An investigational allogeneic cell therapy using cardiosphere-derived cells (CDC) showed an acceptable safety profile with early evidence of efficacy in the treatment of very severe Covid-19 in a case series involving six patients treated at Cedars-Sinai Medical Center in Los Angeles.
All six patients treated with the intravenous allogeneic CDC formulation CAP-1002 (Capricor Therapeutics) as a compassionate therapy required respiratory support prior to treatment, with five on mechanical ventilation.
No adverse events related to the treatment were reported, and four of the six patients were successfully weaned from respiratory support and were discharged from the hospital as of late April.
The other two patients are still alive, but remain intubated, Cedars-Sinai cardiologist Raj Makkar, MD, confirmed to BreakingMED Wednesday, May 13.
“While we are encouraged by these findings, it is important to point out that the only way that we can assess the efficacy of this treatment in a definitive way is with a randomized clinical trial, and that is what we intend to do,” Makkar said.
He added that the clinical trial, which is in the planning stages, is likely to include Covid-19 patients who are not as critically ill as the six in the case series.
“All of these patients required respiratory support and they were all on a downward trajectory when treated,” he said. “They were getting worse and we had nothing else to offer them.”
Cardiosphere-derived cells are stromal/progenitor cells from heart tissue with a distinctive antigenic profile (CD105+, CD45-, CD90low).
In their case series, published in the journal Basic Research in Cardiology, Makkar and colleagues noted that the cells are entirely distinct from the controversial c-kit+ putative cardiac progenitors, which have been the subject of various retracted studies.
Since CDCs were first isolated in 2007, the cells have been tested in more than 200 patients in clinical trials for a variety of conditions with a good safety profile, including in young boys with Duchenne muscular dystrophy.
Makkar said the anti-inflammatory and antifibrotic properties of CDCs in animal models make them a possible target therapy for Covid-19.
“The prior testing gave us reasonable confidence that this treatment was safe,” he said, adding that there is also evidence of a favorable effect on the same type of proinflammatory cytokines that are up-regulated in Covid-19.
Comparisons to mesenchymal stem cells (MSCs) in pre-clinical models suggest that CDCs may also be more effective for paracrine factor secretion and myocardial remodeling.
“Given the safety record of CDCs in humans, and the substantial body of evidence confirming relevant disease-modifying bioactivity, applicability to Covid-19 seemed compelling, particularly in the hyperinflammatory stage of the illness,” the researchers wrote.
All six patients treated with the intravenous CDC formulation had severe, confirmed Covid-19 with respiratory failure and they were not receiving any other experimental agent, with the exception of hydroxychloroquine and tocilizumab.
Lack of clinical improvement or deterioration despite standard care was the primary reason for considering patients for treatment with CAP-1002. Exclusion criteria included known hypersensitivity to DMSO, which is a component of CAP-1002; prior stem cell therapy; pre-existing terminal illness; and need for mechanical circulatory support and dialysis.
“In general, patients with multi-organ failure who were deemed to be too sick for any intervention were excluded from the study,” Makkar and colleagues wrote.
All patients had acute respiratory distress syndrome (ARDS) prior to infusion, with decreased PaO2/FiO2 ratios (range 69-198; median 142), diffuse bilateral pulmonary infiltrates on chest imaging and evidence of preserved cardiac function on transthoracic echocardiography (LVEF range, 50-75%). SOFA scores ranged from 2 to 8 prior to stem cell treatment.
The six patients (age range, 19-75 years) had IV infusions of CAP-1002 containing 150 million allogeneic CDCs, and two of the six had a second dose of the treatment.
Following treatment, four patients (67%) were weaned from respiratory support and discharged from the hospital.
“A contemporaneous control group of critically ill Covid-19 patients (n = 34) at our institution showed 18% overall mortality at a similar stage of hospitalization,” the researchers wrote.
Ferritin was elevated in all patients at baseline (range of all patients 605.43-2991.52 ng/ml) and decreased in five of the six patients (range of all patients 252.89–1029.90 ng/ml).
Absolute lymphocyte counts were low in five of the six patients at baseline (range 0.26–0.82 × 103/μl) but had increased in 3 of these five at last follow-up (range 0.23–1.02 × 103/μl).
“Administration of CAP-1002 as a compassionate therapy for patients with severe Covid-19 and significant comorbidities was safe, well tolerated without serious adverse events, and associated with clinical improvement, as evidenced by extubation (or prevention of intubation,” the researchers wrote.
Stem cell therapy utilizing cardiosphere-derived cells (CDC) showed an acceptable safety profile with early evidence of efficacy in the treatment of very severe Covid-19 in an early case series involving 6 patients treated at Cedars-Sinai Medical Center, Los Angeles.
No adverse events related to the treatment were reported, and four of the six patients were successfully weaned from respiratory support and were discharged from the hospital.
Salynn Boyles, Contributing Writer, BreakingMED
Funding for this story was provided by the Smidt Family Foundation. The cell product, CAP-1002, was provided by manufacturer Capricor Therapeutics.
ResearcherEduardo Marban reported owning founder’s equity in Cariricor Therapeutics, and researcher Linda Marban reported being an employee and owning equity in the company.
Cat ID: 125
Topic ID: 79,125,254,930,287,728,932,570,574,730,933,125,190,926,192,927,151,928,925,934