Atacicept

Available data on atacicept use in pregnant women exposed during clinical trials are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Based on mechanism of action, atacicept may cause immunosuppression in the in utero-exposed infant. There are risks to the mother and infant with untreated IgAN nephropathy in pregnancy.

In animal reproduction studies, no treatment-related malformations were observed in mice and rabbits at atacicept exposures approximately up to 12 times and 4 times, respectively, the clinical exposure at the recommended human dose (RHD).

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of major birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

There are no data regarding the presence of atacicept in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production/excretion.

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

Carcinogenesis

No carcinogenicity studies have been conducted with atacicept-vymj.

Mutagenesis

Atacicept-vymj was not mutagenic or clastogenic in in vitro Ames, in vitro chromosomal aberration, and in vivo micronucleus assays.

Impairment of Fertility

No effects on male fertility were observed in mice dosed once every two days for 4 weeks prior to mating and throughout the mating period with SC atacicept-vymj up to 80 mg/kg, at exposures approximately 20 times the clinical exposure at the RHD, based on AUC.

Increased pre- and post-implantation losses and reduced number of live fetuses were observed in female mice dosed with SC atacicept-vymj once every two days from 14 days prior to mating to GD 7 at ≥20 mg/kg, at exposures approximately 4 times the clinical exposure at the RHD, based on AUC.

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 atacicept was evaluated in a randomized, double-blind, placebo-controlled clinical study in 428 adults with IgAN (Origin 3). The median duration of exposure was 34 weeks in the 214 patients treated with atacicept and 31 weeks in the 214 patients administered placebo.

The most common adverse reactions (reported in ≥5% of patients treated with atacicept and at a higher incidence than placebo) in patients treated with atacicept and placebo, respectively, were infections (32% vs. 28%) and local administration reactions (30% vs. 5%). The most common infection was upper respiratory tract infection (12% vs. 9%), and the most common local administration reactions were injection site reaction (19% vs. 2%) and injection site erythema (6% vs. 1%). Most adverse reactions observed in the atacicept group were mild or moderate in severity and resolved without treatment interruption or discontinuation.