Safety, tolerability, and pharmacokinetics of casimersen in patients with <scp>D</scp>uchenne muscular dystrophy amenable to exon <scp>45</scp> skipping: A randomized, double‐blind, placebo‐controlled, dose‐titration trial

Wagner, Kathryn R.; Kuntz, Nancy L.; Koenig, E.; East, Lilly; Upadhyay, Sameer; Han, Baoqin; Shieh, Perry B.

doi:10.1002/mus.27347

Cited by 105 publications

(73 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There are an increasing number of treatments for specific subpopulations of DMD patients, which have been approved by the US Food and Drug Administration (FDA) or are currently in clinical trial phases. These include Eteplirsen [ 2 , 3 ], Casimersen [ 4 ], Golodirsen [ 5 ], Viltolarsen [ 6 ] and Ataluren [ 7 – 9 ]. However, glucocorticoids (GC) are currently the only widely available recommended treatment in the DMD care considerations [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Growth pattern trajectories in boys with Duchenne muscular dystrophy

Stimpson

Raquq

Chesshyre

et al. 2022

Orphanet J Rare Dis

View full text Add to dashboard Cite

Objectives The objective of this study is to analyse retrospective, observational, longitudinal growth (weight, height and BMI) data in ambulatory boys aged 5–12 years with Duchenne muscular dystrophy (DMD). Background We considered glucocorticoids (GC) use, dystrophin isoforms and amenability to exon 8, 44, 45, 51 and 53 skipping drug subgroups, and the impact of growth on loss of ambulation. We analysed 598 boys, with 2604 observations. This analysis considered patients from the UK NorthStar database (2003–2020) on one of five regimes: “GC naïve”, “deflazacort daily” (DD), “deflazacort intermittent” (DI), “prednisolone daily” (PD) and “prednisolone intermittent” (PI). A random slope model was used to model the weight, height and BMI SD scores (using the UK90). Results The daily regime subgroups had significant yearly height stunting compared to the GC naïve subgroup. Notably, the average height change for the DD subgroup was 0.25 SD (95% CI − 0.30, − 0.21) less than reference values. Those with affected expression of Dp427, Dp140 and Dp71 isoforms were 0.77 (95% CI 0.3, 1.24) and 0.82 (95% CI 1.28, 0.36) SD shorter than those with Dp427 and/or Dp140 expression affected respectively. Increased weight was not associated with earlier loss of ambulation, but taller boys still ambulant between the age of 10 and 11 years were more at risk of losing ambulation. Conclusion These findings may provide further guidance to clinicians when counselling and discussing GCs commencement with patients and their carers and may represent a benchmark set of data to evaluate the effects of new generations of GC.

show abstract

Section: Introductionmentioning

confidence: 99%

Growth pattern trajectories in boys with Duchenne muscular dystrophy

Stimpson

Raquq

Chesshyre

et al. 2022

Orphanet J Rare Dis

View full text Add to dashboard Cite

show abstract

“…Recently, various therapies based on molecular mechanisms, including gene therapy, cell therapy, read-through drugs, and antisense oligonucleotides for exon-skipping, have been studied and subjected to clinical trials: of these, four antisense oligonucleotide drugs (eteplirsen, golodirsen, viltolarsen, and casimersen) have been approved by the United States Food and Drug Administration for use in treating dystrophinopathy [12][13][14][15]. As such, genetic diagnosis of dystrophinopathy is becoming increasingly important.…”

Section: Introductionmentioning

confidence: 99%

Clinical and genetic spectra in patients with dystrophinopathy in Korea: A single-center study

et al. 2021

View full text Add to dashboard Cite

Dystrophinopathy is a group of inherited phenotypes arising from pathogenic variants in DMD. We evaluated the clinical and genetic characteristics of Korean patients with genetically confirmed dystrophinopathy. We retrospectively reviewed medical records (January 2004-September 2020) from the myopathy database maintained at the study hospital and found 227 patients from 218 unrelated families with dystrophinopathy. Clinical phenotypes included 120 (53%) Duchenne muscular dystrophy (DMD) cases, 20 (9%) intermediate phenotype muscular dystrophy (IMD) cases, 65 (29%) Becker muscular dystrophy (BMD) cases, 18 (8%) undetermined phenotypes, and 4 (2%) symptomatic carriers. The median ages at symptom onset and diagnosis were 5.0 years (interquartile range [IQR]: 3.8–8.0) and 12.0 years (IQR: 7.0–21.0), respectively. Total manual muscle test (MMT) scores decreased annually in patients with DMD, IMD, and BMD. Overall, when age increased by 1 year, total MMT scores decreased on average by -1.978, -1.681, and -1.303 in patients with DMD (p<0.001), IMD (p<0.001), and BMD (p<0.001), respectively. Exonic deletion and duplication were reported in 147 (67%) and 31 (14%) of the 218 unrelated probands, respectively. A total of 37 different small sequence variants were found in 40 (18%) of the 218 probands. The reading frame rule was applicable to 142 (94%) of the 151 probands. The present results highlight the long-term natural history and genetic spectrum of dystrophinopathy in a large-scale Korean cohort.

show abstract

“…As the only genetically targeted treatment to currently hold FDA approval, AON-mediated exon skipping therapy is leading the field of precision therapy for DMD, largely due to its favorable safety profile and demonstrated efficacy [ 65 , 66 , 67 ]. Approximately 30% of the DMD population is currently eligible for EST, using one of the four approved options, and this number is set to expand as research surrounding EST continues, providing a promising therapeutic option to an increasingly large subset of DMD patients [ 68 , 69 ].…”

Section: State Of Est For Deletionsmentioning

confidence: 99%

Antisense and Gene Therapy Options for Duchenne Muscular Dystrophy Arising from Mutations in the N-Terminal Hotspot

Wilton-Clark

Yokota

2022

Genes

View full text Add to dashboard Cite

Duchenne muscular dystrophy (DMD) is a fatal genetic disease affecting children that is caused by a mutation in the gene encoding for dystrophin. In the absence of functional dystrophin, patients experience progressive muscle deterioration, leaving them wheelchair-bound by age 12 and with few patients surviving beyond their third decade of life as the disease advances and causes cardiac and respiratory difficulties. In recent years, an increasing number of antisense and gene therapies have been studied for the treatment of muscular dystrophy; however, few of these therapies focus on treating mutations arising in the N-terminal encoding region of the dystrophin gene. This review summarizes the current state of development of N-terminal antisense and gene therapies for DMD, mainly focusing on exon-skipping therapy for duplications and deletions, as well as microdystrophin therapy.

show abstract

Safety, tolerability, and pharmacokinetics of casimersen in patients with Duchenne muscular dystrophy amenable to exon 45 skipping: A randomized, double‐blind, placebo‐controlled, dose‐titration trial

Cited by 105 publications

References 21 publications

Growth pattern trajectories in boys with Duchenne muscular dystrophy

Growth pattern trajectories in boys with Duchenne muscular dystrophy

Clinical and genetic spectra in patients with dystrophinopathy in Korea: A single-center study

Antisense and Gene Therapy Options for Duchenne Muscular Dystrophy Arising from Mutations in the N-Terminal Hotspot

Contact Info

Product

Resources

About