1 INDICATIONS AND USAGE AMONDYS 45 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 45 skipping.

This indication is approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with AMONDYS 45 [see Clinical Studies ( 14 )] .

Continued approval for this indication may be contingent upon verification of a clinical benefit in confirmatory trials.

AMONDYS 45 is an antisense oligonucleotide 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 45 skipping.

This indication is approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with AMONDYS 45 [see Clinical Studies ( 14 )] .

Continued approval for this indication may be contingent upon verification of a clinical benefit in confirmatory trials.

( 1 )

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity reactions [see Warnings and Precautions ( 5.1 )] The most common adverse reactions (incidence >20% and at least 5% higher than placebo) were upper respiratory tract infection, cough, pyrexia, headache, arthralgia, and oropharyngeal pain.

( 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.

In the AMONDYS 45 clinical development program, 76 patients received at least one intravenous dose of AMONDYS 45 (30 mg/kg).

All patients were male and had genetically confirmed Duchenne muscular dystrophy.

Age at study entry was 7 to 20 years (mean 9.9 years).

Most (88%) patients were White, and 9% were Asian.

AMONDYS 45 was studied in a double-blind, placebo-controlled study (Study 1).

Patients in ongoing Study 1 received AMONDYS 45 (n=57) 30 mg/kg or placebo (n=31) intravenously once weekly for up to 96 weeks, after which all patients received or will receive AMONDYS 45 30 mg/kg for up to 48 weeks.

Adverse reactions observed in ≥20% of patients treated with AMONDYS 45 and 5% more frequently than in the placebo group in Study 1 are shown in Table 1 .

Table 1.

Adverse Reactions Occurring in at Least 20% of Patients Treated with AMONDYS 45 and at a Rate at Least 5% More Frequently than in the Placebo Group in Study 1 *Includes upper respiratory infection, pharyngitis, nasopharyngitis, and rhinitis.

Adverse Reaction AMONDYS 45 30 mg/kg Once Weekly (n = 57) % Placebo (n = 31) % Upper Respiratory Tract Infections* 65 55 Cough 33 26 Pyrexia 33 23 Headache 32 19 Arthralgia 21 10 Oropharyngeal Pain 21 7 Other adverse reactions that occurred in at least 10% of patients treated with AMONDYS 45, and that were reported at a rate at least 5% more frequently in the AMONDYS 45 group than in the placebo group, were: ear pain, nausea, ear infection, post-traumatic pain, and dizziness and light-headedness.

6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of AMONDYS 45.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Infusion-related reactions including rash, headache, cough, abdominal pain (including upper abdominal pain), and vomiting occurred within 24 hours from the start of an infusion of AMONDYS 45.

Hypersensitivity reactions, including angioedema and anaphylaxis, have occurred in patients treated with AMONDYS 45.