Safety and effectiveness of ataluren in patients with nonsense mutation DMD in the STRIDE Registry compared with the CINRG Duchenne Natural History Study (2015-2022): 2022 interim analysis

by Selleckchem | Oct 11 2023

Objective: Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, international, multicenter registry of real-world ataluren use in individuals with nonsense mutation Duchenne muscular dystrophy (nmDMD) in clinical practice. This updated interim report (data cut-off: January 31, 2022), describes STRIDE patient characteristics and ataluren safety data, as well as the effectiveness of ataluren plus standard of care (SoC) in STRIDE versus SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS).

Methods: Patients are followed up from enrollment for at least 5 years or until study withdrawal. Propensity score matching was performed to identify STRIDE and CINRG DNHS patients who were comparable in established predictors of disease progression.

Results: As of January 31, 2022, 307 patients were enrolled from 14 countries. Mean (standard deviation [SD]) ages at first symptoms and at genetic diagnosis were 2.9 (1.7) years and 4.5 (3.7) years, respectively. Mean (SD) duration of ataluren exposure was 1671 (56.8) days. Ataluren had a favorable safety profile; most treatment-emergent adverse events were mild or moderate and unrelated to ataluren. Kaplan-Meier analyses demonstrated that ataluren plus SoC significantly delayed age at loss of ambulation by 4 years (p < 0.0001) and age at decline to %-predicted forced vital capacity of < 60% and < 50% by 1.8 years (p = 0.0021) and 2.3 years (p = 0.0207), respectively, compared with SoC alone.

Conclusion: Long-term, real-world treatment with ataluren plus SoC delays several disease progression milestones in individuals with nmDMD. NCT02369731; registration date: February 24, 2015.

Comments:

The Objective section of the given text provides an overview of the study called Strategic Targeting of Registries and International Database of Excellence (STRIDE). This study is an ongoing, international, multicenter registry that focuses on real-world usage of ataluren in individuals with nonsense mutation Duchenne muscular dystrophy (nmDMD) in clinical practice. The report presents updated interim findings as of January 31, 2022, including patient characteristics, safety data of ataluren, and the effectiveness of ataluren plus standard of care (SoC) compared to SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS).

In the Methods section, it is stated that patients are followed up for at least 5 years or until they withdraw from the study. Propensity score matching was used to identify comparable patients from both the STRIDE and CINRG DNHS groups based on established predictors of disease progression.

The Results section provides some key findings from the study. As of January 31, 2022, a total of 307 patients from 14 countries were enrolled. The mean ages at first symptoms and genetic diagnosis were 2.9 years and 4.5 years, respectively. The average duration of ataluren exposure was 1671 days. The safety profile of ataluren was found to be favorable, with most treatment-emergent adverse events being mild or moderate and unrelated to ataluren.

The study's findings, as shown in Kaplan-Meier analyses, demonstrated that the combination of ataluren and SoC significantly delayed several disease progression milestones compared to SoC alone. Specifically, ataluren plus SoC delayed the age at loss of ambulation by 4 years (p < 0.0001) and the age at decline to less than 60% and 50% of predicted forced vital capacity by 1.8 years (p = 0.0021) and 2.3 years (p = 0.0207), respectively.

In conclusion, the long-term real-world use of ataluren in combination with standard of care was found to delay several disease progression milestones in individuals with nmDMD. The study is registered under the identifier NCT02369731, with a registration date of February 24, 2015.