NICE No For AZ's Tagrisso Highlights Flaws of England's New Cancer Drugs Fund

NICE, the HTA institute for England and Wales, has doubts over the long-term benefits of AstraZeneca PLC's Tagrisso (osimertinib) and has initially declined to recommend the drug either for conditional funding through the new Cancer Drugs Fund or for routine NHS funding. The draft guidance "highlights major issues with the current NICE process" with respect to appraising medicines that have been awarded early authorization, says Greg Rossi, business unit head, oncology, at AstraZeneca.

"Due to the uncertainties in the evidence and because it could not be considered cost-effective, the committee concluded that osimertinib did not meet the criteria to be considered for inclusion in the CDF," said NICE.

Tagrisso is licensed for treating adult patients with locally advanced or metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer. It won expedited conditional marketing authorization from the European Commission in February. But despite a new process that gives NICE greater scope to deal with uncertainties regarding clinical data, it still decided not to recommend the drug. The new system that went live on 1 April allows NICE to make one of three recommendations for cancer drugs based on whether the product looks likely to be cost-effective: recommended for routine use on the NHS; rejected for use on the NHS; or recommended for use on the cancer drugs fund. The latter means that the drug is reimbursed through an interim Cancer Drugs Fund for up to two years while the company gathers new evidence to show that the drug is a cost-effective treatment. NICE then takes a second look and decides whether to recommend it for routine funding. NICE usually considers drugs with a cost per QALY of less than £30,000 to be cost-effective.

AstraZeneca put forward a "conservatively-estimated ICER" of just under £43,000 per QALY for osimertinib. NICE could have considered this to be cost-effective if Tagrisso had met NICE's end of life criteria, which allow the institute to consider drugs with a cost per QALY of up to £50,000. To qualify, the firm must show that the drug extends life by three months compared to current standard treatment. AstraZeneca did this extrapolating its early data, but NICE concluded that the data used were too immature and that Tagrisso therefore did not qualify as an end-of-life drug.

AstraZeneca was disappointed with the conclusions, but plans to submit more data before the consultation on the preliminary guidance closes on 14 July. It hopes that this data will mean that Tagrisso qualifies as an end of life drug.

The company also has concerns about the new system for appraising oncology products, which replaced the ill-fated and over-stretched Cancer Drugs Fund. "The changes to the Cancer Drugs Fund are intended to allow drugs with clinical uncertainty, like osimertinib, to be accessed by patients in the NHS. Osimertinib has highly compelling early clinical data in an area of high unmet need and given its accelerated regulatory approval, it should be an ideal candidate able to demonstrate how the new NICE/CDF process could work to improve swift access for patients," said Rossi. But, he added, the draft decision to reject Tagrisso shows big issues with the process when promising innovative medicines are up for review. "While NICE intends to appraise these medicines earlier in their lifecycle, it is less likely that these medicines will have mature overall survival data by that point. NICE must either be more open to the use of accepted alternative cancer endpoints already adopted by the EU regulatory agency and national authorities in other countries, or be more flexible in the degree of uncertainty that committees can accept for entry into the CDF."

AstraZeneca had also put forward a patient access scheme offering a discount on the drug's list price, which is £4,722.30 per pack of 30 80mg tablets and £4,722.30 per pack of 40-mg tablet.

AstraZeneca says that the latest pooled results from the AURA Phase II studies in 411 pre-treated patients with EGFR T790M mutation-positive NSCLC treated with osimertinib 80mg showed a median progression-free survival of 11 months (95% CI: 9.6-12.4 months) and an objective response rate (a measurement of tumour shrinkage) of 66% (95% CI: 61%-71%).

CORRECTION: This article was edited on 6 October to reflect the fact that Tagrisso does not have a PRIME designation in Europe as previously stated by AstraZeneca.