The UK cost-effectiveness watchdog NICE delivered a resounding "no" Feb. 9 to the use on the National Health Service of Bristol-Myers Squibb's Sprycel (dasatinib) and Novartis' Tasigna (nilotinib) in chronic myeloid leukemia patients who are intolerant to Glivec (imatinib, Gleevec in the U.S.).
"The evidence available to support [the clinical effectiveness] of dasatinib and nilotinib was very poor," declared Peter Littlejohns, clinical and public health director at NICE. "The drugs' cost is also very high," he said in a 1 press release announcing a draft guidance on the products.
Sprycel costs about £30,477 per year, and nilotinib about £31,711, according to appraisal documents on NICE's Web site. And these two products also are typically taken for several years, with no evidence-based guidelines in use for when to stop treatment. Based on these prices, the draft guidance documents point to an estimated a cost-per-QALY (quality-adjusted life year, the measure NICE uses to assess cost-effectiveness) of over £100,000 for both drugs; way above NICE's typical £30,000 threshold, even though the estimates were qualified as "highly uncertain."
Those factors plus the NICE announcement language suggest the two products didn't even come close to approval. Bristol and Novartis can't even hope to use one of the loopholes for health service coverage now available to companies, the 2 end-of-life guidance issued by NICE in late-2008. That policy permits a somewhat higher cost-per-QALY than the usual benchmark for drugs that extend life in terminal diseases affecting a small number of patients.
Celgene benefited from this guidance in getting multiple myeloma drug Revlimid (lenalidomide) past the cost-watchdog in early 2009. The available evidence on the drugs' extension of life - an extension typically required to be of at least three months - "is too weak," declared NICE. It's "plausible" that the drugs, both second-generation tyrosine kinase inhibitors, offer such an extension, the NICE documents remark, "but definitely not proven."
But this rather damning announcement includes a hint of one way to keep the door open to coverage. "It would be heartening to hear that pharmaceutical company manufacturers are prepared to share some of the very high cost of these drugs with the NHS," suggested Littlejohns.
That is certainly an appeal for a cost-sharing plan, or patient-access scheme, as NICE calls them. Such schemes have allowed the agency to green-light several expensive drugs that likely would not have otherwise made the cut - including most recently UCB's rheumatoid arthritis treatment Cimzia (certolizumab) ("3 The Pink Sheet', Feb. 1, 2010). Celgene had also put forward a cost-sharing scheme for Revlimid, although this wasn't, in the end, the primary factor that tipped the decision in its favor. (4 'The IN VIVO Blog', Feb. 9, 2009).
NICE's call for companies to propose cost-sharing arrangements to facilitate UK patients' access to novel medicines is understandable, not least given the public attention its often contentious decisions provoke. Indeed, NICE CEO Andrew Dillon said clearly that he'd prefer manufacturers to simply submit such schemes up front rather than waiting for a rejection before thinking one up (see 5 'The Cost-Sharing Solution: The New NICE Ticket,' The RPM Report, February 2009).
Does Cost-Sharing Override Poor Evidence?
Littlejohns' assertions of the two products' poor evidence for efficacy, followed immediately by his call for pharma firms to share costs raises the question of whether the right cost-sharing proposal could effectively override the shortfalls identified in the manufacturers' submissions, particularly around trial data and design.
These shortfalls appear considerable: no studies submitted assessed either drug against a relevant comparator, according to NICE documents, and trials were "heterogeneous in terms of design, population, implementation and analysis".
Questioned about this, NICE reiterated that the quality of the evidence pointing to the drugs' effectiveness was "extremely poor" but that during the consultation on the draft recommendation, manufacturers will have the opportunity to propose a patient access scheme...and we would be happy to look at such a scheme." The draft recommendation is open for comment through March 9.
A NICE spokeswoman subsequently clarified that the agency's intention was not to imply that a cost-share scheme would be enough to change the decision; rather, "we need more evidence [for the drugs' efficacy] as well," she said. "It's about stronger evidence and help on the cost side."
Another negative NICE decision issued on the same day, concerning Novartis' advanced kidney cancer drug Afinitor (everolimus), offers a reminder that patient-access schemes aren't sufficient for approval.
Preliminary guidance around Afinitor came despite both the drug's qualifying for assessment under the end-of-life criteria, and a patient-access scheme whereby the first pack of treatment comes free, with a 5 percent discount on the second pack.
NICE will begin a new appraisal later this year of the CML drugs among patients who are resistant to imatinib (including high-dose imatinib as a comparator). Meantime, patients will continue to have access to the drugs under local funding arrangements, according to a statement by Bristol.
That company declared it was "disappointed" by the draft negative guidance and would "ask NICE to reconsider" its conclusion. It did not mention whether it would include a patient-access scheme, or provide further evidence for its drug's efficacy.
Novartis, meanwhile, doesn't plan to submit a patient-access scheme .The Swiss group, also 'disappointed', said in a statement that it "will continue to work with NICE to provide and evaluate the evidence in support of Tasigna, with the aim of overturning this initial response" before a final decision is issued (likely about four to six weeks after the March 9 deadline for comments on this draft).
"Novartis has not proposed a patient-access scheme. Novartis believes its medicines are cost-effective and will work with NICE to ensure the appropriate evidence is reviewed in order to appropriately appraise these technologies," the statement continued.
- Melanie Senior ( 6 m.senior@elsevier.com )
This article also appeared in "The Pink Sheet" – Feb 15, 2010
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