21 January 2011
The European Medicines Agency (EMA) issued a positive opinion in October 2010 for a licence extension for ranibizumab▼ for the treatment of adults with visual impairment due to diabetic macular oedema (DMO). Approval to market this indication has now been granted. Ranibizumab (Lucentis®) is already licensed for the treatment of neovascular (wet) age-related macular degeneration (AMD). A qualified ophthalmologist experienced in intravitreal injections must administer it.
Commissioners, working with local clinicians and decision-making bodies, will need to identify patients who might be eligible for ranibizumab for this indication and plan for publication of NICE guidance. Consideration needs to be given to any re-structuring of NHS services that may be required.
Diabetic macular oedema (DMO) is the main cause of visual loss in diabetic maculopathy. This diabetic eye disease involves localised damage to the macula, the part of the retina responsible for colour vision and perception of fine detail. DMO occurs as a result of changes in retinal blood vessels. It can lead to severe visual impairment in the affected eye. While treatment of systemic risk factors including dietary modification and blood pressure control may delay progression of the eye disease, the main treatment option for sight-threatening focal, diffuse or mixed DMO is laser therapy (photocoagulation). The aim of this is to prevent further visual loss. There are currently no licensed pharmacological agents to treat DMO.
However, now that a European Market Authorisation has been granted, a NICE appraisal of ranibizumab is underway for this indication, but a publication date is not yet available. According to the final scope, approximately 14% of people with diabetes have DMO and prevalence increases to 29% for diabetics who use insulin for more than 20 years. When DMO is untreated there is a 25 to 30% risk of developing clinically significant macular oedema (CSMO). Moderate visual loss will occur in approximately 24% of untreated eyes after 2 years where CSMO has developed.
The main phase III clinical trial supporting the licence submission has not yet been published in full. RESTORE is a 12-month trial of ranibizumab alone, laser photocoagulation alone or ranibizumab with laser photocoagulation. The primary outcome is a mean change from baseline in Best-corrected Visual acuity (BCVA) over a time period of 12 months. A 24-month open-label extension study of ranibizumab alone is on-going.
Results from RESOLVE a phase II study (n=151), have been published. This was a 12-month study which compared intravitreal ranibizumab 0.3mg or 0.5mg against sham injection. The primary endpoint was the mean average change in BCVA from baseline to month 1 through month12. BCVA was measured using the Early Treatment Diabetic Retinopathy Study (EDTRS) protocols. The mean average change for the ranibizumab pooled group (n=102) was 7.8 letters (Standard Deviation [+/-SD] 7.7) vs. sham of -0.1(9.8) letters; Least squares means (LSM) difference 7.9 letters; P<0.0001. The practical meaningfulness of this outcome measure is difficult to judge as it will depend upon the baseline vision of an individual patient. A more useful outcome measure would be how any improvement in vision improves the practical aspects of daily living.
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