Just looking over the details of one of the class action claims shows this specifically:
If I understand it correctly Mesoblast completed the aGVHD trial then did post hoc analyses of the paediatric subgroups from other trials and chose an arbitrary null control rate that was 20% lower than these historical results.
When the FDA didn't buy it, the company then attempted to rectify things with their analysis of the MAGIC cohort but failed again because the FDA requested control data matched at the individual level instead of the group level that Mesoblast supplied.
The crux of the argument appears to be that Mesoblast knew more than they have suggested about the reservations expressed in the communications from the FDA, but still released very optimistic announcements to investors regarding potential approval and commercialisation of the treatment.
"Disclosures at the End of the Class Period
28. On August 11, 2020, the FDA released briefing materials for its Oncologic Drugs Advisory Committee (“ODAC”
meeting to be held on August 13, 2020. Therein, the FDA stated that Mesoblast provided post hoc analyses of other studies “to further establish the appropriateness of 45% as the null Day-28 ORR” for its primary endpoint. The briefing materials stated that, due to design differences between these historical studies and Mesoblast’s submitted study, “it is
unclear that these study results are relevant to the proposed indication.”
Specifically, the briefing materials stated, in relevant part:
The Applicant submitted the results of Protocol MSB-GVHD0011 to support their marketing application. Protocol MSB-GVHD001 was a prospective, multicenter, single-arm trial of remestemcel-L for treatment of pediatric patients with SRaGVHD grades B-D (excluding grade B skin alone). The primary endpoint of the trial was the proportion of patients in the full analysis set (FAS) with overall response (defined as complete response (CR) + partial response (PR)) at 28 days after initiation of therapy. The protocol was designed to determine if the Day28 overall response rate (ORR) exceeded 45%. The study hypothesis and the null ORR were prespecified in the statistical analysis plan (SAP);
however, the justification provided for the null rate in the Statistical Analysis Plan (SAP) was that it was 20 percentage points lower than that achieved with remestemcel-L in post hoc analyses of the pediatric subgroups in other protocols of remestemcel-L for treatment of aGVHD.
To further establish the appropriateness of 45% as the null Day-28 ORR, the Applicant also provided post hoc analyses of ORR in patients with SR-aGVHD treated with standard care therapies in the pediatric subgroup in the control arm of
Protocol 280, pediatric patients with SRaGVHD in the Mount Sinai Acute GVHD International Consortium (MAGIC) database, and patients with newly-diagnosed aGVHD who failed treatment with steroids but continued on steroids alone in Protocol 265. "
"
http://www.howardsmithlaw.com/Complaints/Mesoblast_Limited_Complaint.pdf
(20min delay)
