Imlygic

IMLYGIC is a genetically modified oncolytic viral therapy indicated for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery.

• Initial dose only: 10⁶ (1 million) PFU per mL solution in 1 mL single-dose vial (light green cap)
  
  
• Subsequent doses: 10⁸ (100 million) PFU per mL solution in 1 mL single-dose vial (royal blue cap)

• Pregnancy: Women of childbearing potential should be advised to use an effective method of contraception to prevent pregnancy during treatment with IMLYGIC. (
  8.1       Pregnancy

  Risk Summary

  Adequate and well-controlled studies with IMLYGIC have not been conducted in pregnant women. No effects on embryo-fetal development have been observed in a study conducted in pregnant mice. The design of the study limits application of the animal data to humans

  [see Data].

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

  Clinical Considerations

  If the patient becomes pregnant while taking IMLYGIC, the patient should be apprised of the potential hazards to the fetus and neonate. Women of childbearing potential should be advised to use an effective method of contraception to prevent pregnancy during treatment with IMLYGIC.

  If a pregnant woman has an infection with wild-type Herpes Simplex Virus Type 1 (HSV-1) (primary or reactivation), there is potential for the virus to cross the placental barrier and also a risk of transmission during birth due to viral shedding. Infections with wild-type HSV-1 have been associated with serious adverse effects, including multi-organ failure and death, if a fetus or neonate contracts the wild-type herpes infection. While there are no clinical data to date on IMLYGIC infections in pregnant women, there could be a risk to the fetus or neonate if IMLYGIC were to act in the same manner.

  Data

  Animal Data

  No effects on embryo-fetal development were observed when IMLYGIC was intravenously administered during organogenesis to immunocompetent pregnant mice at doses up to 4 x 10⁸(400 million) PFU per kg (60-fold higher, on a PFU per kg basis, compared to the maximum clinical dose). Levels of IMLYGIC DNA in pooled fetal blood were at or below the assay detection level. Study design limitations included: 1) administration of IMLYGIC expressing human granulocyte-macrophage colony-stimulating factor (huGM-CSF), which is not biologically active in mice; 2) unknown transplacental kinetics of IMLYGIC following intravenous administration in pregnant mice; and 3) unknown significance of IMLYGIC dose extrapolation from animal to human based on body weight.
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• Lactation: Discontinue drug or nursing. (
  8.2       Lactation

  Risk Summary

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

  Clinical Considerations

  Because medicinal products can be found in human milk, a decision should be made whether to discontinue nursing or to discontinue IMLYGIC while nursing.
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