The National Institute for Health and Clinical Excellence (NICE) has issued draft guidance in which it does not recommend US biopharmaceutical company Alimera Sciences' Iluvien (fluocinolone acetone intravitreal implant) for the treatment of chronic diabetic macular oedema (DMO).

The macula is the central part of the retina responsible for colour vision and perception of fine detail, and DMO occurs as a result of changes in people with diabetes. A reduction in the number of connective tissues around capillaries and an increased amount of a protein, vascular endothelial growth factor (VEGF), causes the blood retinal barrier to become more permeable. This leads to leakage of plasma constituents in the surrounding retina, causing a build-up of excessive fluid (oedema) which disrupts the fovea, the area responsible for sharp vision, and can lead to severe visual impairment in the affected eye.

Iluvien is a corticosteroid which has anti-inflammatory and anti-vascular endothelial growth factor (anti-VEGF) properties. By inhibiting VEGF, fluocinolone can decrease the oedema and limit visual loss and/or improve vision, says NICE, noting that the implant releases fluocinolone acetone for up to three years.

However, NICE's independent appraisal committee has concluded that Alimera Sciences' economic models have underestimated the incremental cost-effectiveness ratio (ICER) for Iluvien, and that a model which relied on more plausible and accurate assumptions would be certain to produce an ICER than exceeded the range considered by NICE to be an effective use of NHS resources.

The appraisal committee members have also concluded that the evidence submitted by the manufacturer did not accurately reflect current clinical practice. For example, the people involved in the trials which were submitted as evidence may not have been as severely affected by chronic DMO as those who would receive fluocinolone intravitral implant in routine clinical practice, and results from the clinical trials might be better than what would be seen in clinical practice, they say.

Professor Carole Longson, director of NICE's Health Technology Evaluation Centre, commented that the panel members are aware that chronic DMO can have a significant effect on the physical and emotional wellbeing of people affected but, unfortunately in this case, they have agreed that the evidence provided could not support a positive recommendation for Iluvien. 

"These draft recommendations are now available for public consultation and the manufacturer and other consultees are able to consider and respond to concerns and comments made by the appraisal committee," Prof Longson added.

Analysts at Cowen & Co described NICE's draft guidance as a "significant blow."

"Not only is the UK a large European market, but NICE is a leading [European Union] cost agency and one whose decisions are closely watched and in many cases followed by the rest of the European country cost agencies," say analysts Simos Simeonidis and Yatin Suneja.

"This makes any potential partners even more skittish about getting involved with Iluvien," they add.

Iluvien has already been rejected twice by the US Food and Drug Administration (FDA). The analysts note that Alimera remains interested in revisiting the US opportunity, either alone or with a partner or through an acquirer, with the hope of reversing the FDA's decision to reject Iluvien's New Drug Application (NDA) and require two additional trials.

But, they add: "we continue to believe that it is extremely unlikely that the FDA would reverse its decision, especially in the absence of any new data, and we don't see a US approval of Iluvien as a realistic scenario."

NICE says it is expecting to publish final guidance on Iluvien's use in chronic DMO this November.