Back to results

print

Fluocinolone acetonide intravitreal insert (Iluvien) for diabetic macular oedema

Source agency:

NHSC

Date of Submission:

15/01/2010

Date of Printing:

05/02/2012

Disclaimer:

This report is work in progress and should not be used for external distribution without permission from the originating agency. Users should be aware that reports are based on information available at the time of research and often on a limited literature search.

Technology, Company & Licensing

Technology name:

Fluocinolone acetonide intravitreal insert

Technology - description:

Fluocinolone acetonide is a corticosteroid which has anti-inflammatory and anti-VEGF pharmacological properties. Fluocinolone acetonide ophthalmic insert (Iluvien) is administered by intravitreal (IVT) insertion and releases fluocinolone acetonide at a targeted initial release rate of either 0.2 or 0.5µg per day for up to 3 years.

Fluocinolone acetonide intravitreal insert is also in phase II trials for wet age-related macular degeneration, bilateral geographic atrophy secondary to age-related macular degeneration and retinal vein occlusion.

Company or developer:

Alimera Sciences, Inc

Reason for database entry:

Fluocinolone acetonide intravitreal insert has the potential to be one of the first licensed pharmacological treatments for DMO. It is a sustained drug delivery system designed to provide therapeutic effect for up to 36 months and may offer advantages over shorter-acting products.

Technology - stage in early warning process:

Assessment complete

Technology - stage of development:

Investigational - phase III

Licensing, reimbursement and other approval:

In phase III clinical trials.

Technology - type(s):

Drug

Technology - use(s):

Therapeutic

Patient Indication & Setting

Patient indications:

Diabetic macular oedema.

Disease description and associated mortality and morbidity:

Diabetic macular oedema (DMO) is a common complication associated with diabetic retinopathy that can lead to severe visual loss. Clinically significant macular oedema (CSMO) is defined as:
• Retinal thickening at or within 500µm of the fovea, and/or
• Hard exudates at or within 500µm of the fovea with associated thickening, and/or
• An area of thickening the equivalent of one optic disc area or more, any part of which is within one disc diameter of the fovea.

DMO occurs mainly as a result of disruption of the blood-retinal barrier, which leads to increased vascular permeability and the accumulation of fluid within the intraretinal layers of the macula. Macular oedema is classified as either diffuse or focal. Diffuse oedema is a generalised thickening caused by extensive capillary dilation or capillary closure whilst focal oedema is associated with a leaking microaneurysm. Hypoxia due to vasoconstriction and capillary loss, up-regulates the expression of vasoproliferative factors such as vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6).

Number of Patients:

It is estimated that up to 10% of patients with diabetes develop macular oedema during their lifetime and, in the UK, it is the most common cause of visual loss in people of working age (3,4). DMO occurs more frequently in insulin dependent type 2 diabetes and appears to be more prevalent as the duration of the diabetes and the severity of the retinopathy worsens (4,5). Data from one study suggests that the incidence of DMO over a 10 year period was 20.1% in patients diagnosed before the age of 30 (younger onset) and 39.3% in patients diagnosed after 30 years (older onset)(5). The Diabetes Control and Complications trial reported that 27% of patients develop macular oedema within 9 years of diabetes onset. In older age onset diabetes the prevalence of developing macular oedema is 3-8% within 3 years of diagnosis compared to 0.5% within 10 years of diagnosis in younger onset diabetes (5). In a younger onset diabetic cohort study, macular oedema was associated with a prevalence of visual impairment of 50% and blindness of 20% compared to 16% and 4% respectively in diabetics without macular oedema (6). If left untreated 24% of eyes with clinically significant macular oedema will have a moderate visual loss within 3 years (5).

Technology - specialities(s):

Ophthalmology

Technology - setting(s):

General hospital and ambulatory care, Specialist hospital

Setting - further information:

 

Impact

Alternative and/or complementary technology:

Additive and substitution

Current Technology:

Assessment of DMO:
• Fluorescein angiography - to determine factors such as pattern of fluid leakage and presence of ischaemia.
• Optical coherence tomography - provides high-resolution imaging of the retina and the detection of increased retinal thickness.
• Retinal thickness analyser - quantifies and monitors retinal thickness.

