Cell therapy for severe angina shows promise, but questions about future use remain

NEW ORLEANS — Patients with severe class III and IV refractory angina treated with stem cell therapy experienced significant improvements in exercise capacity and mortality, according to a meta-analysis of three cell-therapy trials.

During a late-breaking clinical trial session at the Society for Cardiovascular Angiography and Interventions Annual Meeting, Thomas J. Povsic, MD, PhD, FSCAI, associate professor at Duke Clinical Research Institute and interventional cardiologist at Duke University School of Medicine, presented combined patient-level data from three double blind, randomized trials that showing promising results after intramuscular injection of autologous CD34+ cells compared with placebo in patients with refractory angina.

Thomas J. Povsic

In total, the studies included 304 patients (24 in phase 1; 168 in ACT-34 and ACT-34 extension studies; 112 in RENEW). The RENEW pivotal trial was prematurely terminated by the sponsor (Baxter) in December 2013 due to financial considerations.

“I see these patients [with severe refractory angina] frequently and, unfortunately in the current environment we have limited options. … These patients are in dire need of new therapies,” Povsic said during a presentation.

The median age of the population was in the mid-60s. Most were men and white. Patients presented with many risk factors, he said, with diabetes in more than 50%. Approximately 90% percent of patients had prior CABG; the same was true for prior PCI.

Patients treated with CD34+ cell therapy (n = 187) improved total exercise time by 80.5 seconds at 3 months, 101.8 seconds at 6 months and 90.5 seconds at 12 months. In comparison, total exercise time improved by 28.1 seconds to 39.5 seconds during follow-up in the placebo group (n = 89). This resulted in treatment effects of 52.5 seconds (P = .002), 52.9 seconds (P = .009) and 50.9 seconds (P = .027), respectively.

At 24 months, the rate of mortality was 2.6% in the CD34+ cell therapy group vs. 11.8% in the placebo group (P = .003).

Additionally, the rate of MACE was numerically less frequent in the cell therapy group: 29.8% vs. 40% (P = .08).

“There clearly is no signal that there is an excess risk associated with autologous CD34+ cell administration. The trend clearly favors the cell therapy arm,” Povsic said.

The relative risk for angina was also reduced among those who received cell therapy, from 0.9 at 3 months to 0.81 at 6 months to 0.79 at 12 months.

“We believe that this type of cell therapy for refractory angina is particularly promising and may improve both functional status and mortality. It is imperative to explore methods to bring this therapy to patients,” he said.

It is estimated that 10 million to 12 million Americans have refractory angina, and up to 100,000 new cases are diagnosed each year.

When asked during a press conference about the future of cell therapy in patients with refractory angina, Povsic acknowledged that these trials are “extremely expensive” to run. Further, he said, Baxter has divested itself of CD34+ cell therapy.

“The future is cloudy for this therapy,” he said.

“I personally believe this therapy has more data for efficacy and safety than any other therapy for the treatment of refractory angina. There is a new opportunity with passage of the 21st Century Cures Act, where regenerative therapy has a special category called Regenerative Advanced Therapy that allows for a therapy that fulfills a particular medical need to undergo expedited approval. Whether or not these data could be sufficient to allow for consideration of this therapy to be approved … that’s something we would like to explore,” he said.

Reference:

Povsic T. Late-Breaking Clinical Trials I. Presented at: Society for Cardiovascular Angiography and Interventions Annual Meeting; May 10-13, 2017; New Orleans.

Disclosure: The studies were funded by Baxter. Povsic reports no relevant financial disclosures.