Capricor Reports Encouraging Results in its DYNAMIC Trial

Capricor Therapeutics, Inc., located in Beverly Hills, CA, has announced their six-month safety and adverse event data from a Phase I clinical trial of their CAP-1002 product for patients with advanced heart failure. This clinical trial is part of the DYNAMIC or which is short for Dilated cardiomYopathy iNtervention with Allogeneic MyocardIally-regenerative Cells trial whose goal is to evaluate CAP-1002 in patients with advanced heart failure.

CAP-1002 is Capricor’s lead investigational allogeneic, cardiosphere-derived cell (CDC) therapy. Allogeneic means that the cells come from someone other than the patient. The advantage of allogeneic cells is that they come from healthy donors whose cells have not been ravaged by old age or other conditions. These cells do not need to be matched to the patient’s immune system in this case because they help the heart through indirect means (see Tseliou E, et al., J Am Coll Cardiol. 2013 Mar 12;61(10):1108-19).  Cardiospheres are cells taken from the hearts of healthy patients that grow in culture as small balls of cells. Because these cells are derived from the heart and grow as spheres, they are called cardiospheres (see Cheng K, et al., JACC Heart Fail. 2014 Feb;2(1):49-61.).

Cardiospheres have been shown in small clinical trials (the CADUCEUS trial) to replace the heart scar with heart muscle (see Malliaras K, et al., Am Coll Cardiol. 2014 Jan 21;63(2):110-22).  Animal studies in rats showed similar results (see above).

CAP-1002 is an off-the-shelf “ready to use” cardiac cell therapy that consists of cells that come from donor heart tissue and is infused directly into a patient’s coronary artery during a catheterization procedure. This Phase I study is meant to determine if CAP-1002 is safe and effective in treating heart function and structure. In particular, Capricor scientists are interested in determining if CAP-1002 cells can decrease heart scar tissue and promote the growth of heart muscle. In doing so, this regenerative treatment might delay or even prevent the onset of heart failure. The US Food and Drug Administration has granted CAP-1002 an orphan drug designation for the treatment of cardiomyopathy associated with Duchenne Muscular Dystrophy.

Capricor’s Cardiosphere-Derived Cells are a unique therapeutic product that were created in the laboratory of company Co-Founder and Scientific Advisory Board Chairman, Dr. Eduardo Marbán, who is the Director of the Heart Institute at Cedars-Sinai Medical Center.

All patients in this trial have advanced heart failure and have progressed to a more advanced stage of the disease. Patients received CAP-1002 in up to three coronary arteries, which delivers the cells to the more of the diseased parts of the heart. Since these patients have significant fibrosis in all areas of the heart, this delivery system is optimal for these patients. Cell delivery will also utilize methods that do not stop blood flow, which will decrease patient discomfort during cell delivery.

The data from this trial, so far, comes from 14 patients who were diagnosed with either dilated cardiomyopathy or non-ischemic dilated cardiomyopathy. These patients have ejections fractions of 35% or less and are classified as New York Heart Association class III or Ambulatory Class IV heart failure.

The data collected to date show that CAP-1002 cells are safe and well tolerated and produced no adverse cardiac events at one month or six months after they were infused into the patient’s hearts. Although DYNAMIC was designed as a Phase I clinical trial that does not assess the efficacy of CAP-1002 cells, patients have also been tested for their subject wellbeing, exercise capacity (six-minute walk test), ejection fraction, and ventricular volumes.

According to the principal investigator Dr. Raj Makkar of Cedar-Sinai Medical Center, the data so far are rather encouraging, even beyond the positive safety data, since they are seeing “concordance between the clinical improvement and the physiological measurements of trends for improved ejection fraction and reverse re-modeling.” Dr. Makkar, however, emphasized that this clinical trial only tested a small cohort of patients, and these data must be confirmed in larger clinical trials.

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.