Tag Archive for: FDA

Hiram receives the first commercial dose of Elevidys

Children’s National gives first commercial dose of new FDA-approved gene therapy for Duchenne muscular dystrophy

Hiram receives the first commercial dose of Elevidys

On the day before his 6th birthday, Hiram, 5, was the first patient ever with DMD to receive the drug after the U.S. Food and Drug Administration (FDA) approved its use last month.

Children’s National Hospital is the first pediatric hospital to administer a commercial dose of Elevidys (delandistrogene moxeparvovec-rokl), the first gene therapy for the treatment of pediatric patients with Duchenne muscular dystrophy (DMD).

On the day before his 6th birthday, Hiram, 5, was the first patient ever with DMD to receive the drug after the U.S. Food and Drug Administration (FDA) approved its use last month.

“The approval of Elevidys opens a new door for young patients with DMD and their families,” says Sarah Wright, D.O., neuromuscular neurologist at Children’s National. “This disease has had limited targeted treatments to date which can help alter the trajectory of disease.”

The background

On June 22, the FDA approved the use of Elevidys for patients 4 through 5 years of age with DMD with a confirmed mutation in the DMD gene who do not have a pre-existing medical reason preventing treatment with this therapy.

DMD is a rare and progressive genetic neuromuscular disease that predominantly affects males. It is caused by genetic changes in the DMD gene that affects the muscles, leading to muscle wasting that gets worse over time. Symptoms include progressive weakness and loss (atrophy) of both skeletal and heart muscle. Muscle weakness is usually noticeable in early childhood when signs like delayed ability to sit, stand or walk, and difficulties learning to speak manifest in a patient.

How it works

Elevidys is a one-time intravenous gene therapy that aims to delay or halt the progression of DMD by delivering a modified, functional version of dystrophin to muscle cells. The dystrophin gene is the largest known human gene.

“Elevidys is a viral vector (the ‘envelope to deliver the gene of interest’) mediated gene therapy that allows for the introduction of a gene that codes for a shortened form of dystrophin protein, or microdystrophin,” Dr. Wright explains. While not a cure for DMD, trials of Elevidys have demonstrated increases in dystrophin expression and improved functional results in young children with the disease.

“We have years of dedicated work on the part of researchers, clinician leaders and advocacy organizations in the field of muscular dystrophy to thank for this ground-breaking moment,” says Dr. Wright. “The approval of Elevidys offers families of patients ages 4-5 with DMD the option to receive this gene therapy that is designed to target the underlying cause of the disease.”

“The time-sensitivity of this medication illustrates the importance of going to a top academic pediatric hospital early on in neurologic care,” adds Elizabeth Wells, M.D., senior vice president of the Center for Neuroscience and Behavioral Medicine at Children’s National.

What’s next

The neuromuscular team at Children’s National is looking forward to offering this therapy to young patients with DMD and to the completion of additional trials/results for therapies in the DMD drug development pipeline.

“The research and approval of novel therapies provides more options for our DMD patients and their families, which is a critical step toward improving the lives of patients with DMD,” Dr. Wright says.

Dr. Kurt Newman in front of the capitol building

Children’s National leaders provide expertise and support to advance SHIP-MD pediatric innovation initiative

Dr. Kurt Newman in front of the capitol building

“Having spent 30 years on the frontlines of pediatric healthcare as a surgeon, I saw so much innovation focused on adult medicine and not on pediatric populations. Instead, we were trying to adapt adult devices for use in children, which is not an effective solution,” says Dr. Newman.

The advancement of children’s medical devices in the U.S. continues to significantly lag behind adult devices for many reasons. A dedicated group of public and private sector healthcare leaders are working together to change that trend. In culmination of its first stage of work, the System of Hospitals for Innovation in Pediatrics – Medical Devices (SHIP-MD) initiative recently held a dynamic 3-day public workshop to further develop this groundbreaking public-private partnership, which is currently in its pre-consortium/conceptual phase.

Children’s National leaders and clinicians were among the pediatric healthcare experts who contributed to robust discussions about how to build and nurture a public-private partnership system that will safely accelerate the advancement of pediatric medical devices.

