IMLYGIC was derived from a novel primary HSV-1 isolate (JS1, ECACC Accession Number 01010209) that demonstrates enhanced oncolytic activity towards tumor cells, as compared to the commonly used laboratory strains (e.g., 17syn+).
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PARAMETER |
DATA |
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Manufacturer |
Amgen Inc. |
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Transgene |
hGM-CSF Gene |
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Indication |
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. |
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Virus and Serotype |
Wild-type HSV-1 genome (new isolate JS1) |
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Cell Substrate |
African green monkey kidney cells (Vero) |
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Manufacturing platform |
The active substance manufacturing process includes cell expansion, virus infection and production (in roller bottles), harvest, recovery, and purification stages. The purification process consists of endonuclease digestion, clarification by filtration, ultrafiltration/diafiltration (UF/DF), two chromatography steps (IEX, SEC) and a final sterile filtration to produce the active substance. No additional filtration occurs beyond this step in drug product manufacture. The sterile filtration step therefore provides the terminal sterile filtration for the drug product. |
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Dose in vial/final container |
106 (1 million) PFU per mL, 108 (100 million) PFU per mL in single-use vials |
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Dose/patient |
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. |
CLINICAL TRIALS
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NCT |
TRIAL PHASE |
SUBJECTS ENROLLED |
STUDY TITLE |
COUNTRIES |
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NCT00769704 |
3 |
437 |
United States, Canada, South Africa, United Kingdom |
|
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NCT01368276 |
3 |
31 |
An Extended Use Study of Safety and Efficacy of Talimogene Laherparepvec in Melanoma |
United States |
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NCT00289016 |
2 |
50 |
A Study of Talimogene Laherparepvec in Stage IIIc and Stage IV Malignant Melanoma |
United States, United Kingdom |
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NCT02574260 |
2 |
3 |
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| 10/27/2015 | FDA approval date |
| 12/16/2015 | EMA approval date |
| 12/21/2015 | TGA approval date |
A joint meeting of CBER’s Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) and CDER’s Oncologic Drugs Advisory Committee (ODAC) was held on April 29, 2015 in order to provide advice to FDA regarding safety, dosing, and an overall benefit-risk assessment for IMLYGIC. There was extensive discussion, with no clear consensus, regarding whether the efficacy of IMLYGIC was limited to a definable subset of the Study 005 population (e.g., those subjects with less advanced disease). The committee voted 22 to 1 (Yes to No) to the question, “does talimogene laherparepvec have an overall favorable benefit-risk profile to support traditional approval for the treatment of injectable, regionally or distantly metastatic melanoma?”