EMA Recommends Approval of First Oncolytic Immunotherapy Medicine

Talimogene Laherparepvec is indicated for unresectable melanoma with no bone, brain, lung or other visceral metastases

On 22 October 2015, the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product talimogene laherparepvec (Imlygic), intended for the treatment of melanoma.

The applicant for this medicinal product is Amgen Europe B.V.

Imlygic will be available as a solution for injection (1x 10e6 PFU/ml and 1x 10e8 PFU/ml).

Imlygic is a first-in-class advanced therapy medicinal product (ATMP) derived from a virus, that has been genetically engineered to infect and kill cancer cells. The active substance of Imlygic is talimogene laherparepvec, an oncolytic virus derived from HSV-1. The virus has been modified to replicate within tumours and to produce the immune stimulatory protein human GM-CSF, which promotes a systemic anti-tumour immune response and an effector T-cell response.

For decades, standard chemotherapy was the only available treatment for patients with advanced melanoma. In the last three years, the authorisation of targeted treatments, including immunotherapies, BRAF V600 inhibitors and MEK inhibitors, have changed the therapeutic landscape and increasingly benefited patients. However, there is still an important need for new treatments with acceptable safety profiles to continue to improve the outlook for patients with this serious life-threatening disease.

Imlygic is recommended to be injected directly into the melanoma lesions. The efficacy of Imlygic compared with injecting GM-CSF under the skin, was assessed in one randomised controlled trial in adults with unresectable regionally or distantly metastatic melanoma. The study enrolled 436 patients and the efficacy of 295 patients treated with Imlygic was compared with 141 patients treated with GM-CSF.

Analysis of the subset of patients in the study whose disease had not spread to the lung or other visceral organs (249 patients with stage IIIB, IIIC and IVM1a disease) showed a benefit in patients treated with Imlygic compared with patients treated with GM-CSF: 25.2% of those patients treated with Imlygic responded positively (durable response) compared with 1.2% of those patients treated with GM-CSF. A durable response was defined as disappearance of the tumours or at least 50% reduction of tumours lasting at least six months until patients’ health declined or they required subsequent therapy. Exploratory analysis in these patients suggested improvements in survival in patients treated with Imlygic, however this is not yet fully clear. Imlygic has also not been compared with other recently approved medicines for melanoma, which have shown beneficial effects on survival.

Overall the CHMP and Committee for Advanced Therapies (CAT) considered that Imlygic is relatively well-tolerated in patients with cancer and concluded that the medicine's benefits outweigh its risks. A follow-up plan to monitor the efficacy and safety of Imlygic was agreed by the CHMP and the CAT.

The most common side effects are fatigue, chills, pyrexia, nausea, influenza-like illness and injection site pain.

Imlygic is not to be used in patients who are severely immunocompromised (e.g. patients with severe congenital or acquired cellular and/or humoral immune deficiency).

It is proposed that Imlygic be initiated and supervised by a qualified physician experienced in the treatment of cancer.

The CHMP recommendation follows the draft opinion of the CAT, the EMA’s expert committee for advanced therapy medicinal products (ATMPs). ATMPs are innovative medicines that are intended for gene therapy, cell therapy or tissue engineering.

The company received scientific advice from the CHMP on quality, non-clinical and clinical aspects of the application. This is one of the Agency’s main tools to facilitate and stimulate research and development within the European Union (EU).

Detailed recommendations for the use of this product will be described in the summary of product characteristics, which will be published in the European public assessment report and made available in all official EU languages after the marketing authorisation has been granted by the European Commission.

The opinion adopted by the CHMP at its October 2015 meeting is an intermediary step on Imlygic’s path to patient access. The CHMP opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation. Once a marketing authorisation has been granted, each Member State will take a decision on price and reimbursement based on the potential role/use of this medicine in the context of its national health system.