Meeting News

Cell therapy improves coronary flow reserve in coronary microvascular dysfunction

Timothy D. Henry

CD34+ cell therapy in patients with coronary microvascular dysfunction improved coronary flow reserve in addition to angina class and symptoms at 6 months, according to data from the ESCaPE-CMD trial presented at the virtual Society for Cardiovascular Angiography and Interventions Scientific Sessions.

“CD34 (CLBS16, Caladrius Biosciences) is a naturally occurring endothelial progenitor cell that was discovered in 1997,” Cardiology Today Editorial Board Member Timothy D. Henry, MD, FACC, MSCAI, medical director of the Carl and Edyth Lindner Center for Research and Education at The Christ Hospital in Cincinnati and vice president of SCAI, said during the press conference. “Preclinical models actually demonstrated natural ability of CD34 cells to stimulate myocardial angiogenesis.”

Coronary microvascular dysfunction

In this interventional, open-label, proof-of-concept study, researchers analyzed data from 20 patients (mean age, 54 years; 85% women) with coronary microvascular dysfunction, which was defined as a coronary flow reserve of 2.5 or less.

“There’s an increasing number of patients who have ischemia and nonobstructive coronary artery disease,” Henry said during the press conference. “This is predominantly in women, and it’s estimated that 3 million to 5 million people in the United States have this problem. When you do formal coronary reactivity testing, you realize there’s coronary microvascular dysfunction in at least 50% of those patients. This is a generally underrecognized problem, and in particular, in young women who have ongoing chest pain.”

Patients were given 300 x 106 CD34+ cells via intracoronary infusion.

“We did [granulocyte colony-stimulating factor] for 5 days,” Henry said during the press conference. “On the fifth day, we took the CD34+ cells out with apheresis, it was processed centrally and then the cells were redelivered to the site 48 hours later for intracoronary injection.”

Endpoints of interest included safety, adverse events and changes from baseline to 6 months in coronary flow reserve, angina class, angina frequency and Seattle Angina Questionnaire score.

There was a significant improvement in coronary flow reserve from baseline to 6 months (2.08 to 2.68; P = .0045; mean change = 0.62; 95% CI, 0.219-1.024).

“This is actually a very remarkable improvement,” Henry said during the press conference.

At 6 months, there was an improvement in angina class, with more patients considered class I (n = 1 at baseline; n = 8 at 6 months) and class II (n = 4 at baseline; n = 6 at 6 months), and fewer categorized as class III (n = 5 at baseline; n = 1 at 6 months) and class IV (n = 10 at baseline; n = 4 at 6 months). The number of angina episodes per week also improved during this time.

There were improvements in all five domains of the Seattle Angina Questionnaire scores: physical limitation (P = .0026), angina stability (P = .0247), angina frequency (P = .0156), treatment satisfaction (P = .0117) and disease perception (P = .0005).

The trial was safe with no significant adverse effects. One patient had focal dissection.

Potential implications

“Based on these results, our plan is for a large phase 2/3 trial to begin later this year,” Henry said during the presentation. “This really changes overall care for this patient population because we have been able to identify them, they have significant impairment in their quality of life and I think this holds that we might actually have a therapy for them that would be effective in improving their quality of life.”

Douglas W. Losordo

“We are extremely pleased yet not surprised that the full results for the ESCaPE-CMD corroborate the previously reported and very positive partial data from the study,” Douglas W. Losordo, MD, FACC, FAHA, chief medical officer at Caladrius, said in a press release from the company. “The results show an encouraging ability to increase [coronary flow reserve] and potentially reverse [coronary microvascular dysfunction], a disease that disproportionately afflicts more women than men, after a single administration. The outcome from this study brings us one step closer to realizing the promise of CD34+ cell therapy to augment microvasculature in the heart enabling the restoration of health rather than simply management of disease.” – by Darlene Dobkowski

Reference:

Henry TD, et al. Featured Clinical Research. Presented at: Society for Cardiovascular Angiography and Interventions Scientific Sessions; May 14-16, 2020 (virtual meeting).

Disclosures: The trial was funded by Caladrius Biosciences and the NHLBI. Henry reports no relevant financial disclosures. Losordo is an employee of Caladrius.

