Yep whytee – that is probably the nub of it. In the ODAC...

Yep whytee – that is probably the nub of it.

In the ODAC briefing document (p. 20) the FDA stated:

“The time-to-event measures, such as OS (see Applicant's Briefing Document Section 5.3.3), are difficult to interpret in a single-arm trial and will not be discussed further.”

OS in the context of this single arm trial at 4 years will just as persuasive to the FDA as OS was at 1 year. Or as it would be at 20 years.

The FDA have consistently stated to MSB that they want a randomised controlled trial -

“Despite the overwhelming ODAC vote, the FDA recommended that we conduct at least one additional randomized, controlled study in adults and/or children to provide further evidence of the effectiveness of remestemcel-L for SR-aGVHD.”

Why does the FDA want a randomised controlled trial? It wants a trial “to provide confirmatory evidence of the efficacy of the study agent in the treatment of GVHD.”

Why was the MAGIC study rejected the FDA? “The MAGIC cohort comparison was not part of the original statistical analysis plan (SAP) for Protocol MBS-GVHD001 and there was no a priori specified hypothesis.”

Look at the announcement here. Spot a p-value anywhere? No. For the simple reason there was no pre-specified hypothesis tested. Ergo … there is no confirmatory evidence generated.