Global Insight Perspective | |
Significance | U.K. drug watchdog NICE has refused to recommend National Health Service (NHS) funding for Avastin, Nexavar, Sutent and Torisel as treatments for advanced and metastatic forms of renal cell carcinoma. |
Implications | Despite all four drugs offering several months of extended patient survival compared to existing treatments, NICE ruled that none were cost-effective enough to warrant reimbursement on the NHS. The guidance is not final, however, and a second draft will be published following a prolonged consultation period. |
Outlook | The companies affected by the draft guidance will be sure to consider cost-sharing or dose-capping schemes as an alternative way of securing reimbursement in the United Kingdom, following in the footsteps of a growing number of firms that produce innovative but expensive medicines. |
The U.K. National Institute for Health and Clinical Excellence (NICE) has published preliminary guidance on funding for four treatments for advanced and metastatic forms of renal cell carcinoma (RCC). The guidance offers a negative opinion of the drugs' cost-effectiveness, which means that NICE will not be recommending any of them for reimbursement via the National Health Service (NHS) in England and Wales. The four drugs in question are:
- Avastin (bevacizumab), produced by Swiss company Roche;
- Nexavar (sorafenib), made by German firm Bayer Schering Pharma;
- Sutent (sunitinib), manufactured by U.S. pharma giant Pfizer; and
- Torisel (temsirolimus), produced by U.S. drug-maker Wyeth Pharmaceuticals.
The decision was based on evidence presented by a variety of consultees and commentators, but does not take into account views from the manufacturers. Despite finding that all four treatments offered patients "significant gains" in progression-free survival compared with existing standard therapies, NICE ruled that there was insufficient evidence of cost-effectiveness to warrant their regular use by the NHS.
NICE's appraisal committee examined the cost-efficiency case for the four drugs in five separate RCC settings, the full details of which can be read here:
- First-line treatment for patients suitable for immunotherapy
- First-line treatment of patients with a poor prognosis and who are suitable for immunotherapy
- First-line treatment of patients unsuitable for immunotherapy
- First-line treatment of patients with a poor prognosis and who are unsuitable for immunotherapy
- Second-line treatment of patients whose condition has failed to respond to immunotherapy
Avastin's cost-effectiveness estimate of £75,000 (US$146,522) per quality-adjusted life year (QALY) as seen by Roche and of £171,000 per QALY as seen by NICE's appraisal committee were both viewed as being too costly to warrant the drug's inclusion on the NHS as a first-line treatment for people suitable for immunotherapy. NICE said that only a very small amount of information was offered on clinical or cost-effectiveness for Avastin or Sutent compared with standard interferon-alfa monotherapy in treating patients with a poor prognosis but who were still responsive to interferon treatment. NICE ruled that the two drugs "would be unlikely to result in a cost-effectiveness estimate that would be compatible with the best use of NHS resources."
Clinical evidence presented for Torisel as a first-line treatment for people unsuited for immunotherapy, meanwhile, revealed that the Wyeth drug was indirectly compared with another treatment during its efficacy trials, and that the best available supportive care was not used in the trial. This, according to NICE, resulted in Wyeth's cost-effectiveness estimate of £81,200 being a likely under-estimate.
Finally, Nexavar was ruled unsuitable for NHS funding as a first-line treatment for people unsuitable for receiving treatment with immunotherapy, despite the clinical and cost-effectiveness data coming from a small subgroup of the total trials carried out on the drug.
RCC Treatments in the U.K.: A Comparison | |||||
Drug | Producer | U.K. Indication | EU Orphan-Drug Status | Dosage Administration | Price (excl. VAT) |
Avastin (bevacizumab) | Roche | In combination with interferon-alfa, first-line treatment of advanced and/or metastatic RCC | No | Avastin 10 mg/kg body weight once every 14 days, interferon-alfa injection three times per week at escalating doses | Avastin: £924.40 for a 400-mg vial
|
Nexavar (sorafenib) | Bayer Schering Pharma | Treatment of advanced RCC that has failed to respond to interferon-alfa or interleukin-2 therapy, and for people for whom such therapy is unsuitable | Yes | 400 mg twice daily | £2,504.60 for a pack of 112 tablets Average daily cost: £89.45 |
Sutent (sunitinib) | Pfizer | Treatment of advanced and/or metastatic RCC | Yes | 50 mg once daily for four consecutive weeks with two-week rest period (six-week cycle) | £3,363.00 for a pack of 30 capsules Average daily cost: £74.74 |
Torisel (temsirolimus) | Wyeth Pharmaceuticals | First-line treatment of advanced RCC in people with at least three specific prognosis risk factors | Yes | 25 mg infusions over a 30- to 60-minute period once a week. | £515 for a 30-mg vial. |
Source: NICE. | |||||
Renal cell carcinoma is the most common form of kidney cancer, accounting for approximately 90% of all kidney cancers. Within England and Wales, kidney cancer is the 8th most commonly diagnosed cancer in men and the 14th most common cancer in women. Patient survival rates for RCC are poor, with an average of 44%, while only 10% of people with metastatic forms of the disease tend to survive. Standard NHS treatment for metastatic forms of RCC includes interferon-alfa 2a or interleukin-2 immunotherapy, as well as combinations of the two, but patients' median survival time with these forms of treatment is just 3.8 months. The most commonly used interferon drug used in English and Welsh RCC cases, Roferon-A, is manufactured by Roche.
Outlook and Implications
Prescriber and patient groups have spoken out angrily against NICE's preliminary guidance, which they claim will effectively prevent many RCC patients from gaining access to some of the most effective new treatments on the market. NICE's findings are not set in stone, however, and could change once further consultation has been carried out. The draft guidance is now subject to comments until 29 August, after which a second appraisal committee meeting will be held on 10 September. Only then will NICE begin to assemble its final appraisal determination, which may be used as the basis for its finalised guidance.
For Bayer Schering, Pfizer, Roche, and Wyeth, this initial decision will nonetheless come as a shock, given that most regulatory bodies have welcomed the treatments as being among the most promising of a new generation of kidney-cancer treatments. The high cost of innovative drugs is, however, proving to be a divisive issue across markets, and the United Kingdom is not the first to baulk at the price of the latest oncology treatments (see Japan: 2 May 2008: Bayer Schering's Nexavar Refused Reimbursement Status in Japan). As such, the second round of negotiations and assessment will see producers of the four RCC drugs offer more clinical evidence of cost-effectiveness in the areas that NICE has deemed problematic, but they may also individually attempt to strike cost-sharing deals that will see them share the NHS's reimbursement burden. Earlier this week, U.K. drug giant GlaxoSmithKline announced it was hoping to do the same thing for breast-cancer drug Tykerb (lapatinib), and a growing number of pharma companies are turning to novel pricing schemes and reimbursement schemes as the only way to secure widespread market access in the United Kingdom: (see United Kingdom: 5 August 2008: GSK Considers Price-Capping Deal to Secure Tykerb U.K. Reimbursement, Goes DTP from 1 November; United Kingdom: 25 October 2007: Reimbursement with Strings Attached as NICE Issues Final Guidance on J&J's Velcade and United Kingdom: 3 April 2008: NICE Endorses Pioneering Lucentis Reimbursement Scheme, Rejects Macugen in Wet AMD).