Firstly, thank you for some good humoured and excellent recent contributions.
The investigative work of a concerned shareholder in Cynata, a Company who just happens to be several years behind in clinical development using pluripotent MSCs for sr aGVHD , has unearthed some pertinent facts. These facts were of course already contained in the original briefing document to the ODAC panel from the FDA. Not as footnotes but in plain full scale print. Perhaps they should email Professor Halabi, the biostatistician on the ODAC panel (see her present role with Duke Univ below) to point out that n number was eleven . She must have missed the big graph with numbers plotted against patient lots, with corresponding p values showing statistical significance. Well you and I know that the latter scenario is highly improbable….but if you were trying to point out weaknesses in trial design it would be a cheap point worth making…as it would for most ultra orphan designations, for that matter. In choosing only the most severe steroid refractory acute GVHD patients with extremely high mortality outcomes , GVHD001 was able to achieve far greater powering per patient outcome than for any of the Reach trials. A large part of the patient cohort for the Ruxolitinib Reach 1 trial were Grade B patients with much lower risk of mortality risk.
Susan Halabi CV. James B. Duke Distinguished Professor. Biostatistics & Bioinformatics, Division of Biostatistics · [email protected]
Susan Halabi has published extensively on prognostic and predictive modelling and on the design and analysis of clinical trials. She has also served as principal investigator on several awards. Halabi is a member of the National Cancer Institute Genitourinary Committee Steering Committee and a member of the Oncologic Drugs Advisory Committee (ODAC) for the U.S. Food and Drug Administration. She is a co-editor of Oncology Clinical Trials: Successful Design, Conduct and Analysis. Halabi is an Associate Editor for Clinical Trials, Statistics in Medicine and Diagnostic and Prognostic Research. She is a Fellow of the American Statistical Association and the Society of Clinical Trials and has served and continues to serve on numerous data safety and monitoring boards and study sections for the National Institutes of Health.
The simple facts are that our concerned poster does not have access to all the data or the deliberations of the OTP (formerly OTAT) panel. I think they are confused. Firstly, it is my understanding than the new data being generated by Mesoblast came from existing an potency assay data applied during the original trial, where an alternative potency measurement could be referenced at a certain time point to show utility. Now, I am sure the concerned poster would love to know the finer details…but this knowledge is proprietary so he will just have to rely on the bare minimum of statutory required disclosures.
To be fair Silviu has not made it easy for the competitors. Bell Potter clients were advised recently in a non public conference call , which was followed up by a John Hester written update, that the FDA were now prepared to consider the GVHD001 trial in isolation rather than conjoined with the Prochymal trials where there was previously some batch variability. A poster very kindly copy and pasted the Hester email update on this website for all to see. This is crucial piece of evidence in my opinion, which was no doubt communicated to Mesoblast in the written notes following the FDA meeting. The FDA will reprimand companies for falsely reporting guidance from their departments , as Cyto Dyn learnt to their cost recently .
So what our concerned poster really needs to know is, what was so pursuasive in the data to cause the change of heart at the FDA ? I think Mesoblast has now explained the shortcoming of the Prochymal trial (which was nothing to do with them ) to the satisfaction of the FDA .
(20min delay)