Amgen, a company committed to unlocking the potential of biology for patients suffering from serious illnesses, announced that the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMA), has adopted a positive opinion recommending that Imlygic (talimogene laherparepvec) be granted approval 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. If approved by the European Commission, Imlygic would be the first in a class of novel agents known as oncolytic immunotherapies.

Imlygic, administered via intralesional injection, is designed to cause the death of tumour cells and to initiate an anti-tumour immune response.

"We are pleased that Imlygic has received a positive opinion from the CHMP, and if approved by the European Commission, we look forward to continuing to work with European regulatory authorities to bring this innovative therapy to patients," said Sean E. Harper, M.D., executive vice president of research and development at Amgen. "Metastatic melanoma continues to be one of the most difficult-to-treat cancers, often requiring the use of multiple treatment modalities. Despite recent advances, the five-year survival rate for patients who cannot be cured with surgery remains unacceptably low, demonstrating the critical need for additional approaches to control this disease."

The positive CHMP opinion was based on 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 granulocyte-macrophage colony-stimulating factor (GM-CSF). In the 436-patient study, Imlygic significantly improved durable response rate (DRR), the primary endpoint of the trial, in the intent-to-treat population. DRR is defined as the percent of patients with complete response (CR) or partial response (PR) maintained continuously for a minimum of six months. A key secondary endpoint was overall survival (OS). The positive CHMP opinion reflects subgroup analyses where the effect on OS was largest in patients with unresectable melanoma that has not spread beyond the skin or lymph nodes.

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.

Melanoma is a type of skin cancer that is characterized by the uncontrolled growth of melanocytes, which are the cells responsible for providing the pigment to skin. Melanoma is the most aggressive and serious form of skin cancer, and remains a significant public health concern in the European Union (EU). In 2012, it was estimated that there were 56,000 new cases of melanoma in France, Italy, Spain, Germany and the UK causing nearly 9,500 deaths.

Following this CHMP opinion, Amgen expects a decision on the Marketing Authorization from the European Commission in the coming months. Imlygic is also under review by the US Food and Drug Administration.

Imlygic is an oncolytic immunotherapy that is derived from HSV-1, which is commonly called the cold sore virus. Imlygic has been modified to replicate within tumours and to produce the immune stimulatory protein human GM-CSF. Imlygic causes the death of tumour cells and the release of tumour-derived antigens. It is thought that, together with GM-CSF, it will promote a systemic anti-tumour immune response and an effector T cell response.

Imlygic is a genetically modified herpes simplex type 1 virus that is injected directly into tumours. Imlygic replicates inside tumour cells and produces GM-CSF, an immunostimulatory protein. Imlygic then causes the cell to rupture and die in a process called lysis. The rupture of the cancer cells causes the release of tumour-derived antigens, which together with virally derived GM-CSF may help to promote an anti-tumour immune response. However, the exact mechanism of action is unknown.

Amgen has in place a comprehensive clinical development program investigating oncolytic immunotherapies for their potential in melanoma and in a variety of other cancers.

Amgen's recent immuno-oncology focused partnerships include: A collaboration with Merck on developing Imlygic and Keytruda (pembrolizumab), Merck's anti-PD-1 therapy, in melanoma and squamous cell cancer of the head and neck; A collaboration with Roche on a phase 1b study to evaluate the safety and efficacy of Imlygic in combination with Roche's investigational anti-PDL1 therapy, atezolizumab (also known as MPDL3280A), in patients with triple-negative breast cancer and colorectal cancer with liver metastases; A strategic research collaboration and license agreement to develop and commercialize the next generation of novel Chimeric Antigen Receptor (CAR) T cell immunotherapies with Kite Pharma; A research collaborative agreement focusing on Amgen's bispecific T cell engager (BiTE) antibody constructs with MD Anderson's Moon Shots Program; A research and license agreement with Xencor to develop and commercialize novel therapeutics in the areas of cancer immunotherapy and inflammation. The research collaboration brings together Amgen's capabilities in target discovery and protein therapeutics with Xencor's XmAb bispecific technology platform.