Cell Therapy News/Articles, page-8825

Great find Chau

He wasn't joking when he said this:

"This missing link between MSC functional attributes [eg:“potency”] and clinical outcomes remains the Achilles heel of marketing approval in international regulatory jurisdictions."

MOA was mentioned as a limiting factor for approval 16 times in the FDA CRL for SR-GvHD, in fact this is their statement is at the top of the CRL

"FDA’s position is that the product attributes the Applicant has identified as related to potency and activity, however, do not have a demonstrated relationship to the clinical performance of specific DP lots, and that the product’s proposed immunomodulatory mechanism of action has not been demonstrated in vivo in study subjects receiving remestemcel-L. Without a demonstrated relationship with clinical effectiveness and/or in vivo potency/activity, controlling these CQAs may not be sufficient to ensure the manufacturing process consistently produces remestemcel-L lots of acceptable quality"

From our learned friend's Dr Galipeau's peer reviewed paper below - hopefully SI can tuck this one under his wing and bring it out when he next chats to the FDA:

"This concise review examines the relationship between culture-adapted MSC and their effect on macrophage polarization as a cornerstone of pharmaceutical effect in resolving inflammatory and tissue injury syndromes in vivo. The contribution of MSC-borne chemokines, CCL2 in particular, and the recently recognized biological role of CC/CXC chemo-kine heterodimers found in MSC secretome as potent agents of immune modulation provide novel insights in identifying MSC cellular attributes predictive of clinical response"