Overview
11 DESCRIPTION EXONDYS 51 (eteplirsen) injection is a sterile, aqueous, preservative-free, concentrated solution for dilution prior to intravenous administration. EXONDYS 51 is clear and colorless, and may have some opalescence, and may contain white to off-white amorphous particles. EXONDYS 51 is supplied in single dose vials containing 100 mg or 500 mg eteplirsen (50 mg/mL).
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Eteplirsen is designed to bind to exon 51 of dystrophin pre-mRNA, resulting in exclusion of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 51 skipping. Exon skipping is intended to allow for production of an internally truncated dystrophin protein, which was evaluated in Study 2 and Study 3 [ see Clinical Studies ( 14 ) ]. 12.2 Pharmacodynamics All EXONDYS 51-treated patients evaluated (n=36) were found to produce messenger ribonucleic acid (mRNA) for a truncated dystrophin protein by reverse transcription polymerase chain reaction. In Study 2, the average dystrophin protein level in muscle tissue after 180 weeks of treatment with EXONDYS 51 was 0.93% of normal (i.e., 0.
Indications
- 1 INDICATIONS AND USAGE EXONDYS 51 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 [see Clinical Studies ( 14 )] . Continued approval for this indication may be contingent upon verification of a clinical benefit in confirmatory trials.
Common Doses
- 150 mL
Dosage
2 DOSAGE AND ADMINISTRATION 30 milligrams per kilogram of body weight once weekly ( 2.1 ) Administer as an intravenous infusion over 35 to 60 minutes via an in-line 0.2 micron filter ( 2.1 , 2.3 ) Dilution required prior to administration ( 2.2 ) 2.1 Dosing Information The recommended dose of EXONDYS 51 is 30 milligrams per kilogram administered once weekly as a 35 to 60 minute intravenous infusion via an in-line 0.2 micron filter. If a dose of EXONDYS 51 is missed, it may be administered as soon as possible after the scheduled time. 2.
Contraindications
- 4 CONTRAINDICATIONS None. None ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The most common adverse reactions (incidence ≥35% and higher than placebo) were balance disorder and vomiting ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sarepta Therapeutics, Inc. at 1-888-SAREPTA (1-888-727-3782) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Interactions
- No major interactions listed on the FDA label. Always consult a healthcare professional.