Timothy D. Henry

CD34+ cell therapy in patients with coronary microvascular dysfunction improved coronary flow reserve in addition to angina class and symptoms at 6 months, according to data from the ESCaPE-CMD trial presented at the virtual Society for Cardiovascular Angiography and Interventions Scientific Sessions.

“CD34 (CLBS16, Caladrius Biosciences) is a naturally occurring endothelial progenitor cell that was discovered in 1997,” Cardiology Today Editorial Board Member Timothy D. Henry, MD, FACC, MSCAI, medical director of the Carl and Edyth Lindner Center for Research and Education at The Christ Hospital in Cincinnati and vice president of SCAI, said during the press conference. “Preclinical models actually demonstrated natural ability of CD34 cells to stimulate myocardial angiogenesis.”

Coronary microvascular dysfunction

In this interventional, open-label, proof-of-concept study, researchers analyzed data from 20 patients (mean age, 54 years; 85% women) with coronary microvascular dysfunction, which was defined as a coronary flow reserve of 2.5 or less.

“There’s an increasing number of patients who have ischemia and nonobstructive coronary artery disease,” Henry said during the press conference. “This is predominantly in women, and it’s estimated that 3 million to 5 million people in the United States have this problem. When you do formal coronary reactivity testing, you realize there’s coronary microvascular dysfunction in at least 50% of those patients. This is a generally underrecognized problem, and in particular, in young women who have ongoing chest pain.”

Patients were given 300 x 106 CD34+ cells via intracoronary infusion.

“We did [granulocyte colony-stimulating factor] for 5 days,” Henry said during the press conference. “On the fifth day, we took the CD34+ cells out with apheresis, it was processed centrally and then the cells were redelivered to the site 48 hours later for intracoronary injection.”

Endpoints of interest included safety, adverse events and changes from baseline to 6 months in coronary flow reserve, angina class, angina frequency and Seattle Angina Questionnaire score.

There was a significant improvement in coronary flow reserve from baseline to 6 months (2.08 to 2.68; P = .0045; mean change = 0.62; 95% CI, 0.219-1.024).

“This is actually a very remarkable improvement,” Henry said during the press conference.

At 6 months, there was an improvement in angina class, with more patients considered class I (n = 1 at baseline; n = 8 at 6 months) and class II (n = 4 at baseline; n = 6 at 6 months), and fewer categorized as class III (n = 5 at baseline; n = 1 at 6 months) and class IV (n = 10 at baseline; n = 4 at 6 months). The number of angina episodes per week also improved during this time.

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There were improvements in all five domains of the Seattle Angina Questionnaire scores: physical limitation (P = .0026), angina stability (P = .0247), angina frequency (P = .0156), treatment satisfaction (P = .0117) and disease perception (P = .0005).

The trial was safe with no significant adverse effects. One patient had focal dissection.

Potential implications

“Based on these results, our plan is for a large phase 2/3 trial to begin later this year,” Henry said during the presentation. “This really changes overall care for this patient population because we have been able to identify them, they have significant impairment in their quality of life and I think this holds that we might actually have a therapy for them that would be effective in improving their quality of life.”

Douglas W. Losordo

“We are extremely pleased yet not surprised that the full results for the ESCaPE-CMD corroborate the previously reported and very positive partial data from the study,” Douglas W. Losordo, MD, FACC, FAHA, chief medical officer at Caladrius, said in a press release from the company. “The results show an encouraging ability to increase [coronary flow reserve] and potentially reverse [coronary microvascular dysfunction], a disease that disproportionately afflicts more women than men, after a single administration. The outcome from this study brings us one step closer to realizing the promise of CD34+ cell therapy to augment microvasculature in the heart enabling the restoration of health rather than simply management of disease.” – by Darlene Dobkowski

Reference:

Henry TD, et al. Featured Clinical Research. Presented at: Society for Cardiovascular Angiography and Interventions Scientific Sessions; May 14-16, 2020 (virtual meeting).

Disclosures: The trial was funded by Caladrius Biosciences and the NHLBI. Henry reports no relevant financial disclosures. Losordo is an employee of Caladrius.

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