Patients in England and Wales with a certain type of advanced skin cancer will not be getting routine access to Roche's Cotellic/Zelboraf combination on the NHS, after it was turned down by the National Institute for Health and Care Excellence.

The cost watchdog has now published final guidance rejecting use of Cotellic (cobimetinib) with Zelboraf (vemurafenib) for people with advanced BRAF V600 mutation-positive melanoma that has spread and can't be surgically removed, after concluding that it would not represent a cost-effective use of resources.

Cotellic is an inhibitor of MEK 1 and MEK 2 kinases, while Zelboraf is an inhibitor of the BRAF protein. The BRAF protein and MEK 1 and 2 kinases are part of the same cell signalling pathway, and inhibiting these proteins stops proliferation and survival of melanoma cells.

NICE said its committee agreed that the combination offers life-extending benefit compared to Zelboraf alone but that, at a likely incremental cost-effectiveness ratio of more than £100,000 per QALY gained, is simply too expensive when compared to alternative treatments.

About 1,000 people would have been eligible each year for treatment with the combination, the NHS list price for which is around £11,275 for 28 days, so not including the confidential commercial discount that would have been applied should NICE have approved it.

Back in June, the Institute published final guidance endorsing Novartis' oral combination therapy Tafinlar (dabrafenib) plus Mekinist (trametinib) for the same patient group.

The NHS will pay a reduced price for the drugs after a confidential discount was agreed between the company and the Department of Health, but the list price per patient per 28 days is £10,080.