Results – Completed phase 1b/2a study
Research breakthrough confirmed – strong clinical efficacy signal in Phase 2a trial
Data from phase 2a study
If the treatment’s efficacy can be confirmed in a larger study, it could save many patients from a life of significant motor and cognitive impairment, as well as a life dependent on healthcare and assistance, with no ability to work.
Background
Subarachnoid Hemorrhage (SAH):
Annual global incidence: ~600,000 cases.
Aneurysmal rupture causes bleeding into the subarachnoid space, rapidly increasing intracranial pressure.
Despite advances in neurosurgical and intensive care, mortality in severe aSAH (acute SAH) remains 23%, and up to 50% of survivors suffer long-term neurological deficits.
Pathophysiology:
Following rupture, the initial hemorrhage results in local blood accumulation and occasionally in a vasospasm. The rupture also causes a rise in intracranial pressure (ICP) which triggers secondary ischemic injury through a transcriptional event in large and small arteries causing global vascular constriction due to increase in number of vascular contractive receptors, and of inflammation molecules.
These secondary events a few days after the rupture of the aneurysm are associated with reduced cerebral perfusion which contributes to delayed cerebral ischemia (DCI), a major determinant of outcome.
The DCI is also associated with blood–brain barrier disruption, edema, and metabolic crisis.
Currently there are no effective and specific pharmacological treatments to abort the molecular sequel of DCI.
EDV2209 is designed to target the early pathophysiological cascade activated following a severe aSAH, preserving microvascular function and protecting viable brain tissue.
EDV2209 – Drug product
Proprietary drug product developed by Edvince AB.
Originates from research in neurovascular protection at Lund University, led by Professor Lars Edvinsson.
Designed for treatment of acute cerebrovascular injury following subarachnoid hemorrhage (SAH).
Current medication works by blocking activation (phosphorylation) of MEK1/2 and ERK1/2 which inhibits transcription of genes that produce elevated levels of ETB, AT1, 5-HT1B, TxA2 and P2Y6 contractile receptors in the cerebral artery smooth muscle cells as well as of inflammation molecules and proteins associated with BBB activity.
Mechanism of action
Targets the early pathophysiological cascade after aneurysmal rupture initiated by the sudden increase in ICP which starts a molecular process in the artery walls.
Stabilizes vascular function and reduces endothelial dysfunction.
Improves microcirculatory flow and oxygen delivery to at-risk tissue.
Mitigates oxidative stress and inflammation, reducing DCI.
Through its effect on the vascular transcriptional response, increased vasoconstriction is prevented, which would otherwise lead to limited oxygen supply to brain cells causing reduced brain cell activity and damage. MEK1/2 inhibition stops the activation of this cascade and is not neuroprotective per se.
Safety / Toxicity in humans
Evaluated in a Phase 1b/2a clinical trial in aSAH patients, with no major safety concerns.
Well tolerated across all tested dose levels; no treatment-related serious adverse events observed.
Pharmacokinetic data support repeat dosing during the acute phase.
Safety findings consistent with preclinical toxicology and previous clinical exposure to EDV2209.
At present, Edvince has treated 27 patients without any safety concerns related to the IMPD (EDV2209).
Contact
Medicon Village
223 81 Lund. Sweden
info@edvince.com