Date:  November 6, 2007 11:01am (Australian Eastern Daylight Time)

Fenofibrate – First lipid modifying
agent shown to protect diabetic eye

 

FENOFIBRATE is the first and only widely available lipid modifying agent to demonstrate significant protection to the eye of patients with type 2 diabetes, reducing the need for laser therapy in a wide spectrum of patients which should decrease the risk of progressive loss of vision. 

These effects appear independent from blood glucose as well as baseline lipid levels, and are not explained by blood pressure values.

These important, new results are published online in the Lancet today by investigators from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study.

Analyses of the results show that fenofibrate:

• Significantly reduces the requirement for a first laser treatment for diabetic eye disease:
• 31 per cent overall (p = 0.0002)
• 31 per cent (p = 0.002) for maculopathy, a major cause of blindness
• 30 per cent for proliferative retinopathy (p=0.015).
• Significantly decreases the total number of laser therapies by 37 per cent (p = 0.0003).

Additionally, fenofibrate almost halved (49 per cent, p=0.0002) the need for laser therapies in patients who were not known to have diabetic eye disease at study entry when considering all courses of laser therapy.

These protective effects appear to begin after only eight months of treatment and increase throughout the five-year treatment period.

Fenofibrate also demonstrated, in a sub-study, a significant reduction in the progression of eye disease with a:

• 34 per cent reduction in a combined exploratory endpoint (progression of retinopathy grading by 2 steps, development of macular oedema and one or more laser treatments, 16.1% vs. 11.1% - HR 0.66, 95% CI 0.47-0.94; p=0.022).
• Reduction by 79 per cent of the progression of existing retinopathy (14 cases with placebo, 14.6% vs. 3 cases with fenofibrate, 3.1% p=0.004).
• Several other endpoints did not differ significantly between groups such as the occurrence of new retinopathy, of hard exudates or worsening in visual acuity.

These new results from the FIELD trial conducted in Australia, New Zealand and Finland, come from an analysis of the reasons for the reduction in laser therapy reported in the initial FIELD publication and a pre-specified ophthalmology sub-study of the effect of fenofibrate on the progression of diabetic retinopathy in 1,012 patients who had repeated eye examinations.

Lead investigator of FIELD, Professor Anthony Keech of the NHMRC Clinical Trials Centre, University of Sydney, Australia, said: “For the first time we have shown that a widely available lipid modifying agent, fenofibrate, reduces the complications of diabetic eye disease – the major cause of impaired vision in adults in the industrialised world.”

“Importantly, the study also demonstrates that patients without prior known diabetic eye disease (but probably already at early stage of retinopathy) gain significantly from fenofibrate. 

In this group the subsequent need for total laser therapy was almost halved.  Therefore, we can now hope that we can intervene to significantly reduce the progression of retinopathy before it requires laser treatment.”
 
Importance for millions of diabetics
Eye disease, including diabetic retinopathy and macular oedema, affects up to 50 million of the 200 million people with diabetes worldwide, as after about 10 years of diabetes most patients will experience clinically significant changes in their vision.

Even with intensive multifactorial therapy (antihypertensive agents, oral antidiabetic agents, statins) retinopathy either developed or progressed in about half of patients with type 2 diabetes within eight years (STENO 2 study).

Moreover, beyond control of blood pressure and blood glucose, no effective treatment is widely available, according to another FIELD investigator, Professor Paul Mitchell of Westmead Hospital, Sydney, Australia. 

He said: “We have to rely on laser treatment which is only partially effective and can result in diminished visual field and other adverse effects.  Additionally, access to laser treatment is limited in many countries.  Therefore, these results offer an important new treatment option to protect the eye of many patients with type 2 diabetes.”

Other clinical benefits
Additional results from the FIELD Study reported this week at the Scientific Sessions of the American Heart Association in Orlando, show that fenofibrate significantly decreased the risk of non-traumatic amputations by 38 per cent (p = 0.011). Meanwhile, earlier data demonstrated that fenofibrate also significantly reduces microalbuminuria, a marker of the risk of progressive renal disease.

In addition to these microvascular benefits, new data presented at the AHA 2007 demonstrate that fenofibrate reduced total CVD events by 26 per cent in diabetic patients with elevated triglycerides (>2.26mmol/L) and low HDL-cholesterol (<1 mmol/L for men and <1.3 mmol/L for women).

Discussing the implications of these new results, Professor Keech said: “The microvascular benefits of fenofibrate – in the eye, the limbs and the kidney – combined with the reduction in overall cardiovascular events, means that fenofibrate offers an important opportunity to protect patients from the most serious consequences of type 2 diabetes. 

The FIELD study and the detailed examinations in the sub-study represent the largest randomised trial database addressing the effects of a fibrate on diabetic retinopathy and its treatment. The protective effects on the eye alone are enough to support its consideration for many patients but the determination of the stage of the disease as to when to intervene should be considered exploratory.”

For more information, or to arrange an interview, please contact:

Australia: Justin O’Day, Ophthalmologist Peter Colman, Diabetologist Tim Davis, Diabetologist Via:   Beth Quinlivan, University of Sydney Ph:      +61 2 9036 6528 Mob:    +61 0 419 229 134

At the AHA Conference, Orlando, Florida Anthony  Keech, Study Chairman Paul Mitchell, Ophthalmologist Via:  Olivia Rajabaly, Euro RSCG Life Ph:      +33 1 58 47 87 64 Mob:    +33 6 87 24 16 75

Notes to editors

About the study
The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study was conducted in 9795 patients aged 50-75 from Australia, New Zealand and Finland with type 2 diabetes. In addition a sub-study was conducted in 1,012 to evaluate the development of diabetic retinopathy and the symptoms of eye disease. The study was supported by the manufacturer of fenofibrate, Laboratoires Fournier SA, part of the Solvay Group: FIELD was designed, conducted and analysed independently of the sponsor by the FIELD study investigators, and coordinated by the NHMRC Clinical Trials Centre, University of Sydney. Fenofibrate is marketed world-wide by Solvay Pharmaceuticals and Abbott USA.  Results of the latest study are published on-line in the Lancet (http://www.thelancet.com/journals/eop).
The absolute risk reductions in first laser treatment were:

• Overall 1.5 per cent
• Maculopathy 1.0 per cent
• Proliferative retinopathy 0.7 per cent.

About diabetic eye disease
Diabetes-related eye disease is common and if untreated or poorly treated leads to deterioration of vision and ultimately blindness.  It occurs when the small vessels (microvasculature) of the eye are damaged by the consequences of diabetes such as increased glucose and raised blood pressure.  Research also suggests other critically important factors such as inflammation of the small vessels of the eye which significantly increase the risk of damage to the retina.

What are diabetic retinopathy and macular oedema?
Diabetic retinopathy arises from changes in the blood vessels of the retina, a nerve layer behind the eye that senses light.  When these blood vessels become damaged, vision loss occurs by two processes known as “proliferative retinopathy” and “macular oedema”.  Proliferative retinopathy occurs when new vessels bleed into the centre of the eye often resulting in blurred vision.  Macular oedema occurs when fluid leaks from these blood vessels into the centre of the retina or macula, making it difficult to focus.  Both of these conditions may eventually destroy the retina if left untreated.  While laser therapy is a successful treatment in preventing blindness, it may result in the loss of vision when the macula is already involved.