NICE Rejects Three Cancer Drugs from Novartis and BMS

The latest appraisal of the United Kingdom's healthcare guidance and guidelines organisation, the National Institute for Health and Clinical Excellence (NICE), included negative recommendations for Swiss firm Novartis' Afinitor (everolimus) in the treatment of second-line metastatic renal cell carcinoma (RCC), as well as Novartis' Tasigna (nilotinib) and U.S. firm Bristol-Myers Squibb's Sprycel (dasatinib) in the treatment of chronic myeloid leukaemia (CML) in patients who are intolerant to Novartis' Glivec/Gleevec (imatinib).

NICE Guidance on Afinitor

According to the appraisal consultation document, Afinitor is not cost effective in the treatment of patients suffering from RCC. The manufacturer's submission for cost effectiveness was based on a comparison with the best supportive care using a Markov model. This yielded an incremental cost effectiveness ratio (ICER) of £51,613 per quality-adjusted life year (QALY) gained, which incorporated the patient-access scheme agreement between the manufacturer and the U.K. department of health. According to the patient-access scheme, the manufacturer would provide the first treatment pack free of charge, and a 5% discount would be applied to successive packs. NICE's evidence review group was highly critical of the modelling techniques used by the manufacturer in terms of the utility estimates used in the model, the discounting method, and the Rank Preserving Structural Failure Time (RPSFT) method used to derive overall survival estimates. When adjusted for all of these factors, the ICER per QALY gained increased to £75,700 using the RPSFT method to estimate overall survival, and £65,200 using the inverse probability of censoring weighted method. NICE also discussed whether the treatment should be appraised as an end-of-life treatment, using supplementary advice introduced in 2009, and concluded that due to the fact that all criteria are fulfilled, greater QALY weights would be applied. However, the committee reached the conclusion that a higher QALY weighting would not be sufficient to compensate for the high cost of the drug. The committee tried to uncover whether the treatment would be cost effective in specific patient sub–groups, but no such groups were identified. As a result, a preliminary decision was made that Afinitor should not be made available on the National Health Service (NHS). The appraisal consultation document is available here.

NICE Guidance on Tasigna and Sprycel

In a separate appraisal consultation document, Tasigna and Sprycel were jointly evaluated in the treatment of CML in patients who do not respond or are intolerant to Glivec. The ICER per QALY gained for Tasigna in comparison with hydrocarbamide was estimated to be £58,590 for patients with chronic CML, increasing to £79,914 for patients with accelerated-phase CML. For Sprycel, two comparators were used: Tasigna, and high-dose Glivec in patients with accelerated and blast-phase CML. In the former phase, the cost-effectiveness estimates for Sprycel were £135,570, with QALYs of 2.28, and in the latter group cost effectiveness was estimated to be £88,181 with QALYs of 0.46. When NICE reviewed the model it concluded that in the blast phase the ICER per QALY gained for Tasigna was £128,000 in chronic CML, and the ICER per QALY gained for Sprycel stood at £105,000. NICE commented that it was difficult to measure the cost effectiveness of these two drugs due to the lack of suitable comparators; therefore, there are high degrees of uncertainties in the estimates. However, based on the ICER figures generated, both drugs should not be provided on the NHS as they are not deemed to be cost effective. The appraisal consultation document is available here.

Outlook and Implications

This latest guidance is likely to come as a blow to both companies, and it once again demonstrates the difficulties manufacturers face in securing reimbursement for expensive oncology drugs. In terms of the negative opinion on Afinitor in the treatment of RCC, this comes as little surprise, given NICE's recent wave of negative decisions on RCC drugs. In 2009, it rejected drugs such as Avastin (bevacizumab; Roche, Switzerland), Nexavar (sorafenib; Bayer Schering Pharma, Germany), Sutent (sunitinib; Pfizer, U.S.), and Torisel (temsirolimus; Wyeth Pharmaceuticals, U.S.) in the treatment of advanced and/or metastatic forms of RCC. This decision was made despite manufacturers' various patient-access deals and the fact that all the drugs, with the exception of Avastin, qualified for higher QALY weighting under new end-of-life guidance (see United Kingdom: 26 August 2009: NICE Confirms Non-Recommendations in Renal Cell Carcinoma). In contrast to NICE's preliminary negative decision, the equivalent body in France—the Transparency Commission of France's Higher Authority on Healthcare—has just issued a positive decision for Afinitor, which is likely to provide further evidence that the United Kingdom lags behind its European counterparts in terms of the uptake of oncology drugs (see France: 8 February 2010: Novartis's RCC Treatment Afinitor to Be Fully Reimbursed in France). In light of various negative NICE decisions for RCC drugs, it would be important for companies to review their pricing strategies for such drugs in the future, in order to overcome reimbursement barriers.

In terms of the negative decisions on both Tasigna and Sprycel, NICE has indicated that it would welcome a patient-access scheme for these drugs, as this might make it increase the chances of overturning the decision, which might give some hope to both companies. In any case, proposing a patient-access scheme is by no means a sure-fire route to positive reimbursement, as many examples have shown.