Lumosa Therapeutics announced that phase 2b of LT3001 met its primary safety end point, with data indicating its potential for clinical benefit.
Data from a phase 2a trial (NCT04091945) of LT3001, an investigational, new chemical entity antioxidant small molecule drug developed by Lumosa Therapeutics, show that it met the primary safety end point, reporting no occurrence of symptomatic intracranial hemorrhage (sICH).1
Additionally, patients with baseline National Institutes of Health Stroke Scale (NIHSS) scores of 6 and greater showed pronounced neurological improvements, improving by 4 NIHSS points or greater, further suggesting the potential for clinical benefit up to 24 hours after the onset of stroke symptoms. The multicenter, double-blind, single-dose, randomized, and placebo-controlled study was conducted in the US and Taiwan, enrolling 24 participants to receive treatment with LT3001 or placebo within 24 hours after onset of acute ischemic stroke (AIS). Eligible participants were also ineligible to receive intravenous (IV) recombinant tissue-type plasminogen activator and/or endovascular thrombectomy.
Treatment with LT3001 was found to be safe with no evidence of increased risk of sICH observed within 36 hours of dosing. At day 90, investigators saw more subjects achieving excellent functional outcome, based on the Modified Rankin Scale score (mRS 0-1). Pronounced neurological improvement for those receiving LT3001 was observed at day 30, with 78% of patients with baseline NIHSS 6 or greater in the treatment group showing an NIHSS improvement of at least 4 points.1
“LT3001 represents a completely novel drug design in stroke treatment—combining thrombolytic and neuroprotective properties into a single molecule which may confer unique efficacy and safety properties permitting an extended treatment window,” principal investigator Thomas Devlin, MD, PhD, professor of neurology, University of Tennessee Health Science Center, said in a statement.1 “The results from this landmark study pave the way for future studies where LT3001 can be delivered intravenously within a 24-hour time window, either alone or in combination with mechanical stroke treatment. Such studies potentially represent the most impactful clinical studies in the history of stroke treatment.”
Participants in both treatment and placebo groups had a mean age of 62 years (standard deviation [SD], 13) and 68 years (SD, 9), respectively. Those receiving LT3001 had a median NIHSS score of 6 (range, 4-24) and a median time to treatment of 20 hours, compared to those receiving placebo, who had a median NIHSS score of 5 (range, 4-17) and a median time to treatment of 18.5 hours.
LT3001, an antioxidant dual-function molecule that is conjugated to a short peptide, works to effectively restore blood flow in an extended treatment window. The peptide initiates reperfusion while the small molecule aids in reducing reperfusion injury, and the combined effect is thought to improve treatment for patients with AIS, contributing to clot dissolving, antithrombosis, anti-inflammation, and antioxidation.
"Considering the extensive global unmet medical need for patients and their families battling stroke, we are extremely pleased by the outcome of this study," Rongjin Lin, PhD, president and CEO, Lumosa Therapeutics, said in a statement.1
In addition to LT3001’s phase 2a trial, Lumosa Therapeutics is also overseeing a 2-pronged development strategy in the US, Taiwan, and China. In an effort to expand the treatable population, phase 2b multidose trials will include patients with AIS who have no other treatment options, and a phase 2 trial will also study patients with AIS who are undergoing endovascular thrombectomy.
Another recent study, ANGIOCAT, a prospective, open clinical trial (NCT04001738), looked at patients with AIS caused by large vessel occlusion. Investigators concluded that direct transfer to angiography suite (DTAS) within 6 hours of symptom onset was safe, also leading to improved clinical outcomes when compared with direct transfer to computed tomography (DTCT) suite.
At the study’s conclusion, data showed an adjusted common OR of improvement of 1 point on the mRS score of 2.2 (85% CI, 1.2-4.1), favoring DTAS over DTCT (P = .009). To assess the indication of endovascular treatment, a total of 174 patients were randomized 1:1 to DTAS (n = 89) or conventional workflow (n = 85).2