Bristol-Myers Squibb and Novartis are facing a giant hurdle in getting their respective leukaemia drugs Sprycel and Tasigna funded by the National Health Service, after the cost-watchdog issued an amber light for their use.

The National Institute for Health and Clinical Excellence has published appraisal documents rejecting the use of Sprycel (dasatinib) and Tasigna (nilotinib) for the treatment of chronic myeloid leukaemia in patients who experience resistance or are intolerant to therapy with Novartis’ Glivec (imatinib).

Glivec, a first-generation tyrosine kinase inhibitor, is currently the treatment of choice if a stem cell transplant is not possible, based on its ability to slow down the progression of CML and produce high rates of remission in the chronic phase of the disease. According to NICE, the drug is associated with improved five-year survival, boosting the rate from 27.1% in 1990-1992 to 48.7% in 2002-2004 following its addition to routine clinical practice.

However, while only a relatively small proportion of patients - around 3% - are estimated to either develop a resistance to Glivec or be intolerant to therapy right from the start when the disease is in its early, or chronic phase, effective second-line therapies are urgently needed to give these patients another treatment option.

Sprycel is a second-generation oral tyrosine kinase inhibitor that, at nanomolar concentrations, reduces the activity of proteins responsible for the uncontrolled growth of leukaemia cells in patients with CML, and was introduced to the UK market back in December 2006.

Phase III clinical trials of the drug have demonstrated a two-year estimated progression-free survival rate of 80% and an overall survival rate of 91% (based on Kaplan-Meier estimates). But the drug comes with a hefty price tag of £83.50 per 100-mg tablet, which equates to a yearly cost of £30,477.50 on the basis of one pill per day.

Launched in the UK in May 2008, Tasigna also targets the tyrosine kinase enzyme responsible for the reproduction of CML cells, and in clinical trials was effective – i.e. blood cell counts normalised - in 77% of patients in the early stage of CML resistant/intolerant to other therapies. In addition, 40% of patients achieved a complete cytological response with no abnormal chromosomes – the root cause of CML – detected in the bone marrow cells and at 12 months the overall survival rate was 95%.

Like its competitor though the price is on the high side - £21.72 per 200-mg tablet (excluding VAT) – and based on a treatment regimen of 400mg twice daily this works out to be around £31,711.20 per year, NICE noted.

Too much uncertainty
While the Committee ruled that Sprycel and Tasigna are clinically effective for the treatment of CML, despite the fact that it considered the clinical evidence to be “of extremely poor quality”, it concluded that the uncertainty surrounding the magnitude of this gain added to the drugs’ “exceptionally high acquisition costs” means they “cannot be regarded as an appropriate use of NHS resources”.

Is recommendations have not been finalised and following the consultation the Institute may well change its mind, but news of its current position will no doubt come as a disappointment to the estimated 4,000 patients with CML in the UK today who may not be able to take the gold standard therapy.