Dados do Trabalho

Título

SIX-YEAR LONG-TERM SAFETY AND EFFICACY OF GOLODIRSEN IN PATIENTS WITH DMD VS MUTATION-MATCHED EXTERNAL CONTROLS

Introdução

Golodirsen is FDA approved for the treatment of Duchenne muscular dystrophy (DMD) in patients with exon 53 skip-amenable mutations. A first-in-human study (4053-101; NCT02310906) previously provided evidence for the biologic activity and long-term safety of golodirsen for up to ~3 years in a declining population of patients with DMD.

Objetivo

To describe results from Study 4053-101 and the open-label extension (OLE) 4045-302 (NCT03532542) evaluating the safety and efficacy of golodirsen treatment up to ~6 years in patients with progressive disease deterioration.

Método

Post hoc analyses comparing ambulatory and pulmonary function of golodirsen-treated patients with matched (including age, mutation, steroid use) external controls (ECs) were performed.

Resultados

Twenty-five patients received treatment at mean age 8.8 years; 18/25 (72%) completed the OLE up to 6.49 years. Overall, golodirsen was well tolerated: treatment-emergent adverse events were generally mild, nonserious, and unrelated to treatment; there were no treatment-related discontinuations, kidney abnormalities, or port-related infections in the OLE. At year 3, loss of ambulation (LOA) occurred in 4/25 (16%) of golodirsen-treated patients compared with 12/54 (22.2%) age- and mutation-matched ECs, representing a 91.1% risk reduction (HR 0.089; P=0.0224). Over 6 years, 15 golodirsen-treated patients experienced LOA (10.7–19.5 years), with 7 patients still ambulant at OLE completion (12.4–20.3 years). Compared with age- and mutation-matched ECs (n=16), golodirsen-treated patients experienced a median delay in time to LOA of ~2.4 years, representing a 47.4% risk reduction (HR 0.526; P=0.149). A separate post hoc analysis suggested that golodirsen-treated patients (aged ≥10 years) experienced a statistically significant and clinically meaningful attenuation in the annual rate of percent predicted forced vital capacity decline compared with mutation-matched ECs (2.9% vs 6.67%; P<0.01).

Conclusão

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

Referências

none

Fonte de Fomento (se houver)

Sarepta Therapeutics, Inc.

Palavras Chave

Duchenne muscular dystrophy; golodirsen; exon skipping