FDA APPROVAL BASED ON DYSTROPHIN PRODUCTION, AS MEASURED BY SAREPTA WESTERN BLOT.1
Dystrophin protein production was demonstrated at week 48 of Study 3 and at week 180 of Study 2.1
AVERAGE DYSTROPHIN PROTEIN LEVEL IN MUSCLE TISSUE | |
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48 WEEKS ON TREATMENT1 Study 3: Baseline and Week 48 data available for each patient. |
180 WEEKS ON TREATMENT1 Study 2: Week 180 data available for each patient (baseline biopsies not available) |
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- In Study 3, the average dystrophin protein level in muscle tissue after 48 weeks of treatment with EXONDYS 51 (n=12) was 0.44% ± 0.43% (mean ± standard deviation) of healthy subjects* (P<0.05). The median increase after 48 weeks was 0.1%.1
- In Study 2, the average dystrophin protein level in muscle tissue after 180 weeks of treatment with EXONDYS 51 (n=11) was 0.93% of normal (ie, 0.93% of the dystrophin level in healthy subjects*).1
- Study 2 failed to provide evidence of a clinical benefit of EXONDYS 51 compared to the external control group.1
- Due to insufficient information on baseline dystrophin protein levels in Study 1, it was not possible to estimate dystrophin protein production in response to EXONDYS 51 in Study 1.1
*Healthy subjects = people without DMD.
SD = standard deviation.
DYSTROPHIN LEVEL AFTER 48 WEEKS ON EXONDYS 51 TREATMENT VS BASELINE.
Study 3 Sarepta western blot results:
- At Week 48, some patients had an increase in dystrophin over baseline (P=<0.05)
- There was a mean 2.8-fold increase (range -0.19 to +8.40) over baseline in dystrophin in patients treated with EXONDYS 51.1
**Fold change in dystrophin = change from baseline % normal dystrophin/baseline % normal dystrophin

Dystrophin levels assessed by western blot can be meaningfully influenced by differences in sample processing, analytical technique, reference materials, and quantification methodologies. Therefore, comparing dystrophin results from different assay protocols will require a standardized reference material and additional bridging studies.1

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INDICATION
EXONDYS 51 (eteplirsen) is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 51 skipping. This indication is approved under accelerated approval based on an increase in dystrophin in skeletal muscle observed in some patients treated with EXONDYS 51. Continued approval for this indication may be contingent upon verification of a clinical benefit in confirmatory trials.
IMPORTANT SAFETY INFORMATION
Hypersensitivity reactions, including bronchospasm, chest pain, cough, tachycardia and urticaria, have occurred in patients who were treated with EXONDYS 51. If a hypersensitivity reaction occurs, institute appropriate medical treatment and consider slowing the infusion or interrupting the EXONDYS 51 therapy.
Adverse reactions in DMD patients (N=8) treated with EXONDYS 51 30 or 50 mg/kg/week by intravenous (IV) infusion with an incidence of at least 25% more than placebo (N=4) (Study 1, 24 weeks) were (EXONDYS 51, placebo): balance disorder (38%, 0%), vomiting (38%, 0%) and contact dermatitis (25%, 0%). The most common adverse reactions were balance disorder and vomiting. Because of the small numbers of patients, these represent crude frequencies that may not reflect the frequencies observed in practice. The 50 mg/kg once weekly dosing regimen of EXONDYS 51 is not recommended.
The most common adverse reactions from observational clinical studies (N=163) seen in greater than 10% of patients were headache, cough, rash, and vomiting.
Please see the full Prescribing Information for EXONDYS 51 (eteplirsen).
References
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EXONDYS 51 [package insert]. Cambridge, MA: Sarepta Therapeutics Inc.