European Neuromuscular Centre Conference on Pediatric FSHD

by Ally Roets, Tucson, Arizona

I was honored to attend the Pediatric FSHD European Neuromuscular Centre (ENMC) conference in Amsterdam, Netherlands, this past October. I was invited as a parent advocate and as a member of a global community striving for better care and outcomes for those affected by pediatric and early-onset FSHD. This workshop brought together 27 participants, including clinicians, research experts, physical therapists, and patient advocates from 14 countries, to achieve a critical goal: To establish a consensus on how to define, manage, and address pediatric FSHD.

The Continuum of FSHD

One of the most critical takeaways from the conference was the recognition of FSHD as a continuum.  The term “infantile FSHD” was retired in favor of “early-onset FSHD.” The focus will be on describing pediatric FSHD using clear and specific parameters such as age of onset, genetic test results, and other defining characteristics. Clinicians agreed they should be careful in the way they describe early-onset FSHD, to not restrict access to therapies developed for “typical” FSHD. Regardless of age of onset, it is the same disease.

The progression rates, clear predictors of rapid disease progression, and the probability of non-muscle involvement vary significantly along this continuum. At one end of this spectrum are children with rapid weakness and a higher rate of extramuscular manifestations, including hearing loss and vision problems. We know approximately 50% of FSHD diagnoses occur before the age of 18, underscoring the importance of tailored pediatric guidelines and research.

Clinical Management of Pediatric FSHD

A large portion of the meeting was dedicated to establishing pediatric-specific clinical management guidelines for early-onset FSHD. There is an urgent need to create evidence-based, pediatric-specific FSHD guidelines with input from subspecialists including: psychological support, nutritional review, physical and occupational therapy, vision and hearing screening, cardiology and pulmonary baselines and follow-up, and the transition of young people into adult care. A care standards task force was created to develop consensus-based care recommendations for early-onset and pediatric FSHD.  It will supplement the FSHD care guidelines expected to be published this year.

The need for standardized protocols and core outcome measures were also discussed to allow for meaningful comparison of data and ensure consistency across studies and in clinics.  A task force was assembled to come to a consensus on a minimum functional data set for clinical care and research, including trials.

Re-thinking trial design with an eye on access to treatments

Clinical trials are scientific experiments to test whether a novel treatment is well-tolerated and effective. To get data that are easier to interpret, there are inclusion and exclusion criteria to reduce factors that can affect an individual’s response to an experimental treatment. For example, if someone has another illness such as cancer, their disease and treatments might change how they respond to the FSHD drug. Or if someone is very young and their body is still growing, it can be difficult to tease apart which effects are due to the medicine versus natural growth.

However, these challenges are not insurmountable.  Drug companies have run trials in pediatrics and severely affected individuals in the past, and those companies working on FSHD can do the same.  There are mechanisms within the system that can be utilized. This requires innovation, and a willingness to work with the community to bring treatments to all affected individuals.

Individual access to approved treatments has two hurdles: First, is the FDA labeling of the drug.  The FDA can elect, based on data presented by the company, to grant a “narrow” label or a “broad” label.  Narrow label would only include the populations of those individuals represented in the trials (e.g. mildly affected adults).  Conversely, it could grant a broad label, which means anyone affected by the disease (it is usually restricted by age—especially below age 12) can be prescribed the medication.

The second hurdle is the insurance companies.  In the past, insurance companies would normally pay for broad label, FDA-approved treatments. Unfortunately, we are in a different world now. Even if the FDA approves treatment for everyone, there is another important battle to be had: the insurance company. If insurers can find a reason to not pay for a treatment, chances are they will refuse to pay. Faced with a large claim for an expensive new treatment, the insurer can reject the claim. They can say there’s no evidence the drug will work in a person who does not match the population that was studied in the clinical trial. Right now, that would include patients under age 18 or over 65 (or whatever the upper cut-off age is). It would include people who can’t walk. On the other end of the spectrum, it would include mildly affected people.

This new reality, which others, such as people with spinal muscular atrophy (SMA) have already run into, is why we are speaking out now, with great urgency. We must do what we can to broaden the age and functional criteria for inclusion in clinical trials. We must help drug companies find a path to move quickly into trials for children under age 18 and those individuals who can no longer walk—this includes about half (40%) of early-onset individuals who become wheelchair dependent by age 17.

Action items

At the meeting, we brainstormed about ways to overcome the obstacles to pediatric and early-onset clinical trials. These included:

• Clinically meaningful outcomes for these populations;
• More inclusive inclusion/exclusion criteria to avoid overly restrictive designs;
• Assessments based on individuals’ functional abilities, rather than on strictly age-specific cohorts.

Clinicians, researchers, and advocacy groups play a critical role in interacting with regulators and pharmaceutical companies to promote inclusive trial designs that ensure broad access to approved treatments. The inclusion criteria for clinical trials have profound implications for who will ultimately have access to approved therapies. If pediatric or non-ambulatory patients are excluded from clinical trials, it creates significant barriers for these populations to access treatments once approved, because FDA labeling and insurance reimbursement often hinges on evidence gathered during trials. This exclusion perpetuates inequities, leaving the most vulnerable patients—those with early-onset or severe forms of FSHD—without viable treatment options.

While the clinicians and physical therapists work in their task groups, I also left with a few tasks of my own. In cooperation with my European counterpart, we will update the FSHD Society’s “Guide for Schools” to make it globally applicable. Additionally, we will develop a set of FAQs to serve as resources for children and young people with FSHD, and their families.

Final Thoughts

The development of clinical care guidelines that address the unique challenges posed by the severity of the disease in this population is important to improve quality of life and mitigate disease impact. Additionally, ongoing dialogue around the inclusion of early-onset and pediatric patients in interventional clinical trials is vital, as these trials represent hope for transformative treatments. Addressing barriers to trial participation—such as restrictive inclusion criteria—can help ensure these vulnerable populations are represented. Viewing FSHD as a continuum disease further supports this effort, emphasizing the need for inclusivity across all ages and severities.

I would like to thank all the clinicians providing care to our kids, and helping them transition to adult care, and whose voice and expertise we so desperately need to amplify our desperate cry for access to treatments. I left the conference feeling inspired and more determined than ever to continue this vital work. Together, with the support of the global FSHD community, we can provide standardized care and treatment for everyone with FSHD, regardless of severity or age of onset.