RALEIGH, N.C. (WNCN) – Parents of children with ultra-rare diseases are encouraging the Food and Drug Administration to act quickly to approve drugs that could treat their conditions and to take into account the limitations of clinical trials when considering drugs for rare and ultra-rare diseases.
Gilbert Dryden is a happy, seemingly healthy little boy.
“You look at this baby, he does not look like he is in heart failure; he does not look like he has skeletal weakness,” noted Gilbert’s mom, Madison Dryden. “He is developing on par with a typical 7-month-old.”
In fact, Gilbert is living with an ultra-rare genetic condition that, experts say, kills nearly half of babies born with it before they turn five. When Gilbert was 16 days old, he was diagnosed with Barth Syndrome, a life-threatening genetic disorder that affects about 150 people in the United States. According to the Barth Syndrome Foundation, there are at least five known patients in North Carolina.
Barth syndrome causes problems with the heart, muscles and immune system. The diagnosis sounds terrifying, but for Madison, who lives in Colorado, it actually brought relief, as her newborn son lay in a hospital bed in heart failure.
“When we got his diagnosis, I think that was the first time I felt hope because his doctor said, ‘You know, I hate to have to give you a diagnosis, but there’s a treatment,’” Dryden recalled.
Elamipretide is an investigational drug. When Gilbert was diagnosed, the drug maker was in the process of seeking approval from the FDA. Gilbert receives Elamipretide under the expanded access program, also called compassionate use.
“We attribute Elamipretide to that being the reason he is home with us,” his mom said.
The future of the drug is in jeopardy, though. The FDA recently declined to approve it, despite what Barth syndrome researchers felt were positive signs during the consideration process.
“The Advisory Committee voted 10 to 6 in favor that Elamipretide is efficacious for the treatment of Barth syndrome,” explained Lindsay Marjoram, the director of research for the Barth Syndrome Foundation.
Dr. Todd Cade, professor and division chief of physical therapy at Duke University, has been researching Barth syndrome for nearly 20 years. He and Majoram both say they believe that Elamipretide has shown benefits.
“Expanded access has been used on a lot of infants born with heart failure, and it had really amazing results,” Cade noted.
“The drug has an excellent safety profile,” Marjoram added.
Both say it’s challenging to study drugs for ultra-rare diseases.
“Because this is the very first trial in Barth syndrome; they [the drug maker] really didn’t know the timeframe this drug was going to work; they didn’t really know the perfect outcomes to use,” Cade noted.
He explained that data from the initial trial period did not show the drug making a statistically significant difference in patients’ physical function, as it was measured, but patients who remained on the drug after that initial period did show significant improvements.
Marjoram added that the very limited numbers of patients participating in drug trials also present a challenge.
“Drug trials for things like chronic heart disease, lung disease, diabetes, those have the benefit of having thousands and thousands of patients in the trial, and so you can do really elegant statistics,” she said. “We don’t have the luxury of that. We don’t have a current standard of care, and we don’t have a lot of patients.”
Barth syndrome isn’t the only rare disease facing these challenges.
“There are other conditions like MPS and Sanfilippo syndrome that are also in the same boat,” Marjoram stated.
Sanfilippo syndrome is another ultra-rare genetic condition, sometimes known as childhood dementia. The neurodegenerative condition causes children to regress until most die in their mid-teens.
“They lose speech, mobility, ability to feed themselves,” noted Ashley Haywood, the mother of a child with Sanfilippo syndrome.
Haywood and her daughter, Sadie, live in Albemarle, North Carolina. Sadie was diagnosed with Sanfilippo syndrome as a baby. A few years ago, she loved to sing and talk. Now, at age nine, she’s lost many of her abilities.
“She has lost most of her words. She would probably be considered nonverbal,” Haywood noted.
She added that an investigational treatment in clinical trials, known as UX111, gave hope to many families dealing with Sanfilippo syndrome.
“They submitted their letters to the FDA; all of the data looked really good,” Haywood said.
The FDA declined to approve the drug. The company that makes UX111 has said it plans to address the issues the FDA noted and resubmit an application. The maker of Elamipretide has already resubmitted an application to the FDA, and according to the drug maker, federal officials are considering it and hope to provide an answer by the end of September.
In both cases, advocates say time is of the essence. When it comes to Elamipretide: “We’re now entering month 19, and the sponsor is on the brink of bankruptcy,” Marjoram cautioned.
“In Sanfilippo, six months – that’s life or death,” added Haywood. “That’s the difference between a kid communicating in full sentences to being nonverbal, so our argument to the FDA is ‘our kids don’t have time; we can’t wait.’”
More than 45,000 people signed a petition urging the FDA to act quickly when it comes to drugs for rare diseases, and to take into account the limited patient population and resource constraints clinical trials face when considering these treatments.
Although they’re dealing with different diseases, families like the Haywoods and Drydens are working together to get their message across, recording videos and sharing stories online. Gilbert’s mom started this webpage to share her son’s story, while Sadie’s mom chronicles her journey for hundreds of thousands of followers on Facebook.
The two families recently made a video together about applications for Elamipretide and UX111 being declined.
“It’s our last chance,” Haywood said. “We don’t have anything else, so we’re going to push, and we’re going to press the buttons if we need to, and we’re going to do whatever we can for our kids because it’s our only option.”
Last summer, the FDA announced the creation of a Rare Disease Innovation Hub to focus on these rare and ultra-rare diseases. CBS 17 reached out to the FDA about Elamipretide, UX111 and the approval process for drugs for these ultra-rare diseases. We received the following statement: “The FDA continues to be a strong advocate of development of drugs for ultra-rare diseases. However, the FDA is unable to comment on the status of ongoing regulatory files.”
According to Marjoram, the FDA received 75 letters about Barth syndrome and Elamipretide, and one parent of a child with Barth Syndrome was recently granted a meeting with the FDA commissioner and high-level FDA staff. Several other families dealing with Barth syndrome, along with the executive director of the Barth Syndrome Foundation, and Marjoram were included in the meeting, during which they were able to share their experiences.
Marjoram said they also pointed out the experiences of families dealing with other rare diseases, including Sanfilippo syndrome.
Madison Dryden, fears what will happen if Gilbert loses access to the drug he’s taken for most of his life.
“Just the thought of this drug going away is absolutely terrifying,” she said. “Honestly, that’s what I think about all day every day is how much time do we have with our baby because when we had the certainty of Elamipretide, when we’ve had it, it’s like maybe we have a chance of seeing him grow up, and now we’re pretty much in fear that we don’t have that chance anymore because of the process.”
Maggie Newland
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