BioCardia announces interim efficacy results in phase III pivotal CardiAMP Cell Therapy Heart Failure trial.

The external review both confirmed the quality and appropriateness of the work by the Statistical Data Analysis Center at the University of Wisconsin and the DSMB in their review and recommendation. In order to enhance understanding of our heart failure program, BioCardia has taken steps, previously reviewed by the DSMB, to unblind itself to the interim results of the study and was provided a copy of the closed session study report presented to the DSMB for review.

The interim efficacy review by the DSMB did not include the final results of the study but is an analysis of the data as part of the adaptive statistical analysis plan. This review was based on the three-tiered Finkelstein-Schoenfeld (FS) hierarchical analysis of 12-month data, whose composite score comprises the primary efficacy endpoint of the CardiAMP HF study. For the first-tier, all cause death, including cardiac death equivalents such as heart transplant or left ventricular assist device placement at 12 months there were 5.6% of CardiAMP treatment patients versus 5.3% for the control group (p = 0.42). All available follow-up in the patients followed up to 24 months showed a separation between groups with 8.3% all cause death including cardiac death equivalents in the treatment group versus 13.2% in the control group (p = 0.94), corresponding to a 37% relative risk reduction for Tier 1 events for the treated patients compared to control patients on guideline directed medical therapy (GDMT).

For the second-tier, non-fatal major adverse cardiac events (MACCE), excluding those deemed procedure-related occurring within the first seven days and defined as heart failure hospitalization, stroke and myocardial infarction, 16.7% of treatment group had MACCE compared to 15.8% of the control group (p=0.82). All available follow-up data for patients followed up to 24 months showed a separation between groups, with 16.7% MACCE rate in the treatment group versus 23.6% in the control group (p=.76). This corresponds to an 18% relative risk reduction for MACCE over GDMT.

<>For the third-tier of change in Six Minute Walk Test (6MWT) distance from baseline to 12 months , both CardiAMP treatment patients and control patients experienced a clinically meaningful improvement at 12 months which was not statistically different. The treated group median 6MWT at 12M increased 36.1 with a standard deviation of ±70.8 meters, and the control group median 6MWT increased at 12M by 33.4 meters±74.8 meters (p =0.6). Results at 24 months also showed improvements in both groups with the treatment group median improving 1.8 ± 76.1 meters and the control group median improving 17.4 ± 95.7 meters (p=0.33). The improvement in 6MWT at 12M for the control group was greater than was expected in this population.

Based on these measures at one year follow-up, the 250-patient randomized controlled study is unlikely to meet its primary three-tiered FS efficacy endpoint, as seen from the initial 102 randomized patient set assessed at 12-month follow-up (110 patients had been randomized and eight of them had not completed their 12-month follow-up visit at the time of the analysis). This interim randomized study data does not include the study’s roll-in open label cohort of 10 patients treated who did well with 100% survival at two-year follow-up. These limited interim results related to the primary efficacy endpoint have been shared with the Co-National Principal Investigators of the study.

The study’s Co-National principal Investigator, Dr. Carl Pepine, MD, MACC, Professor of Medicine at the University of Florida at Gainesville, said “I am pleased that the aggregate outcomes data show promising low rates of adverse outcomes for a cohort of over 100 subjects with HFrEF due to ischemic heart disease. Furthermore, the study is the first to demonstrate that it is feasible to ‘personalize’ therapy using a novel bone marrow cell population analysis, process the cells at the bedside, and safely administer them by a trans myocardial injection system.”

Dr. Amish Raval, MD, Professor of Medicine at University of Wisconsin at Madison and Co-National Principal Investigator, said “Although the trial interim efficacy results show that the trial is unlikely to achieve its primary endpoint at one year, these results show that, while not statistically significant, there were trends towards patient benefits for the CardiAMP cell therapy over the course of the study, including a reduction in all cause death, including heart death equivalents and MACCE. I congratulate the study investigators on the absence of treatment emergent safety concerns.”

There were additional prespecified outcome measures detailed in the comprehensive SDAC closed session report. We also have significant data for the autologous cell dosing as performed in the study procedure, enabling assessments of efficacy on a patient-by-patient basis, which we will study. Knowledge from these interim details may be incorporated in its ongoing development plans for its autologous CardiAMP and allogeneic CardiALLO cell therapy programs.

“We are actively engaged in identifying patients who responded the most to the therapy and are considering other learnings with respect to trial design to inform this program and our other two ongoing clinical programs,“ said Peter Altman, BioCardia President and CEO. “We anticipate working with the Principal Investigators and Executive Steering committee on these efforts. In parallel we expect to support centers as they complete treatment of previously enrolled patients in the next six weeks and follow these patients in a double blinded fashion as guided by the DSMB.”