Skip to main content
Premium Trial:

Request an Annual Quote

BioCardia Pivots to Biomarker Strategy to Prove Heart Failure Cell Therapy Benefits

Stock photo of medical professional counseling a male patient

NEW YORK – After a hiccup in its bid to prove that an experimental autologous cell therapy could treat ischemic heart failure, BioCardia is ready to try again if it is able to garner enough funds. 

But this time, the Sunnyvale, California-based firm hopes to use a biomarker-informed strategy.

In 2016, BioCardia launched a pivotal Phase III trial to test the efficacy of its investigational autologous cell therapy CardiAMP, or BCDA-01, in patients with ischemic heart failure with reduced ejection fraction. The company is also developing CardiAMP as a treatment for chronic myocardial ischemia and refers to the cell therapy as BCDA-02 in this setting.

However, BioCardia paused the CardiAMP Heart Failure randomized-controlled trial in July based on a recommendation from its data safety monitoring board (DSMB), which, after analyzing interim data, concluded that the study was unlikely to meet the primary endpoint — comparing a treatment arm to a control arm using a composite endpoint including all-cause death, major adverse cardiac events, and improvement in a six-minute walking test. That's in part because patients in the CardiAMP and control arms of the trial had positive outcomes, including low rates of mortality and cardiac events, said BioCardia President and CEO Peter Altman.

"The patients in the trial all did very well," he said. In the trial, the control arm underwent a procedure with an introducer guidewire, but unlike the treatment arm, no cell therapy was delivered. All patients continued guideline-directed therapies in addition to receiving CardiAMP or placebo. Altman stressed that there were no treatment-emergent safety concerns according to the DSMB's analysis.

The trial has since restarted and is continuing, and while the firm is no longer enrolling patients, it is monitoring participants and plans to share a final analysis in Q4 2024.

Additionally, BioCardia plans to launch a new pivotal trial, dubbed CardiAMP Heart Failure II, in which it is homing in on a subset of responders identified in the earlier trial, specifically, those with elevated levels of N-terminal pro B-type natriuretic peptide (NT-proBNP), a biomarker associated with cardiac failure and stress. Altman estimates that elevated levels of NT-proBNP are present in about 70 percent of patients with ischemic heart failure with reduced ejection fraction. The new iteration of the Phase III trial will also use a different composite endpoint including all-cause death, heart failure hospitalizations, and worsening heart failure in patients treated in the outpatient setting.

In both trials, before receiving CardiAMP, patients are screened to determine if they are a candidate for the cell therapy based on an analysis of the potency of their bone marrow cells. If they can receive the treatment, additional bone marrow cells are collected, processed using BioCardia's point-of-care cell processing platform, and administered into a patient's damaged heart tissue through a cardiac catheterization procedure.

Altman declined to disclose the precise characteristics patients' bone marrow cells are screened for but noted that the CD34-positive cell population is of interest. Nearly 70 percent of patients enrolled into the trial have been eligible after the pre-procedure screening, and those who aren't could be candidates for a Phase I/II trial of a related but different cell therapy. Specifically, BioCardia is developing an NK1R-positive allogeneic cell therapy, called CardiALLO (or BCDA-03), as a treatment for ischemic heart failure.

Screening the potency of patients' bone marrow cells is important in the case of CardiAMP, since the autologous treatment is based on the concept that bone marrow cells will stimulate healing in the heart.

In the earlier Phase III study, it is unclear why the event rate was low among the treated and control groups, said Amish Raval, a principal investigator in that trial and a professor in the cardiovascular medicine division at the University of Wisconsin School of Medicine and Public Health. This is an area of ongoing research.

Still, there are positive takeaways from the first trial in terms of safety and feasibility. For example, Raval noted that the process for screening, extracting, and reintroducing cells was "very doable," despite the complex series of steps.

When the CardiAMP Heart Failure II study launches, Raval said he intends to participate.

The US Food and Drug Administration in November approved BioCardia's protocol for the CardiAMP Heart Failure II study, but the firm hasn't yet started it. There is Medicare coverage for the cell therapy and the associated procedure for patients in the treatment and control arms of the trial, which is being conducted with an approved investigational device exemption, and this helps to offset some of the costs. 

However, this reimbursement won't cover all the costs of launching a new trial for BioCardia. "As a company, because of the market reaction to our first program," the original CardiAMP Heart Failure Trial, "we are still recovering from that and looking at how [to] responsibly carry forward CardiAMP Heart Failure II," Altman said. He added that while BioCardia is "actively working on starting" the new trial, it will "need funding as a small company per standard financing and business development activities."

On Tuesday, BioCardia's stock opened at $.46 per share, up 28 percent from its 52-week low of $.36 per share, which the company hit in September in the days following its announcement that it was developing a second study of CardiAMP in a new Phase III trial. The company's stock price at its highest point over the past 52 weeks was $2.92 per share.

In Q3 2023, the most recent quarter for which BioCardia has reported financial results, the firm recorded $357,000 in revenue, up 68 percent from the year-ago quarter. Its Q3 net loss was $2.6 million compared to $3.1 million in the prior-year quarter. 

BioCardia's public announcements about the CardiAMP program in heart failure are "hopeful but not definitive," said Clyde Yancy, chief of the cardiology division at Northwestern University's Feinberg School of Medicine and past president of the American Heart Association.

"With many outstanding questions remaining, one can share in the hopefulness of the sponsor and investigators, while also remaining observant pending the release of more data and completion not only of the interim analyses but completion of this Phase III trial," Yancy said. "Regenerative therapies for heart failure remain an elusive therapeutic quest, yet this is an important uncovered therapeutic space with the potential to augment current evidence-based medical, device, and surgical care."

Altman certainly maintains his optimism for CardiAMP and said that the new trial, if successful, would pave the way for regulatory submissions for CardiAMP as a heart failure treatment in the US.

BioCardia is also in discussions with Japan's Pharmaceutical and Medical Device Agency, which, according to the company, has said it will consider approving CardiAMP in heart failure using follow-up data from patients enrolled in the ongoing CardiAMP Heart Failure Trial. That data, which BioCardia expects to release in Q4, could produce new evidence and efficacy insights. BioCardia has said that although the primary endpoint of the trial was unlikely to be met at the one-year mark, there were trends suggesting that more patients in the treated group may be alive and experiencing fewer cardiovascular events compared to the control group two years post-treatment.

CardiAMP "has great potential for helping many patients," Altman said, acknowledging that at this point, "there's no proof of efficacy, there are only trends toward benefit. … We need to keep our scientific hat on."