AHA: Caladrius single injection helps heart disease that hits women the hardest

We tend to think of heart disease and heart disorders to be, in the main, things that affect men more than women, but this is of course not true.

Women not only suffer from heart disease, but they do so differently from men and are in some cases more susceptible to certain cardiovascular (CV) problems. One of these is coronary microvascular dysfunction (CMD).

Caladrius Biosciences and academic researchers have presented new research at the American Heart Association (AHA) that aims to take the fight to this disease in a new way.

Speaking to FierceBiotech from AHA in Philadelphia, Caladrius Chief Medical Officer Douglas Losordo, M.D., explained of the disease: “Many consider CMD to be the exemplar of the underdiagnosis of heart disease in women. CMD was previously referred to as Syndrome X, signifying the mysterious occurrence of cardiac symptoms in the apparent absence of documented heart disease.

“Patients with CMD have the typical symptoms that occur in patients with blockages in the large blood vessels of the heart (those that can be stented or bypassed), but their arteries have no blockages. Unfortunately, before the development of specific tests to diagnose CMD such as measuring coronary flow reserve, these patients were often dismissed. When a diagnosis of CMD is missed, subjects are untreated, and they remain at a high risk of heart attack and/or cardiovascular-related death.”

Caladrius thinks it may have an answer. Its small trial was centered on CLBS16, a CD34 cell that is a naturally occurring preprogrammed microvessel repair cell. “Our mission is to harness the body’s own ability to restore itself after ischemic injuries by isolating these cells from a CMD patient and administering a concentrated dose to the patient to restore the microcirculation,” Losordo said.

“In our ESCaPE-CMD trial of CLBS16 and previously reported studies, CD34+ cells administered in the heart act to restore microcirculation by promoting the growth of new capillaries. Investigators conducting the ESCaPE-CMD trial of CLBS16 observed that subjects with CMD who received the therapy experienced an increase in coronary flow reserve coincidental with an improvement in symptoms.

“These study results support our theory that cell-based tissue repair and regeneration is possible in patients with CMD, by using a purified, naturally occurring vascular repair cell. This is different from other treatments given the self-healing, restorative capabilities and the fact that this method has shown to increase coronary flow reserve and potentially reverse CMD after a single dose.”

The ESCaPE-CMD trial is an ongoing interventional, proof-of-concept trial that has enrolled 20 patients at two centers, all of whom received a single infusion of CLBS16. Results from the first 17 patients are being reported during the 2019 AHA meeting.

The trial is designed to evaluate the effect of CLBS16 on CMD symptoms and indicators as well as to evaluate adverse events. Specifically, the trial evaluated changes from baseline to six months for coronary flow reserve, angina frequency, Canadian Cardiovascular Society (CCS) angina classification and other cardiovascular metrics.

The trial showed patients experienced statistically significant (p=0.0087) increases in coronary flow reserve after just one intracoronary administration of the patient’s own CD34+ cells as well as significant reductions in angina frequency and improvements in CCS class.

No cell-related adverse events were reported, and the company said complete results of the trial, including the results of the six-month follow-up of the remaining treated patients, are expected by year-end 2019.

There is a need for new treatments, because, currently, helping CMD patients initially includes many of the standard drugs used to treat ischemia or the restriction of blood supply to tissues such as beta blockers, calcium antagonists and nitrates. But Losordo said that control of symptoms with these treatments is often insufficient.