Cellular medicines developer Mesoblast Limited’s (ASX:MSB) allogeneic mesenchymal stem cell (MSC) product candidate Remestemcel-L will be evaluated in a randomised, placebo-controlled trial in 240 patients with acute respiratory distress syndrome (ARDS) caused by coronavirus infection (COVID-19).
This multi-centre Phase 2/3 trial will be conducted as a public-private partnership in a collaboration with the Cardiothoracic Surgical Trials Network (CTSN), which was established by the United States National Institutes of Health’s National Heart, Lung and Blood Institute (NHLBI) as a flexible platform for conducting collaborative trials.
Chief Executive, Dr Silviu Itescu, said Mesoblast holds an Investigational New Drug (IND) Application from the United States Food and Drug Administration (FDA) for use of Remestemcel-L in the treatment of patients with COVID-19 ARDS, and will provide investigational product for the trial.
“This significant public-private partnership is a prime example of how the combined resources of industry and government can be leveraged to evaluate in a most efficient and rigorous manner the potential of innovative therapies to make a meaningful difference to patient outcomes,” Dr Itescu said.
ARDS occurs due to an excessive immune response against the COVID-19 virus in the lungs, with the inflammatory cytokines produced by the immune cells (cytokine storm) destroying the lung tissue. These inflammatory cytokines also can cause damage to other organs such as liver, kidney, and heart.
Mesoblast Chief Medical Officer, Dr Fred Grossman, said Remestemcel-L is being developed for various inflammatory conditions, and is believed to counteract the inflammatory processes implicated in these diseases by down-regulating the production of pro-inflammatory cytokines, increasing production of anti-inflammatory cytokines, and enabling recruitment of naturally occurring anti-inflammatory cells to involved tissues. The safety and therapeutic effects of Remestemcel-L intravenous infusions have been evaluated in over 1,100 patients in various clinical trials.
Remestemcel-L was successful in a Phase 3 trial for steroid-refractory acute graft versus host disease (aGVHD) in children, a potentially fatal inflammatory condition due to a similar cytokine storm process as is seen in COVID-19 ARDS. Additionally, a post-hoc analysis of a randomized, placebo-controlled study in 60 patients with chronic obstructive pulmonary disease demonstrated that Remestemcel-L significantly improved respiratory function in patients with the same elevated inflammatory biomarkers that are also observed in patients with COVID-19 ARDS. Together, these outcomes provide the rationale for evaluating Remestemcel-L in patients with COVID-19 ARDS.
“The mortality rate in moderate to severe ARDS due to COVID-19 can be as high as 80%,” Dr Grossman said.
“Remestemcel-L has demonstrated safety, efficacy and significant survival benefit in aGVHD where inflammation is at the core, similar to ARDS from COVID-19.
“The mechanism of action of Remestemcel-L demonstrated in aGVHD supports the evaluation of Remestemcel-L to safely tame a similar cytokine storm in the lungs that leads to the high mortality in patients with COVID-19.”
