Amgen, an American multinational biopharmaceutical company, announced that the European Commission has approved the use of Imlygic (talimogene laherparepvec) for the treatment of adults with unresectable melanoma that is regionally or distantly metastatic (stage IIIB, IIIC and IVM1a), with no bone, brain, lung or other visceral disease. Imlygic is the first oncolytic immunotherapy to demonstrate therapeutic benefit for patients with metastatic melanoma in a phase 3 clinical trial.

Imlygic is derived from the herpes simplex type 1 virus (HSV-1) , commonly called the cold sore virus. Imlygic has been modified to replicate within tumours and to produce the immune stimulatory protein human granulocyte-macrophage colony-stimulating factor (GM-CSF). Administered via intralesional injection, Imlygic is designed to cause the death of tumour cells and initiate an anti-tumour immune response.

"As the first oncolytic immunotherapy authorised in the European Union, the approval of Imlygic is an important milestone for this new class of drugs, bringing patients with a rare and deadly form of skin cancer a much needed new treatment option," said Sean E. Harper, M.D., executive vice president of research and development at Amgen. "By igniting the body's own immune system Imlygic can initiate an anti-tumour immune response, providing meaningful and durable response rates in the early stage metastatic melanoma patient."

Melanoma remains a significant public health concern in the European Union (EU), with an estimated 22,000 deaths from the disease in 2012. While melanoma is curable when detected in the early stages, metastatic melanoma continues to be one of the most difficult-to-treat cancers because it is highly aggressive and complex. Even with recent new options in immune-oncology, a large number of patients with metastatic melanoma still do not respond to treatment.

The European approval included a review of exploratory subgroup analyses of Study 005/05, referred to as OPTiM. The durable response rate (DRR) in patients with stage IIIB, IIIC and IVM1a disease was 25.2 per cent compared to 1.2 per cent in those treated with GM-CSF. In the study, patients with stage IIIB, IIIC and IVM1a disease achieved an overall response rate (ORR) of 40.5 per cent when treated with Imlygic compared to 2.3 per cent with GM-CSF. The median overall survival (OS) for Imlygic patients with stage IIIB, IIIC and IVM1a disease was 41.1 months compared to 21.5 months for patients treated with GM-CSF. While the pivotal study was not powered to evaluate efficacy in these individual subgroups, patients with no visceral disease derived greater benefit from Imlygic treatment than those with more advanced disease. Due to the exploratory nature of the analysis and based on the current evidence, it has not been established that Imlygic is associated with an effect on OS.

The most commonly reported treatment-related adverse events were fatigue, chills, pyrexia, nausea, influenza-like illness and injection-site pain. Overall, 98 per cent of these adverse reactions reported were mild or moderate in severity. The most common grade 3 or higher adverse reaction was cellulitis. No fatal treatment-related adverse events occurred.

This approval grants a centralized marketing authorisation in the 28 countries that are members of the EU. Norway, Iceland and Liechtenstein, as members of the European Economic Area (EEA), will take corresponding decisions on the basis of the decision of the EC.

OPTiM was a global, randomized, open-label phase 3 trial evaluating the safety and efficacy of Imlygic in patients with stage IIIB, IIIC or IV melanoma when resection was not recommended compared to GM-CSF. In the 436-patient study, Imlygic significantly improved DRR, the primary endpoint of the trial, in the intent-to-treat population. DRR is defined as the per cent of patients with complete response (CR) or partial response (PR) maintained continuously for a minimum of six months. In the study, 16.3 per cent of patients treated with Imlygic achieved a DRR compared to 2.1 per cent of patients treated with GM-CSF (p<0.0001) in the intent-to-treat population. Of the patients who experienced a durable response, 29.1 per cent had a durable CR and 70.8 per cent had a durable PR. In the study, the median time to response was 4.1 months (range: 1.2 to 16.7) in the Imlygic arm.

A key secondary endpoint was OS. In the intent-to-treat population, the median OS was 23.3 months in the group treated with Imlygic compared to 18.9 months for those treated with GM-CSF (p=0.0511). These results were not statistically significant. The ORR for patients in the intent-to-treat population was 26.4 per cent for those treated with Imlygic compared to 5.7 per cent in the GM-CSF arm. In an analysis to evaluate the systemic activity of Imlygic, 34 per cent of patients in the intent-to-treat population had an overall decrease of at least 50 per cent in non-visceral lesions that were not injected.

The most commonly reported adverse reactions (= 25 per cent) in Imlygic-treated patients were fatigue (50.3 per cent), chills (48.6 percent), pyrexia (42.8 per cent), nausea (35.6 per cent), influenza-like illness (30.5 per cent), and injection site pain (27.7 per cent). Overall, ninety eight percent (98 per cent) of these adverse reactions reported were mild or moderate in severity. The most common grade 3 or higher adverse reaction was cellulitis (2.1 per cent)

In the US, Imlygic is 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.