2 The technology

2 The technology

Description of the technology

Cobimetinib (Cotellic, Roche) is an inhibitor of MEK 1 and MEK 2 kinases. Vemurafenib (Zelboraf, Roche) is an inhibitor of the BRAF protein. Both are taken as tablets. The BRAF protein and MEK 1 and 2 kinases are part of the same cell-signalling pathway. Inhibiting these proteins stops proliferation and survival of melanoma cells.

Marketing authorisation

Cobimetinib in combination with vemurafenib is indicated for the treatment of unresectable or metastatic melanoma in adults with a BRAF V600 mutation. Vemurafenib has a marketing authorisation for use as monotherapy for this indication. Cobimetinib does not have a marketing authorisation for use as monotherapy.

Adverse reactions

The following common adverse reactions affect more than 1 in 5 people: diarrhoea, rash, nausea, vomiting, fever, light sensitivity reaction, abnormal liver function tests, and abnormal results for an enzyme related to muscle breakdown (creatine phosphokinase). Less common adverse reactions include swelling of the retina (retinopathy) or effects on cardiac function (reduced left ventricular ejection fraction). People taking cobimetinib plus vemurafenib should be monitored for new and worsening visual disturbances, and for heart function. For full details of adverse reactions and contraindications, see the summary of product characteristics.

Recommended dose and schedule

Cobimetinib: 3 tablets per day for 21 days followed by a 7‑day break (days 22 to 28) before the next cycle is started.

Vemurafenib: 960 mg (4 tablets of 240 mg) twice daily (equivalent to a total daily dose of 1,920 mg).


The company has stated that the cost of cobimetinib (excluding VAT) is £4,275.67 for a 63‑tablet pack of 20 mg tablets.

The company has agreed a patient access scheme with the Department of Health for vemurafenib as monotherapy. It is provided to the NHS with a simple discount to the list price of vemurafenib, with the discount applied at the point of purchase or invoice. The level of the discount is commercial in confidence. The Department of Health considered that this patient access scheme would not constitute an excessive administrative burden on the NHS.

If cobimetinib with vemurafenib had been recommended, the company would have provided vemurafenib for use in combination with cobimetinib with the same discount as that agreed for vemurafenib as monotherapy. Costs may vary in different settings because of negotiated procurement discounts.

  • National Institute for Health and Care Excellence (NICE)