NICE rejects Opdivo in lung cancer as too expensive

Bristol-Myers Squibb's (BMS) Opdivo, the first in a new generation on immunotherapy cancer drugs approved to treat non-small cell lung cancer (NSCLC) has been rejected by NICE in draft guidance.

Opdivo (nivolumab) is the frontrunner in the PD-1 class of checkpoint inhibitor drugs, a new generation of immunotherapy drugs expected to advance treatment across many different tumour types – including lung cancer, the UK's biggest cancer killer.

But England's cost- and clinical-effectiveness body has ruled that, despite being innovative and extending lives of patients by three months compared to existing treatment, Opdivo should not be used to treat patients with squamous NSCLC on the NHS because of its high cost.

The problem rests on the fact that while Opdivo is expected to eventually extend the lives of NSCLC patients significantly, so far clinical trials have only increased overall survival (OS) by three months on average. Set against its high cost – £5,268 a month – NICE has ruled this to be not cost effective.

The drug is being reviewed in adult patients with locally advanced or metastatic squamous NSCLC whose disease has progressed after prior chemotherapy. NICE says there are around 853 patients in this situation every year in England who could benefit from Opdivo – a small number, but part of a wider range of lung cancer patients.

40,000 people are diagnosed with NSCLC in the UK every year, many of whom could eventually benefit from the drug.

Merck says its pivotal clinical study showed Opdivo achieved significantly superior survival rates, with 42% of patients still alive at one year compared with 24% of those treated with docetaxel.

The ruling is in sharp contrast to that for Merck Sharp & Dohme's rival drug Keytruda (pembrolizumab), which gained NICE approval in October for use in advanced melanoma.

Keytruda was given one of the fastest-ever NICE recommendations, getting the final seal of approval just three months after it gained European marketing authorisation. This reflected a push from the UK government to demonstrate its commitment to 'Accelerated Access' – but Opdivo has not be as fortunate.

Both Keytruda and Opdivo were granted the special Early Access to Medicines (EAMS) status in the UK, which allowed the drugs to be used before regulatory approval, although pharma and not the NHS had to cover these costs. Once approved, however, the EAMS system closes down.

Opdivo could also be victim of a change over between the old Cancer Drugs Fund (CDF) and the new one, which is due for launch in April 2016. The CDF is currently closed to newly-launched drugs, which means Opdivo has missed out on special funding which many other cancer drugs have received since 2011.

When the new CDF starts in April, it will only consider drugs launched after this date, which means Opdivo will miss out again.

Professor Dean Fennell, chair of thoracic medical oncology, University of Leicester, a key investigator of the drug in the UK, said Opdivo offered significant improvements in survival and safety over docetaxel.

He said if NICE's decision was not reversed, it would be "a serious blow to lung cancer patients, many of whom can't afford to wait."

A spokesperson for NICE said: "Our independent advisory committee recognised that nivolumab is a promising new treatment. However, even allowing for the extra flexibility they have for making recommendations about new cancer treatments, it could not be considered a cost effective use of NHS resources."

BMS has already offered a discount on the drug (via a Patient Access Scheme or PAS), but this wasn't enough to sway NICE's appraisal committee. It estimated Opdivo's cost per QALY gained as £109-129,000, far above its usual threshold.

Call for 'realistic prices'

NICE's draft guidance is now open to consultation – the trend is increasingly for pharma companies to return to the table with a further discount in these circumstances. Given the ground-breaking status of Opdivo, such a scenario is likely to yield a 'yes' from NICE.

Professor Paul Workman, chief executive of The Institute of Cancer Research, London, a world-class research institute which has helped develop many of the new cancer drugs, says Opdivo is, indeed, highly innovative, but also highly priced.

Prof Workman stated that there was 'no question' the drug is pioneering and extends the life of patients but added: "but at this price it is very clearly too expensive for the NHS to afford."

He has now called on the government, NICE and drug companies to "bring down the cost of immunotherapies to more realistic prices" and enable access for patients.

"New drug combinations will be a cornerstone of the improvements we make in cancer survival rates over the next 10 years and, while innovative drugs should command relatively higher prices, the overall cost of treatment must be affordable," he concluded.