Significant reduction in mortality following single administration of autologous CD34 cells in the orphan indication of No-Option Refractory Disabling Angina (NORDA): Re-analysis of the largest completed study of CD34 cell therapy

Background:
CD34+ cells are naturally occurring vascular progenitors that have been shown to stimulate angiogenesis in ischemic tissue. Ph 1, 2 and a prematurely terminated Ph 3 study all demonstrated reduced angina and improved ETT in patients with No-Option, Refractory, Disabling Angina (NORDA).

Methods:
The data from the Ph 1, 2 and partial Ph 3 studies were licensed from the prior sponsor. Surprisingly a time to event analysis for mortality, as well as a comparison between all treated and control patients, had not previously been performed for ACT-34 trial, the largest cell therapy trial for refractory angina.

Results:
A KM analysis of the data from the phase 2 study reveals that a single administration of CD34+ cells results in a statistically significant reduction in mortality (Fig 1). CD34+ cell administration resulted in a long-term reduction in angina (Fig 2). Single administration of CD34+ cells also resulted in a significant improvement in ETT time for at least 1 yr (Fig 3).

Conclusions:
Auto CD34+ cell therapy for NORDA results in a mortality benefit, as well as a consistent signal of long-term clinical improvement. This new finding in a relatively small study (n=168) has implications for the use of standard of care control groups, especially given recent calculations that the NORDA population is orphan-sized (Benck, Henry 2019). By our estimation ~1% of the prevalent population has been enrolled in these studies raising feasibility questions regarding additional clinical trials and ethical questions regarding the appropriateness of continuing placebo controlled studies of this autologous, minimally manipulated cell therapy.