The trial shows that the drug decreased the mortality rate of stroke from 19% to 11%.
Toronto-based NoNO announced results from the pivotal Phase III ESCAPE-NA1 trial of intravenous nerinetide in patients with acute ischemic stroke who were chosen to undergo endovascular thrombectomy. The drug, without previous administration of alteplase (Genentech’s Activase), provided medically important improvements in the patients. The results were simultaneously presented at the International Stroke Conference in Los Angeles and published in The Lancet.
“Results from the ESCAPE-NA1 Phase III clinical trial are scientifically groundbreaking because it demonstrates important effects of a pharmaceutical therapy in an acute stroke population treated for up to 12 hours after stroke symptom emergence,” said Michael Tymianski, founder, president and chief executive officer of NoNO. “Although patients who had prior administration of alteplase did not appear to benefit, likely due to a reduction of nerinetide plasma levels when alteplase was given first, we are excited by the magnitude and consistency of date in the pre-specified subgroup that were not treated with alteplase as well as the potentially long therapeutic window of nerinetide after stroke onset. In addition, nerinetide was well tolerated.”
The trial shows that the drug decreased the mortality rate of stroke from 19% to 11%.
An ischemic stroke, the most common form, is the result of a clot in blood vessels in the brain. It can kill 2 million brain cells every 60 seconds.
Nerinetide blocks PDS-95, a destructive protein, which during a stroke initiates a cascade of biochemical activity that produces nitric oxide (NO). NO is a free radical that destroys neurons while the blood supply is blocked. This also explains the company’s name, NoNO.
The trial lasted two years and included more than 1,000 patients and almost 50 stroke hospitals globally. Patients received nerinetide along with endovascular treatment, a relatively new treatment for stroke. The procedure is also called a thrombectomy, and involves inserting a catheter through the groin that is then guided through blood vessels into the brain. A device in the catheter captures and removes the blood clot.
“The thrombectomy is enabling for this drug,” said neurologist Michael Hill, who led the study with neuroradiologist Mayank Goyal. “If we had tested this drug five years ago without the thrombectomy, we would have had a negative result.”
The only other drug on the market for treating a stroke is alteplase, nicknamed Brain-O, which breaks up the clot. But there are limitations on the use of the drug, with the results that is only appropriate in about one out of eight ischemic stroke patients.
In part of the trial, nerinetide was dosed in stroke patients with alteplase. In the other part of the trial, patients who were not eligible for alteplase received only nerinetide. Thrombectomies were performed on all the patients.
In patients who received only nerinetide with the thrombectomy, 19% more patients recovered. “It’s the difference between paralysis and walking out of the hospital,” Hill said.
The trial supplies evidence that nerinetide preserves brain cells and their structure until the clot can be removed. Hill notes that prior to thrombectomy, about three out of 10 major stroke patients would recover spontaneously enough to live independently, but seven out of 10 would be disabled or dead. After thrombectomy’s introduction, five in 10 stroke patients can live independently.
And with the evidence from the nerinetide study, that number can likely be six in 10.
Hill told The Globe and Mail, “When I started dealing with stroke, it was only two patients out of 10. The evolution of what we’ve seen over the last 10 years is unbelievable. It’s visibly changing what it means to have a stroke.”
The company is running more studies on nerinetide, including a pivotal trial dubbed 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,” Tymianski said. “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.”
