NICE Rejects Pierre Fabre’s Javlor, Citing Basic Evidence Errors
This article was originally published in The Pink Sheet Daily
Executive Summary
Britain’s NICE has turned down Pierre Fabre’s Javlor for cancer of the urothelial tract, saying the French company’s basic trial structure did not meet its requirements.
The U.K.’s health care cost-effectiveness watchdog has issued final guidance turning down reimbursement for Pierre Fabre Group’s Javlor (vinflunine) for advanced or metastatic transitional cell carcinoma of the urothelial tract. The National Institute for Health and Clinical Excellence’s (NICE) comprehensive rejection will serve as a warning to manufacturers that if their trial structure does not adhere to the basic requirements of health technology assessment bodies, their products will fail to gain reimbursement in Europe.
Javlor is a drug that essentially offers patients an innovative means of tackling these aggressive forms of cancer, as NICE conceded. NICE acknowledged that Javlor is the only treatment licensed for use for advanced or metastatic transitional cell carcinoma of the urothelial tract that has progressed after treatment with platinum-based chemotherapy. It also noted that there is currently no standard treatment for patients whose disease relapses after first-line chemotherapy and who are fit enough to receive further treatment.
This is a gap that Javlor could potentially fill.
Flawed From the Outset
The problem is that the dossier filed by Pierre Fabre – as NICE already said in November 2012 – appears to have been weak on a number of fronts (Also see "Javlor Falls Short Again At NICE; Even Sole Treatment In Class Faces Cost Hurdle" - Pink Sheet, 9 Nov, 2012.).
Evidence came from a single randomized clinical trial (Study 302) which compared Javlor with best supportive care alone. But NICE was concerned by the fact the trial population was younger, fitter and had better renal function than the target population. And while Study 302 excluded patients who had been treated with adjuvant or neoadjuvant chemotherapy, patients in the U.K. would have had access to both types of therapy.
NICE’s conclusion was that the study results could not be generalized to the U.K. population. In essence, the level of uncertainly generated by this discrepancy at an early stage of the assessment meant the argument for Javlor was already lost.
NICE found other negative issues with the drug as well.
The reimbursement watchdog scrutinized the occurrence of adverse incidents arising from treatment with Javlor and noted that grade severe constipation occurred in 16% of patients receiving the drug. This, it said, raised concerns about the tolerability of Javlor.
Cost Per QALY Excessive
The final draw, as is often the case with NICE, was the significantly high incremental cost-effectiveness ratio (ICER) of the drug, when compared with standard care.
NICE estimated that the ICERs per quality-adjusted life year (QALY) would exceed £120,000 (approximately $190,000) – far beyond its traditional £30,000 per QALY threshold.
And NICE also has specific criteria for end-of-life drugs that are designed to make the cost per QALY boundary far more flexible and which could have helped Javlor’s case. To qualify, a drug must be indicated for patients with a short life expectancy (normally less than 24 months), offer at least three additional months of life, and must be directed at small patient populations.
NICE said that the extent of the clinical effectiveness of Javlor compared with best supportive care had not been conclusively demonstrated. This meant there was no convincing evidence that showed Javlor to offer the necessary life extension of at least three months.
Pierre Fabre now has two options if it wants to challenge NICE’s final guidance on the drug.
It can submit a patient access scheme – essentially a price discount – within 16 weeks of the publication of the final guidance. But NICE can only consider these schemes after ministerial approval and confirmation by the Department of Health.
“In view of the fact that the (NICE) Committee considered the most plausible ICER for vinflunine compared with best supportive care to be in excess of £120,000 per QALY gained – well above anything that NICE has previously accepted as cost-effective – it might be argued that such a route might not be practical in this case,” a spokesperson for the reimbursement watchdog said.
The other possible route for a challenge lies through the law courts. The company did not respond to questions on the assessment and its next steps.
NICE did say more research is needed on second-line treatments for transitional cell carcinoma of the urothelial tract. The agency wants studies to investigate the relative safety and efficacy of second-line treatments for transitional cell carcinoma of the urothelial tract, particularly randomized controlled trials.
The problem is that the relatively small patient population – about 800 to 1,500 qualified for Javlor in the U.K. – and NICE’s strict ICER per QALY threshold may simply make the prospect of developing a drug for Britain too unattractive.