FDA Approves First Oncolytic Viral Therapy in the United States

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Howard L. Kaufman, MD

The U.S. Food and Drug Administration (FDA) has approved the biologics license application for talimogene laherparepvec (Imlygic), 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. Talimogene laherparepvec has not been shown to improve overall survival or have an effect on visceral metastases. The agent is the first oncolytic viral therapy approved by the FDA based on therapeutic benefit demonstrated in a pivotal study.1-3

Talimogene laherparepvec is a genetically modified herpes simplex virus type 1 designed to replicate within tumors and produce granulocyte-macrophage colony-stimulating factor (GM-CSF). It is injected directly into melanoma lesions. The agent causes cell lysis, which ruptures tumors, releasing tumor-derived antigens, which along with GM-CSF, may promote an antitumor immune response. However, the exact mechanism of action is unknown.

Pivotal Phase III Trial

The approval of talimogene laherparepvec is based on data from a phase III, multicenter, open-label, randomized clinical trial (OPTiM) comparing talimogene laherparepvec to GM-CSF in patients with advanced melanoma (stage IIIB, IIIC, or IV) that was not surgically resectable.2 The primary endpoint of the study was durable response rate, defined as the percent of patients with complete response or partial response maintained continuously for a minimum of 6 months.

OPTiM enrolled 436 patients. In the study, 16.3% of patients treated with talimogene laherparepvec achieved a durable response compared to 2.1% of patients treated with GM-CSF (P < .0001). Of the patients who experienced a durable response, 29.1% had a durable complete response and 70.8% had a durable partial response. In the study, the median time to response was 4.1 months (range, 1.2–16.7 months) in the talimogene laherparepvec arm.

The most common adverse drug reactions in talimogene laherparepvec–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.2

“Advanced melanoma remains a complex disease to treat, requiring the use of several modalities over the course of a patient’s therapeutic journey,” said Howard L. Kaufman, MD, the principal investigator for the pivotal trial, who is also the Associate Director for Clinical Science at the Rutgers Cancer Institute of New Jersey, and President of the Society for Immunotherapy of Cancer. “As an oncolytic viral therapy, [talimogene laherparepvec] has a unique approach and provides another option for treating eligible patients with unresectable disease that has recurred after initial surgery.”
Amgen, the manufacturer of talimogene laherparepvec, intends to make the drug available imminently to patients with stage III melanoma in the United States. Amgen anticipates the average cost of therapy to be approximately $65,000.  ■


1. Review of FDA hematology/oncology approvals from March 2013 to September 13, 2015 via Accessed September 14, 2015.

2. Andtbacka  H, Kaufman HL, Collichio F, et al: J Clin Oncol 33(25):2812-2814, 2015.

3. Lawler SE, Chiocca EA: Oncolytic virus-mediated immunotherapy: A combinatorial approach for cancer treatment. J Clin Oncol 33:2812-2814, 2015.