MSB to dispute FDA finding in Type A meeting, page-340

This is the questionable part. The FDA have questions about the validity of the null hypothesis and because of this they think it invalidates the "adequate and well controlled" requirement of the single-arm trial. All pieces of evidence seems to suggest the FDA are wrong, so I guess it comes down to how the FDA and Mesoblast can both come to an agreement, bearing in mind that Mesoblast needs to convince the FDA. The FDA justified their stance in their briefing documents, whereas Mesoblast did so during the ODAC meeting.

Failing this, Mesoblast can request the FDA waive the criteria of an "adequate and well controlled" study as mentioned in my previous post:

"The FDA is empowered to waive “any criteria of an adequate and well-controlled study” if an adequate substitute is offered or if compliance with the requirement is unnecessary or impossible.25 Some applicants cure deficiencies by presenting colorable arguments that the FDA’s requirements were impractical or unnecessary. The FDA may grant a waiver if it finds the applicant’s compliance with the requirement is not necessary or not achievable, the applicant has satisfied the requirement through an acceptable alternative, or “[t]he applicant’s submission otherwise justifies a waiver.” While the FDA does not dispense waivers lightly, they remain a potential strategy to overcome certain deficiencies."

I think approval may have also been complicated by the fact Mesoblast were applying for full approval for pediatric patients 18 years of age and under. There are currently no treatments for patients 12 and under, but there is an approved treatment for those 12-18 years. This may have led the FDA to request a randomized, controlled clinical trial and reject the option for accelerated approval. I think Mesoblast will now seek accelerated approval for patients 12 and under.

Another concern the FDA had were concerns around effectiveness, however this can be addressed in confirmatory trials, so appears to be less of an issue.