Early-stage study results from the multi-center MUST-ARDS trial show the ex-vivo adult progenitor cell-expanding therapy is capable of improving 28-day mortality, care burden, and overall safety in patients with ARDS.
Early-stage study results from the multi-center MultiStem Therapy in Acute Respiratory Distress Syndrome (MUST-ARDS) trial show the ex-vivo adult progenitor cell-expanding therapy is capable of improving 28-day mortality, lessened ventilator and ICU burden, and overall safety in patients with ARDS.
In an interview with MD Magazine® after presenting the phase 1/2 results at the American Thoracic Society (ATS) 2019 International Meeting in Dallas, TX, Dr. Geoff Bellingan, intensive care consultant for University College London Hospital, kept measure while discussing the findings and next steps for clinical development.
That said, excitement surrounding the potential pulmonary multi-stem cell therapy was still palpable.
MD Mag: What were the critical findings of the MUST-ARDS trial for MultiStem Cell Therapy?
Bellingan: The critical findings were this was really a phase 1-2 study, so it was essentially a dose and safety study. And the first thing: we met all our primary endpoints on safety, which is fantastic. But we also found some intriguing2 and exciting early indicators that survival ventilator-free days and ICU-free days may also have a positive trend.
The really exciting bit is we've predefined a more severe group of ARDS, and in there the trends were reinforced. And indeed, the ventilator-free days, the ICU-free days, and the mortality was a little more explicit. But remember, it's a small study and really was a dose-finding and safety study primarily.
What is the current state of stem cell therapy in ARDS care?
So this is really important. ARDS mortalities have come down nicely—it was 90% when I was first training in critical care, it's come down to 30% to 40%, but has really stuck at that level for quite a while. So the improved care we're giving, the improved support we're giving, has done marvels. The low tidal volume ventilation has helped, but apart from low tidal volume and maybe prone, we haven't got a new treatment for ARDS.
We tried many, many magic bullets to hit this pathway or that pathway, and we've not really achieved that. The point about stem cells is they are broad, they are pleiotropic, they will affect regeneration repair. They'll move your macrophages from an m1 to an m2 phenotype. They may promote angiogenesis, they may do a variety of actions, and that's exactly what ARDS is. It’s a heterogeneous condition, and probably needs a variety of actions.
So the excitement is we may have a broad treatment for a heterogeneous condition. Good work in animal models to understand that the model should work; good work in large animal models to understand that doses are okay; good work in human ex vivo lung preparations to confirm that. But when our needs move into patients, the first issue with patients is you're giving maybe 900 million cells into the bloodstream. They float through the lungs. Are you giving 900 million pulmonary emboli?
So to make sure that it was safe. And the study was designed primarily to look at the first 4 hours of safety, and it passed all that with flying colors. The excitement was then the 28th day, and we'll see what happens at 90 and 360.
The study, "Primary Analysis of a Phase 1/2 Study to Assess MultiStem® Cell Therapy, a Regenerative Advanced Therapy Medicinal Product (ATMP), in Acute Respiratory Distress Syndrome (MUST-ARDS)," was presented at ATS 2019.