These children have rare terminal diseases. Will they ever get treatment?

Although he had already been potty-trained, at age 5 Nathan Thomas lost his ability to control his bowels or bladder. By age 9, he could no longer speak and though he could still walk, he routinely fell down. He developed hydrocephalus and also had to be fed through a tube. At 12, he died as a result of Hunter syndrome.

His little brother, Easton, now 20, has the same disease and would have made the same painful journey but for one thing. He started enzyme replacement at age 8 months and at age 3 was enrolled in a clinical trial for a therapy that not only replaced the enzyme, but that crossed the blood-brain barrier to limit neurological damage. By the time that therapy was being tested, Nathan was older and a great deal of damage had already been done.

With rare genetic diseases, what’s lost doesn’t come back.

Says their mom, Melissa Thomas of Santaquin, Utah, “Easton is still developmentally delayed, but he’s able to go to an extended high school program. He walks, he talks, he can read, write and do math up to about a fourth-grade level.”

She and her husband James are among parents that hope their child will benefit from a rally outside the U.S. Food and Drug Administration on Wednesday to ask — some say beg because the need is so dire — the federal regulatory agency for a change of heart when it comes to providing access to medications that might help in instances where time is crucial and damage that occurs cannot be undone.

The “March for Rare” is being cohosted by the National MPS Society and Project Alive, which works exclusively with Hunter syndrome, a form of an MPS disease. The organizers told Deseret News that there are “stalled” treatments for several types of the MPS diseases. MPS is shorthand for mucopolysaccharidoses, which are genetic diseases caused by lack of an enzyme to break down cellular waste, leading to build up until it amounts to “toxic storage throughout the body.”

“The goal of the ‘March for Rare’ is to draw attention to the need for research and treatments to continue and to bring stalled medications to the patients who desperately need them,” the group said in a written statement. ”We are devastated with the potential to lose a generation of children — their milestones, their contributions, their growth, their progress and, too often, their lives."

A rare disease is one that affects fewer than 200,000 people in the U.S. There are nearly 7,000 rare diseases, affecting more than 25 million Americans, according to MedlinePlus. Individually, they affect a small number, but as a group they devastate millions.

The Thomases are not among the 150 families with rare diseases from around the country expected to spend Tuesday talking to members of Congress and Wednesday at the FDA. They are, however, among those desperate to have both groups listen. Those going want to talk to lawmakers and policy folks about regulatory delays and the inequities that limit access to therapies that could save lives.

The diseases that therapies are designed to manage move much more quickly than the process of getting those therapies approved.

The parents want the FDA to accept surrogate endpoints like biomarkers instead of waiting for something perfect that may never come. They’re asking for streamlined approval processes like the “plausible mechanism pathway” that will help children with orphan diseases quickly and head off damage.

A mother’s hope

Easton and Nathan are two of Melissa and James Thomas’ 10 children, half biological and half adopted. Among the other three who are biological, one son is not affected and two daughters are carriers of Hunter syndrome, which only shows up in boys. That means any boys they have could get the disease.

Easton, his mom said, “wants nothing more than to be a normal kid, a normal man.” He loves music and video games and due to Hunter syndrome, the things that he loves are limited." She said he loves to dance, but at 16 he had a spinal fusion and has chronic pain. He has hearing loss and cognitive disabilities.

“As a mother, I want nothing more than to see him grow and succeed. Every child should have those opportunities to do that,” she said. She added that watching your child decline to the point of dying is not something a parent should have to endure if there are treatments that could be approved quickly that would help them.

Thomas said her wish is simple: “I just wish the FDA would realize a disease like Hunter syndrome is a terminal illness and without treatment these boys are likely to ultimately pass away, typically from something neurological or respiratory related. And yes, they need to go through a trial-and-error type thing and make sure therapies are safe and effective, but I feel like there needs to be more urgency in the process of getting things approved. How many of these boys are going to pass away or suffer these effects from the disease unnecessarily because of the passage of time?”

She added that while the drugs are expensive, so is the cost of providing care, much of it borne by federally funded insurance.

