The children of FSHD – they exist, too

One community – united effort – cure for all

by Ally Roets, Tucson, Arizona

A few years ago, as we started to hear about clinical trials for promising new drugs for FSHD, I was frustrated to learn that my son Sam was too young to participate. When he turns 18 and is old enough, he will still be excluded because he can no longer walk.

I was assured that as soon as a drug was approved by the Food and Drug Administration (FDA), it would be available to everyone with FSHD. Doctors could prescribe it “off label” to any patient. But then I learned that insurance companies may resist paying for treatment, especially if it’s very expensive. They could argue that there is no clinical trial data to show the drug would help someone like Sam.

It can seem like children with FSHD are often overlooked by researchers. So in 2021, I and other parents formed the Early-Onset Parent Chapter of the FSHD Society. Our goal is to bring awareness to the pediatric FSHD population, and to support and educate parents.

After having in-depth conversations with researchers and clinicians, we discovered that several gaps existed in bringing treatments to the pediatric population. We began educating ourselves on the FDA clinical trial process and realized there are barriers to pediatric clinical trial readiness that need immediate attention:

• Focused and effective parent and patient advocacy is lacking.
• Little natural history exists on persons with onset prior to 18 years of age.
• Clinical trial outcome measures for pediatric and nonambulatory individuals need to be validated.
• Options to include pediatrics and non-ambulatory children in trials need to be explored with the industry partners.

Pediatric and non-ambulatory folks with FSHD were being left out of the drug development process. A small band of parents began tackling these issues with the help of the FSHD Society, Solve FSHD, and other experts in the field.

The FSHD Pediatric Summit

This past September, Solve FSHD convened a landmark FSHD Pediatric Summit in Northern California. They brought together leading pediatric clinicians, biotech companies, FDA regulatory personnel, and parents for two days to discuss barriers facing pediatric trials. The presentations and following discussions shattered preconceived notions and generated ideas to overcome the challenges associated with pediatric trials.

The top takeaway from the summit was that biotech companies are keenly interested in beginning pediatric trials. To get there, juvenile toxicology studies must be completed, and safety must be proven in adults before trials can be expanded to children under 12 years of age.

An additional challenge is the scarcity of data on the natural history of the disease in children. Most research and all clinical trials in FSHD have focused on adults, leaving pediatric patients in the shadows.

Current trials are limited to ambulatory adults between the ages of 18 and 65. We lack data on how FSHD impacts children who are still growing, people in wheelchairs, or seniors who are aging, meaning there is no benchmark to measure a drug’s effects in these groups.

To address these gaps, natural history studies like MOVE have been expanded to children, but participation in the study has been low. Consequently, we have limited knowledge of disease progression, potential biomarkers, and the factors that affect the quality of life for young patients.

Another enlightening outcome from the summit is that more young people have been affected by FSHD than previously reported. It is estimated that approximately 40% to 50% of the adult FSHD population reported symptoms prior to adulthood.

Prioritizing the treatment of children for clinical trials is crucial. Indeed, if children have more rapid progression of symptoms (something many parents can confirm), a company evaluating the efficacy of its treatment could detect a significant improvement in a shorter (i.e., six months) clinical trial.

The urgency to treat early

Early treatment may help attenuate or even prevent the rapid progression of the disease before it leads to severe muscle loss. Waiting until adulthood may result in irreversible muscle loss, which makes addressing the condition in childhood critical.

The urgency of early intervention to improve quality of life is highlighted by the fact that mobility is rapidly lost, with 26% of children ending up in wheelchairs by the age of 18. While previous data suggested that early-onset patients experienced many comorbidities such as cognitive issues or epilepsy, more recent data indicate that most early-onset individuals do not suffer from these issues. This revised understanding can encourage pediatric trials to help guide treatment strategies and expectations.

A critical gap to clinical trial readiness for FSHD is the lack of validated outcome measures of children. Developed for adults, current outcome measures may not capture the unique challenges faced by children with FSHD, such as developmental milestones and quality of life factors.

Several groups are working on developing appropriate outcome measures for pediatric FSHD. This can be accelerated by adaptation of previously validated pediatric motor outcomes such as those in the National Institutes of Health toolbox. The use of advanced technologies, video, and patientreported outcomes is also being explored.

Off-label is not a panacea

Some parents believe that once a drug is approved for adults, they will be able to get that drug prescribed by their child’s doctor “off label,” the practice of using a medication for a purpose or in a manner that is not specifically approved by the regulatory authorities.

This practice comes with important consequences. Insurance companies often will not cover the medication for off-label use, leading to out-of-pocket costs for patients. Without insurance reimbursement, these treatments would likely be out of reach for most families. Additionally, because off-label use lacks the rigorous testing and research typically associated with approved uses, their off-label use could expose patients to unanticipated risks.

Pediatric and non-ambulatory populations often face unique challenges, and excluding them from research can hinder the development of comprehensive treatments. By actively seeking ways to include these individuals in trials and adapting protocols to their needs, companies can contribute significantly to improving the lives of all FSHD patients.

Families must get involved

Parent and patient advocacy groups such as the FSHD Society, Solve FSHD, and other organizations are playing a pivotal role in raising awareness, funding research, and pushing for increased focus on the pediatric FSHD community. Much work still needs to be done – and all of it requires active participation by families.

Because it takes many years to start and run natural history studies, we are exploring the idea of “retrospective studies,” extracting data from our children’s past medical records and personal experiences to yield valuable insights into their disease progression, potential treatment approaches, and long-term outcomes.

This type of collaboration among patients, researchers, and trial developers not only accelerates the pace of medical discoveries but also empowers individuals to play an active role in advancing their own healthcare and that of others facing similar challenges.

Exploring innovative trial designs like run-in periods or crossover studies along with various avenues to early treatment access, including expanded access programs, is crucial to the urgent needs of the pediatric FSHD community.

I left the summit encouraged by the companies’ strong support for pediatric clinical trials. But I am haunted by the most critical question of all: If we build it, will they come?  Families are not showing up in the numbers we need for pediatric natural history studies. Lack of engagement creates the perception that there simply are not many pediatric patients, or that their families are not interested. Researchers and companies may feel it is too risky to launch a pediatric study. We need to show them we exist and are ready to engage.

Advocacy, collaboration, and research are the keys to making progress in the fight against FSHD. As a motivated and vocal community, we must address these issues and work together to pave the way for more effective treatments and a brighter future for all affected by FSHD.

A heartfelt thank you to Eva Chin, executive director of Solve FSHD, for working with the parent group and for pulling together and funding this landmark summit. Also, thank you to all the researchers, clinicians, biotech companies, and regulatory experts for attending the summit and working tirelessly to bring treatments to persons living with FSHD.