Celgene is preparing to appeal a decision by the UK's National Institute of Clinical Excellence that Vidaza (azacitidine) was too expensive for reimbursement by the UK National Health Service. The drug is approved and reimbursed for patients with a rare form of blood cancer known as higher-risk myelodysplastic syndrome (MDS) in over 30 countries.
The March 4 recommendation came despite NICE's acknowledgement that the drug was clinically effective and could prolong patients' lives by about nine months longer than standard treatment.
It also came despite a patient-access scheme proposed by Celgene midway through the appraisal, offering the drug at a 7 percent discount, and despite the drug's meeting the criteria for NICE's "end-of-life" treatment guidelines, which permit a less stringent cost-effectiveness threshold to be applied to products shown to extend survival among patients with terminal disease such as these rare blood cancers.
Carole Longson, Health Technology Evaluation Center Director at NICE, said the agency was "disappointed" not to be able to recommend the drug, which is a novel and effective treatment in an area where there are few alternatives.
The rejection of Vidaza is but the latest in a series of negative decisions by NICE, including stringent limitations on the second-line use of anti-TNF therapies for rheumatoid arthritis suffers, and outright rejections of chronic myeloid leukemia drugs Sprycel (dasatinib) and Tasigna (nilotinib) on Feb. 9, 2010 ('The Pink Sheet', Feb.15, 2010).
Simply Too Pricey
Vidaza is estimated to cost about £45,000 per patient. Even with the discount and the more relaxed cost-effectiveness criteria, the drug's most plausible cost-per-QALY (cost per quality-adjusted life year, which is the measure NICE uses to assess cost-effectiveness) would still be £63,000, according to NICE. That figure is more than double the agency's unofficial threshold of £25,000-£30,000 per QALY.
Unfortunately for Celgene and for the UK's 700 or so MDS patients (plus those with the more serious acute myeloid leukemia), NICE decided that the cheapest comparator for the drug - best supportive care - also was the most appropriate, since it's given to the majority of UK patients. This decision only increased the relative cost of Vidaza; more so, for example, than if the drug had been costed in comparison to chemotherapy.
To make matters more frustrating still, according to Rodney Taylor, deputy chairman of the patient support group MDS UK (who attended most of the appraisal meetings), NICE didn't cost best-supportive care appropriately. In his view, the agency underestimated the cost of blood transfusions.
The agency also chose to consider, of several proposed, a particular mathematical model of survival that further increased the relative cost of the drug.
Celgene Will Fight Back
Celgene plans to appeal the decision, focusing in particular on NICE's choice of comparator. "We feel that NICE should have considered that chemotherapy is sometimes used, even if not always," says Carl Gibbons, Market Access Manager at Celgene UK. "Variation in clinical practice is not an excuse for not including a particular comparator," he continues.
Celgene's management believes that had the chemotherapy comparator been used, in conjunction with the end-of-life guidance, the drug likely would have been approved - even if with restrictions. The company also will argue that the drug meets innovation criteria designed by NICE to increase access to innovative medicines in areas of unmet need, in response to the 2009 Ian Kennedy report into the agency ('The Pink Sheet' DAILY, Sept. 15, 2009). Frustratingly for Celgene, its submission in March 2009 apparently came too early to benefit from the full brunt of NICE's promised attempts to take innovation more fully into account in its judgments ('The Pink Sheet' DAILY, July 23, 2009).
As things stand, "NICE's approach doesn't orphan drugs with low patient populations," opines Sam Pearce, General Manager Celgene UK. A lack of data, not least due to difficulties in collecting it among limited populations, is the problem with drugs like Vidaza, concurs Taylor. NICE requested more data, for example, on quality of life, declaring the existing information to be inadequate. But "it's wrong that NICE should treat these orphan drugs in the same way as they treat everything else," Taylor argues. "It takes a very long time to accumulate reliable data." That's why the agency last year agreed to implement an Innovation Pass scheme, whereby certain highly novel drugs for small populations are granted three years' of reimbursement while data are collected for a formal NICE review ('The Pink Sheet,' July 20, 2009).
Celgene has successfully navigated NICE before. The company's multiple myeloma treatment Revlimid (lenalidomide) made it past the agency in 2009, albeit not thanks to Celgene's patient-access scheme (which wasn't particularly generous) but thanks to the end-of-life guidance. Celgene's then-General Manager, UK & Ireland Andrew Robertson described the decision as "an excellent step forward...and Celgene can say that it led the way" ('NICE Deal, Celgene,' The In Vivo Blog, Feb. 9, 2009).
No More Cost-Sharing Plans - For Now
Not so this time - at least, not for now. But the wording of NICE's press release strongly suggests that the agency is calling for a more aggressive pricing strategy.
That's not Celgene's plan, since according to Pearce, "altering the acquisition cost [of the drug] doesn't have a significant impact on cost-per-QALY." Also, the company can't formally re-submit a patient access scheme at this point; it would have to wait for formal negative guidance first, and a re-appraisal.
Still, cost-sharing schemes are becoming an almost sine qua non for NICE approval these days. Although most are proposed after an initial negative decision or - as in this case - midway through a protracted appraisal process, there are now examples of companies submitting such schemes up-front. UCB did just that for its recently-approved rheumatoid arthritis treatment Cimzia (certolizumab), although in this case the drug joined an existing well-established class of similar anti-TNF treatments, meaning UCB had little chance of approval without the sweetener ('The Pink Sheet,' Feb. 1, 2010).
Companies and patient groups have until March 18 to submit their comments on the Vidaza guidance, ahead of a final consultation by NICE in May.
-Melanie Senior (m.senior@elsevier.com)
This article is reprinted from "The Pink Sheet" DAILY –Mar 4, 2010
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