The company also announced its plans for a modified study protocol that may allow a roadway to approval.
BioCardia’s phase 3 clinical trial (NCT02438306) of its CardiAMP cell therapy, an investigational autologous cell therapy for the treatment of heart failure (HF), is unlikely to meet its primary end point based on the results of an interim analysis, according to an announcement made by the company.1
The study’s primary end point consists of a composite score of a 3-tiered Finkelstein-Schoenfeld (FS) hierarchical analysis that includes outcomes of all-cause death (tier 1), non-fatal major adverse cardiac and cerebrovascular events (MACCE) (tier 2), and change in 6-minute walk test (6MWT) from baseline to month 12 (tier 3). The analysis was conducted when 110 of the planned 250 total patients had been randomly assigned to a treatment group; although, the analysis only included the 102 patients who had reached 12 months of follow-up at the time. BioCardia noted that a separate group of 10 patients in a roll-in open label cohort were treated in the trial and had a 100% survival rate at 2 years of follow-up; this group was not included in the analysis.
Tier 1's definition of all-cause death included cardiac death equivalents, with heart transplant and left ventricular assist device placement noted as examples of cardiac death equivalents. At 12 months, for the group of patients who received treatment with CardiAMP, all-cause-death was 5.6%; by comparison, for the patients in the trial’s control group who received treatment with guideline directed medical therapy (GDMT), all-cause death was 5.3% (P = .42). For all patients with available follow-up who had been followed up to 24 months, all-cause-death in the patients who received CardiAMP was 8.3% and all-cause-death in the patients who received GDMT was 13.2% (P = .94). BioCardia noted that this corresponds to a 37% relative risk reduction for tier 1 events in the treatment group versus the control group.
Tier 2’s definition of MACCEs included heart failure hospitalization, stroke, and myocardial infarction; procedure-related events that occurred within the first 7 days of treatment were not included. At 12 months, among patients who received CardiAMP, 16.7% experienced MACCEs; for patients who received GDMT, 15.8% experienced MACCEs (P = .82). For all patients with available follow-up who had been followed up to 24 months, 16.7% of patients who received CardiAMP experienced MACCEs and 23.6% of patients who received GDMT experienced MACCEs (P = .76), corresponding to a relative risk reduction of 18%.
On the 6MWT at 12 months, patients treated with CardiAMP demonstrated an increase of 36.1 m from baseline (S.D. ±70.8) and patients treated with GDMT demonstrated an increase of 33.4 m (S.D. ±74.8) (P = .6). At the 24-month time point, patients treated with CardiAMP had a median improvement of 1.8 m (S.D. ±76.1) and patients treated with GDMT had a median improvement of 17.4 (S.D. ±95.7) (P = .33). BioCardia stated that the improvement seen in 6MWT at 12 months for the patients who received GDMT was greater than expected for the patient population.
“Although the trial interim efficacy results show that the trial is unlikely to achieve its primary endpoint at 1 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,” Amish Raval, MD, the co-national principal investigator and a professor of medicine at University of Wisconsin at Madison, said in a statement.1“I congratulate the study investigators on the absence of treatment emergent safety concerns.”
Shortly after these results were reported, BioCardia announced that it is exploring the potential of a modified clinical trial protocol as a potential roadway towards FDA approval of CardiAMP.2 Most notably, the company is considering replacing the 6MWT with a more objective outcome measurement. Cardiopulmonary Exercise Testing, which the FDA has indicated a preference towards, was stated as a potential option under consideration, though other options may also be considered. The company also pointed out that with a longer follow-up period, tier 1 and tier 2 outcomes, which are deemed more important than tier 3 outcomes, may have provided a greater push towards an efficacious FS composite score.
“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 2 ongoing clinical programs,“ Peter Altman, the president and CEO of BioCardia, added to the statement.1 “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 6 weeks and follow these patients in a double blinded fashion as guided by the data safety monitoring board.”