Lisa Nainggolan

April 07, 2008

April 7, 2008 (Chicago, IL) The latest study of stem cell therapy has reported mixed results. Although the procedure was shown to be safe in postmyocardial infarction patients with heart failure and implantable cardioverter defibrillators (ICDs) and there was some improvement in patients' symptoms, there was no benefit in terms of ejection fraction or wall thickness between cell therapy and usual medical care.

Dr Patrick Serruys (Thoraxcenter, Rotterdam, the Netherlands) presented the findings of the SEISMIC study with skeletal myoblast cell therapy (MyoCell; Bioheart Inc) during a late-breaking clinical trials session at the American College of Cardiology 57th Annual Scientific Session/i2 Summit-SCAI Annual Meeting last week. "In this patient population, skeletal myoblast cell therapy was not associated with an increase in arrhythmias and appeared safe," he said, "but global left ventricular ejection fraction [LVEF] remained unchanged." Because the trial was open label, he suggested that another study, in which the control group receives a sham procedure, is warranted to properly assess the effects of the therapy on quality of life.

Discussant Dr Nabil Dib (University of California, San Diego) said the SEISMIC trial "was very well designed, and does not show safety concerns that prohibit us from proceeding to a large clinical trial. However, as noted by Serruys, it was open label, and that's important when we assess quality of life." Nevertheless, he said, further study "might show some benefit for patients with adverse ischemic cardiomyopathy, and taken together with the CAUSMIC trial [which Dib conducted], myoblast therapy might have a clinical value."

MyoCell--No Significant Effect on HF but Procedure "Feasible"

In SEISMIC, 47 patients with heart failure and ICDs were randomized on a 2:1 basis to cell therapy or optimal medical treatment. Those who received cell therapy (n=31) underwent a muscle biopsy to extract autologous skeletal myoblasts, which were cultured and implanted into the myocardial scar using a catheter delivery system.

The primary safety end point was the incidence of procedural and device-related serious adverse events at three and six months. The primary efficacy end point was change in LVEF at three and six months, as assessed by MUGA, a radioisotopic technique. Secondary efficacy end points were quality of life, as measured by six-minute walking time, and NYHA class.

A total of 26 patients with ICDs who underwent cell therapy and 14 patients who received optimal medical treatment (control group) were assessed at six months. There was no difference between the two in terms of safety--there were 15 incidents of sustained arrhythmias in the cell-therapy group and 14 incidents in the control group. One patient in the treatment arm died, said Serruys, but that was due to a sudden deterioration of heart failure after two weeks.

Intramyocardial myoblast therapy improved neither global LVEF nor regional wall thickness at six-month follow-up, he noted. LVEF was 29.2% in the cell-therapy group and 32.9% in the control group at six months, and the left ventricle diameter actually increased in the cell-therapy group (54.5 mm, compared with 39.4 mm in the control group) at the end of each contraction.

In terms of symptoms, Serruys said, "the six-minute walk time showed an improvement in the [cell-therapy group] not seen in the control group--they were able to walk an additional 60.3 m, compared with 0.4 m in the control group--but this difference was not statistically significant." Similarly, three patients in the cell-therapy group had some relief of HF symptoms, as gauged by a one-step improvement in NYHA functional class, but one patient had a worsening of NYHA class. One patient in the control group had an improvement in NYHA class, and five experienced worsening HF status.

"These early data indicate that implantation of MyoCell in patients with heart failure is feasible and may provide symptomatic relief, although no significant effect could be detected on global LVEF or LV dimensions at six-month follow-up," Serruys concluded.

Largest Study of Its Kind to Date Underway

A larger, randomized, double-blind, placebo-controlled, multicenter phase 2/3 trial with MyoCell, involving 330 patients with class II or III congestive heart failure--called MARVEL--is currently underway in the US and Europe. The study "is the largest of its kind to date," according to a Bioheart press release [1]. Enrollment began in October 2007, and the lead investigator is Dr Warren Sherman (Columbia University Medical Center, New York).

Serruys reports no relevant financial relationships. Dib is a board member of, and shareholder in, Mytogen Inc, the sponsor of the CAUSMIC trial.

  1. Final data from the Bioheart SEISMIC trial suggest safety, efficacy of autologous stem-cell therapy for treating congestive heart failure. 1 April, 2008. BioHeart website. Available at http://www.bioheartinc.com/seismic_trial_release_040108.pdf

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