Pregnancy

Women of childbearing potential make up a considerable segment of the patient population affected by psoriasis. Since the effect of alefacept on pregnancy and fetal development, including immune system development, is not known, health care providers are encouraged to enroll patients currently taking alefacept who become pregnant.

Reproductive toxicology studies have been performed in cynomolgus monkeys at doses up to 5 mg/kg/week (about 62 times the human dose based on body weight) and have revealed no evidence of impaired fertility or harm to the fetus due to alefacept. No abortifacient or teratogenic effects were observed in cynomolgus monkeys following intravenous bolus injections of alefacept administered weekly during the period of organogenesis to gestation. Alefacept underwent trans-placental passage and produced in utero exposure in the developing monkeys. In utero, serum levels of exposure in these monkeys were 23% of maternal serum levels. No evidence of fetal toxicity including adverse effects on immune system development was observed in any of these animals.

Animal reproduction studies, however, are not always predictive of human response and there are no adequate and well-controlled studies in pregnant women. Because the risk to the development of the fetal immune system and postnatal immune function in humans is unknown, alefacept should be used during pregnancy only if clearly needed. If pregnancy occurs while taking alefacept, continued use of the drug should be assessed.

Nursing Mothers

It is not known whether alefacept is excreted in human milk. Because many drugs are excreted in human milk, and because there exists the potential for serious adverse reactions in nursing infants from alefacept, a decision should be made whether to discontinue nursing while taking the drug or to discontinue the use of the drug, taking into account the importance of the drug to the mother.

Carcinogenesis, Mutagenesis and Fertility

In a chronic toxicity study, cynomolgus monkeys were dosed weekly for 52 weeks with intravenous alefacept at 1 mg/kg/dose or 20 mg/kg/dose. One animal in the high dose group developed a B-cell lymphoma that was detected after 28 weeks of dosing. Additional animals in both dose groups developed B-cell hyperplasia of the spleen and lymph nodes. One-year post-treatment there was no evidence of alefacept-related lymphoma or B-cell hyperplasia in any of the remaining treated monkeys.

All animals in the study were positive for an endemic primate gammaherpes virus also known as lymphocryptovirus (LCV). Latent LCV infection is generally asymptomatic, but can lead to B-cell lymphomas when animals are immune suppressed.

In a separate study, baboons given 3 doses of alefacept at 1 mg/kg every 8 weeks were found to have centroblast proliferation in B-cell dependent areas in the germinal centers of the spleen following a 116-day washout period.

The role of alefacept in the development of the lymphoid malignancy and the hyperplasia observed in nonhuman primates and the relevance to humans is unknown. Immunodeficiency-associated lymphocyte disorders (plasmacytic hyperplasia, polymorphic proliferation, and B-cell lymphomas) occur in patients who have congenital or acquired immunodeficiencies including those resulting from immunosuppressive therapy.

No formal carcinogenicity or fertility studies were conducted.

Mutagenicity studies were conducted in vitro and in vivo; no evidence of mutagenicity was observed