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. Other symptoms include seizures, vision and hearing impairment, severe sleep disturbance, and loss of speech and physical abilities. 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.
They and their advocates aren't asking for some exceptional policy change at the FDA – just recognition that the emerging Sanfilippo treatments are exactly what the agency's "accelerated approval" path is designed to expedite.
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.
As parents like me will attest, however, merely slowing the disease progression of Sanfilippo and thereby retaining quality of life abilities longer is a godsend. But demonstrating such a clinical benefit could take years -- during which some children in the study would be stuck with a placebo -- that is, no treatment. Those in the "no treatment" group may suffer irreversible brain damage and miss the window of opportunity for a therapy to actually work. In other words, the cost of acquisition of the FDA's required data is children's lives. How could that ever be ok?
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.
Investors have stepped up to fund R&D for the accelerated approval approach, but their willingness to put up the sums necessary for traditional approval is doubtful. Already, multiple drug programs aimed at treating the disease have shut down. And without an accelerated approval path for treatments, research into newborn screening for Sanfilippo -- in order to treat it before irreversible symptoms arise -- is unlikely to go forward expeditiously.
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.
I'm confident that beneficial treatments for Sanfilippo exist today. We just need the FDA to break down the barrier to the accelerated approval pathway -- and do so in time for this generation of children. 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 co-founded with her husband to find a cure for their daughter.
