A Phase 1b/2a clinical trial led by Vall d’Hebron University Hospital has yielded groundbreaking safety and efficacy results with the drug ApTOLL, developed by the biopharmaceutical company aptaTargets, in patients with acute ischemic stroke in combination with endovascular therapy (EVT).

The final data was disclosed yesterday at the opening main plenary session of the International Stroke Conference (ISC) in Dallas, United States, by Dr Marc Ribó, an interventional neurologist at the Vall d’Hebron University Hospital, principal investigator of the Stroke Research group of the Vall d'Hebron Research Institute (VHIR) and Chief Medical Officer of aptaTargets, and Dr Macarena Hernández, Chief Scientific Officer of aptaTargets. The ISC is organised by the American Heart Association (AHA) and, from 8 to 10 February, it brings together leading stroke experts from around the world.

ApTOLL is a first-in-class neuroprotective drug that acts on the Toll-like receptor 4 (TLR4) with high specificity, blocking the inflammatory response that occurs after an ischemic stroke. The aptaTargets company developed it using innovative aptamer technology.

Stroke can be caused by a significant decrease in blood flow to the brain or by bleeding caused by a ruptured brain vessel. The first instance is an ischemic stroke, the most frequent type, which represents 85% of all strokes.

APRIL was designed as a multicentre, double-blind, randomised, placebo-controlled trial, in which 151 patients participated, these patients being men and women between 18 and 90 years of age, from 14 hospitals of reference in research and care for neurovascular diseases in Spain and France (*). The patients were randomly assigned to treatment with intravenous ApTOLL in two different doses or with a placebo. All patients in the study underwent mechanical thrombectomy, with or without a thrombolytic agent, according to the clinical guidelines.

The primary aim was to assess ApTOLL’s safety based on four variables: death, symptomatic intracranial hemorrhage, malignant stroke, and recurrent stroke. The secondary, efficacy-related aims included the final infarct volume after 72 hours, the US National Institutes of Health (NIH) stroke score at 72 hours, and the score on the disability assessment scale at 90 days.

ApTOLL met the primary safety endpoints, with the high-dose ApTOLL arm demonstrating a decrease in mortality from 18% to 5% compared to the placebo arm. Additionally, high-dose ApTOLL achieved statistical significance in both reduction of final infarct volume and improvement of the National Institute of Health Stroke Scale (NIHSS) measurements at 72 hours. Of note, 64.3% of patients receiving high dose ApTOLL scored 0-2 mRS at 90 days, which is considered functional independence, while only 46.3% of placebo patients scored 0-2 mRS.

The results obtained in the APRIL trial, led by Vall d'Hebron, “demonstrate ApTOLL’s neuroprotective effect after a stroke occurs, protecting the brain tissue at risk”, explains Dr Marc Ribó. Furthermore, “ApTOLL did not show any interactions with the drugs that are administered for ischemic stroke, meaning that it could be administered to most patients”, emphasizes Dr Ribó.

“We are extremely pleased with the excellent safety, tolerability and efficacy profile confirmed in the APRIL Phase 1b/2a trial. The massive patient benefit seen during the APRIL trial excites us for the future of acute ischemic stroke treatment. We plan to rapidly advance ApTOLL to a Phase 2b/3 clinical trial as well as to expand to other conditions”, comments David Segarra, CEO and co-founder of aptaTargets.

aptaTargets is currently preparing two new Phase 2a trials: the RaceToll trial, with the participation of VHIR, for use in ambulances where ApTOLL is administered to patients with suspected stroke, and the ApSTEMI trial to assess the effects of ApTOLL in acute myocardial infarction. ApTOLL has also shown promising preclinical results in haemorrhagic stroke and multiple sclerosis.

(*) Vall d’Hebron University Hospital in Barcelona (Spain), La Princesa University Hospital in Madrid (Spain), Germans Trias i Pujol University Hospital in Badalona (Spain), A Coruña University Hospital Complex (Spain), Bellvitge University Hospital in L'Hospitalet de Llobregat (Spain), Ramón y Cajal University Hospital in Madrid (Spain), Virgen del Rocío University Hospital in Sevilla (Spain), La Fe University Hospital in Valencia (Spain), Doctor Josep Trueta University Hospital in Girona (Spain), University Clinical Hospital of Valladolid (Spain), 12 de Octubre University Hospital in Madrid (Spain), Toulouse University Hospital (France), Hospital University Hospital of Lille (France) and Hôpital Fondation Adolphe de Rothschild (France).