Pozelimab

Pozelimab has not been studied in combination with intravenous immunoglobulin. Intravenous immunoglobulin may interfere with the endosomal neonatal Fc receptor (FcRn) recycling mechanism of monoclonal antibodies such as pozelimab thereby decreasing serum pozelimab concentrations. Avoid concomitant use of intravenous immunoglobulin with pozelimab. If concomitant use cannot be avoided, monitor patients for worsening of clinical signs and symptoms of CD55-deficient PLE.

Risk Summary

Although there are no data on pozelimab use in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes, monoclonal antibodies can be actively transported across the placenta.

In an animal reproduction study in monkeys, pozelimab-bbfg did not adversely affect embryofetal or postnatal development when administered from pregnancy confirmation through parturition at doses that produced exposure up to 3.3 to 3.8 times the predicted clinical exposures (on an AUC basis; see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other outcome. 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.

Data

Animal Data

In an enhanced pre- and postnatal development study, pregnant female monkeys were subcutaneously administered pozelimab-bbfg at doses of 5 or 50 mg/kg once weekly from confirmation of pregnancy (gestation day 20) through parturition (approximately gestation day 160). No adverse effects were observed on maintenance of pregnancy, pregnancy outcome, or on the development of offspring through postnatal day 90 at doses up to 3.3-3.8 times the predicted clinical exposures.

There are no data on the presence of pozelimab-bbfg in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. Endogenous maternal IgG and monoclonal antibodies are transferred into human milk. The effects of local gastrointestinal exposure and the extent of systemic exposure in the breastfed infant to pozelimab are unknown. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for pozelimab and any potential adverse effects on the breastfed infant from pozelimab or from the underlying maternal condition.

Carcinogenesis and Mutagenesis

Carcinogenicity studies have not been conducted with pozelimab-bbfg. The mutagenic potential of pozelimab-bbfg has not been evaluated; however, monoclonal antibodies are not expected to alter DNA or chromosomes.

Impairment of Fertility

Fertility studies have not been conducted with pozelimab-bbfg. In a 6-month toxicity study in sexually-mature male and female monkeys, pozelimab-bbfg had no adverse effects on histological or functional markers of reproductive function (e.g., estrous cyclicity, testicular volume, ejaculate amount, total sperm count per ejaculate, sperm motility and morphology, and histology of reproductive organs) at doses up to 100 mg/kg/week (11.9 to 13.9-fold the predicted exposures at the recommended clinical doses, on an AUC basis).

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 of pozelimab was evaluated in 10 patients with CD55-deficient PLE (ranging from 3 to 19 years of age) in a single-arm study. The median duration of exposure was 104 weeks (range: 75 to 140 weeks). Adverse reactions reported in two or more patients are summarized in the following table.

Adverse Reactions Reported in Two or More Pozelimab-Treated Patients with CD55-deficient PLE in a Clinical Trial:

^* Composed of similar terms

Additionally, injection site reactions (including dermatitis and erythema), metabolic acidosis, gingival bleeding, increased blood uric acid, increased liver enzymes, hematuria and proteinuria were reported in one patient each.

Vital Signs

Four patients reported elevated systolic and/or diastolic blood pressure readings above the normal range for age at multiple study visits.