All posts by CHOC Children's

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.

Virtual pediatric lecture series: vision screening refresher

CHOC Children’s virtual pediatric lecture series continues with Vision Screening: Refresher for Primary Care Clinicians.

This online discussion will be held Monday, Sept. 28 from 12:30 p.m. to 1:30 p.m. and is designed for general practitioners, family practitioners and other healthcare providers.

Dr. Rahul Bhola, medical director of ophthalmology at CHOC, will present information on several topics, including the milestones of visual development and measuring visual acuity in children. Dr. Bhola will also discuss ways to manage common pediatric ocular disorders, as well as how to determine when a child should be referred to an ophthalmologist.

This virtual lecture is part of a series provided by CHOC that aims to bring the latest, most relevant news to community providers. You can register here.

CHOC is accredited by the California Medical Association (CMA) to provide continuing medical education for physicians and has designated this live activity for a maximum of one AMA PRA Category 1 Credit™.

Please contact CHOC Business Development at 714-509-4291 or BDINFO@choc.org with any questions.

MI 1&2 meeting and journal club

CHOC Children’s MI 1&2 Meeting and Journal Club goes virtual this month to discuss the latest advances in artificial intelligence and innovation.

This two-part lecture will be held Sept. 14 from 4 to 5:30 p.m. and will focus on innovative solutions to problems in pediatric healthcare. This month’s session will feature presentations from several industry partners, including:

  • Casey Clay, director of the escalating behavior program, Thompson Autism Center at CHOC Children’s
  • Adam Blum, VPO/CEO and co-founder of Auger AI
  • Paul Auffermann, chief customer officer of Closed Loop AI
  • Zack Muqtadir, founder of ZL Technovation

The MI1 portion of the meeting will take place from 4 to 4:45 p.m. and discuss medical intelligence, including monitoring model accuracy in medical machine learning and artificial intelligence for healthcare.

The MI2 portion discusses medical innovation and will begin at 4:45 p.m. It will include presentations on the impact of artificial intelligence on healthcare and the future, as well as immersive virtual reality training for caregivers of children with Autism Spectrum Disorder.

You can register to join the MI 1&2 meeting here. Journal Club will take place beforehand, from 3-3:45 p.m., and is accessible by Zoom Meeting ID 811 5578 7821.


CHOC rare disease expert stresses importance of newborn screening

From just a tiny sample of blood, a lab can test for 35 rare diseases in newborns that, if left undetected, could lead to seizures, developmental delays, permanent brain damage or death.

If results are positive for a metabolic disorder, these labs turn to the experts at CHOC Children’s metabolic laboratory for further analysis and treatment of newborns just days old.

September is Newborn Screening Awareness Month, and Dr. Jose Abdenur, director of CHOC’s metabolic laboratory, stresses the importance of these newborn screenings in order to prevent such grim scenarios from playing out.

Dr. Jose Abdenur, director of pediatric metabolic disorders at CHOC Children’s

Newborn screening is a public health program that screens all babies for many serious but treatable genetic disorders, and CHOC is one of the state’s largest referral centers for the program. All babies born in California are required to get screened soon after birth, but the diseases babies are screened for varies by state. In Orange County alone, some 38,000 babies are born every year.

CHOC is the only location on the West Coast for children who need cutting-edge treatment for certain metabolic diseases that can be detected from newborn screenings. Further, CHOC’s metabolics program is a leading destination for children from around the world afflicted with certain metabolic disorders, which are rare genetic disorders that result from a missing or defective enzyme in the body. These include disorders such as galactosemia, which impairs the body’s ability to process and produce energy from the sugar galactose, and adrenoleukodystrophy, which causes the buildup of very long-chain fatty acids in the brain.

“There are many, many very good success stories at CHOC, but there are still many things we can improve,” Abdenur says, citing too many false positives for some conditions that make families feel anxious and worried. “But we continue to get better at this.”

Newborn screening began in the 1980s. Over the decades, the Department of Health and Human Services has added recommended disorders for states to screen for in their newborn screening (NBS) programs. There now are 35 core conditions on the so-called Recommended Universal NBS Panel, as well as an additional 26 secondary conditions.

