NICE, the healthcare guidance body, has issued draft guidance which does not recommend the use of vemurafenib (Zelboraf, Roche Products) for the treatment of unresectable locally advanced or metastatic BRAF V600 mutation-positive melanoma.

The data submitted by the manufacturer came primarily from a trial called the BRIM3, which compared vemurafenib with a current treatment, dacarbazine. The results showed the drug was effective for patients with melanoma with the BRAF V600 mutation. However, the longer-tem effect on survival was uncertain because many of the patients taking dacarbazine were moved onto other treatments such as vemurafenib or ipilimumab when their disease progressed, making comparison difficult.

Treatment with vemurafenib costs around £1,750 per week. The manufacturer of vemurafenib has agreed a patient access scheme with the Department of Health, in which vemurafenib is offered at a lower price (the price reduction is confidential). The Committee agreed that the most plausible cost per QALY for vemurafenib was highly uncertain due to the limitations of the available evidence, but was likely to be considerably higher than £50,000 per QALY gained taking the patient access scheme into account. Roche, the manufacturer of the drug, estimated that it would be £56,400 per QALY

NICE appraisal committees will normally recommend treatments that cost around £30,000 per QALY or less. If, like vemurafenib, a drug meets the criteria to be considered under NICE's supplementary advice for end of life treatments, then a higher cost per QALY may be accepted. There is no set threshold cost per QALY for end-of-life drugs but the highest cost per QALY of such a drug recommended by NICE is £50,000.

Commenting on the draft recommendations Sir Andrew Dillon, Chief Executive of NICE said: "We need to be sure that new treatments provide sufficient benefits to patients to justify the significant cost the NHS is being asked to pay. Vemurafenib is an expensive drug and its long term benefits are difficult to quantify.

"When assessing the cost effectiveness of a treatment, NICE appraisal committees will take numerous factors into account. These include how effective the drug is, its side effects, the effect it can have on the patient's quality of life and also the financial cost. This enables them to determine the cost of using the drug to provide a year of the best quality of life available or quality adjusted life year (QALY).

"Consultees, including the manufacturer, healthcare professionals and members of the public are now able to comment on the preliminary recommendations which are available for public consultation. Roche can also provide further comment on the evidence it provided and have the opportunity to submit a further patient access scheme if they wish."

The draft guidance has been issued for consultation; it has not been issued to the NHS. Until final guidance is issued, NHS bodies should make decisions locally on the funding of specific treatments. Once NICE issues its final guidance on a technology, it replaces local recommendations across the country.

Comments received during this consultation will be fully considered by the Committee and following this meeting the next draft guidance will be issued.

Ends

Notes to Editors

About the guidance

1. The draft guidance will be available at TA269 from 15 June 2012. Embargoed copies of the draft guidance are available from the NICE press office on request.

2. Evidence from the BRIM3 study indicate that treatment offers an extension to life of at least an additional 3 months, compared with current NHS treatment.

3. Vemurafenib costs £1750 for one pack of 56 x 240-mg tablets (1 week's supply). Treatment for an average duration of 7 months (30 weeks) would cost £52,500

The manufacturer of vemurafenib has agreed a patient access scheme with the Department of Health, in which a discount on the list price of vemurafenib is offered. The size of the discount is commercial-in-confidence.

4. Patients with advanced or metastatic malignant melanoma are usually treated with carboplatin-based chemotherapy or dacarbazine, or given best support care.

5. The manufacturer estimated the ICER for vemurafenib compared with dacarbazine was £56,400 per QALY gained including the patient access scheme. Alternative estimates for overall survival, proposed by the Evidence Review Group, increased this estimate to £133,100 per QALY gained. The Committee agreed that the most plausible ICER for vemurafenib was highly uncertain and likely to be considerably higher than £50,000 per QALY gained.

6. Vemurafenib met the criteria for being a life-extending, end-of-life treatment. However, the Committee considered that the magnitude of additional weight that would need to be assigned to the original QALY benefits for people with advanced melanoma would be too great for vemurafenib to be considered a cost-effective use of NHS resources.

7. The Committee heard from the manufacturer and clinical specialists that the total number of people who would be eligible for treatment with vemurafenib was less than 1,000 each year in England and Wales

8. The Scottish Medicines Consortium will publish guidance on this topic in September 2012.

9. The Appraisal Committee felt that the evidence from the BRIM3 study was uncertain as many of the patients receiving dacarbazine transferred to vemurafenib and patients whose disease progressed after treatment with dacarbazine were able to receive a range of other therapies including ipilimumab and investigational treatments.

About NICE

10. The National Institute for Health and Care Excellence (NICE) is the independent organisation responsible for providing national guidance and standards on the promotion of good health and the prevention and treatment of ill health

11. NICE produces guidance in three areas of health:

• public health - guidance on the promotion of good health and the prevention of ill health for those working in the NHS, local authorities and the wider public and voluntary sector
• health technologies - guidance on the use of new and existing medicines, treatments, medical technologies (including devices and diagnostics) and procedures within the NHS
• clinical practice - guidance on the appropriate treatment and care of people with specific diseases and conditions within the NHS.

12. NICE produces standards for patient care:

• quality standards - these reflect the very best in high quality patient care, to help healthcare practitioners and commissioners of care deliver excellent services
• Quality and Outcomes Framework - NICE develops the clinical and health improvement indicators in the QOF, the Department of Health scheme which rewards GPs for how well they care for patients

13. NICE provides advice and support on putting NICE guidance and standards into practice through its implementation programme, and it collates and accredits high quality health guidance, research and information to help health professionals deliver the best patient care through NHS Evidence.