After taking another look at the 10Q, bottom of page 17, into page 18, my take is that the trial is going well (extension of prior 'results'), but that due to the 'control arm' failing to give them a meaningful comparison (ie, so many in the control FAIL to meet a standard of expectation, its useless for comparison sake) its FUTILE to continue the trial.
So as I read this again, and based on prior 'results' as described below, I will defer back to that comment not so long ago that its likely based on what they already know, and what they expect to see, that they are expecting to ask the FDA for an early termination and proceed to an NDA submission.. (marked some in italics, some in bold, but not sure what it will look like as 'preview' doesn't translate to final view)
Safety and feasibility data from the first 75 patients enrolled on the SIERRA trial, which represents 50% of the total of 150 patients to be enrolled in the trial, was presented in an oral presentation at the Transplantation & Cellular Therapy (“TCT”) Meetings of the American Society for Transplantation and Cellular Therapy (“ASTCT”) and Center for International Bone & Marrow Transplant Research (“CIBMTR”) in February 2020. It was reported that 100% of patients (31/31) on the study arm that received a therapeutic dose of Iomab-B received a BMT, with a median time to BMT of 30 days, and all patients achieved neutrophil and platelet engraftment in a median time of 20 days despite a high median blast count of 30%. On the control arm, only 18% of patients (7/38) achieved remission after salvage therapy, and then received a BMT with a median time to BMT of 67 days and median blast count of 26%. Of the 82% of patients failing to achieve a CR with conventional care (31/38), 20 patients were eligible to cross over to receive Iomab-B followed by transplant. These patients are considered as having failed the primary endpoint of the study. All crossover patients who received the therapeutic dose of Iomab-B (20/20) received a BMT, with a median time to BMT of 64 days and they achieved engraftment in a median time of 19 days despite high median blast count of 35% at time of crossover. It was also reported that 100-day non-relapse transplant-related mortality (100-day TRM) of the study or Iomab-B arm was only 6% (2/31) of patients that received a BMT compared to 29% of patients (2/7) who received a BMT after salvage therapy on the control arm. The universal engraftment rate and low 100-day TRM rate of the Iomab-B arm resulted in 29 patients potentially evaluable for the primary endpoint compared to 5 patients in the control arm, a nearly six times difference.
We have reached 75% enrollment in the SIERRA trial. We expect to present safety and feasibility data including rates of BMT engraftment, 100-day TRM and key safety metrics from 113 patients, representing 75% of the planned 150-patient enrollment, as we did on the first 25% and 50% of patients. In addition, rates of CR and rates of patients that did not achieve CR who then received Iomab-B, defined as failures for the primary endpoint, will be reported for patients randomized to the control arm.
The SIERRA trial is powered to show a two-times difference in the primary endpoint of dCR at 180 days at full enrollment of the study. The SIERRA trial design allowed for up to two ad hoc interim analyses of the primary endpoint exercisable at our discretion and triggered by an enrollment range of 70 to 110 patients. We exercised a single ad hoc interim analysis in the second quarter of 2020 based on the data reported from SIERRA thus far that is consistent with prior findings with Iomab-B and have updated and shared the updated SIERRA trial protocol and statistical analysis plan with the FDA to reflect the single ad hoc interim analysis. With a single ad hoc interim analysis exercised, the final analysis on full enrollment of 150 patients would be conducted with a p-value of 0.046 defining success of the trial. The interim analysis is expected to be completed in the fourth quarter of 2020 and could result in a recommendation for early termination of the trial for futility of one of the arms, or a continuation of the trial. The company intends to consult with the FDA should the recommendation be to terminate the study due to futility of the control arm.