The workshop was developed and guided by a multi-stakeholder group including the Critical Path Institute (C-Path), the U.S. Food and Drug Administration’s (FDA) Center for Devices and Radiological Health (CDRH), AdvaMed, the American Academy of Pediatrics (AAP) and leaders of pediatric health systems.

Lee Beers

“We must strive to improve medical devices for children, which historically lag five to 10 years behind adults. For many children, that can be a lifetime,” says Dr. Beers.

Reflecting its ongoing commitment to bridging the pediatric innovation gap, Children’s National Hospital experts co-led discussions throughout the program, which explored ways to improve children’s health by transforming the existing medical device ecosystem to stimulate investment and innovation in pediatric devices.

Children’s National Hospital President and CEO Kurt Newman, M.D., and Lee Beers, M.D., medical director for the Child Health Advocacy Institute at Children’s National Hospital served as opening session speakers, providing their insights into the current state of innovation in pediatric devices and why a new approach, such as SHIP-MD, is vitally needed.

“Having spent 30 years on the frontlines of pediatric healthcare as a surgeon, I saw so much innovation focused on adult medicine and not on pediatric populations. Instead, we were trying to adapt adult devices for use in children, which is not an effective solution,” says Dr. Newman. “Children’s National Hospital is proud to contribute to SHIP-MD’s pioneering efforts to address this critical disparity and reform pediatric device development in order to ensure that children, regardless of their age or condition, have access to the life-changing treatments and technologies they need to grow up stronger.”

An op-ed recently penned by Dr. Newman in STAT further explores the importance of public-private partnerships like SHIP-MD that are focused on fast-tracking innovation in medical devices for children.

Beers, who also serves as president of AAP, highlighted the fact that, as medical technology continues to advance, children are not reaping the benefits.

Kolaleh-Eskandanian

“Through the SHIP-MD initiative, we can work to ensure that the discipline of medical device development is equally understood and appreciated by its participating hospitals,” says Dr. Eskandanian.

“We must strive to improve medical devices for children, which historically lag five to 10 years behind adults. For many children, that can be a lifetime,” says Beers. “Much more needs to be done to address the countless hurdles that prohibit children from accessing the technology they need. The disproportionate rate of disease in minority children is another indicator that we must not cut corners as we look to improve pediatric innovation access.”

Kolaleh Eskandanian, Ph.D., M.B.A., P.M.P., vice president and chief innovation officer at Children’s National Hospital and principal investigator for the FDA-funded National Capital Consortium for Pediatric Device Innovation (NCC-PDI), co-led the Qualifying Hospital Criteria panel, which addressed the importance of expanding the SHIP-MD network to medical institutions that have the infrastructure for the safe conduct of research.

“Through the SHIP-MD initiative, we can work to ensure that the discipline of medical device development is equally understood and appreciated by its participating hospitals. As champions of pediatric innovation, we must work to provide equitable access to device trials for every patient that qualifies,” says Eskandanian. “The goal of the Qualifying Hospital Criteria group is to introduce criteria that hospitals must meet in order to provide a safe environment to conduct pediatric medical device research and trials.”

Co-leading the Regulatory panel was Francesca Joseph, M.D., FAAP, a pediatrician at Children’s National Hospital and co-investigator for NCC-PDI. This workshop explored opportunities to address regulatory needs by refining current processes and considering new options to promote advancement of pediatric medical devices.

Francesca Joseph

Co-leading the Regulatory panel was Dr. Francesca Joseph, a pediatrician at Children’s National Hospital and co-investigator for NCC-PDI.

In the closing session, Eskandanian and other panel experts recapped the workshop and discussed core factors that will help determine whether or not SHIP-MD’s network is prepared to enter Phase II, the consortium phase. This phase includes the development of a strategic plan that incorporates the short, medium and long-term goals needed to create and implement the framework enabling the official launch of SHIP-MD.

