First-in-Human Phase 1b/2a Trial Shows Safety with MEK 1/2 Inhibitor EDV2209 as A Novel Treatment for Spontaneous Subarachnoid Hemorrhage

We report findings from a Phase 1/2a clinical trial (EUCT No. 2024-514590-22-00, STOP-DCI), an interventional, randomized, double-blind, placebo-controlled, multiple ascending-dose, first-in-human trial to determine safety and evaluate clinical outcome for the MEK 1/2 inhibitor EDV2209 in patients with severe spontaneous subarachnoid hemorrhage (SAH). In Phase 1b (N = 11), three cohorts received a single intracerebral ventricular (ICV) bolus (8.55 µg, 17-28.5 µg). In Phase 2a (N = 16), two cohorts were given three ICV injections of 28.5 µg EDV2209 or placebo over 18 h, beginning within 8 h of SAH onset.The study found an equal distribution of adverse events between treatment and placebo with no treatment-associated safety concerns. Outcomes and mortality were as expected or better for patients with severe SAH in the patients treated with EDV2209. Pharmacokinetics were reproducibly stable in the CSF with no detectable levels of EDV2209 in plasma.Treatment with EDV2209 was considered safe and was interpreted to provide potential benefit for improving patient outcome following severe SAH. These results provide a rationale to continue with a Phase 2b / 3 study powered to determine efficacy as well as safety.