Investigational Drug Study Leads to FDA Approval for Fenfluramine in Treatment for Dravet Syndrome

Children who experience seizures associated with Dravet syndrome have a new medication option, thanks to research at CHOC Children’s that helped gain the recent approval of the U.S. Food and Drug Administration (FDA).

Dravet syndrome is a sodium channelopathy that causes an intractable, difficult-to-control form of epilepsy beginning in the first year of life, as well as significant developmental and motor impairments. Many patients with this rare and severe type of epilepsy experience prolonged and unrelenting seizures and are at risk for SUDEP (sudden unexpected death in epilepsy).

Dravet syndrome is difficult to treat with the antiepileptic medications currently available in the United States, but the FDA has recently approved FINTEPLA® (fenfluramine) for the treatment of seizures associated with Dravet syndrome in patients 2 years of age and older. Dr. Mary Zupanc, pediatric epileptologist and co-medical director of the CHOC Children’s Neuroscience Institute, was a key investigator in one of the two international drug studies that led to U.S. FDA approval.

Dr. Mary Zupanc
Dr. Mary Zupanc, pediatric epileptologist and co-medical director of the CHOC Children’s
Neuroscience Institute

“The drug we recently trialed, fenfluramine, showed a significant reduction in convulsive seizures and overall seizures, which helped improve the quality of life not only for patients with Dravet but for their families as well,” Dr. Zupanc said.

Study 1 trialed 0.2 mg/kg/day or 0.7 mg/kg/day. The patients on the higher dose had a 70% reduction relative to placebo in monthly convulsive seizure frequency. And 70% of the patients on the higher dose had at least a 50% reduction in their monthly convulsive seizures compared to 7.7% of patients on placebo. Patients on the lower dose of fenfluramine had a 31.7% reduction relative to placebo in monthly convulsive seizure frequency, and 34.2% of patients on the lower dose had at least a 50% reduction in their monthly convulsive seizures.

In addition to reducing the monthly convulsive seizure frequency in patients whose seizures were not adequately controlled on one or more antiepileptic drugs, most study patients responded to treatment with fenfluramine within three to four weeks, and the effects remained consistent over the treatment period. Dr. Zupanc remarked that fenfluramine’s effectiveness could be “life-changing” for patients with Dravet.

Fenfluramine — used on its own and also paired with phentermine in the popular weight-loss combination known as “fen-phen” — was withdrawn from the U.S. market in 1997 after reports of heart valve disease and continued findings of pulmonary hypertension. Due to these risks, subjects received frequent EKGs and echocardiograms throughout the investigational trial. No valve disease or hypertension was found, but a decrease in appetite and some observations of a minor increase in irritability were noted.

Dr. Zupanc is optimistic about fenfluramine’s application for Dravet, but advised that it is only part of an overall treatment plan. “If a physician has a patient with Dravet syndrome, I would make sure the patient gets referred to a Level 4 epilepsy program, the highest designation for epilepsy centers,” Dr. Zupanc said. “CHOC is a level 4 epilepsy center, which means we do investigational drug studies, vagus nerve stimulation, epilepsy surgery, ketogenic diet and provide a full-service epilepsy program with six epileptologists with board-certification in epilepsy. Because we have participated in these [investigational] studies, we are on the ground floor and know how to dose these drugs and adjust these medications.”

Our Care and Commitment to Children Has Been Recognized

CHOC Children’s Hospital was named one of the nation’s best children’s hospitals by U.S. News & World Report in its 2020-21 Best Children’s Hospitals rankings and ranked in the neurology/neurosurgery specialty.

Learn how CHOC’s neuroscience expertise, coordinated care, innovative programs and specialized treatments preserve childhood for children in Orange County, Calif., and beyond.

CHOC recognized as one of nation’s best children’s hospitals

CHOC Children’s is one of a select group of pediatric facilities nationwide to have been ranked today as a best children’s hospital by U.S. News & World Report.

The following CHOC specialties are honored in the 2020-21 Best Children’s Hospitals rankings: neonatology; cancer; diabetes and endocrinology; neurology and neurosurgery; orthopaedics; pulmonology; and urology. Both orthopaedics and diabetes and endocrinology earned a “Top 20” spot.

