Rebisufligene etisparvovec

There are no data on the use of rebisufligene etisparvovec in pregnant women. No animal reproductive and developmental toxicity studies have been conducted to assess whether rebisufligene etisparvovec can cause fetal harm when administered to a pregnant woman. Women who are pregnant or desire to become pregnant should not be treated with rebisufligene etisparvovec.

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

There are no data regarding the presence of rebisufligene etisparvovec in human milk, the effects on the breastfed infant, or the effects on milk production. The development and health benefits of breastfeeding should be considered along with the mother's clinical need for rebisufligene etisparvovec and any potential adverse effects on the breastfed infant from rebisufligene etisparvovec or from the underlying maternal condition.

No animal studies have been performed to evaluate the effects of rebisufligene etisparvovec on carcinogenesis, mutagenesis, or impairment of fertility.

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 of rebisufligene etisparvovec was evaluated in 33 pediatric patients with MPS IIIA who received a single intravenous infusion of rebisufligene etisparvovec in 3 clinical studies: 2 open-label, single-arm studies (Study 1 and Study 3) and 1 long-term follow-up study (Study 2) which enrolled patients who participated in one of the prior studies. Twenty-seven patients received the recommended dose of 3.0 × 10¹³ vg/kg. The mean age at the time of treatment was 38.5 months (range: 3.0 months to 9.2 years) and the mean weight was 17.1 kg (range: 3.9 to 31.2 kg). Patients treated with the recommended dose were 96% White and 4% of multiple race; 11% were Hispanic or Latino. The median duration of follow-up following rebisufligene etisparvovec infusion was 4.1 years (range: 7.0 months to 7.8 years).

Adverse reactions in patients who received the recommended dose of 3.0 × 10¹³ vg/kg of rebisufligene etisparvovec (N=27) in clinical studies are listed in the following table.

Adverse Reactions Occurring in ≥5% of Patients Following Treatment with Rebisufligene etisparvovec:

^a Includes aspartate aminotransferase (AST) increased, alanine aminotransferase (ALT) increased, and gamma-glutamyl transferase (GGT) increased.
^b All adverse reactions were of Grade 1 or Grade 2 severity.
^c Includes abnormal behavior, affect lability, aggression, agitation, irritability, nervousness, anxiety, attention deficit hyperactivity disorder, behavior disorder, insomnia, mental status changes, and related behavioral terms.
^d Includes white blood cell count decreased, leukopenia, lymphocyte count decreased, lymphopenia, and neutropenia.
^e Includes platelet count decreased and thrombocytopenia.
^f Includes seizure, epilepsy, status epilepticus, partial seizures

Hepatotoxicity

In clinical trials, 85% (23/27) of patients receiving the recommended dose of rebisufligene etisparvovec experienced adverse reactions associated with liver enzyme elevations (AST, ALT, and/or GGT). Most liver enzyme elevations were less than Grade 3 in severity, and none were associated with elevations of total bilirubin. A single Grade 3 ALT elevation in one patient occurred in the setting of gastroenteritis 62 days following rebisufligene etisparvovec infusion and resolved spontaneously within 8 days. The time to first onset was most frequently within the first 14 days and ranged from 2 days to 30.3 months following rebisufligene etisparvovec infusion. All liver enzyme elevations resolved within 6 days to 40.6 months of onset, except in 2 patients where slight elevations persisted.

Neutropenia

In clinical trials, 22% (6/27) of patients receiving the recommended dose of rebisufligene etisparvovec experienced neutropenia. One patient experienced Grade 3 neutropenia, and the remaining events were of Grade 1 or 2 severity.