Not asking for perfect

Sarah Napier of Project Alive said that “rare disease communities have seen promising therapies slowed or stalled in regulatory review, leaving patients with progressive conditions vulnerable while they wait for timely approval pathways and equitable standards.”

There are alrady first-generation enzyme replacement therapies for the body, but not the brain. Nothing has been approved for the brain in MPS cases, though clinical trials have been successful, as far as parents are concerned.

Now that Hunter syndrome is part of the newborn screening panel in Utah, Thomas said, there would be potential to start replacing the enzyme immediately and getting help to the brain to possibly avoid any damage for those children.

But the regulatory process doesn’t work that way. Families can access unapproved treatments only through clinical trials. If there’s no treatment approved, the children in clinical trials may be able to stay on the trial therapy until something does get approved. But when clinical trials are closed to new participants, more children are locked out of them and thus out of hopeful treatments that are stuck in regulatory limbo. If something less effective is approved for whatever reason later, those who were in a clinical trial lose access to the trial therapy.

A heartbreaking loss

Sharon King’s daughter Taylor had a form of Batten disease called CLN1 disease. Her mom describes her as a “beautiful, bright light: an unexpected gift and the gem of her family of five. As a young child, Taylor outpaced many of her peers, even teaching herself to read before kindergarten. She dreamed of becoming a pop star or a veterinarian.”

Taylor died at age 20.

Her rare disease was diagnosed at age 7 and Taylor “defied expectations — learning braille, attending school dances, participating in talent shows and even running two 5K races after losing most of her vision. As the tragic effects of CLN1 disease tightened their grip — eventually robbing Taylor of her vision, speech, mobility and the ability to swallow food — her courage inspired her family, friends and others to fight for a better future for people like her,“ said King, of Durham, North Carolina.

That fight is the heart of the march on the FDA.

King told Deseret News about attending a conference and looking at the audience filled with people who have a relationship to MPS, including adults living with a form of it, their life extended and enhanced by clinical trials. “The impact is incredible, to see what availability, what having a drug can do, the difference it can make, how it can impact a life, give our families and the individuals living with these conditions not only a better life, but potentially a longer life,” she said.

Terri Klein, CEO at the National MPS Society, which supports 12 disorders, has a daughter who’s 34 with a rare disorder that doesn’t have a treatment yet. The disorder, mucolipidosis, affects maybe 1 in 2 million children. It’s ultra rare. The organization, she said, supports about 2,200 households. Other groups support those with other rare diseases.

Klein said it’s frustrating to know there’s a treatment that crosses the blood-brain barrier and reduces the toxic heparan sulfate in the brain, halting the disease, but not having it available to children who are losing ground with every second that passes. “We’re able to now be able to treat body and brain so that the children with Hunter syndrome or with Sanfilippo syndrome that receive the gene therapy are certainly better off than those that didn’t.”

Plus, neurocognitive wins are not the only way to count success, Klein added. A better quality of life for the child and the family is very important.

“I think we’re at an inflection point with the FDA in terms of understanding that our families aren’t looking for the child to have reversal of brain damage. That isn’t possible. We’re actually asking them to help save this child’s life because the quality of life has significant value among humanity and they deserve to have that. Without the treatment, we already know the answer. It’s death,” Klein said.

While children who were enrolled in the trials for those therapies likely continue to have access, newborns diagnosed now and in the future, do not have access to the newest treatments— nor do their families have hope that damage can be forestalled if clinical trials have closed.

“We’re not waiting for perfection,” Klein said. “We can’t wait; the children don’t have time.” She noted that with cancer people can get chemotherapy that may not save their lives but will extend them. She likens the situation with rare diseases that have some therapies that aren’t yet approved to waiting to start chemotherapies until cancer reaches stage 3 or 4.

“I’m not understanding how our rare disease patients have to succumb to these types of decisions when other well-known diseases are being approved with treatment that actually don’t work but are trying to buy time for patients and bring quality of life and some dignity,” she said.

“Why are we demanding perfection for rare disease families when we have really, really good?”

King added that families with Batten disease “do not experience research and development timelines in years; we experience them in lost abilities.”