“At CHOC, we are committed to the highest standards of care, safety and service – and this honor reflects that unwavering dedication,” said Dr. James Cappon, CHOC’s vice president, chief quality and patient safety officer and interim chief medical officer. “Not only does this recognition of our excellence in these subspecialties, including two on the top 20 lists, validate our efforts, but it also offers our patients and families additional assurance of our commitment to their health and safety.”

The Best Children’s Hospitals rankings were introduced by U.S. News in 2007 to help families of children with rare or life-threatening diseases find the best medical care available. Only the nation’s top 50 pediatric facilities are distinguished in 10 pediatric specialties, based on survival rates, nurse staffing, procedure and patient volumes, reputation and additional outcomes data. The availability of clinical resources, infection rates and compliance with best practices are also factored into the rankings.

The U.S. News Best Children’s Hospitals rankings rely on clinical data and on an annual survey of pediatric specialists. The rankings methodology factors in patient outcomes, such as mortality and infection rates, as well as available clinical resources and compliance with best practices.

Learn more about Best Children’s Hospitals rankings.

CHOC recognized as one of nation’s best children’s hospitals

CHOC Children’s is one of only 50 pediatric facilities in the nation to earn recognition as a best children’s hospital by U.S. News & World Report. The following CHOC specialties are honored in the 2019-20 Best Children’s Hospitals rankings: diabetes/endocrinology, cancer, neonatology, neurology/neurosurgery, pulmonology and urology. Cancer ranked in the “top 20.”

“The national recognition for CHOC’s cancer program is well-deserved. There’s nowhere else I’d rather have gone through treatment than CHOC,” says 17-year-old Sydney Sigafus, CHOC patient and cancer survivor. “Everyone who works at CHOC cares about you as a person, not just a patient. I was included in every decision and conversation about my care.”

The Best Children’s Hospitals rankings were introduced by U.S. News in 2007 to help families of children with rare or life-threatening diseases find the best medical care available. Only the nation’s top 50 pediatric facilities are distinguished in 10 pediatric specialties, based on survival rates, nurse staffing, procedure and patient volumes, reputation and additional outcomes data. The availability of clinical resources, infection rates and compliance with best practices are also factored into the rankings.

“We understand how scary it can be for parents whose children are dealing with life-threatening illnesses or injuries. That’s why we are committed to the highest standards of care, safety and service,” says Dr. James Cappon, CHOC’s chief quality officer. “While we are proud of our accolades, including being named a best children’s hospital, we remain focused on preserving the magic of childhood for all kids, whether they are seriously ill or healthy, or somewhere in between.”

More information about the Best Children’s Hospitals rankings can be found here.

In the Spotlight: Irfan Ahmad, M.D.

In addition to treating newborn babies requiring critical care, neonatologist Dr. Irfan Ahmad strives to involve family members in the care of their infant, which he says is essential for providing the best possible care for babies in the CHOC Children’s neonatal intensive care unit.

“I always include parents as part of the care team when treating a baby in the NICU, especially the mother. A mother and her baby were a single unit up until right before the delivery,” Dr. Ahmad says. “Parents are an essential part of the healing team, and building a strong physician-parent relationship is an important aspect of patient- and family-centered care.”

Surgical NICU

An internationally trained neonatologist, Dr. Ahmad also serves as medical director of the surgical neonatal intensive care program at CHOC.

Irfan Ahmad, M.D.
Irfan Ahmad, M.D.

The program will take up residence in CHOC’s recently-opened NICU, which features 36 private rooms with the latest technology and innovations in neonatal care. The 25,000-square-foot unit is nearly triple the size of CHOC’s prior NICU space, and will allow parents to stay overnight with their babies.

“We strongly believe in mother-baby bonding and the value of breast feeding, and our new private NICU rooms are designed to optimize that,” he says.

The recently-opened NICU also features three rooms with surgical lights, allowing minor procedures to be performed at the bedside.

