In a plea to the U.S. Food and Drug Administration (FDA), advocates are urging regulators to utilize regulatory tools, including the accelerated approval pathway, to expedite the development and approval of treatments for rare diseases. With over 7,000 rare diseases affecting more than 30 million Americans, children and families grappling with these conditions are in desperate need of treatments and hope.

One disease group that highlights the urgency for accelerated approval is the mucopolysaccharidoses (MPSs), a class of genetic metabolic conditions. Mark Dant, a parent whose child has an MPS disorder, and Dr. Matthew Ellinwood, a chief scientific officer at the National MPS Society, are familiar with the challenges faced by these patients. Regrettably, the FDA has yet to utilize accelerated approval, even for promising drug candidates.

Characterized by developmental delay, chronic pain, enlarged organs, and early death in severe cases, the 12 subtypes of MPS collectively impact one in every 25,000 children. However, this plight is not unique to MPS patients, as countless individuals affected by various rare diseases find themselves in a similar predicament. Currently, regulators seldom approve potential treatments without lengthy, logistically challenging, and ethically problematic clinical trials, even if alternative regulatory pathways are available.

The traditional FDA approval process, which requires two randomized, placebo-controlled clinical trials confirming safety and clinical benefits, does not align well with rare diseases. The rarity of these conditions results in finding enough patients for traditional trials nearly impossible. Researchers often have to rely on international recruitment, which incurs additional expenses and obstacles.

Furthermore, rare diseases like MPS progress rapidly, making the enrollment of patients with severe symptoms into traditional trials especially challenging. One such disease, MPS III, also known as Sanfilippo syndrome, is a fatal neurodegenerative disorder that resembles a combination of autism and Alzheimer's disease. Unfortunately, potentially effective therapies may not show a measurable clinical benefit within the two-year timeline of traditional clinical trials, leading to the abandonment of promising treatments.

Fortunately, the FDA has an accelerated approval process designed for diseases unsuited to standard clinical trials. Instead of demonstrating a measurable clinical benefit, drugs seeking this kind of approval can be evaluated based on surrogate endpoints or biomarkers. For diseases like Sanfilippo syndrome, a biomarker exists in the form of a reduction in heparan sulfate levels, a complex carbohydrate found in the body's tissues. Several studies suggest that reducing heparan sulfate levels can positively impact patient outcomes.

Despite the existence of a recognized biomarker and the potential for accelerated approval, none of the drug candidates for MPS have been granted this designation yet. The lack of accelerated approval has not only cast doubts on some programs but has also led to the closure of others, leaving patients and families without potential life-saving treatments.

The development of new treatments for rare diseases is indisputably challenging due to the limited number of potential patients and the low probability of recouping research and development investments. However, the science behind MPS and heparan sulfate is well understood, emphasizing the need for the FDA to review promising drugs appropriately through accelerated approval. By doing so, not only will patients be saved, but also a renewed interest in rare disease research can be sparked.

The question now remains whether the FDA will heed the call to action. With more than 30 million Americans suffering from rare diseases anxiously watching, the need for accelerated approval has never been more critical.