The FDA in recent years has been tough on cell and gene therapy makers, particularly when its comes to approving the labor-intensive and complicated manufacturing process. The agency now has its eyes set on Mesoblast's cell therapy candidate—and an early review doesn't look positive.
An FDA advisory committee on Thursday will question Mesoblast's ability to consistently manufacture effective doses of its Ryoncil (remestemcel-L), an investigational cell therapy for pediatric acute graft vs. host disease (GVHD), according to briefing documents posted online.
In those documents, the FDA argued that Mesoblast's pivotal phase 3 data for Ryoncil did not demonstrate that the therapy's proposed mechanism of action was actually linked to positive clinical outcomes. Ryoncil is composed of culture-expanded mesenchymal stromal cells (MSCs) that Mesoblast links to the reduction of pathogenic inflammation in GVHD patients.
"While (Ryoncil) and other MSC-based investigational products have demonstrated apparent immunomodulatory effects in in vitro experiments, the ability of (Ryoncil) to reduce inflammation as measured by inflammatory biomarkers in humans receiving the product has not been demonstrated," the FDA said.
Moreover, the FDA questioned Mesoblast's manufacturing of the therapy, saying other MSC-based therapies show "significant functional heterogeneity" between patients and that the biotech's expansion of MSCs in culture through donor banks could dilute doses over time.
Ryoncil is scheduled for a full FDA review Sept. 30. While advisory committee votes are non-binding, the FDA often follows its committees' opinions.
A Mesoblast spokeswoman could not be reached for comment by press time.
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