The FDA has informed Spectral Medical Inc. more evidence is needed before it can approve the Toronto-based med tech's PMX cartridge, billed "as the first targeted treatment for patients with septic shock." Spectral CEO Paul Walker told BioWorld MedTech the FDA acknowledged an unmet need for therapies in septic shock patients who face a high risk of death, but that the company's analysis of this subgroup could not meet requirements contained in FDA guidance documents.
"While the FDA didn't give us the approval we might have wanted," said Walker, "it very clearly stated what we need to get there."
More data methods needed
In January, Walker identified a major stumbling block in a phase III pivotal trial during which PMX failed to show a significant improvement in the 28 day mortality rate for 450 patients with sepsis (See BioWorld MedTech, Feb. 1, 2018.) At the time, Walker said many patients were extraordinarily sick and unlikely to benefit from the treatment, or died before undergoing both PMX treatments.
Walker's hope is that the FDA will approve PMX for those patients in the U.S. suffering from sepsis and for whom "absolutely nothing else can be done." The first study of PMX showed a 42 percent relative risk reduction in 28 day mortality in a protocol subgroup of these seriously ill patients. However, the FDA preferred to see "prospective hypothesis-confirming data" from an entire study patient group, i.e., larger than the 194 patients in the first study treated for sepsis and septic shock.
"We just didn't have enough of the patients that we wanted in order to make it statistically significant," said Walker. "So we're going to have to add some more patients, but not in the difficult way we had to do the first time." With the number of patients "still to be agreed on," Walker said, "we don't think it's going to take all that long to come to agreement with the FDA or approximately 45 days."
The FDA encouraged Spectral to utilize mechanisms other than the randomized placebo-controlled trial used the first time and provided the company "with several less burdensome examples, including single arm studies, data obtained outside the U.S. and real world registries," said Walker. In addition, the FDA offered to discuss Spectral's proposal for further data collection in order to develop a mutually agreeable plan, a plan Walker anticipates will cost substantially less in money and time compared to the first trial.
Nothing like it
North American physicians currently treat sepsis using antibiotics and intravenous fluids to clear endotoxin through the liver and the kidneys. PMX is the first direct mechanism to remove endotoxin from the blood stream itself, passing the patient's blood through a polystyrene mesh-covered cartridge coated with the antibiotic Polymyxin-B, which traps and neutralizes the endotoxin, reducing inflammation and improving vascular function after two two-hour hemoperfusion sessions.
Just as important as the PMX cartridge's ability to neutralize endotoxin in the blood has been Spectral Medical's development of a test for the presence of the toxin. Higher levels of endotoxin detected using the Endotoxin Activity Assay (EAA) are correlated with both a risk for developing sepsis and a higher risk of mortality. Once the EAA measures the endotoxin, PMX removes it from the bloodstream.
Last month, Walker complimented investors in his publicly traded company [0.32CAD 0.06 (16.67 percent)] for their patience as it wends its way through the FDA approvals process. Are they still hanging in? You bet, said Walker. Everybody's been very supportive, he said. "On a day when the Dow Jones is down 350 points, we're down 20 percent, but we've been up as well as down. They're appears to continuing support among our major shareholders. We're closer than we've ever been, and we can get there."