FDA Grants Rare Pediatric Disease Designation for Mesoblast’s Cell Therapy to Treat Rare Heart Condition

Rare Daily Staff

The U.S. Food and Drug Administration has granted Rare Pediatric Disease designation to Mesoblast for its allogeneic cell therapy Revascor as a treatment for children with the potentially life-threatening heart condition hypoplastic left heart syndrome.

HLHS is a severe congenital heart disease in which the left side of the heart does not fully develop and effective pumping of oxygenated blood by the left ventricle to the rest of the body is reduced. Without immediate surgery after birth, the prognosis is dismal with HLHS overall being responsible for 25 percent to 40 percent of all neonatal cardiac mortality.

In the longer term, surgery that creates a two-ventricle series circulation with the left ventricle (LV) pumping blood to the body and the right ventricle pumping blood to the lungs is the ideal anatomic repair. Unfortunately, achievement of this objective is limited by the inability in most patients for the left ventricle to grow sufficiently to support the circulation to the body.

Revascor is an allogeneic preparation of immunoselected and culture-expanded mesenchymal precursor cells that have been shown previously to have multiple mechanisms-of-action that may be beneficial to children with HLHS, including neovascularization, anti-fibrosis, anti-apoptosis, immunomodulation, reduction in inflammation, and reversal of endothelial dysfunction. In the DREAMHF randomized sham-placebo controlled prospective trial of Revascor in 565 randomized adult patients with heart failure with low ejection fraction (HFrEF), a single intramyocardial administration of Revascor into the left ventricle resulted in significant improvement in LV ejection fraction at 12 months, indicative of strengthened overall LV systolic function.

Results from a blinded, randomized, placebo-controlled prospective trial of Revascor conducted in the United States in children with HLHS were published in the December 2023 issue of the peer reviewed The Journal of Thoracic and Cardiovascular Surgery Open.

In the HLHS trial conducted in 19 children, a single intramyocardial administration of Revascor at the time of staged surgery resulted in the desired outcome of significantly larger increases in left ventricular (LV) end-systolic and end-diastolic volumes over 12 months compared with controls as measured by 3D echocardiography.

These changes are indicative of clinically important growth of the small left ventricle, facilitating the ability to have a successful surgical correction, known as full biventricular (BiV) conversion, which allows for a normal two ventricle circulation with the surgically repaired left ventricle taking over circulatory support to the body. Without full BiV conversion the right heart chamber is under excessive strain with increased risk of heart failure and death.

The FDA grants Rare Pediatric Disease designation to incentive development of new treatments for serious or life-threatening diseases that primarily affect children ages 18 years or younger with fewer than 200,000 people affected in the U.S. The RPDD program allows for a sponsor who receives an approval to qualify for a priority review voucher (PRV) that can be deemed to receive an expedited six-month priority review for any subsequent marketing application or may be sold or transferred. Most recently, Sarepta Therapeutics sold a PRV for $102 million.

“Given the impressive enlargement of the left chamber we have seen in these children treated with Revascor in the randomized controlled trial and the increased ability to successfully accomplish life-saving surgery, we plan to meet with FDA to discuss the potential for this trial to support accelerated approval in this indication,” said Mesoblast CEO Silviu Itescu.

Photo: Mesoblast CEO Silviu Itescu