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Page 347 Gonzalez Castillo et al. J Transl Genet Genom. 2025;9:338-51 https://dx.doi.org/10.20517/jtgg.2025.57

A further consideration is the initial expanded label for Elevidys in nonambulatory boys. Families may
anticipate outcomes comparable to those observed in younger, ambulatory patients. However, in later
disease stages, functional gains are less likely.

This underscores the need for risk stratification for potential cardiac and liver events following gene
therapy, particularly in older patients. This should be addressed during the screening process to ensure
informed decision-making.

Large-scale registries, such as the Strategic Targeting of Registries and International Database of Excellence
(STRIDE) Registry and the Cooperative International Neuromuscular Research Group Duchenne Natural
History Study (CINRG DNHS), provide robust data to help differentiate between perceived and actual
efficacy. For example, in the STRIDE registry, patients receiving ataluren plus standard of care showed a
delay in loss of ambulation. On the other hand, data from the CINRG DNHS has shown that glucocorticoid
treatment for ≥ 1 year increases median age at loss of ambulation and other functional milestones by
2.1-4.4 years [81,82] .

Although gene therapies offer life-changing benefits for patients, the unprecedentedly high cost represents a
challenge for reimbursement. Some payers may deny coverage, and others might include several filters
before approval which can delay treatment. Various alternative payment models have been proposed and
used to pay for these therapies in the United States and internationally. Some of these models address the
high budgetary impact of gene therapies by spreading costs over multiple years (amortization) or across
multiple patients (risk spreading), to make the cost among the population of patients more predictable.
Other models focus on the clinical uncertainty of high-cost therapies by using performance-based
agreements. In an outcome-based payment model, compensation is directly linked to the drug’s
performance and payment is adjusted based on a predefined outcome, either at the individual level or across
the treated population . This model has also been combined with amortization, allowing the benefit of
[83]
spreading costs over time.

More efforts to implement innovative solutions are needed to ensure patient equitable access to
[83]
treatment .
CONCLUSIONS
Variable results have been reported from multiple clinical trials targeting dystrophin restoration. In general,
modest clinical benefits were observed, showing slowed disease progression, but long-term efficacy and
durability remain uncertain. Emerging therapies for dystrophin restoration hold promise to address
limitations of current treatments, including transfection efficacy, immunotoxicity, alternative
immunosuppression regimens, and AAV delivery. Future advancements in dystrophin restoration will
require both optimization of current therapeutic strategies and integration of sensitive biomarkers and
comprehensive outcome measures to accurately assess clinical response. Additionally, real-world data will
be essential to understand the impact across diverse patient populations and guide evidence-based clinical
implementation. Nevertheless, multidisciplinary care and steroids remain the mainstay of treatment.

DECLARATIONS
Authors’ contributions
Initial draft, conceptualization, writing and editing: Gonzalez Castillo Z
Writing and editing: Nelson L