IMPACT OF ETEPLIRSEN TREATMENT INITIATION DELAYS ON LOSS OF AMBULATION INCIDENCE AMONG AMBULATORY PATIENTS WITH DUCHENNE MUSCULAR DYSTROPHY
Author(s)
Lauren Sedita, MS, Alexa Klimchak, MA, Carol Schermer, MD, Louise Rodino-Klapac, PhD, Katherine Gooch, PhD;
Sarepta Therapeutics, Inc., Cambridge, MA, USA
Sarepta Therapeutics, Inc., Cambridge, MA, USA
OBJECTIVES: Eteplirsen is approved for treating exon 51 skip-amenable patients with Duchenne muscular dystrophy (DMD). Real-world evidence (RWE) has described eteplirsen as slowing time to loss of ambulation (LoA) versus external controls. This study estimated the impact of delaying eteplirsen treatment initiation on LoA for ambulatory populations.
METHODS: A simulation model of two diagnosed ambulatory exon 51-skip amenable DMD populations (all ages and those with time to rise ≥5 seconds [late ambulatory, LA]) was developed to estimate cumulative LoA incidence over 5 years. Different treatment scenarios were assessed: standard of care (SoC) only (corticosteroids and medical management) from Cooperative International Neuromuscular Research Group (CINRG) registry data of exon 51-skip amenable patients, SoC plus immediate eteplirsen treatment, and SoC plus delayed eteplirsen treatment (0.5-2-year delays). A 0.38 hazard ratio estimated from previous RWE of eteplirsen versus external controls was applied at treatment initiation to estimate eteplirsen-treated risk over time.
RESULTS: Immediate eteplirsen treatment for all ambulatory patients reduced cumulative LoA incidence versus SoC over the horizon, including at Year 3 (13.5% vs 29.2%) and Year 5 (24.8% vs 47.8%), representing a 15.7% and 23.0% absolute risk reduction, respectively. Treatment initiation delays of 0.5-2 years increased LoA incidence to 15.8%-23.4% at Year 3 (2.4%-10.0% increase over immediate treatment) and 26.6%-32.5% at Year 5 (1.7%-7.7% increase over immediate treatment). Cumulative 5-year LoA incidence for LA patients was 99.4% with SoC versus 69.4% with immediate treatment. Treatment delays of 0.5-2 years increased incidence by 4.9%-19.2% versus immediate treatment.
CONCLUSIONS: Extrapolating evidence from real world studies, this model suggests eteplirsen reduces the cumulative LoA incidence versus SoC alone regardless of timing. However, even a 6-month delay in treatment initiation would increase the cumulative LoA incidence within 5 years versus immediate treatment, and this impact worsens with longer delays.
METHODS: A simulation model of two diagnosed ambulatory exon 51-skip amenable DMD populations (all ages and those with time to rise ≥5 seconds [late ambulatory, LA]) was developed to estimate cumulative LoA incidence over 5 years. Different treatment scenarios were assessed: standard of care (SoC) only (corticosteroids and medical management) from Cooperative International Neuromuscular Research Group (CINRG) registry data of exon 51-skip amenable patients, SoC plus immediate eteplirsen treatment, and SoC plus delayed eteplirsen treatment (0.5-2-year delays). A 0.38 hazard ratio estimated from previous RWE of eteplirsen versus external controls was applied at treatment initiation to estimate eteplirsen-treated risk over time.
RESULTS: Immediate eteplirsen treatment for all ambulatory patients reduced cumulative LoA incidence versus SoC over the horizon, including at Year 3 (13.5% vs 29.2%) and Year 5 (24.8% vs 47.8%), representing a 15.7% and 23.0% absolute risk reduction, respectively. Treatment initiation delays of 0.5-2 years increased LoA incidence to 15.8%-23.4% at Year 3 (2.4%-10.0% increase over immediate treatment) and 26.6%-32.5% at Year 5 (1.7%-7.7% increase over immediate treatment). Cumulative 5-year LoA incidence for LA patients was 99.4% with SoC versus 69.4% with immediate treatment. Treatment delays of 0.5-2 years increased incidence by 4.9%-19.2% versus immediate treatment.
CONCLUSIONS: Extrapolating evidence from real world studies, this model suggests eteplirsen reduces the cumulative LoA incidence versus SoC alone regardless of timing. However, even a 6-month delay in treatment initiation would increase the cumulative LoA incidence within 5 years versus immediate treatment, and this impact worsens with longer delays.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
SA53
Topic
Study Approaches
Disease
SDC: Musculoskeletal Disorders (Arthritis, Bone Disorders, Osteoporosis, Other Musculoskeletal), SDC: Neurological Disorders, SDC: Pediatrics, SDC: Rare & Orphan Diseases, STA: Personalized & Precision Medicine