Pfizer’s strong new commitment to oncology could be undermined by restrictions on access to new therapies through the UK’s National Health Service, the company has warned.

Speaking last week at a press briefing in London, Dr David Gillen, medical director for Pfizer UK, pointed out that the company’s oral kidney cancer drug Sutent (sunitinib) first received conditional approval from the European Medicines Agency in July 2006 for second-line use in advanced renal cell carcinoma.

The first-in-class tyrosine kinase inhibitor gained European approval for first-line use in advanced and/or metastatic RCC in January 2007. Yet the UK’s National Institute for Health and Clinical Excellence is not due to deliver its cost-effectiveness verdict on Sutent until early next year.

In the meantime, Pfizer’s drug has fallen victim to the postcode lottery. According to oncology consultant Professor John Wagstaff, 77 primary care trusts/local health boards are currently funding Sutent and Novartis’ Nexavar (sorafenib) for the treatment of metastatic RCC in the UK. The drugs cost around £3,000 to £3,500 per patient per month.

Even where Sutent is covered by the NHS, the amount of form-filling required in some cases to clear the prescription may effectively consign the drug to the back burner. In South Wales, where Wagstaff practises, it takes about 45 minutes to complete the necessary clearance for each patient, the consultant said.

UK is poor man of Europe
The impact of ‘NICE blight’ can be seen in the local sales figures for Sutent. The UK accounts for only around 3% of Sutent’s sales in Europe compared with 31% in Germany, Gillen noted. As Wagstaff commented at the briefing, “we really are the poor man of Europe” in terms cancer mortality, treatment options and spending on new therapies.

For example, two thirds of renal cancer patients are prescribed only standard interferon-alpha therapy while in France, Italy, Spain and Germany just 6-8% of patients get interferon-alpha. This is despite an objective response rate of about 31% for Sutent versus 6% for interferon-alpha. In another five out of 10 Sutent patients the cancer stops growing for a significant length of time, Wagstaff added.

Pfizer’s drug has also been shown to more than double progression-free survival compared with interferon-alpha, from around five months to a median 11 months. And in 1-2% of patients the cancer is completely eradicated, Wagstaff noted.

Survival data
What Pfizer has not reported yet are data on overall survival, although there have been indications of a trend towards improved median survival versus interferon-alpha. The latter drug increases the chance of being alive after one year by 30%. This gap in the knowledge base for Sutent should be remedied by data scheduled to be presented at the 44th annual meeting of the American Society of Clinical Oncology in Chicago, which starts this Friday.

Lack of overall survival data has already proved an impediment to NHS funding of Sutent in Scotland, where NICE’s counterpart the Scottish Medicines Consortium ruled in June 2007 that Pfizer’s drug was not sufficiently cost-effective for the treatment of advanced and/or metastatic RCC.

Now the NICE verdict is awaited “with bated breath”, Wagstaff said. Both he and Gillen questioned whether the Institute’s much disputed quality-adjusted life-year measure was the right criterion to be applying to end-of-life treatments.

The end result of these restrictions is that “patients are suffering”, Gillen told the briefing. They also rack up uncertainty for companies already struggling with an “unacceptable” attrition rate in research and development. Some 7,000 compounds are being screened to generate every one or two drugs, around 30% of Phase III protocols fail to produce a viable result, and one in five regulatory submissions is drawing a blank.

Pfizer recently had a couple of bad experiences of its own, most notably with the abrupt termination of the development programme for its HDL cholesterol booster torcetrapib in December 2006, wiping out a more than US$1 billion investment. And in April 2008 the company’s late-stage oncology portfolio was rocked by the Phase III failure of the melanoma treatment tremelimumab (CP-675206).

While a review of the interim trial data for tremelimumab showed the compound would not demonstrate superiority to standard chemotherapy, Gillen pointed out that it achieved a response rate of around 7%. The regulatory hurdle was 10% but interleukin-2 – which is used in high doses to treat metastatic melanoma – was originally approved for this indication with a 8% response rate, Gillen added.

Trial impact
At least with regulators there is an opportunity for dialogue about study designs, he observed. Until recently there has been no provision for dialogue with NICE. In this respect, Gillen said, the Institute’s offer of early scientific advice to pharmaceutical companies ahead of Phase III – pioneered in a successful pilot with Novartis – is a welcome development that will help global R&D teams to develop studies better aligned with NICE’s cost-effectiveness assessments.

All the same, the current UK environment can look distinctly chilly at a time when Pfizer is spending US$1.6 billion on oncology, 60% more than in 2005. The longer-term impact of limited access to new therapies could be a shrinking pool of patients on which to test the next generation of anticancers, Gillen warned.

Future trials in renal cancer will call for patients who have failed on Sutent, he noted. But it will be hard making a comparison with the existing standard of care if patients do not have access to it.

In the pipeline
Dr Jayeta Chakrabarti, medical advisor for Pfizer UK, gave a flavour of the company’s R&D efforts in oncology, which accounts for around one third of all Pfizer’s clinical trials in the UK.

The current pipeline includes compounds at all stages of development based on four central technology platforms: anti-angiogenics, including Sutent and axitinib, a selective inhibitor of vascular endothelial growth factor receptors 1,2 and 3; immunotherapies, described as a “new and powerful tool” in the cancer armamentarium; signal transduction inhibitors; and a new wave of cytotoxic agents.

One measure of that commitment is the number of abstracts Pfizer will be presenting at the ASCO meeting this year: 73 in total, compared with 52 abstracts in 2007 and 26 in 2006.