The US Food and Drug Administration (FDA) has approved talimogene laherparepvec (Imlygic, Amgen), which is the first oncolytic viral therapy to receive approval from the agency.
The drug is indicated for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma that recurred after initial surgery.
Talimogene laherparepvec is a genetically modified herpes simplex virus type 1 that is designed to replicate within tumors and produce the immunostimulatory protein granulocyte-macrophage colony-stimulating factor (GM-CSF). It is injected directly into the melanoma lesions causing cell lysis. This in turn ruptures the tumors and releases tumor-derived antigens, which, along with GM-CSF, may promote an antitumor immune response.
However, according to the manufacturer, the exact mechanism of action is unknown.
"Advanced melanoma remains a complex disease to treat, requiring the use of several modalities over the course of a patient's therapeutic journey," commented Howard L. Kaufman, MD, the principal investigator for the pivotal trial (OPTiM) that led to the drug's approval, in a statement issued by the company.
"As an oncolytic viral therapy, [Imlygic] has a unique approach, and provides another option for treating eligible patients with unresectable disease that has recurred after initial surgery," said Dr Kaufman, who is associate director for clinical science at the Rutgers Cancer Institute of New Jersey and president of the Society for Immunotherapy of Cancer.
A treatment course with talimogene laherparepvec consists of a series of injections directly into the melanoma lesions. After the initial injection, a second dose is administered 3 weeks later, followed by additional doses every 2 weeks for at least 6 months, unless other treatment is required or until there are no remaining injectable lesions to treat.
Earlier this week, the product was recommended for approval in Europe by the European Medicines Agency. It had also been recommended by the FDA's Oncologic Drugs Advisory Committee and the Cellular, Tissue, and Gene Therapies Advisory Committee last April, by a vote of 22 to 1.
The outcome of the advisory meeting was somewhat of a surprise, as the FDA briefing document released prior to the meeting contained many queries and stated that it was unclear whether the product offers an acceptable benefit-risk profile in a therapeutic field in which many new therapies have recently been launched.
The FDA's approval is based on efficacy data that comes from the OPTiM study, a randomized, controlled trial conducted in adults with unresectable regionally or distantly metastatic melanoma. The study enrolled 436 patients, with 295 patients treated with talimogene laherparepvec compared with 141 patients treated with GM-CSF.
The primary endpoint was the durable response rate (DRR), defined as the rate of complete response plus partial response continuously lasting ≥ 6 months and beginning within the first 12 months. Secondary endpoints included overall survival and the overall response rate.
The DRR was significantly higher among patients receiving the experimental drug than among those given GM-CSF (16.3% vs 2.1%; odds ratio, 8.9; P < .001). Of the patients who experienced a durable response, 29.1% had a durable complete response and 70.8% had a durable partial response. The median time to response was 4.1 (range: 1.2 to 16.7) months in the arm receiving talimogene laherparepvec.
The overall response rate was also higher with talimogene laherparepvec (26.4% vs 5.7%; P < .001). In all, 32 (10.8%) patients receiving talimogene laherparepvec experienced a complete response, compared with just one (< 1%) patient receiving GM-CSF.
The median time to treatment failure was 8.2 months with talimogene laherparepvec and 2.9 months with GM-CSF (hazard ratio [HR], 0.42). Median overall survival was 23.3 months and 18.9 months, respectively (HR, 0.79; P = .051), which just missed being statistically significant.
The most common side effects observed in clinical study participants were chills, pyrexia, injection-site pain, nausea, flulike symptoms, and fatigue. The most common serious events included disease progression, cellulitis, and pyrexia, none of which occurred in more than 2% of patients.
Because it is a modified live oncolytic herpes virus therapy, herpetic infection can also occur. Its use is contraindicated in pregnant women and immunocompromised patients, including patients with a history of primary or acquired immunodeficient states, leukemia, lymphoma, AIDS, or other clinical manifestations of infection with human immunodeficiency viruses, and patients on immunosuppressive therapy, because of the risk for life-threatening disseminated herpetic infection.
Talimogene laherparepvec is manufactured by BioVex Inc, a subsidiary of Amgen Inc.
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Cite this: FDA Approves Imlygic, First Oncolytic Viral Therapy in the US - Medscape - Oct 27, 2015.