’s blood vessels can be stopped, and potentially reversed, allowing the pregnancy to be prolonged until the baby can be safely delivered and start life with fewer complications.
References
https://www.who.int/news-room/fact-sheets/detail/pre-eclampsia