Additional Relevant Details
In addition to a number of protocol changes intended to improve patient enrollment and study flow, the IDE Supplement, submitted at the end of May, proposed a change in the primary efficacy endpoint from Amputation Free Survival (AFS) to Change in Transcutaneous Oxygen Pressure (TcPO2). The Company believes that published literature in peer reviewed journals over many years has shown a strong correlation between improvements in TcPO2 over time and limb salvage, a correlation which has since been reinforced by Cesca’s own feasibility study data. The Company had previously concluded that Amputation-Free Survival (AFS) would not be practical as a primary endpoint for the study because it couples limb-related outcomes with all-cause mortality, a characteristic that unreasonably burdens the statistical analysis necessary to specifically demonstrate treatment effectiveness in preventing amputations among late stage CLI patients.The FDA has approved the changes in Cesca’s pivotal trial design as proposed in the IDE Supplement, including the use of Change in TcPO2 as the primary measure of efficacy. There are now no regulatory impediments to the Company enrolling patients and beginning the trial. However, in its feedback, the FDA also indicated that regardless of the outcome of the study, it would require the Company to further validate TcPO2 as a surrogate for clinical outcome for the proposed indication prior to granting marketing (PMA) approval. In light of this, the Company is now engaged in a follow-on dialog with the FDA to explore various alternative pathways to securing a PMA.