Icotrokinra

The available data on the use of icotrokinra during pregnancy are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In an animal reproduction study in rabbits, oral administration of icotrokinra to pregnant rabbits during the period of organogenesis at a dose 157 times the maximum recommended human dose (MRHD) based on AUC comparison resulted in maternal body weight loss, low food consumption, late pregnancy loss, and an increased fetal incidence of fused ribs.

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, and other adverse outcomes. 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 on the presence of icotrokinra in human milk, the effects on the breastfed infant, or the effects on milk production. When administered to lactating rats, icotrokinra was detected in the plasma of nursing pups. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for icotrokinra and any potential adverse effects on the breastfed infant from icotrokinra or from the underlying maternal condition.

In a 6-month transgenic rasH2 mouse study, no drug-related tumors were observed at oral doses of icotrokinra up to 500 mg/kg/day (76 times the MRHD based on AUC comparison). In a 2-year rat carcinogenicity study, no drug-related tumors were observed at oral doses of 20 mg/kg/day (16 times the MRHD based on AUC comparison).

Icotrokinra was not genotoxic in an in vitrobacterial reverse mutation assay (the Ames test), an in vitrohuman lymphocyte chromosomal aberration assay, or an in vivorat micronucleus and Comet assays.

In male rats, icotrokinra had no adverse effect on mating, fertility or early embryonic development of their offspring at oral doses up to 20 mg/kg/day (114 times the MRHD based on AUC comparison).

In female rats, icotrokinra had no adverse effect on estrous cyclicity, mating, fertility, or early embryonic parameters at oral doses up to 70 mg/kg/day (335 times the MRHD based on AUC comparison).

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 icotrokinra was evaluated in two placebo-controlled trials (Trial PSO-3 and Trial PSO-4) and two placebo- and active-controlled trials (Trial PSO-1 and Trial PSO-2). A total of 2367 adults and pediatric subjects 12 years of age and older who weigh at least 40 kg with moderate-to-severe plaque psoriasis received icotrokinra 200 mg orally once daily. Of these, 648 subjects were treated with icotrokinra for at least one year.

Data from these four trials were pooled to evaluate the safety of icotrokinra compared to placebo for 16 weeks.

Adverse Reactions

Weeks 0 to 16

Table 1. Adverse Reactions that Occurred in ≥1% of Subjects in the icotrokinra Group and More Frequently than in the Placebo Group in Trials PSO-1, PSO-2, PSO-3, and PSO-4 through Week 16*:

^* percentages based on Cochran-Mantel-Haenszel (CMH) adjusted proportions.
^† Fungal infection includes tinea pedis (n=4), tinea versicolor (n=2), oral candidiasis (n=2), onychomycosis (n=1), skin candida (n=1), urinary tract candidiasis (n=1), vulvovaginal candidiasis (n=1), fungal skin infection (n=1), genital infection fungal (n=1), ear infection fungal (n=1), laryngitis fungal (n=1). Two subjects experienced more than 1 event.

Adverse reactions that occurred in <1% of subjects in the icotrokinra group and at a higher rate than in the placebo group through Week 16 in Trials PSO-1, PSO-2, PSO-3, and PSO-4 were: gastritis, abdominal discomfort, and one fatal case involving upper gastrointestinal bleeding in a subject with underlying risk factors. A relationship of this event to icotrokinra is not established.

Adverse Reactions in Pediatric Subjects 12 Years of Age and Older

The safety of icotrokinra was evaluated in pediatric subjects 12 years of age and older who weigh at least 40 kg with moderate-to-severe plaque psoriasis in two placebo-controlled trials (Trial PSO-3 and Trial PSO-4). A total of 72 pediatric subjects were treated with icotrokinra 200 mg orally once daily. Of these, 45 subjects were treated with icotrokinra for at least one year. The adverse reactions observed in pediatric subjects were consistent with the most common adverse reactions (≥1%) observed in the overall population.