Ever since her 15-year-old son Cole was diagnosed with a rare, progressive illness called Hunter syndrome when he was 2, Kim Stephens has been waiting. Waiting to see if Cole will lose his ability to walk. Waiting to see if Cole, who stopped speaking at about 9 years old, will lose more cognitive skills. And waiting in agony each year to see if Cole will be able to celebrate another birthday, since Hunter syndrome often kills before age 21.
Stephens has been waiting for something else, too: hope for a medical breakthrough.
Last week, she got that when the Food and Drug Administration granted accelerated approval for a revolutionary new drug for Hunter syndrome. It was a development Stephens worried she would not see during Cole’s lifetime.
“I’ve been in fight-or-flight mode since his diagnosis,” said Stephens, who lives in Carrboro, North Carolina. Now, she said, “I can breathe.”
Like other children with Hunter syndrome, Cole is deficient in an enzyme required to break down certain molecules. Over time, toxins accumulate, and the genetic disorder ravages children’s organs, including their heart — and in many cases, their brain, leading to dementia-like symptoms. The condition, also called mucopolysaccharidosis type II, or MPS II, affects about 500 people in the U.S., nearly all of them boys.
Experts believe the newly approved drug, an intravenous enzyme replacement therapy manufactured by Denali Therapeutics, will be a game changer — especially because the current standard of care slows only the physical aspects of the illness. Denali’s drug also targets cognitive decline.
The new drug will not reverse regressions that have already occurred. But it could extend children’s lives and prevent many symptoms from showing up for those who receive it early.
“If we take a child, very young, and can treat them prior to damage, now the potential is almost unlimited,” said Dr. Joseph Muenzer of the Muenzer MPS Research and Treatment Center at the University of North Carolina at Chapel Hill, which sees children with Hunter syndrome and other rare mucopolysaccharide diseases.
“We don’t know how well they’ll do in the future, but they’ll do dramatically different than they would have otherwise,” he said.
Before he started to regress, Stephens’ son, Cole, was learning to read and could talk in full sentences. As the disease set in, speaking became difficult: He could string together a few words, and then say just one word — “Mommy” — before he became entirely nonverbal. Despite now being a teenager, he is more like a 3-year-old developmentally, Stephens said.
The FDA’s approval of the Denali drug was a welcome surprise not just to families of children with Hunter syndrome, but to the rare disease community as a whole. In recent months, the FDA has come under fire for rejecting a string of promising treatments for rare diseases, prompting patient advocates to stage a mock funeral with a coffin outside of agency headquarters and triggering an investigation by Sen. Ron Johnson, R-Wis., who, prior to the Denali approval, accused the FDA of “looking for excuses to say no” to treatments.
In an email to NBC News, the FDA said the number of approvals and rejections under this administration “are consistent with historical data over the last decade.” It pointed to a statement from FDA Commissioner Dr. Marty Makary, who called the Denali approval a “milestone day for children and their families battling Hunter syndrome.” He added, “We will continue to do everything we can to accelerate treatments for rare diseases.”
Those who have watched children suffer from Hunter syndrome and other rare diseases are hopeful that will be the case, including Muenzer, who was a principal investigator for the Denali trial.
“These are terrible disorders,” Muenzer said. “Just because they’re a minority doesn’t mean we should ignore them.”
Denali’s drug, called Avlayah, is the first FDA-approved treatment in the U.S. in 20 years for Hunter syndrome — and the first one that penetrates the blood-brain barrier, enabling it to halt the neurologic complications of the disease.
Experts like Muenzer believe Avlayah has the potential to extend life expectancy based on promising data from a clinical trial that showed that after 24 weeks, the levels of a key biomarker in cerebrospinal fluid associated with the disease were reduced so much, 93% of pediatric participants had levels comparable to individuals without Hunter syndrome.
For many families of children with the condition, the approval of the drug meant more than just an exciting new treatment. It also meant recognition of their children’s value.
In New Berlin, Wisconsin, 6-year-old Roran Jaskulski was diagnosed with Hunter syndrome when he was 4. He has always been nonverbal, and his mother, Kylie Jaskulski, said she worries that because Roran can’t speak, people who don’t know him may question if he has anything to offer to others — a heartbreaking mischaracterization of her energetic, affectionate child who loves to cuddle while he falls asleep and excitedly runs into school each day.
“He brings so much joy,” Jaskulski said. “He brings happiness and peace to every person he interacts with.”
Jaskulski said at first, receiving Roran’s diagnosis felt like the worst day of her life. But as time went on, she realized the powerlessness to prevent her son from deteriorating was even more torturous.
If her insurance approves the Denali drug for Roran, she said, “maybe I don’t just have to stand by and watch.”
Like other children with Hunter syndrome, Roran receives a weekly infusion of the current standard of care, a drug called Elaprase approved by the FDA in 2006. The infusions help to stabilize his physical decline, though not entirely: In recent months, Jaskulski has noticed Roran developing weakness and pain on the left side of his body, affecting his gait. He also has mild hearing loss.
A patchwork of states from California to Rhode Island include Hunter syndrome on newborn screenings, with more states expected to start testing for it at birth in the future. That means children will have a better shot at preventing cognitive impairment if they take the new drug early, doctors say.
Most Hunter syndrome kids have the severe form of the disease, which has a life expectancy of between 10 and 20 years. Those with the non-neurological form of Hunter syndrome, which does not significantly affect the brain, can live into adulthood, though they still face progressive physical problems, primarily of their airways and heart.
The prospect of the new treatment is exciting for families of kids on both ends of the disease. In Newkirk, Oklahoma, Christina Coldwell’s 3-year-old grandson Kashton Estes has Hunter syndrome without cognitive problems, and he receives Elaprase infusions, which he refers to as “going to get his Spider-Man juice.” The treatment has been successful: Coldwell said the little boy “talks up a storm,” runs, jumps and rides a bicycle.
Still, she is eager to get Kashton on the new Denali drug. Two of his cousins also have the genetic disorder, Coldwell said, and the family wants to stave off future health problems in all three kids.
“We’re not asking for much: Just give us the medicine to keep our children alive,” she said.
When asked about insurance coverage for its drug — which has a list price of $5,200 per 150-milligram vial — Denali Therapeutics said it has had “constructive” discussions with payers and said enabling Hunter syndrome families to have quick access to Avlayah is a “top priority.” It also said it is looking to expand the drug’s clinical evidence for young adults, since at the moment, it is only indicated for pediatric patients. Denali also said that it aims to use its blood-brain barrier technology for a wide range of other conditions, including other neurodegenerative diseases.
Stephens, the mother of 15-year-old Cole, cannot wait to start her son on the drug. She has dedicated her life to helping not only Cole, but others like him: In 2022, she became the executive director at Muenzer’s MPS research and treatment center at UNC-Chapel Hill.
When news broke last week that the FDA had granted accelerated approval to the new drug, Stephens ran through the treatment center to tell patients and staff. Everyone hugged and cried.
Stephens knows Denali’s drug cannot undo the regressions Cole already has. It won’t enable him to go to college or to enter the workforce. But she said she’s still incredibly grateful for it.
“My hope is he stays stable,” Stephens said. “Stable with a progressive disease is a win.”
