CHICAGO – A biomarker-defined subpopulation of patients with heart failure is more likely to benefit from BioCardia's experimental CardiAMP cell therapy, researchers reported at the American College of Cardiology's annual scientific meeting this past weekend.
The results from the randomized, controlled Phase III CardiAMP Heart Failure (HF) trial that the company halted two years ago reaffirm the rationale behind BioCardia's revamped Phase III trial, in which it is homing in on patients with elevated levels of N-terminal pro B-type natriuretic peptide (NT-proBNP), a biomarker associated with cardiac failure and stress.
"This is the motivation for the subsequent CardiAMP HF II trial that hopefully will start this summer," Amish Raval, a professor in the cardiovascular medicine division at the University of Wisconsin School of Medicine and Public Health, said during a featured clinical research session at the meeting.
Raval on Sunday reported results from the initial Phase III trial of the treatment, in which he was a principal investigator. In that study, investigators enrolled patients with ischemic heart failure with reduced ejection fraction to receive either a sham procedure or CardiAMP.
BioCardia is betting that this cell therapy, made from autologous bone marrow cells, can stimulate healing in the heart. CardiAMP comprises bone marrow mononuclear cells that are collected and processed using BioCardia's point-of-care cell processing platform before being administered into a patient's damaged heart tissue through a cardiac catheterization procedure. In the control arm of the study, patients underwent a procedure with an introducer guidewire but no cell therapy.
BioCardia launched the CardiAMP HF trial in 2016 to test the efficacy of CardiAMP; however, the company paused and then stopped the study in 2023 after determining that based on interim data, it was unlikely to meet its primary endpoint. Specifically, patients who received CardiAMP were unlikely to best those in the control arm based on a composite endpoint that factored in all-cause death, major adverse cardiac events, and improvement in a six-minute walking test. BioCardia leadership at the time said patients in the control arm had better outcomes than they expected. All patients in the clinical trial were able to continue guideline-directed therapies in addition to receiving CardiAMP or the sham procedure.
Since 2023, BioCardia has resumed monitoring patients in the CardiAMP HF trial, though it's no longer enrolling new patients. It has also kicked off enrollment in the new, pivotal CardiAMP HF II trial, which will incorporate the NT-proBNP biomarker and focus on a different composite endpoint that includes tracking improvement in quality of life, but not the six-minute walking test.
Before it stopped recruiting patients, BioCardia had enrolled 115 patients into the CardiAMP HF trial, who now have up to two years of follow-up data. While the clinical trial did not meet its primary endpoint, there were trends suggesting CardiAMP had positive clinical benefits in patients, including reducing mortality and major adverse cardiovascular events, Raval said.
Patients treated with CardiAMP tended to do better than patients who received the sham procedure on many of the measures included in the primary composite endpoint, such as all-cause death and nonfatal heart failure hospitalizations. However, "those wins were negated by a reduction of wins in the six-minute walking test distance endpoint," Raval said, noting that treated patients did not best the control group based on changes from baseline.
There were "general trends" toward reduced major adverse cardiovascular events in the treated group compared to the control group over two years, he said, though it was not statistically significant.
In a post hoc analysis, investigators identified patients with elevated NT-proBNP as a subgroup that experienced stronger positive trends, underscoring the potential of focusing on this patient population in the CardiAMP HF II trial. Among patients with elevated NT-proBNP at baseline, there was an 86 percent risk reduction in mortality for those on CardiAMP, for example.
CardiAMP was well tolerated in the Phase III trial, which bodes well for the CardiAMP HF II trial. Three patients developed pericardial effusions, but all were successfully drained, Raval said.
Mary Walsh, medical director of the heart failure and cardiac transplantation programs at Ascension St. Vincent Heart Center in Indiana, who was not involved in the CardiAMP HF trial, noted the need for new therapies to treat this population of patients with ischemic heart failure with reduced ejection fraction, whose disease remains despite being on other medications.
"This is a patient group for whom we have little left to offer," she said at the meeting.
She raised concerns that in the CardiAMP HF trial, more than 90 percent of patients in the treatment and control arms were White, and about 90 percent in both arms were male. She also questioned what the eligible patient population that would benefit from the cell therapy might look like, since, before receiving CardiAMP, all patients must be screened based on an analysis of the potency of their bone marrow cells. In the CardiAMP HF trial, 72 of the initial 303 patients who were screened for the study became ineligible after this step.
Raval said additional research is needed in this area. He expects to see similar eligibility based on cell population analysis in the CardiAMP HF II trial, but he cautioned that since the next trial will focus on sicker patients with elevated NT-proBNP, the number of patients excluded based on this analysis may increase. He said investigators will also study if there are ways to further refine the cell population assay for identifying best responders.
"We'll be studying that over the next several months," he said.