Experts Push For More DMD Clinical Trials To Include Patients Who Can’t Walk
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by
Ree Webster
After Wilfredo Hernández and Griselle Mendez’s son Alejandro, was diagnosed with the rare disease, Duchenne muscular dystrophy (DMD), difficulties in finding effective treatments led them to move abroad, to any country where they might be able to receive the necessary help. Talking to the Rare Disease Advisor, Hernández said:
“It was very hard on us. We were devastated…
“After the grief passed, we decided to take action, and move anywhere in the world he could get help.”
The family enrolled Alejandro in a clinical trial that utilized drisapersen to treat DMD, and this required the family to fly to the Nationwide Children’s Hospital in Columbus, Ohio, for weekly infusions. The trial however, developed by BioMarin, was later discontinued due to potentially high toxicity levels. The father recalled:
“It was 6 months on the drug or placebo, and then a 6-month washout period. And then we had to do it again…
“It was really hard, since most of the flights were overnight. That’s when we decided to move to the US mainland.”
Since there were no DMD clinical trials in Puerto Rico, the family, eventually relocated to Atlanta, Georgia in order to have easier access to the trials, and to receive the necessary support.
What Is Duchenne Muscular Dystrophy DMD?
Duchenne Muscular Dystrophy (DMD) is a genetic disorder characterized by progressive muscle weakness and degeneration, primarily affecting boys. It is caused by mutations in the DMD gene, which leads to a lack of dystrophin—a protein crucial for muscle strength and function. Symptoms typically appear between ages 2 and 5, with children often experiencing difficulty walking, frequent falls, and muscle stiffness.
Over time, DMD affects the heart and respiratory muscles, significantly impacting life expectancy. While there is no cure, treatments such as physical therapy, medications, and assisted ventilation can help manage symptoms and improve quality of life.
If you’d like to find out more about DMD, read our in-depth article on the rare disease Duchenne Muscular Dystrophy DMD?
Clinical Trials Helping DMD Patients Typically Excluded From Experimental Treatment
Alejandro was then put on eteplirsen (Exondys 51), an antisense oligonucleotide created to help restore dystrophin. These weekly infusions typically take 2 hours. He also takes 3 heart medications, as well as vitamin D and other medications to fight osteoporosis.
Now aged 20, and having being wheelchair for the past 10 years, Alejandro noted the positive effects the trials had on his life:
“For having a disability, I feel really good…And I look better than most people with Duchenne my age.”
Alejandro is enrolled at Georgia Gwinnett College, where he studies computer science. He hopes to graduate as a programmer. He also enjoys video games, plays sports, and is part of the Atlanta Sting, a soccer team for people in power wheelchairs.
In the meantime, his parents continue to hunt for more clinical trials that could help their son. A lot of resources and news is available for Duchenne Muscular Dystrophy news. However, clinical trials for Duchenne remain scarce for those who can no longer walk as they’re often excluded without exception.
More Patients Benef From Inclusion in DMD Clinical Trials
Another family experiencing similar hardships, Sarah and Dan Kasner of Minneapolis, Minnesota, also have 2 boys with Duchenne: Caleb, 10, and Duncan, 9. The brothers were diagnoses just 6 weeks apart back in 2018, where it was found that they same rare mutation: a deletion of exons 6 through 17. Sarah Kasner said.
“They didn’t present upon diagnosis as typical Duchenne kiddos, and it took us more than 2 years to get that diagnosis…
“We went to 4 different neurologists til we found one we were comfortable with. The first couple were doom and gloom. The others said ‘your kids’ lives will look different than kids who were diagnosed 10 years ago.’”
“But now we’re 6 years into this, and nothing looks different,” she added. “Both are in wheelchairs. In the beginning, gene therapy was on the table, but now we know it’s not an option because of the perceived cardiac involvement with exons 8 and 9.”
