April 24, 2020 – By Mark Terry – Melbourne, Australia and New York-based Mesoblast Limited announced that in a study of COVID-19 patients with moderate to severe acute respiratory distress syndrome (ARDS), there was 83% survival with two intravenous infusions of the company’s experimental allogeneic mesenchymal stem cell candidate Ryoncil (remestemcel-L).
Ryoncil is currently under priority review by the U.S. Food and Drug Administration (FDA) for steroid-refractory acute graft versus host disease (acute GVHD). It is also under development for other rare diseases.
In the study, nine out of 12 patients, or 75%, successfully came off ventilators within 10 days, and the 83% figure refers to the patients coming off the ventilator in the first five days. Seven of the patients have been discharged from the hospital. All the patients had received other experimental therapies before receiving remestemcel-L. They were treated under an emergency Investigational New Drug (IND) application or via expanded access protocol at New York City’s Mt. Sinai hospital.
By comparison, Mesoblast indicated that only 9%, or 38 out of 445 COVID-19 patients on ventilators at a major referral hospital network in New York City were well enough to come off ventilator support when treated with standard of care during the same period in March and April 2020. At a second major referral hospital network in New York City, there was only 12% survival (38 out of 320) among ventilator-dependent COVID-19 patients. These poor survival rates were consistent with earlier published research out of China where mortality rates greater than 80% were reported in patients with COVID-19 and moderate to severe ARDS.
“The remarkable clinical outcomes in these critically ill patients continue to underscore the potential benefits of remestemcel-L as an anti-inflammatory agent in cytokine release syndromes associated with high mortality, including acute graft versus host disease and COVID-19 ARDS,” said Silviu Itescue, chief executive officer of Mesoblast. “We intend to rapidly complete the randomized placebo-controlled Phase II/III trial in COVID-19 ARDS patients to rigorously confirm that remestemcel-L improves survival in these critically ill patients.”
Mesoblast’s technology focuses on proprietary mesenchymal lineage adult stem cells (MLCs) found in multiple tissues where they play a role in maintaining tissue health. They are rare cells originating around the blood vessels that respond to signals linked to tissue damage, and which secrete molecules that promote tissue repair and modulate immune responses.
Remestemcel-L is believed to counteract the inflammatory processes in inflammatory conditions by down-regulating the production of pro-inflammatory cytokines and increases production of anti-inflammatory cytokines. The safety and efficacy of the therapy has been evaluated in more than 1,100 patients in several clinical trials, including the successful Phase III trial for steroid-refractory aGVHD in children. A post-hoc analysis of a study in 60 patients with chronic obstructive pulmonary disease (COPD) showed the therapy significantly improved respiratory function in patients with the same elevated inflammatory biomarkers seen in patients with COVID-19 ARDS.
Fred Grossman, the company’s chief medical officer, stated, “There is a significant need to improve the dismal survival outcomes in COVID-19 patients who progress to ARDS and require ventilators. We have implemented robust statistical analyses in our Phase II/III trial as recommended by the U.S. Food and Drug Administration (FDA) in order to maximize our ability to evaluate whether remestemcel-L provides a survival benefit in moderate/severe COVID-19 ARDS.”
The FDA cleared the company’s New Drug Application to use remestemcel-L in COVID-19 ARDS on April 5.