Vamorolone

Duchenne muscular dystrophy (DMD) is a severe X-linked muscular disorder caused by the absence of dystrophin. Standard therapies prolong survival; however, there is an increasing need for disease-modifying approaches and sensitive evaluation tools. This review presents a summary of the recent advances in DMD therapeutic strategies and multidimensional evaluation approaches, emphasizing their clinical applicability and future perspectives. In this study, a comprehensive review of the current literature was conducted focusing on mutation-specific therapies (exon skipping and gene therapy), non-mutation-specific pharmacological interventions (steroids, vamorolone, and histone deacetylase inhibitors), and emerging modalities such as cell-based therapy. The clinical outcome measures used across the disease stages were also examined, ranging from functional motor tests and imaging biomarkers to digital endpoints and quality of life (QOL) indices. Exon skipping and microdystrophin gene therapies have shown promising results in restoring partial dystrophin expression. Vamorolones and givinostat are alternative drugs with improved safety profiles. Time-based motor tests (such as time to sand, 10 m run) and digital biomarkers (Stride Velocity 95th Centile) enable the earlier detection of disease progression. Natural history data, including large registry-based datasets, enhance the interpretation of clinical trials. Patient-reported outcomes and disease-specific QOL measures, such as the DMD-QoL, are increasingly being incorporated to assess meaningful treatment benefits. The therapeutic landscape of DMD is evolving toward combination and personalized approaches. Multidimensional stage-specific evaluations are essential to capture functional changes and their therapeutic effects. Ongoing research on gene-, pharmacological-, and cell-based therapies, coupled with robust outcome assessments, may further improve patient care and QOL.

Objective: This meta-analysis evaluates the efficacy and safety of vamorolone, a dissociative glucocorticoid, compared with traditional glucocorticoids in treating Duchenne muscular dystrophy (DMD), aiming to assess its potential as a safer alternative with comparable therapeutic benefits. Data Sources: A systematic search was conducted in PubMed (MEDLINE), Embase, and Web of Science from inception till June 2024. Search terms included (Vamorolone) AND (Corticosteroids OR Glucocorticoids OR Prednisone) AND (Duchenne Muscular Dystrophy OR related terms). Only randomized controlled trials (RCTs) and observational studies were included, with no language restrictions. Study Selection and Data Extraction: From 276 identified reports, 135 were screened after duplicate removal, and 30 underwent full-text review. Five studies (2 RCTs, 2 observational, 1 nonrandomized trial) involving 370 patients were included. Two reviewers independently extracted data on efficacy (TTSTAND, TTRW, TTCLIMB velocities) and safety (height percentile, body mass index-z score, osteocalcin, P1NP) using Microsoft Excel, resolving discrepancies through consensus. Data Synthesis: Vamorolone significantly improved TTSTAND (MD = −0.03, 95% confidence interval [CI] = −0.06 to −0.004, P = .02), TTRW (MD = −0.11, 95% CI = −0.22 to −0.01, P = .04), and TTCLIMB velocities (MD = −0.04, 95% CI = −0.08 to −0.003, P = .03). Safety outcomes showed enhanced height percentile (MD = 16.28, 95% CI = 6.31–26.25, P = .001) and bone biomarkers (osteocalcin: MD = 15.68, P < .00001; P1NP: MD = 158.34, P < .00001), with no significant body mass index-z score difference. Conclusions: Vamorolone offers comparable efficacy with traditional glucocorticoids in DMD, with improved motor function and safer profiles in growth and bone health, suggesting its potential to transform DMD management.