A Combined Prospective and Retrospective Comparison of Long-Term Functional Outcomes Suggests Delayed Loss of Ambulation and Pulmonary Decline with Long-Term Eteplirsen Treatment.

Abstract

BACKGROUND:

Studies 4658-201/202 (201/202) evaluated treatment effects of eteplirsen over 4 years in patients with Duchenne muscular dystrophy and confirmed exon-51 amenable genetic mutations. Chart review Study 4658-405 (405) further followed these patients while receiving eteplirsen during usual clinical care.

OBJECTIVE:

To compare long-term clinical outcomes of eteplirsen-treated patients from Studies 201/202/405 with those of external controls.

METHODS:

Median total follow-up time was approximately 6 years of eteplirsen treatment. Outcomes included loss of ambulation (LOA) and percent-predicted forced vital capacity (FVC%p). Time to LOA was compared between eteplirsen-treated patients and standard of care (SOC) external controls and was measured from eteplirsen initiation in 201/202 or, in the SOC group, from the first study visit. Comparisons were conducted using univariate Kaplan-Meier analyses and log-rank tests, and multivariate Cox proportional hazards models with regression adjustment for baseline characteristics. Annual change in FVC%p was compared between eteplirsen-treated patients and natural history study patients using linear mixed models with repeated measures.

RESULTS:

Data were included from all 12 patients in Studies 201/202 and the 10 patients with available data from 405. Median age at LOA was 15.16 years. Eteplirsen-treated patients experienced a statistically significant longer median time to LOA by 2.09 years (5.09 vs. 3.00 years, p < 0.01) and significantly attenuated rates of pulmonary decline vs. natural history patients (FVC%p change: -3.3 vs. -6.0 percentage points annually, p < 0.0001).

CONCLUSIONS:

Study 405 highlights the functional benefits of eteplirsen on ambulatory and pulmonary function outcomes up to 7 years of follow-up in comparison to external controls.

• Authors: Olga Mitelman, Hoda Z Abdel-Hamid, Barry J Byrne, Anne M Connolly, Peter Heydemann, Crystal Proud, Perry B Shieh, Kathryn R Wagner, Ashish Dugar, Sourav Santra, James Signorovitch, Nathalie Goemans, investigators from the LNMRC Natural History study, Craig M McDonald, investigators from the CINRG Duchenne National History Study, Eugenio Mercuri, investigators from The DMD Italian Group, Jerry R Mendell
• Journal: Journal of neuromuscular diseases (J Neuromuscul Dis) Vol. 9 Issue 1 Pg. 39-52 ( 2022) ISSN: 2214-3602 [Electronic] Netherlands
• PMID: 34420980 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial)

Chemical References

• Morpholinos
• eteplirsen

Topics

• Adolescent
• Child
• Disease Progression
• Humans
• Male
• Mobility Limitation
• Morpholinos (administration & dosage, pharmacology)
• Muscular Dystrophy, Duchenne (drug therapy, physiopathology)
• Outcome Assessment, Health Care
• Prospective Studies
• Registries
• Retrospective Studies
• Time Factors
• Vital Capacity
• Walk Test