It was not a case of third-time lucky for a Roche’s Avastin after the National Institute for Health and Clinical Excellence turned down the drug yet again for the treatment of colorectal cancer.

Despite two consultations following its original draft guidance in November 2009, the Institute is sticking with its decision that Avastin (bevacizumab) is simply too costly for use on the National Health Service in England and Wales given the benefit it offers patients with the disease.

Crucially, the watchdog claims current evidence suggests patients taking Avastin and chemotherapy for metastatic colorectal cancer may survive on average for six weeks longer than those receiving chemotherapy and placebo, and it says half of patients benefiting from the drug will receive even less of a survival benefit.

Despite requests from the Institute, it said no new information or opinion had been offered by the company or other stakeholders during either of the two consultations to further support the drug’s use, in combination with oxaliplatin and either 5-fluorouracil plus folinic acid or capecitabine, on the NHS in this setting.

In addition to concerns over its survival benefit, Avastin is considered by the Institute to be a “very expensive” drug. According to Roche estimates, around 6,500 people per year might be eligible for treatment, and if all of these receive Avastin, the total bill to the NHS could potentially hit a whopping £135 million per year.

Under a proposed patient access scheme (PAS), Roche said it would provide Avastin to the NHS at a cost of around £20,800 per patient in the first year and cover the cost of treatment thereafter (including oxaliplatin), as well as an upfront payment for each patient starting first-line treatment with the drug.

But this did not impress the cost watchdog after it concluded that the effect of the PAS on cost-effectiveness was actually nowhere near that suggested by the Swiss drug giant. Both its independent appraisal committee and the Department of Health felt the scheme “was complex and the administrative costs were underestimated in the manufacturer’s calculations".

“The very complex patient access scheme proposed by the manufacturer did not reduce the cost effectiveness estimates by anywhere near as much as the manufacturer suggests,” noted NICE Chief Executive, Sir Andrew Dillon. “Using the price that the NHS actually pays for oxaliplatin, the cost per QALY would actually be around £70,000 and not £25 - £30,000 as suggested by Roche,” he said.

Disappointing decision

“We are disappointed not to be able to add to this range of treatment options, but we have to be confident that the benefits justify the considerable cost of this drug, and the evidence for [Avastin] is just not as clear as it is for other treatments,” Dillon stressed, defending the decision.

Avastin, which is Roche’s top-selling drug with sales of 1.61 billion francs in the last quarter, has had mixed fortunes of late. In October, the drug showed promise a trial assessing its effect in patients with ovarian cancer, pushing it closer to a filing in Europe for this indication next year.

But In September the oncology blockbuster failed in another late-stage trial as a potential treatment for colon cancer, while its future as a treatment for advanced HER2-negative breast cancer remains in doubt in the US as regulators consider whether to revoke its licence in this setting.