Phase 2 Clinical Trial that Tests Stem Cell Treatment for Heart Attack Patients to be Funded by California Institute for Regenerative Medicine

A new stem cell therapy that treats heart attack patients with cells from a donor has been approved to begin a Phase 2 clinical trial.

Capricor Therapeutics Inc. a regenerative medicine company, has developed this treatment, which extracts donor stem cells from the heart called “cardiosphere-derived cells,” and then infuses them into the heart of the heart attack patient by means of a heart catheter procedure, which is quite safe. These stem cells are introduced into the heart to reduce scarring in the heart and potentially replace dead heart muscle cells. One clinical trial called the CADUCEUS trial has already shown that cardiosphere-derived cells can reduce the size of the heart scar.

In a previous phase I study (phase I studies typically only ascertain the safety of a treatment), cardiosphere-derived cells were infused into the hearts of 14 heart attack patients. No major safety issues were observed with these treatments, and therefore, phase 2 studies were warranted.

Alan Trounson, Ph.D., president of the California Institute for Regenerative Medicine (CIRM), which is funding the trial, said this about the phase 2 trial approval: “This is really encouraging news and marks a potential milestone for the use of stem cells to treat heart disease. Funding this type of work is precisely what our Disease Team Awards were designed to do, to give promising treatments up to $20 million dollars to develop new treatments for some of the deadliest diseases in America.”

Capricor was given approval by the National Heart Lung and Blood Institute (NHLBI) Gene and Cell Therapy (GST) to move into the next phase of clinical trials after these regulatory bodies had thoroughly reviewed the safety data from the phase 1 study. After NHLBI and GST determined that the phase 1 study met all the required goals, CIRM also independently reviewed the safety data from the Phase 1 and other aspects of the Phase 2 clinical trial design and operations. Upon successful completion of the independent review, Capricor was given approval to move forward into the CIRM-funded Phase 2 component of the study

Capricor CEO Linda Marbán, Ph.D., said, “Meeting the safety endpoints in the Phase 1 portion of the trial is a giant leap forward for the field and for Capricor Therapeutics. By moving into the Phase 2 portion of this trial, we can now attempt to replicate the results in a larger population.”

For the next phase, an estimated 300 patients who have had heart attacks will be evaluated in a double-blind, randomized, placebo-controlled trial. One group of heart-attack patients will include people 30 to 90 days following the heart attack, and a second group will follow patients 91 days to one year after the incident. Other patients will receive placebos and neither the patients nor the treating physicians know who will receive what.  This clinical trial should definitely determine if an “off-the-shelf” stem cell product can improve the function of a heart attack patient’s heart.

The California Institute for Regenerative Medicine (CIRM) is funding this clinical trial, and for this CIRM should be lauded.  However, when CIRM was brought into existence through the passage of proposition 71, it sold itself as a state-funded entity that would deliver embryonic stem cell-based cures.  Now I know that director Alan Trounson has denied that, but Wesley Smith at the National Review “Human Exceptionalism” blog and the LA times blogger Michael Hiltzik have both documented that Trounson and others said exactly that.  Isn’t ironic that one of the promises intimated by means of embryo-destroying research is now being fulfilled by means of non-embryo-destroying procedures?  If taxpayer money is going to fund research like this, then I’m all for it, but CIRM has to first clean up its administrative act before they deserve a another penny of taxpayer money.

CADUCEUS Clinical Trial Shows that Cardiosphere-Derived Stem Cells Can Regrow Heart Muscle After a Heart Attack

Cedars-Sinai Heart Institute is home to the CADUCEUS clinical trial. CADUCEUS stands for cardiosphere-derived autologous stem cells to reverse ventricular dysfunction. In this clinical trial, patients who had experienced a heart attack (and had left ventricular ejection fractions between 25% – 45%) were split into two groups. One group was given standard medical care for a heart attack patient and the other group was given standard care plus heart-based stem cells known as CDCs, which is short for “Cardiosphere-Derived Cells.” Patients assigned to receive CDC infusions of 12-25 million cells into the infarct-related artery 1.5 – 3 months after the heart attack.

The results 6 months after the stem cell infusion revealed that none of the patients in either group had died, developed tumors in their hearts or had experienced any major adverse heart-related event. Also Magnetic Resonance Imaging analysis of patients from both groups showed that those patients treated with CDCs displayed reductions in the mass of the heart scar, and increases in living, heart muscle mass. Additionally, the ability of the region of the heart that had experienced the heart attack contracted better in those patients who had received the CDC infusion. Also, the thickness of the wall of the heart was thicker in those patients who had received CDC infusions. Unfortunately, changes in other heart-specific functions such as EDV (end-diastolic volume), ESV (end-systolic volume), and LVEF (left ventricular ejection fraction) did not differ between the two groups by 6 months, which is difficult to reconcile with the structural changes in the hearts. .

Inventor of the procedures and technology used in this study, Eduardo Marbán, MD, PhD, who is also the director of the Cedars-Sinai Heart Institute, noted, “While the primary goal of our study was to verify safety, we also looked for evidence that the treatment might dissolve scar and regrow lost heart muscle. This has never been accomplished before, despite a decade of cell therapy trials for patients with heart attacks. Now we have done it. The effects are substantial, and surprisingly larger in humans than they were in animal tests.”

Shlomo Melmed, MD, dean of the Cedars-Sinai medical faculty and the Helene A. and Philip E. Hixon Chair in Investigative Medicine added, “These results signal an approaching paradigm shift in the care of heart attack patients. In the past, all we could do was to try to minimize heart damage by promptly opening up an occluded artery. Now, this study shows there is a regenerative therapy that may actually reverse the damage caused by a heart attack.”

An initial part of this study was conducted in 2009. In that study, Marbán and his colleagues used a patient’s own heart tissue to grow specialized heart stem cells. These specialized stem cells were injected back into the patient’s heart in an effort to repair and re-grow healthy muscle in a heart that had been injured by a heart attack. This experiment, at that time, was the first of its kind.

The results of that initial study were quite encouraging. The 25 patients, who participated in the study, had an average age of 57 and had suffered heart attacks that left them with damaged heart muscle. Each patient underwent extensive imaging scans to precisely locate the exact location and severity of the scars generated by the heart attack. Patients were treated at Cedars-Sinai Heart Institute and at Johns Hopkins Hospital in Baltimore.

Of these patients, eight received conventional medical care for heart attack survivors (prescription medicine, exercise recommendations and dietary advice) and were the control patients in this study. The remaining 17 patients were randomized to receive the stem cells underwent a minimally invasive heart biopsy, under local anesthesia that utilized a catheter inserted through a vein in the patient’s neck. From this catheter, doctors removed small pieces of heart tissue, about half the size of a raisin, that were taken to Marbán’s laboratory at Cedars-Sinai, where they were subjected to culture methods invented by Marbán to grow and expand the heart-based stem cells.

During a second, minimally invasive [catheter] procedure, the expanded heart-derived cells were reintroduced into the patient’s coronary arteries. Patients who received stem cell treatments experienced an average of 50 percent reduction in their heart attack scars 12 months after infusion while patients who received standard medical management did not experience shrinkage in the damaged tissue.

Marbán explained, “This discovery challenges the conventional wisdom that, once established, scar is permanent and that, once lost, healthy heart muscle cannot be restored.”

This phase I study definitely shows that the CDC infusion procedure is safe, which warrants the expansion of this procedure to a phase 2 study.