There are currently no efficient drugs to treat SAH, despite numerous attempts, leaving patients with bleak prospects.
Emerging treatments
It has been tried to give neuroprotective agents to help the brain cells survive. A large number of such agents have been tested over the last several decades, but the outcome has been miserable. Procedures using stem cells have, unfortunately, not proved successful either. Studies with intracerebral stem cell transplantation in stroke could not be controlled and led to the formation of brain tumors. Administration of a calcium channel antagonist dilates the healthy part of the brain and reduces the flow from the ischemic region, causing even greater damage. Treatment with numerous vasodilators has also been tried. These studies also failed because the ischemic region already releases molecules that maximally relax brain arteries in the ischemic regions. Edvince has made a direct comparison of nimodipine versus EDV2209, which showed that only EDV2209 had a significant positive effect. During the period 2010–2020 the experimental drug clazosentan, an endothelin receptor blocker, was studied in several trials. Edvince made a direct head-to-head comparison between clazosentan and EDV2209 in which only the latter had a positive effect. At present, no new drugs for the treatment of SAH are being developed according to Global Data and clinicaltrials.gov.
A novel approach
The Edvince approach is unique and fundamentally different from all previous and unsuccessful attempts to treat stroke and SAH patients. It represents a paradigm shift in how we can improve therapy in stroke, with the potential to revolutionize the outcome.
It is crucial to maintain the blood vessels in the brain open, thereby allowing brain cells to receive oxygen and nutrients to prevent widespread and prolonged cell death in the brain.
The new approach takes the sequence of events that occur when a patient suddenly is hit by a stroke as its starting point.
What happens first when a person gets a blood clot in a brain artery, or in the event of bleeding hemorrhage (aneurysm rupture), is a critical drop in blood flow and a dramatic increase in intracranial pressure. The so-called shear stress (product of flow and pressure in the vessel)goes down locally and activates a group of proteins called integrins in the extracellular matrix of the brain artery walls. Once this happens, the integrins signal to the focal adhesion kinase, which in turn signals the “ras-raf-MEK-ERK” pathway which then turns on transcription and further on translation and production of contractile receptors and inflammation proteins. It takes several hours before this sequence of events is completed. This mechanism is designed by nature to protect the brain and limit tissue damage but unfortunately produces an overshoot that causes severe damage due to the fact that the brain circulation is based on end arteries. The deep understanding of the complex mechanisms evoked by stroke, followed by extensive testing of inhibitors at different stages of the cascade, led to a breakthrough discovery.
Inhibition of the MEK kinase provides the largest time window for therapy and was identified as a successful therapeutic target in SAH in order to maintain the blood vessels in the brain open and thereby reduce brain damage.
Extensive testing with the Company’s EDV2209 in advanced animal models for SAH has clearly demonstrated the therapeutic promise of the molecule and the novel approach which is now ready to be evaluated clinically in SAH patients.
Main properties
Improved chance of recovery and survival and decreased risk of brain damage
Reduction of healthcare costs, including surgery, intensive care and rehabilitation
Lower cost to society as less patients are permanently impaired and return to work
Opportunity to expand the market, as no effective drugs are available for SAH