Tiffany Ruben will never forget what her pediatrician said when her son Jacob was diagnosed with a rare and fatal genetic disorder called Niemann Pick Disease Type C (NPC). She had never heard of it, so she wanted to start raising awareness and raising money to find a cure.
"'Why would anybody care about your disease?'" she recalled the doctor saying. "'It only affects so little people in the population of the world.’”
Ruben found hope for her son in a drug called adrabetadex. Now that hope is dwindling, as the company that makes adrabetadex announced it will stop production of the drug in October. The drug company says a clinical trial couldn't prove any benefit for the drug; parents say they believe the drug buys their children precious time.
Jacob underwent eight months of treatment before he died, just shy of turning 8 in 2019. His brothers Mason, 5, and Logan, 3, both have NPC and have been on infusions of the drug for the past three years. Almost immediately, Ruben, a 38-year-old from Las Vegas, could see a difference.
“They have just developed so much more than my oldest ever did,” Ruben said.
At 7, Jacob had frequent seizures, wore a helmet, used a gastrostomy tube and needed a walker or a wheelchair. Mason plays baseball and eats “like a champ,” his mom said.
True, they are different people, but “he’s so much further along than my Jacob was,” Ruben said.
Pharmaceutical company explains
Mallinckrodt Pharmaceuticals, the company that makes adrabetadex, announced it will stop manufacturing the drug in October 2021. Dr. Steven Romano, executive vice president and chief scientific officer at Mallinckrodt, explained that any pharmaceutical therapy has risks and benefits. Normally, when the benefits outweigh the risks, it's considered acceptable. When the company evaluated the data on adrabetadex, it couldn't determine that children taking the medication improved.
Hearing loss is one risk of adrabetadex; it's also a component of NPC. "That's the risk side of the equation," Romano said.
"The benefit, unfortunately, doesn't outweigh the risks because we can't clarify the benefits," he told TODAY. "That's very disappointing to the families, of course, because, they were hoping obviously that that we, as the sponsor, would find a way forward. But that requires having a certain level of confidence in the efficacy."
The study looked at 57 patients with NPC over 52 weeks. None of the children identified in this article were part of the study. There was a control group where some of the patients did not receive adrabetadex. The data did not show a difference between the groups.
"What we saw was that neither of these populations actually got worse," Romano explained. "What you would typically expect in a degenerative condition is that over the period of time that you're studying, the patients who are not getting treated ... would actually show a detriment in their function or worsening of their condition, and we didn't see that."
What's more, many of the children in the study were on another drug, miglustat, but the research doesn't clearly indicate what therapy slowed the progression of NPC. Romano said researchers couldn't ask patients to stop their other medications just to study adrabetadex because it would be unethical.
"We were looking hard to see if we could find a difference between our drug and and and the background treatment," Romano said. "It actually looks as though (miglustat) was contributing to stability of disease in many of these patients."
Despite the research from the company, parents say they think the drug makes a difference.
“It has absolutely changed the course of Marian’s life,” Sara McGlocklin, 37, of Monrovia, California, told TODAY Parents of her 5-year-old daughter with NPC. “She’s developed across the board. Her speech: She could just say single words, and now she talks in sentences. And she could sing a song and all that fun, normal kid stuff.”
What is NPC?
NPC is a rare genetic disorder sometimes called “childhood Alzheimer's disease.” Those with it often develop normally then start regressing, though it affects everyone differently, according to the National Organization for Rare Disorders. Often children with NPC seem clumsy and struggle with writing or drawing. As they regress, swallowing becomes challenging. With NPC, a genetic mutation means their bodies can’t properly move cholesterol from the cells, which results in damage that can lead to widespread symptoms and ultimately, death.
“The final consequences continue the degeneration and destruction of the cells,” Dr. Alvaro Serrano Russi, medical geneticist and director of the Newborn Screening Program at Children's Hospital Los Angeles, told TODAY Parents. “The consequences in children is going to be continuous loss of motor milestones and finally they become disabled and pass away.”
There’s no cure for NPC. Parents know that adrabetadex infusions are just buying them time.
“Our kids do have a fatal disease,” McGlocklin said. “This medication gives them so much more time and quality of life and gives them so many more experiences.”
McGlocklin’s daughter Marian was diagnosed with NPC when she was 18 months old.
“She couldn't walk, she couldn't stand up on her own... Even when she would try to sit, she would lose her balance and fall over sometimes. She was so weak,” McGlocklin said.
Now, Marian is a “dynamo,” her mom said. She dances ballet and swims; she loves playing babysitter with her dolls and watching "The Pioneer Woman."
“She’s very charismatic and loving and sweet,” McGlocklin said. “She tells terrible knock-knock jokes. She’s very determined.”
McGlocklin started a group called Don’t Give up on NPC in the hopes that another company will take over making the medication that she believes has transformed Marian’s life.
“As a parent you want to protect your child and help your child,” she said.
Jenna Weets’ son Jeg was diagnosed in 2017. After learning about adrabetadex, she felt hopeful.
“It’s gotten a lot easier to raise money for NPC, but it’s still not enough,” the 32-year-old from Morrison, Illinois told TODAY Parents. “That’s our fear. What if a treatment doesn’t come fast enough for him?”
Jeg, 7, is a junior drag car racer who loves dirt bikes and basketball.
“He has the best handwriting in his class,” Weets said. “If this drug did not work, he wouldn’t be able to do these things.”
The future for children with NPC
Serrano Russi treats Marian and says that the future for children with NPC will be murky after adrabetadex is no longer available.
"It’s difficult to know if we discontinue the treatment, what would be the effect," he said.
Having a loved one with a rare disease remains frustrating. Researchers face challenges because there are fewer people to study, and the condition may progress very differently in different people.
“Sometimes," Serrano Russi said, "we diagnose patients very late and then you have a lot of damage already being done by the condition. It makes any intervention or medication more difficult.”
Other drugs might work for children with NPC. Families who have experienced success with adrabetadex worry about how effective the other treatments are. Ruben said her sons tried a new treatment that causes so much tummy upset that her children cannot eat sugar, dairy or gluten, and still they can have terrible bouts of diarrhea. Her doctor called it “biological warfare on their bellies.”
“My mouth dropped,” she said. “Who wants to do that to their kid?”
Serrano Russi submitted a letter of support for Marian so she can continue treatment through October. McGlocklin, Weets and Ruben want another company to start producing adrabetadex.
“We fight for our kids’ diagnosis. We fight to get them access to treatment and therapies. And now we have to fight again,” Weets said. “These kids, they should be able to enjoy their lives and whatever time we have with them.”
CORRECTION/CLARIFICATION: (March 20, 11:36 a.m. ET) An earlier version of this story incorrectly identified another drug used to treat NPC as migalastat. The correct name is miglustat.
The story has also been updated to reflect the fact that none of the children identified in the story participated in the research trial for the drug adrabetadex.