Stem Cell Therapy Benefits Patients with Severe Inflammation, Trial Data Show
Remestemcel-L, Mesoblast’s lead candidate stem cell therapy for inflammatory diseases, improves lung function and exercise capacity in people with chronic obstructive pulmonary disease (COPD) and a high degree of inflammation, data from a post-hoc analysis of a Phase 2 trial show.
Findings were presented in an oral presentation at the 2020 International Society for Cell & Gene Therapy (ISCT) annual meeting, which took place virtually May 28–29.
Remestemcel-L contains around 100 million of adult-derived mesenchymal stem cells (MSCs), cells that are able to give rise to nearly all tissues found in the body, including bones, muscles, and connective tissue.
MSCs are also thought to have strong immunomodulatory and anti-inflammatory properties, able to counteract the overactivation of the immune system and excessive inflammation. For that reason, remestemcel-L is being investigated as a potential therapy for acute graft-versus-host disease (GVHD, a potential life-threatening complication of bone marrow transplant), and several other autoimmune and inflammatory diseases, including Crohn’s disease and COPD.
During ISCT, Mesoblast presented a post-hoc analysis of a Phase 2 trial (NCT00683722) that investigated the safety and efficacy of multiple doses of remestemcel-L in patients with moderate-to-severe COPD.
The trial, which concluded in August 2010, enrolled 62 patients who were randomly assigned to either four monthly intravenous infusions of remestemcel-L, containing about 100 million MSCs or to a placebo that lacked MSCs.
Patients were then monitored for two years. During follow-up, they completed several tests designed to assess their lung function and exercise capacity.
Lung function was evaluated based on two parameters: forced vital capacity (FVC), which measures the total amount of air a patient is able to exhale after a deep breath; and forced expiratory volume in one second (FEV1), which measures the total amount of air exhaled in one second after a deep breath.
Exercise capacity was assessed by the six-minute walk distance (6MWD) test, which looks at total distance a patient is able to cover while walking for six minutes.
The goal of this post-hoc analysis was to compare the effects of remestemcel-L relative to the placebo in patients who had high blood levels of the inflammatory marker C-reactive protein (CRP; 2 mg/mL or more) — a protein whose levels rise in the presence of inflammation — to patients with low blood levels.
Compared with placebo, remestemcel-L led to significant improvements in both lung function and exercise capacity measures in patients with high C-reactive protein levels at day 120 (about four months post-treatment).
Investigators also found these improvements to be more pronounced in those who had the highest blood levels of CRP (4 mg/mL or more), suggesting remestemcel-L is particularly beneficial for those with extensive inflammation. Among these patients, both FVC and FEV1 increased from baseline (study start), while they decreased in the placebo group. 6MWD also rose by a mean of 52 meters (about 171 feet) from baseline, while it dropped by about 3 meters (almost 1 foot) in those given a placebo.
“The correlation between highest CRP levels and greatest degree of response to remestemcel-L suggests that the inflammatory component of the lung disease may trigger and be amenable to the immunomodulatory effects of treatment with remestemcel-L in patients with acute inflammatory conditions,” Fred Grossman, chief medical officer of Mesoblast, said in a press release.
“Since recurrent hospitalization rates and mortality in COPD are associated with both high levels of CRP and progressive decline in the six-minute walk test, these results suggest that remestemcel-L could provide longer-term benefits for COPD patients with high levels of inflammation,” Grossman added.
These findings also “provide a compelling rationale” for the new Phase 3 trial (NCT04371393) assessing remestemcel-L’s safety and efficacy in about 300 people with acute respiratory distress syndrome (ARDS) associated with COVID-19, he said.
Top-line findings from this trial are expected in April 2021.