Real-world data showing that boys with Duchenne muscular dystrophy (DMD) treated with ataluren (Translarn, PTC Therapeutics, Inc., South Plainfield, NJ) preserved the ability to walk for 3.5 years longer than given standard-of-care (SoC) treatment alone. Pulmonary function was also preserved in those treated with ataluren. The analysis compared children treated with ataluren in a real-world setting from the STRIDE registry with a matched cohort in a long-term natural history study, CINRG (NCT01125709). In addition, no new safety signals were observed in the individuals treated with ataluren, consistent with what has been shown in previous clinical trials. The interim data have been published in the Journal for Comparative Effectiveness Research. Final data from the STRIDE registry is expected in 2025.
Children treated with ataluren in a real-world setting as part of the STRIDE registry were able to walk independently for an additional 3.5 years compared with a propensity-score matched cohort in the CINRG natural history study, with a median age at loss of ambulation of 14.5 years and 11 years, respectively (72% relative risk reduction).
Analyses from the registry demonstrated that ataluren sustained the ability of boys with DMD to complete everyday tasks by years compared with the natural history cohort. In timed function tests, ataluren sustained their ability to stand up from lying down, in under 5 and 10 seconds, for 3 years longer than in boys treated with SoC alone. Boys treated with ataluren were also still able to climb 4 stairs in under 5 and 10 seconds for 1.5 and 3.6 years longer, respectively, compared with boys on SoC alone.
In addition, the analysis showed a trend toward delayed worsening of pulmonary function in routine clinical practice for individuals treated with ataluren, compared to the matched individuals in CINRG. Researchers evaluated FVC, a traditional measure of lung function in individuals with DMD that correlates with disease progression and mortality. The STRIDE data showed that 32.1% of standard of care individuals from the natural history cohort had an FVC of <50%, compared to only 2.2% of individuals receiving ataluren. However, the authors state that given the low number of events and the shorter duration of follow-up of participants in the STRIDE registry compared to CINRG in these interim analyses, it is premature to draw firm conclusions from these results. After loss of ambulation and loss of the use of the arms, the respiratory muscles of people with DMD start to progressively deteriorate, leading to the risk of life-threatening respiratory complications and the need for ventilation support.
"DMD is a devastating disease that causes irreversible muscle wasting and progressively robs young people of their ability to walk, move, and breathe naturally without a ventilator, and it reduces their autonomy in daily life tasks," said Dr. Andrés Nascimento, Pediatric Neurology, Neuromuscular Diseases Unit, SJD Children's Hospital, Barcelona, Spain. "In a real-world setting, children and adolescents treated with Translarna experience a delay in the disease progression, are able to maintain more mobility, and have a higher level of physical autonomy concerning the course of the natural history of the disease. This is not only clinically relevant, but especially important for the quality of life of patients and their families."
Mark B. Skeen, MD
Robert Shavelle, PhD, FAACPDM; Jordan Brooks, PhD, MPH; David Strauss, PhD, FASA; and Amytis Towfighi, MD
Thomas P. Leist, MD