In addition to metabolic disorders, newborn screening can detect disorders related to hematology and immunology — such as sickle cell disease — as well as endocrine disorders, pulmonary diseases including cystic fibrosis, and such neurological conditions as spinal muscular atrophy.

How CHOC Children’s transformed its telehealth services during COVID-19

Between July 2019 and mid-March 2020, CHOC Children’s had completed 182 telehealth visits. After the onset of COVID-19 and to date? Since then, tens of thousands of visits have provided safe, high-quality care for pediatric patients at CHOC — and that number continues to grow.

So, how did CHOC elevate its telehealth offering so quickly and seamlessly?

It took a whole lot of teamwork, says Lisa Stofko, CHOC’s telehealth manager.

Tech steps

“We collaborated with CHOC’s information services department and had video technology set up within 72 hours,” she says. “This was essential, as we wanted to ensure patients were still getting the care they needed, and clinicians had the technology they needed to carry out appointments.”

To conduct telehealth appointments, CHOC clinicians primarily use a special version of Zoom, a video conferencing software with extra layers of protection. Clinicians also have access to InTouch, Health, PingMD and Doxy.me as well.

Patient safety remains paramount to providers, regardless of whether a visit is in-person or virtual. To ensure the protection of private health information during virtual visits, the telehealth team at CHOC collaborates closely compliance and information security.

“We want to remind families that CHOC’s doors have remained open, whether that be in person or virtually,” Lisa says. “We serve some vulnerable populations and we want to accommodate them safely.”

Increasing physician and patient comfort level

Although telehealth offerings predated the COVID-19 pandemic, some physicians had more experience conducting virtual visits than others. To increase comfort levels with new platforms, training videos were delivered to more than 700 providers.

Many patients and families were new to virtual visits as well. The telehealth team at CHOC wanted to make visits as easy as possible on families, so they prioritized replicating the in-person visit as closely as they could.

For clinic visits where patients are visited by multiple specialties, Zoom breakout rooms are utilized. This complex workflow requires close coordination with compliance and information services to ensure HIPAA compliance.

“Telehealth is not one-size-fits-all. The way one specialty care clinic operates may have a different flow than another,” Lisa says. “To make the process of adapting to virtual visits as easy as possible on families, we have interviewed providers and clinical staff on their typical in-person workflow and done our best to replicate that virtually.”

Before the appointment begins, families receive clear communication from their provider’s office on how to prepare themselves for a telehealth visit. The team recognizes patient-facing tech support as an essential part of ensuring a seamless appointment. Care coordinators empower patients with education and support for the continuum of care. Materials are translated into Spanish and Vietnamese. And just like with in-person appointments, translators are available during virtual visits, too.

Ensuring patient satisfaction

To measure patient satisfaction with the telehealth experience, CHOC’s telehealth team launched a satisfaction survey which is sent to patients within 24 hours after their appointment via text, email or phone. To date, results have consistently hovered around 91%, compared to a benchmark of 86%.

“We continue to monitor survey results and identify opportunities to further improve patient experience,” Lisa says.

Ongoing optimization

A 20-member steering committee was established from key stakeholders from across CHOC’s health system — including administrative executives and physicians — to further improve the telehealth experience and capabilities at CHOC.

Future plans include additional features to further replicate the in-person experience. The team is working toward kicking off and wrapping up a patient’s online appointment with a virtual visit from the same medical assistant. This would provide not only proper intake protocols, but also quality customer service and a personal touch.

Another tactic the team is working on implementing is streamlined notifications for parents – especially those of medically complex children who may have multiple telehealth visits with various specialists in the same day.

“We want to make sure that parents are easily able to keep track of appointments, and that we are not under or over communicating to them, causing additional stress,” Lisa says.

Moving forward, the CHOC telehealth team is doubling down on its commitment to ensuring telehealth remains a safe, high-quality and stress-free experience for providers and patients alike.

“There is a difference between a two-way video and telehealth,” Lisa says. “We are committed to making telehealth a seamless experience for both patients and providers, and ensuring that it replicates the safe, quality care patients are used to receiving in person.”

Learn more about telehealth at CHOC.