Randomized phase 2b dose-escalation trial of stem cell therapy with laromestrocel for aging frailty.

Laromestrocel significantly improved 6-minute walk test distance compared to placebo at month 9.

• The improvement was 63.4 m (95% CI: 17.1–109.6 m; p = 0.0077) at month 9.
• At month 6, improvement was 41.3 m (95% CI: -2.4–84.9 m; p = 0.0635), which did not reach statistical significance.
• The 6MWT was the primary endpoint of the trial.
• Improvements were described as 'clinically meaningful' and 'dose- and time-dependent.'

The trial enrolled 148 ambulatory individuals with frailty in a randomized, dose-finding design.

• The study was registered as ClinicalTrials.gov #NCT03169231 with N = 148.
• The trial was a randomized phase 2b dose-escalation design.
• Participants were ambulatory individuals with frailty.
• The intervention used human bone marrow-derived allogeneic mesenchymal stem cells (MSCs) branded as laromestrocel.

Increased 6MWT distance correlated with PROMIS Physical Function score.

• The correlation between 6MWT improvement and PROMIS Physical Function score was noted as a key secondary finding.
• PROMIS Physical Function is a patient self-reported outcome measure.
• This linkage supports the clinical relevance of the 6MWT improvement observed.

Increasing doses of laromestrocel were associated with decreases in soluble (degraded) TIE2 levels.

• Soluble TIE2 is the degraded form of tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (TIE2), the cognate receptor for the angiopoietins.
• The decrease in soluble TIE2 was dose-dependent.
• Soluble TIE2 was identified as a potential biomarker of laromestrocel responsiveness.
• This finding suggests a mechanistic pathway through which laromestrocel may exert its effects.

Frailty is described as a syndrome lacking effective therapies that decreases healthspan in older individuals.

• The paper characterizes frailty as associated with hypomobility and other features of aging.
• No currently approved or effective therapies for frailty were identified in the background.
• The study positions laromestrocel as a candidate therapy for this unmet medical need.