During his talk, Dr. Newman also shared the strategic steps being taken by Children’s National that complement the SHIP-MD initiative in advancing pediatric device innovation. Among these is the creation of the Children’s National Research & Innovation Campus (CNRIC), the first-of-its-kind pediatric research and innovation hub located in Washington, D.C., which includes on-site partners JLABS, Johnson & Johnson Innovation’s life science incubator, and Virginia Tech University. The campus will nurture a rich ecosystem for pediatric innovation in the nation’s capital.

Karun-Sharma-and-kids-MR-HIFU

FDA approves MR-HIFU system to treat osteoid osteoma

Karun-Sharma-and-kids-MR-HIFU

“This FDA approval encourages and further motivates our focused ultrasound program to continue to develop and expand clinical applications of MR-HIFU in the pediatric population,”  said Karun Sharma, M.D., Ph.D.

After garnering successful clinical trial results at Children’s National Hospital, the United States Food and Drug Administration (FDA) recently announced the approval of Profound Medical’s Sonalleve MR-guided High Intensity Focused Ultrasound (MR-HIFU) system for the treatment of osteoid osteoma (OO) in the extremities. OO is a benign, but painful bone tumor that occurs most commonly in children and young adults. This marks the first focused ultrasound regulatory approval that will directly impact pediatric patients and it is the sixth indication to earn approval in the United States.

Nine patients were treated in a pilot trial designed to evaluate the safety and feasibility of MR-HIFU ablation treatment in patients with painful OO. The procedure was performed without any technical difficulties or serious adverse events in all nine patients, and resulted in complete pain relief with no further pain medication usage in eight out of nine patients.

“This FDA approval encourages and further motivates our focused ultrasound program to continue to develop and expand clinical applications of MR-HIFU in the pediatric population,” said Karun Sharma, M.D., Ph.D., director of Interventional Radiology and associate director of clinical translation at the Sheikh Zayed Institute for Pediatric Surgical Innovation (SZI) at Children’s National. “This completely non-invasive and radiation-free aspects of this therapy are especially relevant for growing children.”

Researchers at Children’s National have moved beyond OO are also evaluating MR-HIFU treatment for patients with relapsed and refractory bone and soft tissue tumors. “This is especially important as these patients don’t have any other good treatment options,” said Dr. Sharma. “For these tumors, we are using not only thermal ablation, but also other modes and biomechanisms of focused ultrasound such as mild hyperthermia to facilitate targeted, enhanced drug delivery and histotripsy (i.e., mechanical tissue fractionation) to enhance cancer immunotherapy. We also hope to move into MR-HIFU brain application in pediatrics.”

At Children’s National, a multidisciplinary team of physicians and scientists use MR-HIFU to focus an ultrasound beam into lesions to heat and destroy the tissue in that region, with no incisions at all. In 2015, Children’s National doctors became the first in the U.S. to use MR-HIFU to treat pediatric osteoid osteoma. The trial, led by Dr. Sharma, demonstrated early success in establishing the safety and feasibility of noninvasive MR-HIFU in children as an alternative to the current, more invasive approaches to treat these tumors. Since then, the Children’s National team has built an active clinical trials program and become a leader in translation of focused ultrasound for the treatment of relapsed pediatric solid tumors.

tiny stent illustration

Thinking small for newborns with critical congenital heart disease

tiny stent illustration

Illustration of a hybrid stage I palliation with bilateral bands on the lung vessels and a stent in the ductus arteriosus for patients with small left heart structures.

A new LinkedIn post from Kurt Newman, M.D., president and CEO of Children’s National Hospital, tells a story about the hospital’s cardiac surgeons and interventional cardiologists working with the U.S. Food and Drug Administration (FDA) to bring a better-sized, less-invasive vascular stent to the U.S. for the first time. The stent holds open a newborn’s ductus arteriosus, a key blood vessel that keeps blood flowing to the body, until the baby is big and strong enough to undergo a serious open-heart procedure for repair of hypoplastic left heart syndrome.