Management of DMO:
• Laser photocoagulation (focal or grid) is the first line of treatment as a damage limitation exercise irrespective of visual acuity, and can reduce the risk of visual loss by 50%.
• Intravitreal ranibizumab (anti-VEGF) is unlicensed for this indication, but undergoing trials.

Health Impact:

-

Diffusion:

-

Cost, infrastructure and economic consequences:

-

Ethical, social, legal, political and cultural impact:

-

Evidence & Policy

Clinical evidence and safety:

Trial: NCT00344968; fluocinolone acetonide intravitreal insert (low and high doese) vs sham procedure; phase III.
Sponsor: Alimera Sciences.
Status: Ongoing.
Source of information: BioSpace (7); Trial registry (8).
Location: EU, USA, Canada, India.
Design: Randomised, dose comparison.
Participants and schedule: n=956; adults; diabetic macular oedema. Randomised to fluocinolone acetonide intravitreal insert 0.45µg or 0.23µg per day vs sham procedure. Patients allowed standard care including laser photocoagulation as needed.
Follow-up: 3 years.
Primary outcome: Visual acuity at 24 and 36 months - improvement in best corrected vision ≥15 letters.
Secondary outcome: Retinal thickness at 24 and 36 months.
Key results: Trial A - 24 month interim results: Improved BCVA of ≥15 letters for low dose, high dose and control respectively (p values vs, control): 26.8% (p=0.029), 26.0% (p=0.034) and 14.7%.
Trial B - 24 month interim results: Improved BCVA of ≥15 letters for low dose, high dose and control respectively (p values vs, control): 30.6% (p=0.030), 31.2% (p=0.027) and 17.8%.
Adverse effects: At 24 months intraocular pressure increase of ≥30mmHg for low dose, high dose and control respectively: 16.3%, 21.6% and 2.7%; trabeculectomy to reduce eye pressure: 2.1%, 5.1% and 0%; cataract formation 80%, 87.5% and 43.6%.
Trial: NCT00490815; dose comparison; phase II.
Sponsor: Alimera Sciences.
Status: Ongoing.
Source of information: Trial registry (9); company.
Location: USA.
Design: Randomised, dose comparison.
Participants and schedule: n=30 (estimate); adults; DMO. Randomised to fluocinolone intravitreal insert 0.5µg or 0.2µg per day.
Follow-up: 3 years.
Primary outcome: Fluocinolone acetonide in plasma and aqueous humour.
Secondary outcome: Retinal thickness.

Economic evaluation:

-

Ongoing research:

-

Ongoing or planned HTA:

-

Web link:

http://www.nhsc-healthhorizons.org.uk/outputs/specialties/

References and sources:

1. National Institute for Health and Clinical Excellence. Type 2 diabetes: the management of type 2 diabetes (update). Clinical guideline CG66. London: NICE; May 2008 (review May 2012).
2. Scottish Intercollegiate Guidelines Network. Management of diabetes. Clinical guideline 55. Edinburgh: SIGN; November 2001.
3. Negi A and Vernon SA. An overview of the eye in diabetes. Journal of the Royal Society of Medicine 2003; 96:266-272.
4. National Institute of Health Research Health Technology Assessment programme (NIHR HTA). Improving the value of screening for diabetic macular oedema using surrogate photographic markers. Abstract of ongoing project.http://www.hta.ac.uk/project/1703.asp Accessed 10 September 2009.
5. Bhagat N, Grigorian RA and Tutela A. Diabetic macular edema: pathogenesis and treatment. Survey of Ophthalmology 2009; 54: 1-32.
6. Moss SE, Klein R and Klein BE. The 14-year incidence of visual loss in diabetic population. Ophthalmology 1995; 97: 415-419.
7. BioSpace. Alimera Sciences announces positive results from the two phase 3 FAME(TM) trials of Iluvien(R)in patients with diabetic macular edema. http://www.biospace.com/news_story.aspx?StoryID=166289&full=1 Accessed 23rd February 2010.
8. ClinicalTrials.gov Fluocinolone acetonide implant compared to sham injection in patients with diabetic macular edema. http://clinicaltrials.gov/ct2/show/NCT00344968 Accessed 10 September 2009.
9. ClinicalTrials.gov. Pharmokinetic and efficacy study of fluocinolone acetonide inserts in patients with diabetic macular edema. http://clinicaltrials.gov/ct2/show/NCT00490815 Accessed 10 September 2009.

Notes: