Drugmakers Novartis and Bristol-Myers Squibb were dealt a blow on news that the National Institute for Health and Clinical Excellence has rejected kidney cancer drug Afinitor and leukaemia treatments Tasigna and Sprycel.

The cost watchdog for the National Health Service in England and Wales has published appraisal documents outlining its preliminary recommendations for Novartis’ Afinitor (everolimus), which reject its use as a second-line agent for renal cell carcinoma (RCC).

Afinitor won European approval back in August last year on the back of Phase III data showing that the drug - a once-daily, oral treatment that inhibits the mTOR protein - more than doubled the average time without tumour growth or death in patients with advanced kidney cancer (4.9 versus 1.9 months) and reduced the risk of disease progression or death by 67%.

But following a review of clinical data within Novartis’ submission, the Institute’s Appraisal Committee concluded that while there was sufficient evidence to show that the drug can boost progression-free and overall survival compared with best supportive care, “the magnitude of the overall survival gain was uncertain”.

In addition, despite reviewing the drug under guidelines for appraising life-extending, end-of-life treatments, as Afinitor’s incremental cost effectiveness ratio was calculated by NICE’s Expert Review Group to be between £65,200 and £75,700 the therapy was considered simply too expensive for NHS use.

“Everolimus is an expensive drug and we have to be sure the evidence on its effectiveness is robust before we recommend it,” explained Professor Peter Littlejohns, NICE Clinical and Public Health Director, and he stressed: “We do not want to divert NHS funds to a treatment that costs more but doesn’t help people live longer”.

A patient access scheme proposed by Novartis, under which the Swiss drugmaker offered to provide the first treatment pack of Afinitor to the NHS free of charge and subsequent packs at £2,822 (a 5% discount), also failed to sway the Committee’s decision.

Not looking good for Tasigna, Sprycel
Meanwhile, the Institute has also updated its draft guidance on the use of Novartis Tasigna (nilotinib) and Bristol-Myers Squibb’s Sprycel (dasatinib) to treat chronic myeloid leukaemia (CML) in patients intolerant to Novartis’ Glivec (imatinib).

NICE published preliminary recommendations rejecting both drugs in November, but despite taking additional comments from stakeholders made during the consultation process into accoun, and carrying out additional analyses to address concerns raised over its cost-effectiveness modelling, the Institute said it is sticking with its initial guidance barring the drugs from the NHS in this setting.

Phase III clinical trials of Sprycel have shown a two-year estimated progression-free survival rate of 80% and an overall survival rate of 91%, but the drug comes with a hefty price tag of around £30,477.50 per patient per year based on one pill per day.

Tasigna also performed well in clinical trials, normalising blood cell counts in 77% of patients in the early stage of CML resistant/intolerant to other therapies and a 12-month survival rate of 95%. But it also comes at a very high price, working out at about £31,711.20 per year based on a treatment regimen of 400mg twice daily.

“The Committee heard from clinical specialists that in their opinion dasatinib and nilotinib are clinically effective. However, the evidence available to support this was very poor, with no studies comparing either drug to other treatments,” said Littlejohns. “The cost of the drugs is also extremely high and before committing limited NHS resources to fund them, we need to be sure they are effective,” he said, and added that it would be “heartening to hear that the pharmaceutical company manufacturers are prepared to share some of the very high cost of the drugs with the NHS”.

Even if the Institute sticks with its guidance it may not be the end of the line for these drugs as treatments for CML on the NHS, as the cost regulator is about to start a review of current guidance on the use of high dose Glivec for the condition, which will incorporate an appraisal of Tasigna and Sprycel in patients who are resistant (rather than intolerant) to the treatment.

Both sets of draft guidance for RCC and CML are now open to consultation until early March.