These findings, which were consistent over three different domains of clinical outcome in patients who did not receive alteplase were bolstered further by pharmacokinetic data from trial participants showing that patients who were treated with alteplase had an approximately 60% reduction in plasma nerinetide levels as compared with patients who did not receive alteplase. Separate non-clinical studies by NoNO Inc. have shown that prior alteplase administration can lower plasma nerinetide concentrations because alteplase activates plasmin, an enzyme that cleaves nerinetide.
Nerinetide had a safety profile comparable to placebo.
“Compared to placebo, almost 20 per cent more patients who received nerinetide along with endovascular treatment, but did not receive alteplase, recovered from a devastating stroke – a difference between paralysis and walking out of the hospital,” said Michael Hill, M.D., one of the ESCAPE-NA1 global coordinating investigators. “In the patients who received both drugs, the alteplase negated the benefits of the nerinetide.
“The study provides evidence of the validity of a biological pathway that protects brain cells from dying when they are deprived of blood flow. Nerinetide targets a protein in brain cells called PSD-95 which links the deprivation of blood flow to signals that mediate the final stage of the brain cell’s life. It does so by stopping the production of the free radical nitric oxide within the cell. Images of patients’ brains from the study show the expected size of the damage from the stroke is reduced when nerinetide is administered and EVT is performed among patients not concurrently receiving alteplase. We really believe this is a new scientific observation. There is evidence nerinetide promotes brain cell survival, offering neuroprotection until we can extract the clot. It opens the door to a new way of treating stroke.”
NoNO Inc. are conducting further studies of nerinetide including an ongoing pivotal trial called FRONTIER.
“FRONTIER could provide important confirmation of the effects of nerinetide seen in ESCAPE-NA1, as well as its effectiveness when it is given before alteplase,” said Dr. Tymianski. “Patients in FRONTIER, who are enrolled with suspected strokes by paramedics in the field, are treated with nerinetide in the ambulance prior to arrival to the stroke hospital and before alteplase would be administered. This should allow nerinetide to reach neurons before it is impacted by alteplase. FRONTIER may provide evidence for the benefits of nerinetide in even broader stroke populations, and complements ESCAPE-NA1 as we seek to provide future patients with opportunities for a better life.”