Despite being for different reasons, the Kasner’s also had a hard time getting their boys enrolled in a clinical trails for DMD. They had attempted to enroll Caleb in a trial for CAP-1002, which which an infusion of cardiosphere-derived cells developed by Capricor Therapeutics was administered every 3 months, however, this didn’t work out. The mother explained:
“They had in a protocol that you had to be on a growth hormone for at least 2 years, and he had been on it for 1 year. So after 4 days of testing, they caught that, and he did not get into that trial…
“Then we wanted to get Dunky into an Edgewise [Therapeutics] trial to preserve muscle, but his BMI was too high. The time to stand had to be less than 10 seconds, and his time was 11.2 seconds…
“I feel like we spend so much time with all these inclusion and exclusion criteria, and we don’t even understand why.”
Susan Ward, PhD, founder and executive director of the collaborative Trajectory Analysis Project (cTAP), also wonders why; especially being as research has shown over half of the patient with Duchenne experienced lung and upper limb problems prior to becoming unable to walk. Ward hopes the requirement are somewhat broadened to allow a larger population of patients eligible for trials of therapies to treat Duchenne.
In July 24, 2024, cTAP announced a study that it conducted, published in PLOS One, found that more than half of patients with Duchenne experienced clinically significant deficits in pulmonary and upper limb function before losing the ability to walk. Dr. Ward explained that cTAP was formed a decade ago to resolve the problems resulting from repeated failed clinical trials in DMD. A total of $25,000 in seed money was utilized by the nonprofit group CureDuchenne to launch the new program, which now gets funding from around 30 other patient advocacy groups, hospitals, universities, and drug manufacturers. Ward said:
“Companies—even though they were doing their very best to design thoughtful trials—nevertheless were not getting statistical significance that the regulators could accept for approval. The trials were too noisy…
“Because boys are progressing [in their disease] at different rates, some patients are getting stronger, some are fairly stable, and some are declining within almost any given range, and that causes a lot of variation. That means that in practice, you need a lot more patients in a trial to be able to see the effect of a drug than you would if everybody was on pretty much the same path.”
Ward went on to explain: Clinical trials in Duchenne can include as few as 12 to as many as 300 patients, though most these days range from 150 to 180 participants:
The reason we put cTAP together is to see how we can improve trials and help drug companies design them better. Its purpose in life has been to find a way of getting rid of as much noise as possible. We want to get to a point where there’s no such thing as a clinical trial in which the results are ambiguous. You want to have a clear, ‘It worked,’ or a very clear, Unfortunately, it did not work,.
CureDuchenne’s founder and CEO, Debra Miller, got involved after her son was diagnosed with the DMD over 20 years ago. Now her son Hawken, who is 27 and much older than the average patients with Duchenne, owes thanks to better therapies and overall healthcare, which are contributing to an increasing number of men with DMD who are able to into 30s and 40s.
“I know that if Hawken had been in a clinical trial, he would have completely messed it up…
“Because his endpoint results would have been so strong, it would have competed with the treated group and skewed the placebo group higher.”
Instead of clinical trials Miller and Dr. Ward sought the support of major pharmaceutical companies and got leading researchers to contribute their data sets over the years.
“Our mission is that every patient will have a treatment. We don’t want anybody excluded. If these boys are not able to participate in clinical research, it’s very possible that the drug, if approved, won’t include them. Also, there’s a lot of competition for patients. If all these trials are designed for little kids, we won’t have enough patients to fill them, and we won’t understand how these drugs work in older patients.”
Tim Revell of Austin, Texas, are also passionate about this topic. He and his wife, Laura, are parents of Timothy and Andrew, aged 20 and 17 respectively, both of whom have Duchenne.
Andrew is currently undergoing a trial for nonambulatory patients with Duchenne taking place at the University of Florida in Gainesville. Half of the patients receiving the gene therapy delandistrogene moxeparvovec-rokl (Elevidys®), which earned approval on June 21, 2024, for patients 6 years old and up. The other half are receiving placebo. Later on the 2 groups will switch. Tim Revell explained:
“Timothy couldn’t be in the study because he had received stem cell therapy, even though that was 6 years ago…
“This is literally the only thing available for Andrew. There are so few treatments available for nonambulatory boys and young men with Duchenne. We need these drug companies to continue to develop treatments to help older boys.”
