Bringing Our Science to the Bedside

Children's Hospital of Philadelphia was a lead study site for the clinical trial that led to the approval of the first treatment for Friedreich's ataxia (FA) — an inherited neurodegenerative disorder that affects one in 50,000 people worldwide. Omaveloxolone (Skyclarys®, Biogen) is a once-a-day oral pill designed to improve neurological function and slow the progression of the disease.

"As the first approved drug for FA, this is a major event not only for FA but also for all ataxias and the rare disease community," said David Lynch, MD, PhD, director of the Friedreich's Ataxia Program, and an attending neurologist in the Division of Neurology at CHOP. "We are grateful for the support of the Friedreich's Ataxia Research Alliance (FARA), whose generous funding supported the background research that paved the way for this development, and to the patients who participated in the trials that led to this approval."

Dr. Lynch led studies showing that omaveloxolone — a potent activator of a transcription factor that regulates the cellular defense against oxidative stress — was shown to be effective at improving symptoms and slowing progression of the disease. The therapy sent patients "back in time," on average by a year or two, and kept them at that disease state for three to four years.

The U.S. Food and Drug Administration's accelerated approval of the first gene therapy for Duchenne muscular dystrophy (DMD) was a major win for the field of gene therapy and for the one in 3,500 boys who are affected by the debilitating genetic disorder, according to Children's Hospital of Philadelphia experts. Most patients with the condition, which causes progressive muscle degeneration, do not live past young adulthood.

The drug, known as SRP-9001 (Elevidys®, Sarepta), is the 13th FDA-approved gene therapy. The approval was based on data from a small sub-group of patients, while a larger trial continues. CHOP, which houses one of the largest DMD treatment clinics in the country, is a participating research institution in Sarepta's ongoing, multinational Phase III clinical study to test the safety and efficacy of the drug. As part of the trial, two CHOP patients received a dose of the irreversible gene therapy.

While data from the large trial will not be available for several months, “time is of the essence for DMD patients and their families,” said John Brandsema, MD, an attending neurologist at CHOP with expertise in treating children with neuromuscular disorders. For them, the fast-tracked approval of Elevidys offers a dose of hope.

"We're facing a tremendous foe, and for decades, scientists have been hammering away with various research attempts," Dr. Brandsema said. "Now we have what many of us believe is the first therapy that really is making a difference. It's not a cure, but we think these boys are potentially going to have many more functional years and a very different quality of life."

Crizotinib (Xalkori®, Pfizer) — a first-generation anaplastic lymphoma kinase (ALK) inhibitor for patients with unresectable, recurrent, or refractory inflammatory ALK-positive myofibroblastic tumors (IMT) — received approval from the U.S. Food and Drug Administration.

Data from two multicenter clinical trials — one led by researchers at Children's Hospital of Philadelphia through the Children's Oncology Group (COG), which included 14 pediatric patients — and another trial that included seven adult patients supported the approval of crizotinib for IMT in July 2022.

Yael Mossé, MD, an attending physician at CHOP's Cancer Center and a professor of Pediatrics at the Perelman Medical Center at the University of Pennsylvania, has studied ALK alterations in the context of several cancers, including neuroblastoma. She was the principal investigator for the pediatric trial that led to crizotinib's FDA approval for anaplastic large cell lymphoma (ALCL) in January 2021, and now for IMT.

"The approval of Xalkori for ALK-positive IMT will bring hope to many pediatric patients and families who previously had highly limited treatment options," Dr. Mossé said. "It is very exciting to have approval for frontline unresectable IMTs. This is an important milestone for these patients, and for pediatric oncology researchers within COG and CHOP, who continue to seek out more rational therapies."

The Hemostasis and Thrombosis Center (HTC) at Children's Hospital of Philadelphia celebrated 50 years of providing comprehensive care to children and adolescents with hemophilia and other inherited bleeding or clotting disorders. The Center was founded in 1973 as one of the first of its kind in the country. It is considered a Center of Excellence for the diagnosis, treatment, and prevention of bleeding and clotting disorders, serving as a national resource for other institutions.

"What started at CHOP as caring for 48 patients a year with hemophilia has grown into providing care for over 1,000 children with all types of bleeding and clotting disorders at our Center," said Center Director Leslie Raffini, MD. "It's been an incredible journey to witness the advancement of treatment options for our patients, which today includes an FDA-approved potentially curative gene therapy for patients with hemophilia B."

CHOP launched the Novel Therapeutics for Bleeding Disorders (NoT Bleeding) Frontier Program in 2023, which is housed in CHOP's HTC. This program will establish a national referral center for novel therapies in hemophilia and other rare bleeding disorders and develop novel therapeutic approaches, including drug repurposing, novel monoclonal antibodies, and gene therapies.

Children's Hospital of Philadelphia Care Network implemented a first-of-its-kind program that provides teens with a comprehensive evaluation of real-world driving skills in a safe, controlled environment. The program builds on a decade of research from the Center for Injury Research and Prevention and is supported by a gift from NJM Insurance Group. 

Offered to adolescents during acute and well visits, the Virtual Driving Assessment (VDA) program identifies skills needed to be a safe driver and addresses the three most common serious crash risks: a lack of scanning needed to detect and respond to hazards, going too fast for road conditions, and being distracted by something inside or outside of the vehicle.

Once fully operational across the CHOP Care Network, researchers plan to measure the program's effect on licensing and crash data among young people in New Jersey and Pennsylvania.

"It's important that we ensure patients at CHOP learn how to be safe drivers so they can avoid involvement in crashes and the negative health consequences of crashes," said Elizabeth Walshe, PhD, a research scientist who investigates how cognitive development in young drivers may influence driver safety. "This study will help us identify teens at higher risk for crashes, based on their individual factors, and inform how we tailor driver training for these groups of teens."