Overview
11 DESCRIPTION IMLYGIC (talimogene laherparepvec) is a sterile suspension for intralesional injection. IMLYGIC is a live, attenuated HSV-1 that has been genetically modified to express huGM-CSF. The parental virus for IMLYGIC was a primary isolate, which was subsequently altered using recombinant methods to result in gene deletions and insertions.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action IMLYGIC has been genetically modified to replicate within tumors and to produce the immune stimulatory protein GM-CSF. IMLYGIC causes lysis of tumors, followed by release of tumor-derived antigens, which together with virally derived GM-CSF may promote an antitumor immune response. However, the exact mechanism of action is unknown. 12.3 Pharmacokinetics Biodistribution (within the body) and Viral Shedding (excretion/secretion) IMLYGIC viral DNA levels in various tissues and secretions were determined using a quantitative polymerase chain reaction (qPCR) assay. Infectious IMLYGIC at the injection sites and at some potential herpetic lesions was also quantified using viral infectivity assays.
Indications
- 1 INDICATIONS AND USAGE 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. Limitations of use : IMLYGIC has not been shown to improve overall survival or have an effect on visceral metastases. 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.
Common Doses
- 4 mL
- 1 mL
- 2 mL
- 0.5 mL
Dosage
2 DOSAGE AND ADMINISTRATION For intralesional injection only. Do not administer intravenously. Administer IMLYGIC by injection into cutaneous, subcutaneous, and/or nodal lesions. ( 2.1 ) Recommended starting dose is up to a maximum of 4 mL of IMLYGIC at a concentration of 10 6 (1 million) plaque-forming units (PFU) per mL. Subsequent doses should be administered up to 4 mL of IMLYGIC at a concentration of 10 8 (100 million) PFU per mL. ( 2.1 ) 2.
Contraindications
- 4 CONTRAINDICATIONS Immunocompromised Patients ( 4.1 ) Pregnant Patients ( 4.2 ) 4.1 Immunocompromised Patients IMLYGIC is a live, attenuated herpes simplex virus and may cause life-threatening disseminated herpetic infection in patients who are immunocompromised. Do not administer IMLYGIC to immunocompromised patients, including those with a history of primary or acquired immunodeficient states, leukemia, lymphoma, AIDS or other clinical manifestations of infection with human immunodeficiency viruses, and those on immunosuppressive therapy [see Nonclinical Toxicology ( 13.2 )] . 4.
Side Effects
- 6 ADVERSE REACTIONS The most commonly reported adverse drug reactions (≥ 25%) in IMLYGIC-treated patients were fatigue, chills, pyrexia, nausea, influenza-like illness, and injection site pain. The following adverse reactions are discussed in greater detail in another section of the label: Herpetic Infection [see Warnings and Precautions ( 5.2 )] Injection Site Complications [see Warnings and Precautions ( 5.3 )] The most commonly reported adverse drug reactions (≥ 25%) in IMLYGIC-treated patients were fatigue, chills, pyrexia, nausea, influenza-like illness, and injection site pain.
Interactions
- 7 DRUG INTERACTIONS IMLYGIC is sensitive to acyclovir. Acyclovir or other antiherpetic viral agents may interfere with the effectiveness of IMLYGIC. No drug interaction studies have been conducted with IMLYGIC.