Delandistrogene moxeparvovec

The safety and efficacy of delandistrogene moxeparvovec in patients with hepatic impairment or elevated GGT have not been studied.

Postpone delandistrogene moxeparvovec administration in patients with acute liver disease until resolved or controlled. Delandistrogene moxeparvovec therapy should be carefully considered in patients with preexisting liver impairment or chronic hepatic viral infection. These patients may be at increased risk of acute serious liver injury.

In clinical trials, liver function test increase was commonly reported in subjects following delandistrogene moxeparvovec infusion.

Delandistrogene moxeparvovec is not intended for use in pregnant women.

In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

There is no information available on the presence of delandistrogene moxeparvovec in human milk, the effects on the breastfed infant, or the effects on milk production.

No animal studies have been performed to evaluate the effects of delandistrogene moxeparvovec on carcinogenicity, mutagenesis, or impairment of fertility.

The most common adverse reactions (incidence ≥5%) reported in clinical studies were vomiting, nausea, liver function test increased, pyrexia, and thrombocytopenia.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the 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.

The safety data described in this section reflect exposure to a one-time intravenous infusion of delandistrogene moxeparvovec in 85 male subjects with a confirmed mutation of the DMD gene in three on-going clinical studies, including two open-label studies and one study that included a double-blind, placebo-controlled period. Prior to delandistrogene moxeparvovec infusion, patients in the delandistrogene moxeparvovec treatment group had a mean age of 7.08 years (range: 3 to 20) and mean weight of 25.91 kg (range: 12.5 to 80.1). 73 subjects received the recommended dose of 1.33 × 10 ¹⁴ vg/kg, and 12 received a lower dose. Table 3 below presents adverse reactions from these three clinical studies.

The most common adverse reactions (incidence ≥5%) across all studies are summarized in Table 3.

Adverse reactions were typically seen within the first 2 weeks (nausea, vomiting, thrombocytopenia, pyrexia), or within the first 2 months (immune-mediated myositis, liver function test increased). Vomiting may occur as early as on the day of the infusion.

Table 3. Adverse reactions (Incidence ≥5%) following treatment with delandistrogene moxeparvovec in Clinical Studies:

^a Includes: AST increased, ALT increased, GGT increased, GLDH increased, hepatic enzyme increased, transaminases increased, blood bilirubin increased
^b Transient, mild, asymptomatic decrease in platelet counts

In the double-blind, placebo-controlled trial (Study 1 Part 1), subjects 4 to 7 years of age (N=41) received either delandistrogene moxeparvovec (N=20) at the recommended dose of 1.33 × 10¹⁴ vg/kg (n=8) or lower dose (n=12) or received placebo (N=21). Table 4 below presents the most frequent adverse reactions from Study 1 Part 1.

Table 4. Adverse reactions occurring in delandistrogene moxeparvovec-treated subjects and at least 10% more frequently than in placebo in Study 1, Part 1:

^a Includes: AST increased, ALT increased, GGT increased, GLDH increased, hepatic enzyme increased, transaminases increased, blood bilirubin increased.