Exondys 51 extends survival in DMD, long-term study shows
Youngest patients lived 80% longer than peers who weren't treated
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Up to eight years of Exondys 51 treatment (eteplirsen or AVI-4658) extended survival in Duchenne muscular dystrophy (DMD) patients over a wide range of ages, a long-term study concluded.
Patients treated for longer periods had the lowest risk of death.
The study, “Survival among patients receiving eteplirsen for up to 8 years for the treatment of Duchenne muscular dystrophy and contextualization with natural history controls,” was published in the journal Muscle & Nerve.
Exondys 51, developed by Sarepta Therapeutics, is an approved therapy for people with DMD amenable to exon 51 skipping. It works by increasing the amount of dystrophin protein, which is lacking in DMD patients. The gene that encodes dystrophin is made up of individual sections called exons. Exon-skipping therapies are designed to get muscle cells to skip over one or more exons when the gene is read to produce protein, allowing production of a shortened version of dystrophin.
Clinical data have demonstrated Exondys 51’s favorable safety profile and ability to slow disease progression, delaying declines in motor and breathing function.
Study covered data since U.S. approval in 2016
A team including scientists at Sarepta and multiple international institutions conducted the study to assess the overall survival among DMD patients who had received Exondys 51 in the U.S. since its approval in 2016.
Survival data were collected from SareptAssist, Sarepta’s patient support program, which gathers administrative information on the majority of patients who received Exondys 51. Clinical characteristics or functional assessments were not included.
The study enrolled 579 DMD patients treated with Exondys 51. The patients began treatment between the ages of 1 and 35, with exposure time ranging from zero to 8.6 years.
For a control group, the team reviewed published literature and extracted survival data from studies that followed the natural history of the disease, or the progression of DMD in patients over time in the absence of treatment. Among the 1,224 patients included in the primary control group, which included U.S. and European populations, 307 deaths were recorded.
A total of 29 deaths were recorded among DMD patients treated with Exondys 51 over a follow-up of 2,119 person-years, a figure calculated by multiplying the number of people in the study by the time each person spends in the study.
Longer treatment leads to longer survival
Data showed that patients treated with Exondys 51 lived significantly longer than those in the natural history group, surviving to a median age of 32.8, vs. 27.4 for those not treated, representing a 5.4-year difference. Compared with U.S. controls only, Exondys 51 extended survival by 8.6 years.
The therapy was associated with a 66% relative decrease in the risk of death compared to controls. After adjusting for age at the study’s start (baseline), Exondys 51-treated patients had a 35% lower risk of death. Moreover, the youngest treated patients had an 80% higher survival rate than the age-matched controls.
A subgroup of Exondys 51-treated patients ages 10-28, for whom deaths were most likely to occur, had a significantly higher likelihood of survival than DMD controls.
Patients treated with Exondys 51 for less than two years had a median survival age of 28.1. Still, those treated for 2-4 years or more than four years had not reached the median survival time, “indicating that longer [Exondys 51] treatment was associated with longer survival time,” the researchers wrote.
Accordingly, those treated for more than four years had an 85% lower risk of death than patients treated for less than two years.
“The clinical data presented in the current study suggest that eteplirsen [Exondys 51] may prolong survival in patients with DMD across a wide age range,” the researchers concluded. “Further analyses should be conducted on survival impact of DMD therapies as more data become available.”
As for study limitations, they noted that “although almost half of eteplirsen-treated patients had been exposed to treatment for [more than four] years, a significant number of patients had [less than two] years of exposure, which may not be sufficient time for the impact of eteplirsen to be evident.”
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