Golodirsen Eases Ambulatory, Pulmonary Function Decline in DMD

In patients with progressing Duchenne muscular dystrophy (DMD), golodirsen treatment over 6 years delayed loss of ambulation by a median of 2.4 years compared with matched controls, according to a poster presented at the recent MDA Clinical & Scientific Conference in Orlando, Florida.

The abstract reported efficacy and safety findings from post hoc analyses of study 4053-101 (NCT02310906) and the open-label extension 4045-302 (NCT03532542), which evaluated golodirsen in patients with progressive disease deterioration. The treatment is approved by the US Food and Drug Administration for the treatment of DMD in patients with exon 53 skip-amenable mutations.

In all, 25 patients, with mean age of 8.8 years, received golodirsen; 18 completed the open-label extension up to 6.49 years, reported Eugenio Maria Mercuri, MD, PhD, of Catholic University, Rome, Italy, and coauthors. The analyses compared golodirsen-treated patients with external controls matched for age, mutation, and steroid use.

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At year 3, loss of ambulation occurred in 4 patients treated with golodirsen compared with 12 of 54 age- and mutation-matched external controls, according to the abstract. The risk reduction with golodirsen was 91.1%.

Over 6 years, loss of ambulation occurred in 15 patients treated with golodirsen, and 7 patients remained ambulatory. Compared with 16 age- and mutation-matched external controls, golodirsen was associated with a median delay to loss of ambulation of 2.4 years, demonstrating a 47.4% risk reduction, researchers reported.

Regarding pulmonary function, the annual rate of percent predicted forced vital capacity decline was 2.9% in patients treated with golodirsen compared with 6.67% in mutation-matched external controls.

Golodirsen was well tolerated, analyses showed. No treatment-related discontinuations, kidney abnormalities, or port-related infections occurred in the open-label extension.

“Overall, golodirsen treatment up to ~6 years demonstrates a favorable, consistent safety profile and supports its long-term efficacy vs mutation-matched external controls,” researchers wrote. “This is the longest follow-up of safety and functional benefit of golodirsen in a declining DMD population.”

Reference

Mercuri EM, Muntoni F, Seferian AM, et al. Six-year long-term safety and efficacy of golodirsen in patients with DMD vs mutation-matched external controls. Poster presented at MDA Clinical & Scientific Conference; March 3-6, 2024; Orlando, Florida.