He writes, “Why is this important? At less than 6 lbs., these patients have arteries that are thinner than a toothpick – less than 2mm in diameter. Currently, the stent used in these children is an FDA approved device for adult vascular procedures, adapted and used off-label in children. It is not always well suited for the smallest babies as it is too large for insertion through the artery and often too long as well. The extra length can create immediate and long-term complications including obstructing the vessel it is supposed to keep open.

“While I am proud of the talent and dedication of our Children’s National cardiac surgery and interventional cardiology teams, I tell this story to illustrate a larger point – innovation in children’s medical devices matters. What’s unfortunate is that development and commercialization of pediatric medical devices in the U.S. continues to lag significantly behind adults…We can and must do better.”

Read Dr. Newman’s full post on LinkedIn.

expired drugs

Fewer than half of California pharmacies provide correct drug disposal info

expired drugs

Fewer than half of California pharmacies provided correct prescription drug disposal details, a percentage that dropped if “secret shoppers” made their call on a weekend, according to a brief research report published online Dec. 31, 2019, in Annals of Internal Medicine.

The callers pretended to be well-meaning parents who were trying to safely dispose of unneeded antibiotics and opioid-based prescription painkillers after their child’s surgery. Fewer than half of the California pharmacies they called provided correct prescription drug disposal details, a percentage that dropped sharply if the “secret shoppers” made their call on a weekend, according to a brief research report published online Dec. 31, 2019, in Annals of Internal Medicine.

“The Food and Drug Administration advises consumers about how to safely dispose of unneeded medicines and, because pharmacists can play an integral role in this conversation, the American Pharmacists Association says prescription medication disposal should follow FDA guidelines,” says Rachel E. Selekman, M.D., MAS, a pediatric urologist at Children’s National Hospital and the study’s first author. “We found very few California pharmacies permitted take-back of unneeded medications. There was also a striking difference in the accuracy and completeness of drug disposal information depending on whether they answered the call on a weekday or a weekend. That suggests room for improvement,” Dr. Selekman says.

The multi-institutional research team, led by Primary Investigator and senior author Hillary L. Copp, M.D., MS, at University of California, San Francisco, identified licensed pharmacies located in urban and rural settings in California. That state that accounts for 10% of all U.S. pharmacies. They wrote a script that guided four male and two female “secret shoppers” to ask about what to do about leftover antibiotics (sulfamethoxazole-trimethoprim tablets) and a liquid opioid-based painkiller (hydrocodone-acetaminophen). From late-February to late-April 2018, they called 898 pharmacies from 8 a.m. to 8 p.m., asking about the correct way to dispose of these medicines.

According to the FDA, consumers should mix most unused medicines with an unappealing substance, like kitty litter, place it in a sealed container and toss the container in the trash.  Medicines that can be harmful to others, like opioids, should be flushed down the sink or toilet. Many pharmacies have programs or kiosks to handle unused prescription medicines.

Of the pharmacies surveyed in California:

  • 47% provided correct information about disposing of antibiotics
  • 29% provided correct information about how to dispose of both antibiotics and opioids
  • 19% provided correct information about how to dispose of opioids
  • 49% provided correct antibiotic disposal information and 20% provided correct opioid disposal information on weekday calls
  • 15% provided correct antibiotic disposal information and 7% provided correct opioid disposal information on weekend calls

Asked specifically about drug take-back programs, just 11% said their pharmacy had one that could be used to dispose of antibiotics or opioids.

“Unused prescription medications can be misused by others and can result in accidental childhood poisonings,” Dr. Selekman adds. “The bottom line is that we often talk about how to address the problem of too many unused medications lingering in homes. There are many reasons this is a problem, but part of the problem is nobody knows what to do if they have too many prescription medicines. Because of this research, we have discovered that pharmacies don’t uniformly provide accurate information to our patients. Patients, families and health care professionals who advise families should work together to help improve and expand safe disposal options for these powerful medications.”

