First study of its kind to focus on new therapy for hypoplastic left heart syndrome
A pioneering stem cell therapy aimed at improving survival for infants born with hypoplastic left heart syndrome (HLHS) has entered a pivotal U.S. clinical trial, marking a potential breakthrough in the treatment of one of the most devastating congenital heart defects.
HLHS is a rare condition in which the left side of the heart fails to develop properly, leaving newborns with only a single functioning right ventricle and either no or a very undersized left ventricle. Without surgical intervention within the first days of life, the condition is universally fatal.
Children undergo three stages of surgery that rework the heart and the connecting vessels to place the right ventricle into the left ventricle position. The first surgery is the Norwood, the second is the Glen and the third is the Fontan. But even with this standard three-stage surgical reconstruction developed in the 1980s, survival remains poor. A right ventricle pumping to support the entire body will eventually lead to heart failure, which requires a fourth surgery for a heart transplant.
"Even with the successful surgery, you've got a right ventricle in the left ventricle position, and I think as our cardiovascular audience knows, that that is a big problem, because the right ventricle is the weaker of the two chambers. It's thinner, less capable of generating force. As it sits in that left position for life, it's going to fail, and the failure rate is extremely high. Only 50% of the kids live till 15 years of age transplant free," explained Joshua Hare, MD. He is a professor of medicine, molecular and cellular pharmacology, and biomedical engineering, director of regenerative medicine and the Interdisciplinary Stem Cell Institute (ISCI) at the University of Miami.
He is leading the effort to test whether mesenchymal stem cell therapy can strengthen the right ventricle and extend survival. Hare is also co-founder and chief science officer of Longeveron, which is developing the investigational therapy, laromestrocel (Lomecel-B), designed to boost the performance of the failing right ventricle, and possibly eliminate the need for a heart transplant.
"The main goal is to improve the clinical outcomes, and that means a reduction in congestive heart failure events, a reduction in the need for transplant and a reduction in the occurrence of death. That's the primary goal," Hare said.
The ongoing ELPIS II pivotal Phase 2b trial has enrolled 40 infants with HLHS across 12 top U.S. pediatric heart centers. Children undergoing the second stage of surgery at around four months of age are randomized to receive either standard surgical care, or the surgery and adjunct therapy intracardiac injection of Lomecel-B. The trial will follow patients for one year, with outcomes including survival, freedom from transplant, and measures of right ventricular function. Hare said this is the first pivotal study of its kind.
The therapy builds on promising early-phase results. In a first-in-human study of 10 children treated with stem cell injections during surgery, all patients were alive and transplant-free at five years, an outcome far better than historical averages, Hare said.
The mechanism of action may involve stimulating new blood vessel growth and potentially activating the heart’s own limited capacity for cardiomyocyte regeneration. Because children have greater regenerative potential than adults, researchers believe the therapy may be especially effective when given in infancy.
"That first five years of life is the key period where the majority of the morbidity and mortality happens to the children. So if they make it past five, their chance of getting to 15 is much higher," Hare said.
Importantly, the procedure adds only minutes to surgery, uses an off-the-shelf cell product and has shown no safety concerns to date.
Results from the pivotal trial are expected after the one-year follow-up period, with longer-term tracking planned for up to five years.
Dave Fornell has covered healthcare for more than 17 years, with a focus in cardiology and radiology. Fornell is a 5-time winner of a Jesse H. Neal Award, the most prestigious editorial honors in the field of specialized journalism. The wins included best technical content, best use of social media and best COVID-19 coverage. Fornell was also a three-time Neal finalist for best range of work by a single author. He produces more than 100 editorial videos each year, most of them interviews with key opinion leaders in medicine. He also writes technical articles, covers key trends, conducts video hospital site visits, and is very involved with social media. E-mail: [email protected]