BioCardia Gets FDA Greenlight for Modified CardiAMP Heart Failure II Trial

The FDA has given the go-ahead to BioCardia for its planned phase 3 clinical trial of its investigational CardiAMP autologous cell therapy, intended for the treatment of patients with ischemic heart failure, according to a company announcement.¹ The trial seeks to build upon the data established in the ongoing phase 3 CardiAMP Heart Failure trial (NCT02438306), which has completed its enrollment and is expected to read out its final data set in the final quarter of 2024.

The proposed study includes an eligibility requirement that patients demonstrate a prespecified NT-proBNP level at baseline, supported by the indications of the existing data.^2-5 The proposed primary efficacy end point has also been modified from the ongoing study—it is a similar hierarchical composite evaluation, but will now include all-cause death, the cardiac death equivalents of heart transplant and left ventricular assist device implantation, heart failure hospitalizations, worsening heart failure events treated as an outpatient, and change in quality-of-life. The follow-up duration for the end point will range from a minimum of 12 to a maximum of 24 months.

Peter Altman, PhD, the president and chief executive officer of BioCardia, said in a statement that “CardiAMP Heart Failure II has strong support from our clinical investigators who have reviewed the interim trial results in detail and have first-hand knowledge of this great unmet clinical need. We expect that we can perform this study efficiently at world-class clinical centers based on the extensive experience of the ongoing trial and its positive clinical outcomes.”¹ Additional modifications to the new trial include simplification of clinical site logistics and study cost reductions, with the company noting that the Medicare reimbursement support that is in place for both study groups is expected to offset the clinical costs.

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Among the individuals in the ongoing trial with NT-pro BNP levels greater than 500 pg/mL—part of the aforementioned eligibility for the proposed CariAMP Heart Failure II trial—the data up to 2 years suggest improvements over the control group with a 59% in the relative risk reduction in mortality, a 13% improvement in all-cause death and cardiac death equivalents (CardiAMP group: 9%; control group: 22%); and a 54% in relative risk reduction of MACCE, with a 21% reduction with CardiAMP therapy (18%) compared with the control group (39%).⁵

The established data from an interim analysis of the ongoing trial were presented at the 2018 American Heart Association (AHA) Scientific Sessions, held November 10-12, 2018, in Chicago, Illinois,² and later published in the International Journal of Cardiology in 2020.^3,4 Those data included a 10-patient ‘roll in’ cohort that included individuals with prior myocardial infarction and ejection fraction 20% to 40%, who are on optimal medical therapy with New York Heart Association heart failure (NYHA HF) class 2-3 symptomatic heart failure. Altogether, 100% of those patients had successful bone marrow aspiration (BMA), bone marrow mononuclear cell (BM-MNC) isolation, and cell delivery with no periprocedural serious adverse events. Significant improvement was shown at 6 months in measures of 6-minute walk distance (6MWD), with a 20.5% relative improvement (+47.8 m; P = .01) that showed a 12-month trend toward improvement (+46.4 m; P = .06).; significant improvement in NHYA functional class (P = .037); and a trend toward improvement in (Minnesota Living with Heart Failure Questionnaire) MLWHFQ score for a 31% relative change (P = .21).³

In July 2023, more interim trial results were reviewed by the study’s Data Safety Monitoring Board (DSMB) that suggested it was not likely to meet the primary end point for efficacy at 12 months.⁵ This was partly because the outcomes in body study groups were positive, and no treatment emergent safety concerns were acknowledged by the DSMB. Those who received the cell therapy who were followed up with at 24 months showed a 37% relative risk reduction of cardiac death equivalents and an 18% relative risk reduction in major adverse cardiac and cerebrovascular events (MACCE).

REFERENCES
1. BioCardia Announces FDA Approval of CardiAMP Heart Failure II Protocol for Autologous Cell Therapy for Ischemic Heart Failure. News release. BioCardia Inc. November 14, 2023. Accessed November 22, 2023. https://finance.yahoo.com/news/biocardia-announces-fda-approval-cardiamp-121500750.html
2. Johnston, PV, Duckers, HJ, Raval, AN, Cook, TD, Traverse, JH, Abraham, WT, Altman, PA, Pepine, CJ. The CardiAMP Heart Failure Trial: Efficacy Outcomes from Roll-In Phase. Presented at: AHA Annual Scientific Sessions; November 10-12, 2018; Chicago, IL. Abstract 16158. https://www.ahajournals.org/doi/10.1161/circ.138.suppl_1.16158
3. Raval AN, Johnston PV, Duckers HJ, et al. Point of care, bone marrow mononuclear cell therapy in ischemic heart failure patients personalized for cell potency: 12-month feasibility results from CardiAMP heart failure roll-in cohort. Int J Cardiol. 2021;326:131-138. doi:10.1016/j.ijcard.2020.10.043
4. Published Peer-Reviewed Initial Data From BioCardia Pivotal Phase 3 Clinical Trial of CardiAMP Demonstrates Improvement in Heart Failure Patients Measured by Exercise Outcomes and Cardiac Function. News release. BioCardia Inc. October 26, 2020. Accessed November 22, 2023. https://www.biocardia.com/investors/press-releases/id/1037?pressReleaseId=87
5. BioCardia Announces Completion of Enrollment in Phase III CardiAMP HF Trial and Plans for CardiAMP HF Trial II. News release. BioCardia Inc. October 11, 2020. Accessed November 22, 2023. https://www.biocardia.com/investors/press-releases/id/1037?pressReleaseId=171