Amgen has announced that the FDA has approved the Biologics License Application for Imlygic (talimogene laherparepvec), 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. Imlygic has not been shown to improve overall survival or have an effect on visceral metastases. Imlygic is the first oncolytic viral therapy approved by the FDA based on therapeutic benefit demonstrated in a pivotal study.
Imlygic is a genetically modified herpes simplex virus type 1 designed to replicate within tumors and produce an immunostimulatory protein called granulocyte-macrophage colony-stimulating factor (GM-CSF). Imlygic causes cell lysis, or death, which ruptures tumors, releasing tumor-derived antigens, which along with GM-CSF, may promote an anti-tumor immune response. However, the exact mechanism of action is unknown.
The approval of Imlygic is based on data from Study 005/05, referred to as OPTiM. OPTiM was a phase III, multicenter, open-label, randomized clinical trial comparing Imlygic to GM-CSF in patients with advanced melanoma (stage IIIB, IIIC, or IV) that was not surgically resectable. The primary endpoint of the study was durable response rate (DRR), defined as the percent of patients with complete response (CR) or partial response (PR) maintained continuously for a minimum of six months.
OPTiM enrolled 436 patients. In the study, 16.3% of patients treated with Imlygic achieved a durable response compared to 2.1% of patients treated with GM-CSF (p<0.0001). Of the patients who experienced a durable response, 29.1% had a durable CR and 70.8% had a durable PR. In the study, the median time to response was 4.1 (range: 1.2 to 16.7) months in the Imlygic arm.
The most common adverse drug reactions in Imlygic treated patients were fatigue, chills, pyrexia, nausea, influenza-like illness and injection site pain. Most adverse reactions reported were mild or moderate in severity and generally resolved within 72 hours. The most common grade 3 or higher adverse reaction was cellulitis.