Most members of the Oncologic Drugs Advisory Committee (ODAC) voted yes when asked whether the data support the efficacy of remestemcel-L in children with steroid-resistant graft-versus-host disease, boosting Mesoblast’s chances of receiving approval for the cell therapy from the US Food and Drug Administration (FDA) later this year. The FDA is due to make a decision by the end of next month.
Typically, the FDA goes along with the recommendations of its advisory committees, approving the drugs the experts support and rejecting those they vote down. However, the FDA has gone against its advisory committees on occasion in the past.
The briefing document prepared by the FDA to inform the ODAC discussion contains evidence that the agency has doubts about mesenchymal stem cell (MSC) therapy remestemcel-L. Manufacturing is a major theme of the FDA briefing document.
As the document states, Mesoblast defined critical quality attributes (CQAs) that, in the view of the company, are related to the potency and activity of the cell therapy. The FDA takes a different view.
In outlining the topics it wanted ODAC to discuss, the FDA said the product attributes “do not have a demonstrated relationship to the clinical performance of specific [drug product] lots.” The FDA sees that as a potential problem.
“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,” the agency wrote in its briefing document.
Elsewhere in the briefing document, the FDA said the CQAs identified by Mesoblast “may have some value in assuring a consistent manufacturing process.” However, the perceived lack of a “demonstrated relationship with clinical potency” left the FDA unsure whether Mesoblast’s CQAs are sufficient in isolation to “ensure adequate control of clinical effectiveness of individual lots.”
The FDA comments are part of a broader debate about MSCs. Studies have shown batch-to-batch variability in MSCs taken from different donors and expanded under different conditions.
In discussing how such concerns relate to remestemcel-L, the FDA cited its own 2014 paper on the challenges posed by MSCs. The authors of the paper concluded that while “many stakeholders portray MSCs as well understood, homogeneous cell types with predictable properties” there is in fact “significant diversity in how sponsors have defined, manufactured, and described MSCs in regulatory submissions to the FDA.”
