Duchenne Trials Aren’t Easy on Families or Patients, Even for Those Able to Qualify, PPMD Founder Says

Getting your son into a Duchenne muscular dystrophy (DMD) clinical trial can be difficult, given the narrow criteria for eligibility — like walking ability — associated with such trials.

Even for families who qualify, the experience can be draining, said Pat Furlong, founder and CEO of Parent Project Muscular Dystrophy (PPMD).

“The emotional and physical burden on these kids is extraordinary, so we have to be careful about protocol design,” Furlong said at the recent 2018 World Orphan Drug Congress in Maryland. “There’s also uncertainty on the part of a parent. Their kid is taking a drug that’s never been in other humans before. So,  they’re watching for the other shoe to drop.”

Furlong, whose organization was established 24 years ago, lost two sons to Duchenne. The progressive muscular disease — caused by a lack of the dystrophin protein — usually strikes boys between the ages of 3 and 5 and affects about 1 in 5,000 male births; about 300,000 boys and young men have DMD worldwide.

Pat Furlong, founding president and CEO of Parent Project Muscular Dystrophy. (Photo by Larry Luxner)

“My sons were diagnosed with Duchenne at a time when there were no clinical trials,” she said. “Right now, we have 46 companies looking at replacing expression of dystrophin or restoring dystrophin.”

For that reason, Furlong’s organization — whose 2018 Annual PPMD Conference takes place June 28-30 in Scottsdale, Arizona — is involved in an ongoing study of the burdens of Duchenne clinical trials.

PPMD sponsored a meeting on this topic at the National Institutes of Health (NIH) last  year, with patents, parents, clinicians, academics and industry representatives from the United States, Great Britain and the Netherlands present. Findings are summarized in a report, “Unique Burdens of Pediatric Clinical Trials in Duchenne Muscular Dystrophy, April 20-21, 2017, Bethesda, Maryland, USA,” published in the Therapeutic Innovation and Regulatory Science journal.

Furlong said that Duchenne, which affects boys almost exclusively, generally doesn’t reveal itself until age 3, with diagnosis usually following a year later. Most patients can still walk until they are 12 or 13, and lose their ability to move their arms in their late teens. The median age of death is 21.

Yet, getting into a trial is an ordeal in itself.

“There is significant pressure for families to find and enroll their child into the study they feel is best for their son, with the treatment that they believe could prevent, slow down or halt progression of this disease,” the study states. “Certainly sponsors must set expectations about eligibility prior to consenting patients, as well as a clear understanding of endpoints and expected outcomes, but nevertheless many families have their sons screened and experience disappointment when they fail to qualify for a trial.”

Financial status is another consideration, especially for families who must make repeated trips to a trial site that may be in another state and require overnight stays in hotels.

“Participating in clinical trials is expensive for families,” Furlong said. “Travel is a burden. It helps to have a company that can reimburse you.”

Parents also may question enrolling a child in Duchenne clinical trials for other reasons.

“The risk of randomization to placebo, which may be necessary for scientific integrity in the absence of rigorously collected contemporary natural history data,” is a significant barrier to participation, the study notes.

And the sheer details of interpreting what a trial aims to do can be intimidating. “The search for better outcome measures has resulted in protocols being stacked with multiple secondary and exploratory outcome measures, some of which are redundant,” the report states. “The number of measures is fatiguing and time-consuming, increasing the burden on the child and parent.”

Yet, another limitation is that trial inclusion criteria can be extremely narrow. In most of the 29 studies now underway, Furlong said, boys must be older than 5 and able to walk — but not too well.

According to the report: “Often children fail because their performance on primary outcome measures, such as the 6-minute walk test (6MWT) indicate that they may either be walking too well to see a change in ambulation during the trial, or too slow, indicating that they may be in danger of losing ambulation within the time frame of the study. If children are walking too well … parents are forced to watch their child continue to decline while waiting for another trial, hoping that their son does not lose the ability to walk in the meantime.”

As Furlong puts it, “in your lifetime of Duchenne, you may have only one opportunity to participate in a trial” and that alone “places a lot of stress on these families.”