In addition to Drs. Selekman and Copp, the research team includes co-authors Thomas W. Gaither, M.D., MAS, Zachary Kornberg, BA, and Aron Liaw, M.D., all of whom were at the University of California, San Francisco, School of Medicine, Division of Pediatric Urology at the time the study was performed.

tubes filled with pink liquid

Manufacturing technologies lag behind breakthroughs in CAR-T cancer treatment

tubes filled with pink liquid

Drug companies around the country are banking on the cutting-edge cancer treatments known as CAR-T, but many manufacturing processes are holding back the treatment from reaching the market. With the success of CAR-T, which essentially re-trains T Cells to identify and target the cancer-causing cells, many manufacturers still need to catch up in the development process.

Currently, there are nearly 700 CAR-T studies in the database ClinicalTrials.gov, including 152 industry-sponsored trials that are active, recruiting or enrolling by invitation. According to market research firm, Coherent Market Insights, they predict the CAR-T market will grow to $8 billion worldwide by 2028 from $168 million in 2018.

Catherine Bollard, M.B.Ch.B., M.D., director of the Center for Cancer and Immunology Research at Children’s National Health System, was featured in a recent Bloomberg Law article stating that academics, industry participants and medical product regulators are trying to catch up with the technology and determine the best standards for developing these products. Although this is an exciting and positive time in the field of oncology, it also presents a big learning curve.

Making these cells requires extracting patients T cells. They are then genetically engineered in a laboratory to produce proteins that allow them to identify cancer-causing cells. The new cells are then multiplied and then reintroduced into the body to kill off the cancer cells. The entire process can take a few weeks to complete.

“This is not a drug,” Bollard said. “This is a living biologic, and it comes from the patient and individuals. There’s so much variability.”

Along with manufacturing challenges, the outlook on creating more therapies is looking good. The FDA predicts that it will be approving 10 to 20 gene therapy products a year by 2025. Other companies are working to develop a manufacturing platform that can help reduce the complexity of the current system and ultimately make CAR-T manufacturing easier to scale.

Kwitkin-family-photo

A rare diet: Could you survive on six grams of protein a day?

Clara Barton

Clara Rose Kwitkin was born at a healthy 7 pounds, 14 ounces on Nov. 12, 2018.

 

Children’s National Health System introduces clinic to help adults with phenylketonuria, a rare inherited disorder, experiment with Palynziq, an FDA-approved drug that helps the body process phenylalanine.

“What can you eat?” is a common question for picky eaters, particularly individuals with phenylketonuria (PKU), a rare inherited metabolic condition that prevents an enzyme in the body from processing the amino acid phenylalanine (Phe), a building block of protein.

About one in 10,000 or 15,000 people in the U.S. with PKU, approximately 50,000 people worldwide, understand this line of questioning. 

“It’s emotional,” says 27-year-old Ashley Kwitkin, a Northern Va. resident and new mom, about the complexities of following a low-Phe diet.

When Kwitkin previously went “off diet,” meaning eating more than six grams of protein a day, the equivalent of a handful of almonds, she felt the consequences: irritability, moodiness and poor concentration. Her body couldn’t process Phe.

The National Institutes of Health mentions excessive levels of Phe can lead to toxic levels in the blood and tissues, and even cause brain damage.

Kwitkin’s motivation during pregnancy quickly changed. “It’s not just me anymore,” notes Kwitkin, who gave birth to Clara Rose Kwitkin on Nov. 12. “It’s me and my child. The moment we met her, our lives changed forever.”  

If Kwitkin went off her PKU-approved diet while pregnant, she may have increased the chance that her baby would have been born with intellectual disabilities, heart problems, delayed growth, microcephaly or behavioral problems.

Fortunately, Kwitkin received medical clearance from her doctors to move forward with a safe and healthy pregnancy. While she is a carrier for PKU, her husband is not – which meant their child had less than a 1 percent change of being born with this rare disease.

Like many adults with PKU, Kwitkin is grateful for advancements with early disease detection and treatment. If she had been born six decades earlier, she may have been hospitalized for neurological impairments, before PKU was recognized, screened for and treated with a low-Phe diet to support cognitive development.

Kwitkin is grateful for the popularity of gluten-free, PKU-friendly products and specialty food stores – compared to when she was growing up and had to order medical bread, which cost $13 a loaf and came out of a can. This trend makes it easy to find PKU-friendly meals to eat.