The only Surgical NICU on the West Coast, CHOC’s program is comprised of a multidisciplinary team including neonatologists, pediatric surgeons and anesthesiologists.

“What inspires me the most about care being delivered at CHOC is the combination of passion for helping babies, multidisciplinary interactions, use of modern technology and an atmosphere of teaching,” Dr. Ahmad says. “From dedicated neonatologists present 24 hours a day in the NICU, nurses constantly advocating for best care, nutritionists and pharmacists rounding with the team, physical therapists, wound care teams, lactation specialists and social workers all working together to help a fragile small baby has no parallel.”

Dr. Ahmad’s Surgical NICU team also offers extracorporeal life support (ECLS), also referred to as extracorporeal membrane oxygenation (ECMO) for patients. CHOC is the only facility in Orange County that offers ECLS, which supports the heart and lungs by taking over the heart’s pumping function and the lung’s oxygen exchange until they can recover from injury, surgery or illness.

In addition to neonatologists, the dedicated ECLS team is composed of cardiothoracic and pediatric surgeons, intensive care physicians, nurses, respiratory therapists and cardiopulmonary perfusionists who are experts in their fields and have received additional education to manage the complex equipment and medical needs of the children needing this life-saving technology.

In addition to stewarding the Surgical NICU, Dr. Ahmad’s special clinical interests include caring for babies who require surgery, including those born with structural abnormalities such as diaphragmatic hernia, intestinal obstruction and imperforate anus. His clinical interests also include babies who develop the intestinal infection necrotizing enterocolitis or who have intestinal perforation. His most common diagnoses include intestinal obstruction and trachea-esophageal fistula.

Mandibular Distraction Program

Dr. Ahmad is especially passionate about caring for babies with difficulty breathing due to an undersized or recessed lower jaw, which can be caused by a condition called Pierre Robin Sequence.

In 2008, Dr. Ahmad helped launch a mandibular distraction program at CHOC. Dozens of infants have benefited from mandibular distraction osteogenesis, which involves a plastic surgeon placing a special device in the small lower jaw to expand it, prompting new bone growth over a period of two to three weeks.

Traditionally, babies with this condition have been treated by placing a tracheostomy that remains in place for several years until the child outgrows the condition. Mandibular distraction is a more permanent solution that takes a few months to complete, allowing a baby to go on to have a normal, healthy development.

Constant quality improvement

Passionate about quality improvement, Dr. Ahmad serves as director of quality improvement for NICUs affiliated with CHOC Children’s Specialists. He has participated in several quality improvement initiatives with Vermont Oxford Network and California Perinatal Quality Improvement Collaborative. This includes a project to improve the transition of care for surgical cases from one team to another, decreasing delivery room intubations and preventing premature newborn babies from developing hypothermia.

As the director of quality improvement for CHOC’s network of nine NICUs, he partners with quality improvement teams at each unit in carrying out improvement projects based on local needs. The team currently has nine simultaneous quality improvement projects in the hospitals where CHOC neonatologists round.

Passionate about educating the next generation of pediatricians and neonatologists, Dr. Ahmad also serves as NICU education director for UC Irvine’s pediatric residency program and is an associate clinical professor of pediatrics at UC Irvine. He also trains neonatology fellows through CHOC’s partnership with Harbor-UCLA Medical Center’s neonatal-perinatal medicine fellowship program.

His current research efforts include studying the breathing patterns of full-term babies in order to refine inclusion criteria for the mandibular distraction procedure. He is also currently studying the clinical outcomes of CHOC’s surgical NICU program.

Pursuing his calling to care for children

Dr. Ahmad attended medical school at Aga Khan University in Pakistan. He completed a residency in pediatrics at the University of Oklahoma and a fellowship in neonatal-perinatal medicine at UC Irvine. He has been on staff at CHOC for 10 years. He knew from an early age that he wanted to care for children, so pursuing a pediatrics residency after medical school was a natural choice.

“I was exposed to various specialized fields like cardiology and oncology, but I wanted to take care of the whole patient. I also wanted to see when I could have the most impact on the life of a person,” Dr. Ahmad says. “During my residency when I worked in the NICU, I noted that good care in the first few minutes of life was so critical. Effective resuscitation, followed by intensive care in the NICU could make all the difference for the patient, who can then live a long and accomplished life.”

