CHMP recommends Imlygic (talimogene laherparepvec) to treat unresectable melanoma- Amgen

Amgen has 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, previously known as T-vec) 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.

The positive CHMP opinion was based on a global, randomised, open-label Phase III 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% of these adverse reactions reported were mild or moderate in severity. The most common grade 3 or higher adverse reaction was cellulitis.

Comment: Amgen is collaborating with Merck on a study combining the PD-1-blocking Keytruda (pembrolizumab) with Imlygic in melanoma and head and neck cancer, and Roche has agreed to combine its atezolizumab, a PD-L1 therapy, with Imlygic in breast and colon cancers.

Comment: A joint FDA Advisory Panel has voted to recommend approval to T-Vec (now Imlygic), voting 23-1 in favour that the drug has a favourable benefit risk ratio in metastatic melanoma but expressed reservations and rejected an accelerated approval. Some committee members were concerned that the phase III trial (005/05) showed a durable response (the percentage of patients whose melanomas did not grow for six months or longer) but not a convincing improvement in overall survival and they noted that the drug did better in early disease patients.