Expanding her palate is one of the reasons Kwitkin is following the results of a new clinic at Children’s National to help people with PKU experiment with Palynziq, an enzyme substitution therapy that helps people with PKU digest Phe.

Palynziq was approved by the Food and Drug administration on May 24, 2018 and a team of metabolic dietitians and geneticists at Children’s National have been helping a handful of adult PKU patients test out the treatment, slowly, over a preliminary period.

To prescribe the drug in a medically-supervised setting, the doctors introduced the injectable enzyme treatment to participants in small .25-mg doses, which started on Aug. 20, 2018, and monitored their progress as they worked up to the standard 20-mg treatment, a milestone many in the group reached in November 2018.

If the treatment continues to go well, based on the results of the FDA’s recommended titration schedule, the medical team will enroll additional participants in its clinic and share the results with other medical centers.

The timing of the new Palynziq clinic is also perfect for Kwitkin. If the drug works for her in the future, she won’t have to make three dinners: one for her, one for her husband and one for Clara Rose. While Kwitkin is currently off the low-Phe diet, she looks forward to resuming a PKU-friendly diet in the future – especially as she and her husband consider having a second child.

Kwitkin’s PKU-friendly diet consists of “safe” foods, such as unlimited amounts of peaches, apples, cabbage and green beans, which contain zero traces of Phe, and portioned amounts of low-Phe foods: pasta, bread, baked potatoes and specialty-ordered, low-protein items.

While planning for pregnancy, Kwitkin adjusted her protein intake to eight grams of protein a day. During pregnancy, she ate up to 19 grams of daily protein – to satiate her body’s needs and the needs of her baby – and regularly checked in with Erin MacLeod, Ph.D., a metabolic dietitian at Children’s National who is guiding the Palynziq clinic.

Kwitkin-family-photo

Ashley Kwitkin and her husband look forward to expanding their family in the future.

While the new Palynziq therapy carries potential benefits, such as the ability to join a family potluck without counting grams of protein, have second servings of broccoli, a carefully-portioned vegetable on the PKU diet, or thinking clearly while eating a low-Phe diet, a motivating factor for many of MacLeod’s patients, the treatment also carries risks. 

Potential side effects of Palynziq include severe allergic reactions – swelling of the face, lips, eyes and tongue – as well as shortness of breath, a faster heart rate, rashes, confusion, lightheadedness, nausea and vomiting.

So far, minor side effects, such as rashes and injection-site soreness, are noted among participants in the Palynziq trial at Children’s National. The full 20-mg prescription could be increased or decreased, based on how a person’s immune system responds to the foreign agent. If all continues to go well for the participants, they will take the recommended dose, equivalent to about 20 injections a week, and check in with the medical team every three months during the first year. Based on their benefit-risk assessment of the new drug, they can then segue into bi-annual visits if they want to continue with the treatment.  

“Our goal is to help participants decide if this therapy is a good fit for them, based on their lifestyle and health preferences,” notes MacLeod. For some people, MacLeod explains, such as those entering college or who form strong social connections around food, and who may experience the impact of going ‘off diet,’ this treatment could change their lives. Others, such as those who are in the process of moving to a new city or are in a busy period of their lives, may prefer following a strict low-protein diet compared to taking daily enzyme injections.

Another factor Kwitkin and MacLeod will keep in mind as the Palynziq clinics advance is the treatment’s variability. For example, Kuvan, the first drug of its kind is an enzyme therapy developed to help the body break down Phe. The drug was approved by the FDA in 2007, but only works in a small portion of the PKU population – about 10 percent of patients with a mild form of the condition. Instead of eating high-Phe foods, Kuvan users follow a mild-protein diet.

MacLeod views this type of individualized meal planning and how her patients react to food as a science, which drew her to the field. She works with 70 to 100 PKU patients each year from infancy to adulthood, including patients in their 60s, to help them meet their unique metabolic needs.

MacLeod is also tracking the use of gene therapy in metabolic disorders in addition to how the gut flora, or gut bacteria, helps PKU patients modulate and break down Phe.

