My 13-year-old daughter Eliza suffers from a rare, fatal disease known as Sanfilippo Syndrome. The neurodegenerative illness causes children to gradually lose their mental abilities starting around age three. Children diagnosed with the disease typically die in their teens.
Worst of all, despite what appears to be a major medical breakthrough on treatments for Sanfilippo, the Food and Drug Administration has refused to funnel the medicine through a faster approval process that is the only hope these children have.
The traditional approval path for new medications at the FDA entails randomized trials demonstrating a clinical benefit from the treatment. However, at least since the development of life-saving HIV/AIDS treatments, the agency has recognized that the traditional approval process can needlessly delay delivery of effective treatments to patients with serious progressive diseases.
That's where the accelerated approval path comes in. To be cleared for patient use, new medications on this path need to show a change in biomarkers known as 'surrogate endpoints' -- in effect, measured physiological changes that predict forthcoming clinical improvements.
The Sanfilippo treatments meet this criterion by helping to break down a toxic metabolic compound called heparan sulfate, which builds up in the brains and bodies of children with Sanfilippo. Yet regulators have not yet aligned their perspective with the widely accepted scientific understanding that heparan sulfate is the inciting toxic substance. They are accordingly insisting on traditional randomized trials showing clinical benefits.
Subjecting the Sanfilippo treatments to this standard is both impractical and deeply unethical. As a pediatrician as well as a parent of a child with Sanfilippo, I've seen firsthand throughout my career how quickly breakthrough therapies can transform a deadly childhood disease into a manageable chronic condition. And there's no medical reason why that can't happen with Sanfilippo.
The FDA's insistence to date on traditional approval is unworkable for several reasons. First, demonstrating a clinical benefit in the case of Sanfilippo is a significant challenge. By the time doctors diagnose the condition, a child is usually beyond the age at which large and swift improvement from treatment is possible.
Another challenge is that Sanfilippo is so rare that assembling enough patients to conduct a traditional trial is a difficult and expensive undertaking in its own right. The disease affects just one in 70,000 children.
What's most frustrating about this situation is that the FDA has the tools it needs to break the logjam. In fact, regulators created the accelerated approval program in large part to accommodate medicines for rare diseases like Sanfilippo. All that's necessary right now is for the FDA to recognize that randomized trials to demonstrate cognitive efficacy are not appropriate in this case. And that reduction of the primary disease biomarker, heparan sulfate, is an acceptable and scientifically sound surrogate endpoint.
If the agency continues to subject promising treatments to a standard that is neither reasonably fit nor achievable, then our best chance at bringing relief to suffering children with Sanfilippo will pass us by.
Dr. Cara O'Neill is a pediatrician and the chief science officer of the Cure Sanfilippo Foundation, which she cofounded with her husband to find a cure for their daughter.