Dr. Ahmad finds inspiration in the strength of his patient’s families, and is continually renewed and humbled by their gratitude.

“I have been impressed by the strength of the families who have a sick little baby in the NICU. It is extremely difficult to have your newborn on a ventilator struggling for life. Yet, we see the moms and dads holding on to hope and being there for their baby,” Dr. Ahmad says. “Neonatology is a very difficult field with long hours taking care of very sick babies. The gratitude you get from parents when the baby is finally well and going home and the amazing photographs and cards that are sent to us makes everything worthwhile.”

In his spare time, Dr. Ahmad enjoys golfing with his children and developing his photography skills.

Learn more about neonatal services at CHOC Children’s.

CHOC Children’s Opens New NICU with All Private Rooms

CHOC Children’s Hospital has opened its new neonatal intensive care unit (NICU) with 36 private rooms, a feature that will allow parents the opportunity to stay close to their newborns receiving intensive care.

A patient room in CHOC’s new NICU

The 25,000-square-foot unit nearly triples the size of the hospital’s previous Level 4 NICU, which included an open layout that grouped patients in pod-style beds.

The new unit, located on the fourth floor of CHOC’s Bill Holmes Tower, creates a homey atmosphere with sleeping quarters and storage space outfitted in warm colors and wooden accents to help parents feel more comfortable while their infants receive highly specialized care for extended periods of time.

“CHOC is proud to offer private rooms to our smallest patients and their parents,” said Dr. Vijay Dhar, medical director of CHOC’s NICU. “No one’s vision of parenthood includes a NICU stay, but our new unit will provide parents with the space and privacy to get to know their new baby, and reassurance that they’ll be nearby while their newborn receives the highest level of care.”

Private NICU rooms are a new standard for improved patient outcomes. Benefits for babies cared for in single-family rooms include higher weight at discharge and more rapid weight gain. Also, they require fewer medical procedures and experience less stress, lethargy and pain. Researchers have attributed these findings to increased maternal involvement.

A nurses station in CHOC’s new NICU

A private-room setting provides space and privacy sought by parents to breastfeed, practice skin-to-skin bonding, and be more intimately involved in their baby’s care. Further, individual rooms allow parents to stay overnight with their newborn, and give staff more access and interaction with the family and patient.

In addition to private rooms, the new space includes other features that will enhance patient care. Should an infant need a sudden surgical procedure, three rooms within the unit can quickly be converted into space for surgeries. The unit will also include a life-saving extracorporeal membrane oxygenation (ECMO) unit. Rooms that adjoin can be used to accommodate triplets.

Safety features include same-handed rooms, wherein equipment is positioned in the same location among all rooms to reduce human error; room-adjacent nursing alcoves; and an in-unit nutrition lab for the preparation of breast milk and formula.

CHOC’s new unit also features a family dining space, a room dedicated for siblings, a lactation room and other amenities to ensure the comfort of the entire family.

The CHOC Children’s Foundation has raised $4,381,984 toward the new NICU, including lead gifts from the Argyros Family Foundation, Credit Unions for Kids and philanthropist Margaret Sprague.

For several decades, CHOC has served infants requiring the highest level of care. With the unit’s opening, CHOC’s neonatal services now include 72 beds at CHOC Orange and the CHOC Children’s NICU at St. Joseph Hospital, and 22 beds at CHOC Children’s at Mission Hospital. In addition, a team of premier CHOC neonatologists care for babies at hospitals throughout Southern California.

A room dedicated for NICU patients’ siblings

A suite of specialized services comprises the CHOC NICU: the Surgical NICU, which provides dedicated care to babies needing or recovering from surgery; the Small Baby Unit, where infants with extremely low birth weights receive coordinated care; the Neurocritical NICU, where babies with neurological problems are cohorted; and the Cardiac NICU, which provides comprehensive care for neonates with congenital heart defects.

Visit www.choc.org/nicu to learn more about CHOC’s neonatal services.