In a world awash with billion-dollar profits for drugs to treat the most common ailments ─ hypertension, acid reflux, diabetes, high cholesterol, and so on ─ patients with FSH muscular dystrophy may believe that rare conditions like theirs will never get the time of day from the pharmaceutical industry.
In fact, this is no longer true. With the passage of the Orphan Drug Act (ODA) in 1983, new incentives were created to attract companies to take on rare diseases (defined as having fewer than 200,000 patients in the US). These include tax breaks, market exclusivity, and millions of dollars in waived fees.
In many respects, the law has been a resounding success. Prior to the Act’s passage, the Food and Drug Administration (FDA) had approved only 34 drugs for orphan diseases. Since then, more than 600 orphan disease indications have been approved.
Apart from a few trials of drugs intended to increase muscle size, however, drug developers showed little interest in FSHD, even in the decades following the ODA. This changed dramatically with the publication in 2010 of a “unified model” for the genetic basis of FSHD. This hypothesis, from an international research team led by Silvère van der Maarel (the first recipient of an FSH Society grant), proposed that the genetic alteration in FSHD activated a gene called DUX4 to damage muscles.
About the same time, researchers equipped with better genetic tests and patient data began to realize that FSHD is more common than previously thought. Estimates of its prevalence rose from one in 20,000 to as high as one in 5,000. Once believed to be ultra-rare, FSHD is now viewed as one of the most common forms of muscular dystrophy.
As researchers unraveled how DUX4 expression leads to FSHD, they began to think about ways to intervene. The drug industry took notice. Our phones at the FSH Society started receiving calls from companies asking, What are the symptoms, and what is the impact on people’s lives? How many have it? Where are they? Are there doctors who see many patients? How hard would it be to conduct a clinical trial? If a treatment was developed, would people want to take it?
Fortunately, we could tell companies what they needed to know, thanks to years of work by the pioneering researchers and leaders at the FSH Society. We have a good understanding of the disease and the variable ways in which it affects people. The Society had funded research to develop “FSHD in a dish” cell-based and animal models, early-stage drug and gene therapy work, and clinical measurement tools. We had compiled the largest global database of patients and families, and are able to contact them on behalf of researchers and companies seeking volunteers for their studies.
It is remarkable to see all of this painstaking work converging around a collective goal ─ to get a treatment onto the market by the year 2025. This March 12, the FSH Society convened industry researchers, academic leaders, advocacy groups, and FDA representatives to assess how ready the FSHD field is for clinical trials. We discussed gaps in the data and tools ─ natural history studies, biomarkers, imaging methods, clinical measurements ─ and developed a plan to fill those gaps as quickly and efficiently as possible.
We call this enterprise our Therapeutic Accelerator Project. Our goal is to complete the work over the next three years. We will do so by acting as the “general contractor” to coordinate all of the stakeholders to collaborate on these projects. We intend to enlist the most capable labs, eliminate redundancy, and shorten the timelines to get the work done.
Substantial funds ─ $15 million over three years ─ are needed to complete this monumental task on schedule. This February, the FSH Society launched a campaign to raise the needed funds from a combination of industry partners and philanthropists.
In addition to funding, we will need a substantial investment of something equally valuable and even scarcer ─ the time and effort of patients willing to volunteer for the pivotal Therapeutic Accelerator studies. Did you know that across all medical research, 85 percent of trials face delays and 30 percent never get off the ground due to a lack of volunteers? We cannot let this happen in FSHD.
Our patients and families are waiting.