U.K. drug cost regulator NICE has rejected Novartis SA's Lucentis (ranibizumab) for treating visual impairment due to diabetic macular edema, in a final draft guidance issued July 15, saying that it is not a cost-effective use of National Health Service resources when compared with laser therapy.

Novartis immediately said it would appeal the decision, although the company is keeping the grounds for appeal confidential.

The institute concluded that Novartis had made a series of unrealistic assumptions in the evidence that it had submitted on the use of Lucentis in diabetic macular edema. It is thus taking a similar position to the one that it took with the draft appraisal in March, when it also rejected Lucentis for use in the condition Also see "U.K.'s NICE Rejects Lucentis For Macular Edema; Avastin Remains Poised For Appraisal" - Pink Sheet, 4 March, 2011.).

Since then, Novartis has submitted additional analyses to NICE, but the appraisal committee said in the final draft guidance that it was still unable to recommend Lucentis for diabetic macular edema. And in the meantime, a competing product, Allergan Inc.'s Ozurdex (dexamethasone), has been recommended for use in the treatment of diabetic macular edema by NICE Also see "NICE Recommends Ozurdex For Macular Edema; Off-Label Comparative Analysis Carries The Day" - Pink Sheet, 7 June, 2011.).

Novartis' Revised Model Unhelpful

In its revised submission to NICE, Novartis modeled the use of ranibizumab treatment for the "better-seeing" eye only, rather than for the "worst-seeing" eye as it had done in the draft appraisal. It also had included the increased mortality risk from having diabetes, as well as the increased mortality risk associated with diabetic macular edema.

This led to an incremental cost-effectiveness ratio (ICER) for ranibizumab compared with laser photocoagulation therapy of £30,277 ($48,880) per quality adjusted life year (QALY) gained, at the upper limit of the range NICE considers an effective use of NHS resources. The analysis used a "commercial-in-confidence" discount to the U.K. list price of ranibizumab of £742.17 per vial, as part of a patient access scheme negotiated between the company and the government's department of health.

However, NICE's evidence review group (ERG) and its appraisal committee were still concerned about the assumptions made in the Novartis analysis, and the lack of any comparison with Roche Holdings' Avastin (bevacizumab), which also is used to treat diabetic macular edema.

The appraisal committee was concerned about six assumptions in the analysis that it considered unrealistic. When the assumptions were adjusted, the ICER invariably became higher. For example, Novartis did not account for the need to treat both eyes in a large proportion of patients, and underestimated the amount of ranibizumab that patients were likely to need. The company also assumed that the relative benefit of ranibizumab over laser therapy lasted indefinitely, and that hypoglycemic control was as tight in patients in clinical practice as it was in clinical trials, assumptions that the appraisal committee believed were all unrealistic.

Novartis also declined to compare Lucentis with Avastin, saying there was no robust evidence base for the use of Avastin in macular edema. Furthermore, the compound has not been in long-term use in the NHS, and there was no widely accepted dosage. However, the ERG pointed out that it had found details of 29 published studies it considered relevant to the use of intraocular bevacizumab in diabetic macular edema, and concluded that the manufacturer's view of bevacizumab was "unjustifiably negative".

Although the appraisal committee was likewise concerned about whether it should have required a comparison with Avastin, it concluded that because Lucentis was being rejected, further analyses were not strictly necessary.

No Decision Yet On Avastin Appraisal

NICE conducted a pre-scoping exercise at the end of 2010 to evaluate whether it was feasible to appraise Avastin for AMD and other eye conditions. It concluded that it was possible if there was input from regulators.

However, the start of such an appraisal requires the department of health to ask for such a review, and NICE confirmed to "The Pink Sheet" DAILY that it hadn't heard from the department whether it wanted the appraisal to go ahead or not.

Lucentis was recommended by NICE for use in the treatment of another eye condition, wet age-related macular degeneration (AMD), in 2008 Also see "NICE Okays U.K. Coverage Of Lucentis With 14-Dose Cap; Macugen Not Approved" - Pink Sheet, 27 August, 2008.).

- John Davis (j.davis@elsevier.com)

Novartis To Appeal NICE's Rejection Of Lucentis For Diabetic Macular Edema

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