“Milestone in Cancer therapy” Imlygic (talimogene laherparepvec), the first FDA-approved oncolytic virus therapy, for the treatment of melanoma lesions in the skin and lymph nodes.

October 27, 2015.

The U.S. Food and Drug Administration approved novel Imlygic (talimogene laherparepvec), the first FDA-approved oncolytic virus therapy, for the treatment of melanoma lesions in the skin and lymph nodes.

Imlygic programs viruses to attack only cancer cells and gives patients more humane options – potentially ‘a complete change in the game’ in treatment.

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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.

CLINICAL PHARMACOLOGY

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 stimulate an immune response to kill melanoma cells in the tumour and elsewhere in the body & promote an antitumor immune response.

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Talimogene laherparepvec or T-VEC — divides into copies repeatedly until the membranes, or outer layers, of the cancer cells burst.

However, the exact mechanism of action is unknown.

Safety and Efficacy

  • The safety and efficacy of Imlygic were evaluated in a multicenter study (OPTiM Study) of 436 participants with metastatic melanoma that could not be surgically removed.
  • The participants’ melanoma lesions in the skin and lymph nodes were treated with Imlygic or a comparator therapy for at least six months, or until there were no remaining injectable lesions.
  • The study showed that 16.3 percent of the study participants who received Imlygic experienced a decrease in size of their skin and lymph node lesions, lasting for a minimum of six months, compared to 2.1 percent of the study participants receiving the comparator therapy.
  • However, Imlygic has not been shown to improve overall survival or to have an effect on melanoma that has spread to the brain, bone, liver, lungs, or other internal organs.

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.

DOSAGE AND ADMINISTRATION

  • Administer IMLYGIC by injection into cutaneous, subcutaneous, and/or nodal lesions.

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  • Recommended starting dose is up to a maximum of 4 mL of IMLYGIC at a concentration of 106 (1 million) plaque-forming units (PFU) per mL. Subsequent doses should be administered up to 4 mL of IMLYGIC at a concentration of 108 (100 million) PFU per mL.

CONTRAINDICATIONS

  • Immunocompromised Patients
  • Pregnant Patients.

WARNINGS AND PRECAUTIONS

  • Accidental Exposure to IMLYGIC: Accidental exposure may lead to transmission of IMLYGIC and herpetic infection. Healthcare providers and close contacts should avoid direct contact with injected lesions, dressings, or body fluids of treated patients. Healthcare providers who are immunocompromised or pregnant should not prepare or administer IMLYGIC. If accidental exposure occurs, exposed individuals should clean the affected area.
  • Herpetic Infection: Patients who develop herpetic infections should be advised to follow standard hygienic practices to prevent viral transmission.
  • Injection Site Complications: Consider the risks and benefits before continuing IMLYGIC treatment if persistent infection or delayed healing develops.
  • Immune-Mediated Events: Consider the risks and benefits of IMLYGIC before initiating treatment in patients who have underlying autoimmune disease or before continuing treatment in patients who develop immune-mediated events.
  • Plasmacytoma at Injection Site: Consider the risks and benefits in patients with multiple myeloma or in whom plasmacytoma develops during treatment.
  • IMLYGIC is sensitive to acyclovir. Acyclovir or other antiviral agents may interfere with the effectiveness of IMLYGIC.

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.

Pyrexia, chills, and influenza-like illness can occur at any time during IMLYGIC treatment, but were more frequent during the first 3 months of treatment.

Imlygic is manufactured by BioVex Inc., a subsidiary of Amgen Inc., based in Thousand Oaks, California.

Reference:

FDA Newsroom.

Prescribing Information