ANAHEIM, CALIF. (FRONTLINE MEDICAL NEWS) – One-time infusion of cardiosphere-derived cells into the three major coronary arteries seemed to prevent and perhaps even reverse cardiac scarring, as well as improve arm function, in the open-label phase 1-2 HOPE-Duchenne trial of 25 boys with advanced Duchenne muscular dystrophy.

“Decreased scarring is really a big deal because this is counter to the natural history of Duchenne, where all the scars progress, senior investigator Ronald G. Victor , MD, said at the American Heart Association scientific sessions. “It was gratifying to see that the changes in scar coincided with improved regional systolic wall thickening, particularly in the inferior wall of the left ventricle, which is the very area disproportionately affected early and thus severely in Duchenne.”

The reason for the excitement is that Duchenne muscular dystrophy, a genetic disorder affecting mostly boys, is one of the toughest diagnoses in pediatric medicine. “It’s a devastating muscle-wasting disease leading to progressive fibrosis in both skeletal and cardiac muscle.” Boys lose the ability to walk by age 12-15, and typically die from heart or respiratory failure by age 25, said Dr. Victor, professor of cardiology and chair of cardiology research at Cedars-Sinai Medical Center, Los Angeles.

Glucocorticoids are the only thing that help to date, prolonging ambulation by about 3 years, but with Cushingoid features and other well-known side effects.

Cardiosphere-derived cells (CDCs) – cardiac progenitor cells – have shown some promise for heart failure. They don’t seem to engraft and grow, but rather to release extracellular vesicles packed with proteins, RNA, and other bioactive molecules. “They act as a role model to get endogenous cells to do the right thing. That’s what we think,” Dr. Victor said.

The HOPE-Duchenne trial [Halt Cardiomyopathy Progression in Duchenne] randomized 12 boys with Duchenne to usual care and 13 others to usual care plus a single infusion of 75 million CDCs divided equally among the left anterior descending, circumflex, and right coronary arteries. The cells were derived from donated heart muscle. The specific CDC preparation tested was “CAP-1002” from Capricor Therapeutics , the study’s sponsor.

The boys were aged 12-22 years, with a mean age of 17.8 years. They had left ventricle scarring in at least four MRI segments; their mean left ventricle ejection fraction was just below 50%; 68% were wheel-chair bound, and all were on stable steroid regimens.

At 12 months, cardiac scarring had increased about 5% in the control group, but decreased by about 7% in the treatment arm, although with no change ejection fraction improvement (P = .03).

Skeletal muscle was assessed by mid-level and distal performance of upper limb scoring, a measure of arm function developed specifically for Duchenne. “For patients who have lost ambulation, the ability to use a joystick to drive a scooter, the ability to feed themselves and use a computer and cellphone are absolutely key to quality of life,” he said.

At 12 months, performance of upper limb scores were largely unchanged in the control group, but improved in about half of the treated boys. “A couple were quite dramatic,” Dr. Victor said. The differences were statistically significant (P = .007) when limited to subjects who started with scores below 55 points, with 58 points meaning normal function.

On the safety side, nothing unusual happened in the control arm, except a femur fracture.

One boy in the treatment arm went into ventricular fibrillation during the diagnostic angiogram. Five had periprocedural atrial fibrillation. All 13 had periprocedural troponin elevations, versus two boys in the control group over the entire course of the study. Dr. Victor didn’t report any deaths, but safety concerns are probably why Capricor is shifting to intravenous infusion for the next trial, HOPE-2.

Dr. Victor noted that troponin leaks “wax and wane” over time in Duchenne, so the transient increases in the treatment arm “were superimposed on a baseline of abnormal cardiac enzymes.”

The Food and Drug Administration has green-lighted the company’s HOPE-2 trial to start enrollment in early 2018, with a larger number of patients and intravenous CDC delivery at 3 month intervals.

Several investigators were Capricor employees. Others were consultants or reported ownership interests. Dr. Victor was the principal investigator at Cedars-Sinai, and was on the trial’s steering committee. The University of Florida, Gainesville, and Cincinnati Children’s Hospital Medical Center, Ohio, were the other two study sites.

SOURCE: Ronald Victor, MD; 2017 AHA Scientific Sessions abstract number S1177


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