“A lot of research is happening right now,” adds MacLeod about accelerations with PKU therapy. “I’ve seen how patients respond to new treatments, including a carefully-measured, low-Phe diet, and how their lives start to change once they can think clearly and feel better, which is a motivating factor and goal for many of our patients. I’ve also seen others pursue their dreams, which in Kwitkin’s case was to become a parent and history teacher.”

Like Kwitkin and others impacted by PKU, MacLeod looks forward to ongoing developments and research for this rare disease.

 

Doctors-working-with-Digital-Tablet

New network will advance treatments for children

Doctors-working-with-Digital-Tablet

Three leaders from Children’s National Health System are among the investigators of a new FDA-funded program created to launch a global clinical trials network. The initial $1 million grant from the Food and Drug Administration (FDA) establishes a network among the Institute for Advanced Clinical Trials for Children (I-ACT for Children), the National Capital Consortium for Pediatric Device Innovation (NCC-PDI) (affiliated with Children’s National), PEDSnet, the James M. Anderson Center for Health Systems Excellence and the Critical Path Institute, to address the unmet medical needs of children by improving quality and efficiency in developing innovative pediatric drugs and devices.

Along with the fiscal 2017 funds, there is a potential for $1 million in funding each year for an additional four years to I-ACT for Children, contingent on annual appropriations and the availability of funding. I-ACT for Children is a new independent, nonprofit organization that works to improve the planning and completion of pediatric clinical trials. PEDSnet and the Anderson Center will serve as the network’s data and learning core, while the Critical Path Institute will serve as the regulatory science core and NCC-PDI will serve as the medical device core.

From Children’s National, the investigators include: Peter Kim, M.D., Ph.D., vice president of the Sheikh Zayed Institute for Pediatric Surgical Innovation; Kolaleh Eskandanian, Ph.D., executive director of the Sheikh Zayed Institute and NCC-PDI and Johannes van den Anker, M.D., Ph.D., division chief of Clinical Pharmacology and vice chair of Experimental Therapeutics.

“We are pleased that this grant addresses innovative reengineering of the pediatric device trials system,” says Eskandanian. “In contrast with drug trials, device trials are generally less optimally understood in academic medical centers and clinical sites.”

She explains that children have medical device needs that are considerably different from adults. Designing devices for children requires considerations such as growth and development, anatomical and physiological differences. Often, the lack of available devices for children forces clinicians to use an adult device off-label or to improvise. Off-label use may be the only option, but such use can bring risks of serious adverse events that could be avoided if there were more FDA–approved pediatric devices.

“Thanks to partnership with I-ACT we will be able to address the pressing need to improve clinical trials and post-market monitoring of pediatric devices,” says Eskandanian.

Leading the network as principal investigator is Edward Connor, M.D., president of I-ACT for Children and an emeritus professor of Pediatrics, Microbiology, Immunology, and Tropical Medicine at George Washington University School of Medicine and Children’s National.

Work has been initiated to integrate network components and engage public and private shareholders. Next steps include selecting priority projects for implementation in 2018 and beyond, and scaling the network in North America and abroad.

Funding for this work was made possible, in part, by the Food and Drug Administration through grant 1 U18 FD 006297. Views expressed in written materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does any mention of trade names, commercial practices, or organization imply endorsement by the United States Government.

Children’s National Chief of Allergy and Immunology helps move gene therapy forward

Catherine Bollard

Catherine Bollard, M.D., MBChB, Chief of the Division of Allergy and Immunology, recently shared her expertise on an FDA panel that unanimously expressed its support for a pediatric cancer T-cell therapy called CTL019.

On July 12, 2017, a U.S. Food and Drug Administration advisory committee unanimously expressed its support for CTL019 – a pediatric cancer T-cell therapy. If the FDA follows the advice from the 10-member Oncologic Drug Advisory Committee (ODAC) – which included Children’s National Health System’s Catherine Bollard, M.D., MBChB, Chief of the Division of Allergy and Immunology and Director of the Program for Cell Enhancement and Technologies for Immunotherapy – CTL019 will become the first gene therapy to hit the market.

