Sanfilippo Syndrome: A Doctor and Mother’s Message to the FDA

Eliza is now 13 years old and was diagnosed at the age of three with a neurodegenerative disorder known as Sanfilippo syndrome.

Eliza’s mother, Dr. Cara O’Neill, a pediatrician and Chief Scientific Officer of the Sanfilippo Foundation, wrote an opinion editorial published on January 5, 2024.

Dr. O’Neill describes the symptoms as typically beginning as early as three when the children experience seizures, gradual loss of hearing, vision, and speech. Their physical abilities begin to decline. Most children with the disorder may not live past their teens.

About the Appeal

Dr. O’Neill is making a public appeal for the FDA to facilitate the approval process for an apparent medical breakthrough that is, at the moment, the only hope for these children.

According to the FDA’s definition, its Accelerated Approval program allows earlier approval for drugs that treat serious health conditions. Also, based on surrogate endpoints, the drug must fulfill an unmet medical need.

Eliza’s mother is not requesting a change in policy. She is asking the FDA to recognize that Eliza’s condition fits the Agency’s definition of a serious illness and a fatal disorder.

To be clear, Dr. O’Neill is urging the FDA to acknowledge that the Sanfilippo treatments fit the parameters laid out by the agency’s “accelerated approval” program.

About Accelerated Approval

Years ago, an AIDS diagnosis was considered a death sentence. Now, thanks to therapeutic advancements, a young person diagnosed with AIDS may live on par with the general population.

Eliza and other young children with Sanfilippo would like that same opportunity.

The FDA’s traditional approval route to develop new medications involves randomized clinical trials proving a treatment’s benefit. After attempting to quell the HIV/AIDS epidemic, the FDA recognized that the standard approval pathway causes delays in the most vital therapies for patients with fatal progressive diseases.

Dr. O’Neill then referenced a major breakthrough treatment for Sanfilippo, stating that, to her knowledge, it may be the only hope currently for these young Sanfilippo patients.

She made it clear that she believes the FDA’s expedited approval process could give the children and their families hope.

About Sanfilippo Syndrome

When a child is born with Sanfilippo syndrome, or mucopolysaccharidosis (MPS) type III, one of the genes that makes enzymes to break down heparan sulfate (a sugar molecule) is defective.

Without the use of the defective gene, heparan sulfate accumulates in the cells, keeping them from working properly. This results in damage to organs and is detrimental to growth, behavior, and mental development.

Until the child has a thorough medical workup, it may take years to receive an accurate diagnosis. Due to its rarity, a child’s symptoms may be classified as autism or developmental delay.

The new Sanfilippo treatments break down heparan sulfate, which is a toxic metabolic compound that has built up in the bodies and brains of children with Sanfilippo.

Dr. O’Neill comments that the FDA has not yet joined many in the medical community by acknowledging heparan sulfate as a causative agent and toxic substance.

Instead, she continues, the FDA is insisting on the traditional trials and presentation of clinical benefits.

Dr. O’Neill claims that it is highly impractical to subject Sanfilippo treatments to this standard. The doctor reflects on the breakthrough therapies she has witnessed during her career and how they can transform a childhood disease with no hope of survival into a very manageable chronic disorder. She emphasizes that there is no medical explanation for that not happening.

The Case Against Traditional Approval

Dr. O’Neill outlined her objection to the FDA’s traditional approval pathway, claiming that it is unworkable in this case for several reasons. The first reason pertains to proving clinical benefit. When diagnosed, the child is usually past the age where treatment can significantly improve their condition.

Instead, the doctor said that, as a parent, simply slowing the progression of the disease and, as a result, retaining the quality-of-life abilities for a longer period, is well beyond their expectations.

Demonstrating a clinical benefit may take years. In fact, some of the children in the trial may be assigned a placebo, which in effect means “no treatment.” This group could have irreversible damage to their brain and be deprived of the chance to receive the therapy, which might have been effective.

Dr. O’Neill states that the cost of acquisition of the data required by the FDA equates to children’s lives. She questions how that could possibly be allowed to happen.

Another Challenge

The doctor points out that since Sanfilippo is a rare disease, attempting to assemble patients for a traditional trial is expensive and extremely difficult. It is estimated that one in 70,000 children is affected worldwide. Investors tend to shy away from funding the traditional approach. Several drug programs designed to treat the disease have already shut down.

As aforesaid, minus accelerated approval pathways for treatments, the treatment of Sanfilippo before irreversible symptoms take over is very slim.

Dr. O’Neill explains that the most frustrating issue involves the fact that the FDA could easily break the logjam. It is noteworthy that regulators created the accelerated approval pathway with the intent of accommodating therapies for diseases similar to Sanfilippo. Most importantly, the reduction of the primary biomarker, namely heparan sulfate, is in itself scientifically sound.

Dr. O’Neill again asks the FDA to break down its barrier to the accelerated approval path and especially in time to help the children in this generation.

The doctor further states that the FDA is subjecting promising treatments to an unreasonably and non-achievable standard. That means that children in this generation, like Eliza, will be left out.

Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia (AML) six years ago. During this period of partial remission, Rose researched investigational drugs to be prepared in the event of a relapse. Her husband died February 12, 2021 with a rare and unexplained occurrence of liver cancer possibly unrelated to AML.

Follow us