At this year’s LINNC Paris Course (14–16 September, Paris, France and virtual), audiences heard that the ESCAPE-NEXT trial (sponsored by NoNO Inc.), which has already started enrolling patients and is expected to be completed by August 2022, could represent a major step towards the “dream” therapeutic approach of combining neuroprotection and endovascular therapy (EVT) for acute ischaemic stroke. This viewpoint was presented by Mayank Goyal, director of imaging and endovascular treatment in the Calgary Stroke Program at the University of Calgary’s Hotchkiss Brain Institute (Calgary, Canada).
Goyal began by recapping results from the ESCAPE-NA1 study—a multicentre, randomised controlled trial that assessed the safety and efficacy of the neuroprotective agent nerinetide (NA-1; sponsored by NoNO Inc.) in treating acute ischaemic stroke. A subgroup analysis of the trial’s results found that this drug improved clinical outcomes—demonstrated by a 10% increase in modified Rankin Scale (mRS) scores of 0–2 at 90 days—in patients who did not also receive intravenous tissue plasminogen activator (IV-tPA) therapy, or “alteplase”, but this improvement was not seen in patients who received concurrent alteplase and nerinetide treatments.
He also noted that another “interesting journey” is underway in trials investigating the effectiveness of IV-tPA itself, including the recent presentation of results from the SWIFT-DIRECT trial at the 7th European Stroke Organisation Conference (ESOC 2021; 1–3 September, virtual). While he added that an upcoming meta-analysis of this trial and others may uncover some benefit to EVT alone in certain subgroups, it is likely that the overall status quo of giving stroke patients IV-tPA plus EVT will remain unchanged by these findings.
Goyal relayed that presentation of ESCAPE-NA1’s findings to the US Food and Drug Administration (FDA) has now led to a second trial, dubbed ESCAPE-NEXT, being devised to further assess nerinetide. He claimed that this trial is similar in many ways to the original study, but only includes patients who are not concurrently receiving IV-tPA. Should ESCAPE-NEXT confirm the results of ESCAPE-NA1 in patients not receiving alteplase, combining the data should “dramatically reduce” the likelihood of false positive results, he added. The trial is currently ongoing across 88 global sites and has enrolled 81 patients already. The maximum enrolment in ESCAPE-NEXT will be 1,020 patients, with an interim analysis scheduled after enrolment reaches 510 patients.
“Obviously, I have no idea how this story will play out—but, let us jump forward two years and say that the results from the trial are positive,” Goyal proposed. “For the first time, we will have a neuroprotective agent approved for human use.” He went on to note that this would be a major step forward, as a total of 1,073 of these drugs have been tried and have ultimately failed to date, and may stimulate a significant increase in investment as well as leading to many other new drug products being trialled as a result.
“So, as a conclusion, are we on the cusp of a revolution? I hope so, although we will find out for sure in two years’ time,” Goyal stated. “The dream is that—if a stroke is detected at a patient’s house—we give them nerinetide as they are being transported to receive EVT.” He further concluded that it is important to prepare for the practical implications of the ESCAPE-NEXT results because, if nerinetide is approved, physicians will need to consider its role under the context of the already-approved IV-tPA in stroke care more generally. In a discussion following his presentation, Goyal also noted that, if the trial produces positive results and nerinetide is approved for use in stroke, it will likely be used to treat patients who do not qualify for IV-tPA, or it will be given ahead of IV-tPA.