TORONTO – The Toraymyxin (PMX) hemoperfusion cartridge developed by Toronto’s Spectral Medical Inc. and used successfully to treat patients during the avian and swine flu pandemics is being eyed to help COVID-19 patients in Canada. Specifically, an emergency interim order from Health Canada expands its use to include treatment of COVID-19 patients with high levels of endotoxin in their blood and in acute respiratory failure.
“This is for end-stage patients who are in septic shock,” Paul Walker, Spectral’s president and CEO, told BioWorld. “We know that some COVID patients are endotoxemic, and that, in those circumstances, there may be a good use for our hemoperfusion adsorption cartridge by taking endotoxin out of the bloodstream.”
Shutting down a deadly toxin
COVID-19 first attacks the lungs, so a patient is placed on a ventilator. Many patients subsequently end up on dialysis due to renal failure. It’s a subset of these patients that can have the toughest time medically because of high levels of endotoxin in their blood, causing acute respiratory distress syndrome and cardiovascular failure.
Spectral successfully detected increased levels of endotoxin activity in Asia, Italy and the U.S. using an assay approved by the U.S. FDA in 2003. The next step, Walker explained, was to develop a therapy, passing the patient’s blood through a polystyrene mesh-covered cartridge bonded with the antibiotic Polymyxin-B that traps and neutralizes the endotoxin. This reduces inflammation and improves vascular function, said Walker.
“This is a direct blood filter. Blood containing high levels of endotoxin goes in one end; the cartridge then selectively removes endotoxin from the bloodstream and returns it to the patient.”
According to bench test results, each cartridge can remove up to 20 micrograms of endotoxin. Of note, 300 peer-reviewed papers assessed the PMX’s impact on 10,000 patients around the world and found a serious adverse event rating of less than 0.1%. Approved for use in Japan, Europe and now Canada, the goal, said Walker “is to get it approved in the United States.”
Cutting endotoxin may help COVID-19 patients
Two clinical trials are instructive in the use of Spectral’s PMX in the fight against COVID-19. In 2016, the phase III Euphrates trial failed to show a significant improvement in the 28-day mortality rate for 450 patients with sepsis. However, a clinically meaningful 10% reduction in 28-day mortality for a subset of end-stage patients showed promise for the sickest of the sick – those for whom “absolutely nothing else can be done,” Walker said at the time.
Two years later, the Tigris study, a prospective, open-label analysis of 150 patients, was announced. The hope is to see a reduction in the 28-day mortality using two PMX hemoperfusion cartridges over a 24-hour period vs. standard of care.
“Our hope for that specific group of very ill patients with septic shock and a treatable level of endotoxin in their blood is that we can save their lives,” said Walker. “That hope extends more immediately to patients with COVID-19 under Canada’s emergency interim order.”
Not only does PMX provide the opportunity to save lives, said Walker, it also could relieve the stress on scarce critical care devices, such as ventilators.
Baxter jumps in
Spectral Medical revealed Feb 4 an exclusive agreement with Deerfield, Ill.-based Baxter International Inc. to distribute the blood filter in the U.S. and Canada. In addition to gaining access to many hospitals, Spectral will receive a series of milestone payments, including an up-front rights payment from Baxter of $5 million.
Attention now swings to results from Spectral’s Tigris trial, which is expected to be completed in late 2021. Baxter plans to commercialize the PMX filter and assay following successful completion of the trial and subsequent FDA approval. Spectral already has made its PMX cartridge available to more than 200,000 patients in Japan and Europe.