“Many of these children with recurrent cancer are out of other options to treat their illness,” said Dr. Bollard. “We are encouraged by these findings and the potential for this therapy to improve outcomes and quality of life.”

CTL019 is a chimeric antigen receptor (CAR) T-cell therapy, comprised of genetically modified T cells that target CD19, an antigen expressed on the surface of B cells. Also known as tisagenlecleucel, the therapy targets a single type of cancer called acute lymphoblastic leukemia and was created by Novartis.

In clinical trials, CTL019 showed unparalleled effectiveness. Of the 68 patients who received the drug, 52 responded almost immediately, and their cancer disappeared within the first three months. Seventy-five percent of those patients remained cancer-free six months after treatment. The therapy has one main side effect: an immune reaction called cytokine release syndrome, which can be deadly, with extended spiking fevers and other symptoms.

However, because of CTL019’s high efficacy, FDA scientists asked the ODAC panel to focus on the therapy’s safety and manufacturing challenges rather than whether or not it works.

Several committee members, including Dr. Bollard, expressed apprehension about the T-cell subpopulations’ heterogeneity, which could affect safety and efficacy. Another issue for consideration by the ODAC panel was the long-term side effects of CTL019 and the possibility that the T-cell modification could go awry, causing secondary cancers in the future.

Despite these concerns, the committee concluded that the strong efficacy data and the near-term benefits of CAR-T therapy more than tipped the scales in favor of the therapy. ODAC members were also pleased with Novartis’ plan to minimize risk, which includes limiting CTL019 distribution to selected centers with CAR T-cell therapy experience, and extensive, long-term post-marketing surveillance plans.

The FDA is not required to follow the ODAC panel’s advice when making its final decision, but it often does so. A final decision by the FDA is anticipated by late September.

Read more about the story in the Philadelphia Inquirer, Medpage Today and Healio.com.

Children’s National Heart Institute experts partner with FDA and nation’s leading cardiology organizations to advance pediatric drug development

New joint health policy statement offers roadmap for immediate changes in clinical trial design to save children’s lives

Families with children suffering from rare and difficult-to-treat cardiovascular diseases may soon have better access to drugs to treat their often life-threatening conditions. For the first time, experts from the U.S. Food and Drug Administration (FDA), the American College of Cardiology, the American Heart Association and the American Academy of Pediatrics are working together to describe the challenges and opportunities to improve pediatric drug research as shared in a joint statement published online June 29 in the Journal of the American College of Cardiology and Circulation: Cardiovascular Quality and Outcomes.

“Children should have access to the latest advances in treatment and the best care. By challenging the status quo and designing new, safe and effective alternative study designs, we can give them the best opportunity to grow up stronger,” notes David Wessel, M.D., executive vice president and chief medical officer, Hospital and Specialty Services at Children’s National Health System. Dr. Wessel is internationally recognized for his pioneering work in caring for children with heart disease. As the senior author of the new joint statement and principal investigator of the STARTS-1 trial, which is the catalyst for this collaboration, he says he is “optimistic about this forward progress.”

According to the statement, less than 50 percent of drugs approved for use in the United States have sufficient data to support labeling for dosing, safety and efficacy in children. Additionally, a 2008 report by Pasquali et al, which reviewed more than 30,000 records of hospitalized children with cardiovascular disease, found that 78 percent received at least one off-label medication and 31 percent received more than three.

There are numerous challenges in the development and approval of medications for children – especially those with rare diseases – but the paper’s lead author, Craig Sable, M.D., associate division chief of cardiology at Children’s National, says we can and need to do better.

“While randomized clinical drug trials remain the gold standard in advancing care for adults with cardiovascular disease, relying solely on these types of trials for children unnecessarily limits the drugs approved for use in children,” says Dr. Sable. “Through this unique collaboration that unifies the voice of leaders in pediatric cardiology and the FDA, our goal is to provide a framework to better define which drugs are needed and how we can create novel study designs to overcome the current trial barriers.”

To read more about the barriers and ideas presented, please find the full statement here.