NICE Javlor ''torture'' could have international ripple effect
This article was originally published in Scrip
NICE, the health technology appraisal institute for England and Wales, has again decided that there is not enough conclusive evidence to recommend Pierre Fabre's Javlor (vinflunine) for treating bladder cancer after prior platinum treatment has failed. The decision is a disaster and other markets as far afield as Mexico could take up the decision too, said Martin Grange, Pierre Fabre's UK managing director. "The impact NICE has on the world is devastating," he said.
According to today's final appraisal determination, NICE's appraisal committee decided that there was not enough evidence on the clinical effectiveness of Javlor compared with best supportive care to recommend it for treating advanced or metastatic transitional cell carcinoma or the urothelial tract that has progressed after platinum-based chemotherapy.
Javlor is the only treatment licensed for this indication and there is no standard therapy for patients whose disease relapses after first-line chemotherapy and who are still able to receive further treatment. "We haven't had anything new for 30 years and the only product we get is going through torture through NICE and we are not going to get access to it," said Mr Grange. Ten year survival data taken between 1971 and 2007 by Cancer Research UK shows that out of around 20 cancers, bladder cancer is the only one with worsening survival rates.
This is the second FAD NICE has produced rejecting the drug. Pierre Fabre appealed the first and NICE had to take another look at the drug. The company had claimed NICE had acted unfairly when it compared Javlor against unlicensed chemotherapy agents, rather than best supportive care, as outlined in the original draft scope (scripintelligence.com, 21 July 2012).
The revised comparator did little to sway NICE, which said there were doubts about the overall survival. It pointed out that there was just one randomised clinical trial, the 302 study, to support the drug and that the data from this trial could not be generalised to the entire potential UK population. Among other things, the committee was concerned that there was no data on patients with a better prognosis than those included in the trial. "The Committee concluded that the nature and availability of the evidence base would result in significant uncertainty regarding the effectiveness of vinflunine for the whole licensed population compared with best supportive care," said the FAD.
Nor was the committee persuaded on the drug's survival benefits. It had doubts about the firm's modelling, which showed an overall survival benefit of 3.2 months. The committee concluded there was not enough evidence to show the drug extended life by up to three months and therefore decided it did not fulfil NICE's end-of-life criteria. It concluded that most likely incremental cost-effectiveness ratio was higher than £120,000 per quality adjusted life year, said NICE.
However, Mr Grange said that that there was nothing more the firm could have done to convince NICE to recommend the drug. "What they say is deliberately misleading," he said. "NICE has interpreted it as only effective in the group of patients with poor prognosis, but only patients with poor prognosis will choose to be randomised to best supportive care. Would you toss a coin to receive best supportive care or an active treatment that could extend your life if you are fit enough for chemotherapy?" He added that the drug had been proved to work in the most difficult circumstances and that regulators had acknowledged that the drug was active where others had failed, ie after failure on platinum-based therapy.
NICE is turning its back on drug development, he said. He pointed out that the life cycle of many cancer drugs began in end-of-life settings and gradually moved further up the treatment pathway as more evidence is generated in clinical settings over a number of years.
Javlor is available in some areas through the Cancer Drugs Fund. Approved in 2009, it is also widely available in other European countries.
However, NICE's guidance could have some impact on this, particularly in markets without their own HTA infrastructures that are increasingly driven by austerity. Markets such as these are increasingly referring to NICE. Mr Granger said he had received requests for the firm's NICE submission for other drugs from countries including Mexico, Belgium, Greece and Spain, as well as Eastern European markets. He is concerned that the same will happen with Javlor. "They want to know the context of the decisions ... It is devastating in a number of countries, anywhere there is austerity, like Spain. They are looking for reasons not to spend money on new drugs," he said.