Spectral's PMX reduces mortality in septic shock trial

Executive Summary

• Spectral Medical and Vantive announced top-line results from the Phase 3 Tigris trial evaluating Polymyxin B Hemoadsorption (PMX) for endotoxic septic shock.
• The trial met its primary endpoint, showing a 95.3% posterior probability of benefit for PMX on 28-day mortality, with an adjusted odds ratio of 0.67.
• Secondary endpoints showed significant improvements, including a 99.4% posterior probability of benefit for 90-day mortality and a 17.4% absolute reduction in mortality at 90 days.
• Spectral plans to submit the final premarket approval (PMA) module to the FDA by the end of October 2025, with Vantive set to commercialize the therapy in the US and Canada upon approval.

Key Details

• Trial Design: Phase 3, randomized, controlled, multicenter study in the US.
• Population: 157 patients randomized 2:1 (106 PMX + standard care vs. 51 standard care alone).
• Inclusion Criteria: Adults with endotoxic septic shock defined by Endotoxin Activity Assay (EAA) level between 0.60 and 0.90, plus MODS >9 or SOFA >11.
• Primary Endpoint (28-day mortality):
  • Met prespecified goal: 95.3% posterior probability of benefit.
  • Observed 28-day mortality: 38.7% with PMX vs. 45.1% with standard of care (6.4% absolute difference).
  • Adjusted odds ratio: 0.67 (95% CI: 0.39 to 1.08).
  • Unadjusted absolute risk reduction: 8.3% (18% relative risk reduction).
• Key Secondary Endpoint (90-day mortality):
  • 99.4% posterior probability of benefit.
  • Observed 90-day mortality: 43.4% with PMX vs. 60.8% with standard of care (17.4% absolute difference).
  • Adjusted odds ratio: 0.54 (95% CI: 0.32 to 0.87).
  • Number Needed to Treat (NNT) to save one life at 90 days: 8.1.
• Statistical Methodology: Bayesian analysis incorporating data from the prior Euphrates trial (179 patients) alongside Tigris data.
• Regulatory Timeline: Spectral intends to submit the final PMA module (Module 3) to the FDA by the end of October 2025.
• Commercialization: Vantive holds exclusive distribution rights for PMX in the US and Canada and plans to commercialize both EAA and PMX upon FDA approval.
• Safety Profile: Consistent with historical use; over 360,000 units sold worldwide with no new safety signals reported.

Notable Quotes

• Dr. John Kellum, Chief Medical Officer, Spectral Medical: "We are pleased to announce that the fully adjusted Bayesian analysis met our prespecified goal of greater than 95-per-cent posterior probability of benefit for 28-day mortality... Furthermore our 90 days results provide important confirmation that benefits with PMX are persistent."
• Chris Seto, CEO, Spectral Medical: "The results from Tigris represent a significant milestone for Spectral as we continue advancing toward our goal of improving outcomes in endotoxic septic shock... These findings further support our planned FDA PMA submission and our efforts to make this therapy available to the patients who need it most."
• Professor Claudio Ronco, Director, IRRIV: "The results that we see today are a clear confirmation of what we observed more than 16 years ago with the Euphas trial... The benefit for survival from PMX becomes even more dramatic at 90 days where it exceeds 17 per cent."