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. 2025 Feb;14(1):211-225.
doi: 10.1007/s40120-024-00685-8. Epub 2024 Nov 26.

Caregiver Global Impression Observations from EMBARK: A Phase 3 Study Evaluating Delandistrogene Moxeparvovec in Ambulatory Patients with Duchenne Muscular Dystrophy

Craig M McDonald  1 , Jacob S Elkins  2 , Sai Dharmarajan  2 , Katherine Gooch  2 , Teofil Ciobanu  3 , Claire J Lansdall  3 , Alexander P Murphy  4 , Fiona McDougall  5 , Eugenio M Mercuri  6 , Ivana Audhya  7 ; EMBARK Study Group
Affiliations

Caregiver Global Impression Observations from EMBARK: A Phase 3 Study Evaluating Delandistrogene Moxeparvovec in Ambulatory Patients with Duchenne Muscular Dystrophy

Craig M McDonald et al. Neurol Ther. 2025 Feb.

Abstract

Introduction: Duchenne muscular dystrophy (DMD) is a rare, progressive, debilitating neuromuscular disease. The early childhood onset and debilitating nature of the disease necessitate decades of caretaking for most patients. Caregivers have a critical role in evaluating patients' physical functioning and/or response to treatment. Using DMD-specific caregiver-reported scales, the impact of delandistrogene moxeparvovec gene therapy on caregivers' perceived change in patient disease status or severity was evaluated using the Caregiver Global Impression of Change and Severity (CaGI-C and CaGI-S, respectively).

Methods: In the Phase 3 randomized, double-blind, placebo-controlled trial (EMBARK; NCT05096221), the CaGI-C at week 52 and change from baseline to week 52 in CaGI-S were evaluated in a post hoc analysis. The CaGI-C assesses caregivers' impressions of change in DMD symptoms, physical ability, ability to perform daily activities, and overall health. The CaGI-S evaluates current severity of DMD symptoms, physical ability, ability to perform activities of daily living, and overall health. Data were evaluated using multi-domain responder index (MDRI) and ordinal regression analyses.

Results: MDRI analyses across all four CaGI-C items yielded a treatment difference of 1.7 (95% confidence interval [CI]: 0.90-2.5) favoring delandistrogene moxeparvovec; a treatment difference of 1.1 (95% CI 0.30-1.9) was observed for the CaGI-S favoring delandistrogene moxeparvovec. After adjusting for age, ordinal regression analysis showed a nominally significant increase in the odds of achieving a better rating for delandistrogene moxeparvovec-treated patients on all four CaGI-C items (≥ 3.8-fold increase). After adjusting for baseline severity and age, ordinal regression analysis showed a nominally significant increase in the odds of improvement on all four CaGI-S items (≥ 2.2-fold increase).

Conclusion: These exploratory findings captured by caregiver-reported outcomes add to the totality of evidence that supports the clinical benefits of delandistrogene moxeparvovec for patients with DMD.

Trial registration number: ClinicalTrials.gov identifier, NCT05096221.

Keywords: Caregiver; Delandistrogene moxeparvovec; Duchenne muscular dystrophy; Gene therapy; Global Impressions scale.

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Conflict of interest statement

Declarations. Conflict of Interest: Jacob S. Elkins, Sai Dharmarajan, Katherine Gooch, Ivana Audhya: Employees of Sarepta Therapeutics, Inc., and may hold stock/options in the company. Teofil Ciobanu: Employee of F. Hoffmann-La Roche Ltd. Claire J. Lansdall: Employee of F. Hoffmann-La Roche Ltd. and shareholder of F. Hoffmann-La Roche Ltd. Alexander P. Murphy: Employee of Roche Products UK and may hold shares in F. Hoffmann-La Roche Ltd. Fiona McDougall: Employee of Genentech, Inc.and shareholder of F. Hoffmann-La Roche Ltd. Craig M. McDonald: Reports grants from Capricor Therapeutics, Catabasis, Edgewise Therapeutics, Epirium Bio, Italfarmaco, Pfizer, PTC Therapeutics, Santhera Pharmaceuticals, Sarepta Therapeutics; and has a consultancy/advisory role with Biomarin, Capricor Therapeutics, Catalyst, Edgewise Therapeutics, Italfarmaco, PTC Therapeutics, F. Hoffmann-La Roche Ltd, Santhera Pharmaceuticals and Sarepta Therapeutics. He has received honoraria from PTC Therapeutics and Sarepta Therapeutics. Eugenio M. Mercuri: Reports receiving fees from AveXis, Biogen, and F. Hoffmann-La Roche Ltd. Ethical Approval: EMBARK was conducted in accordance with the provisions of the Declaration of Helsinki and Good Clinical Practice guidelines. Trial protocol and all amendments were approved by an institutional review board and ethics committee at each site. The full list of institutional review boards and ethics committees is available in the Supplementary Information. Informed consent, including consent to publish, was obtained from parent(s)/legal guardian(s), and patients’ assent was obtained when indicated.

Figures

Fig. 1
Fig. 1
Stacked bar chart by CaGI question, showing the proportion of patients who improved, maintained, and deteriorated by treatment group. A CaGI-C and B CaGI-S. Only patients with a valid response at week 52 were included: A N = 119, B N = 111. Patients with missing responses were excluded. ADL activities of daily living, CaGI-C Caregiver Global Impression of Change, CaGI-S Caregiver Global Impression of Severity
Fig. 2
Fig. 2
Ordinal regression analysis showing the odds ratios of achieving a better rating in CaGI response. Only patients with a valid response at week 52 were included. *All p-values are nominal
Fig. 3
Fig. 3
Subgroup analysis of the proportion of improvers in the CaGI-S by age. Changes in CaGI-S by age group (4–5 years and 6–7 years). Only patients with a valid response at week 52 were included. CaGI-S Caregiver Global Impression of Severity
See this image and copyright information in PMC

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