Improving access to cell and gene therapy in pediatrics

Nearly 30 years ago, Children's Hospital Los Angeles supported one of the first clinical trials for a pioneering stem cell gene therapy for children with a life-threatening form of severe combined immunodeficiency (SCID). Called ADA-SCID—a type of "bubble boy disease" caused by mutations in the adenosine deaminase (ADA) gene—this rare disorder leaves babies with virtually no immune system.

CHLA treated six of 10 babies in that early trial. That study was an important step toward the development of this novel gene therapy, which in 2016 was approved by the European Medicines Agency. The next generation ADA-SCID gene therapy was even more effective, curing 48 out of 50 children in a larger trial in the U.S. and United Kingdom.

Then, the unthinkable happened. The company that had licensed the therapy decided to shelve it—putting it out of reach of the patients who desperately needed it.

"You had all this potential, but it was behind lock and key," says Alan S. Wayne, MD, Pediatrician-in-Chief at Children's Hospital Los Angeles, who worked on that first trial earlier in his career when he was at the National Institutes of Health. "For years, no one could get to it."

The therapy is now available through a limited clinical trial. But it's just one example of the many innovative treatments for kids that disappear from development after showing promising results. That's why Dr. Wayne is helping to lead a national effort aimed at ensuring that successful therapies in pediatrics don't fall through the cracks.

In July, he co-led the Think Tank: Access 4 Kids program at Children's National Hospital in Washington, D.C.—a gathering of pediatric health care leaders focused on improving access to cellular and gene therapies for children. He also recently co-authored a paper on the topic in Nature Medicine.

"In pediatrics, by definition nearly everything is a rare disease," says Dr. Wayne, the Pasadena Guild Chair at CHLA. "Unfortunately, it's often not financially viable for companies to develop and market complex, expensive therapies for a small number of patients. We need newer and better models."

New models for small markets

Developing these new models is especially important because of the emergence of cell and gene therapies to treat and cure pediatric diseases.

"These are paradigm-changing therapies," Dr. Wayne says. "The question is: How do we pay for the development of these therapies? And once we prove effectiveness, how do we sustain access for children?"

To find answers to those questions, he moderated a special session at Access 4 Kids focused on establishing innovative approaches for developing and commercializing therapies for small pediatric markets.

The session included presentations from Peter Marks, MD, Ph.D., Director of the Center for Biologics Evaluation and Research at the Food and Drug Administration; immune-oncology expert Crystal Mackall, MD, of Stanford University; health economist Rena M. Conti, Ph.D., of Boston University; Craig Martin, CEO of Orphan Therapeutics Accelerator; and Surajit Sen, Partner, Life Sciences, at EY-Parthenon.

Dr. Marks shared a recent FDA proposal to streamline approvals for gene therapies that are based on the same technology platform as previously approved treatments. Other speakers presented the possibility of public-private partnerships and new models for reimbursing government and private insurers.

Creating a new enterprise

One model discussed—which was also featured in the paper—proposes creating a new entity outside the traditional pharmaceutical model.

Called the Pediatric Advanced Medicines Biotech (PAMB), the proposed organization would be funded by government and philanthropy to lead late-stage development and commercialization of pediatric cell and gene therapies.

To do this, PAMB would partner with major universities and academic medical centers to manufacture products in current good manufacturing practice (cGMP) facilities. Children's Hospital Los Angeles, for example, established one of the nation's first academic cGMP facilities in the 1990s and opened a new, larger cGMP facility with USC last year.

PAMB would also work closely with regulatory bodies to help bring novel cell and gene therapies for these rare and ultra-rare diseases to the market.

"This is a complex issue, and there likely won't be a one-size-fits-all answer," Dr. Wayne notes. "The think tank was an excellent way to bring everyone together so we can move new approaches forward."

Creating these solutions will be key to ensuring that pediatric medicine can fully realize the promise of gene therapies, he adds.

"The primary challenge with gene therapy is no longer the technology. It's the financial sustainability," Dr. Wayne says. "We need to ensure that successful therapies are available for the children who need them."

More information:
Crystal L. Mackall et al, Enhancing pediatric access to cell and gene therapies, Nature Medicine (2024). DOI: 10.1038/s41591-024-03035-1

Provided by Children's Hospital Los Angeles