Casimersen

There are no human or animal data available to assess the use of casimersen during pregnancy. In the U.S. general population, major birth defects occur in 2% to 4% and miscarriage occurs in 15% to 20% of clinically recognized pregnancies.

There are no human or animal data to assess the effect of casimersen on milk production, the presence of casimersen in milk, or the effects of casimersen on the breastfed infant.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for casimersen and any potential adverse effects on the breastfed infant from casimersen or from the underlying maternal condition.

Carcinogenesis

Carcinogenicity studies have not been conducted with casimersen.

Mutagenesis

Casimersen was negative in in vitro (bacterial reverse mutation assay and chromosomal aberration assay in CHO cells) and in vivo (mouse bone marrow micronucleus) assays.

Impairment of Fertility

Fertility studies in animals were not conducted with casimersen. No effects of casimersen were observed on the male reproductive system following weekly administration to male mice at subcutaneous doses up to 960 mg/kg for 26 weeks or to male monkeys at intravenous doses up to 640 mg/kg for 39 weeks. Plasma exposures at the highest doses tested in mouse and monkey were approximately 9 and 35 times, respectively, that in humans at the recommended human dose of 30 mg/kg/week.

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 casimersen clinical development program, 76 patients received at least one intravenous dose of casimersen (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.

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

Patients in ongoing Study 1 received casimersen (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 casimersen 30 mg/kg for up to 48 weeks.

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

Adverse Reactions Occurring in at Least 20% of Patients Treated with Casimersen 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.

Other adverse reactions that occurred in at least 10% of patients treated with casimersen, and that were reported at a rate at least 5% more frequently in the casimersen group than in the placebo group, were: ear pain, nausea, ear infection, post-traumatic pain, and dizziness and light-headedness.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of casimersen. 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 casimersen.

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