The first approval of fenofibrate (Lipidil, Abbott) for a new indication — to slow the progression of existing diabetic retinopathy in people with type 2 diabetes — was granted in Australia last week.
Fenofibrate has been known as a cholesterol-lowering agent for the past decade. "But we discovered that fenofibrate had a major beneficial effect on eye disease and disability," explained Anthony Keech, MD, professor of medicine, cardiology, and epidemiology at the University of Sydney, in an interview with Medscape Medical News.
Dr. Keech has led much of the research into fenofibrate use in diabetic retinopathy, and he stressed the importance of treating it early, before the condition worsens to the point of needing laser surgery. "Laser surgery is very effective at preventing retinal hemorrhages but destroys the treated retina. Early treatment also helps prevent the need for intraocular injections of anti-[vascular endothelial growth factor] VEGF drugs and associated risks," he noted.
Diabetic retinopathy is the most common cause of vision loss in adults of working age. "It is one of the most feared complications of diabetes, with more than 50% of people with type 2 diabetes having retinopathy after 10 years of disease," Dr. Keech added.
Without effective treatment, 10% of patients will have severe visual impairment after 15 years of diabetes and will be unable to read or drive a car, and around 2% will be legally blind.
FIELD Study Led by Dr. Keech
The approval by Australia's Therapeutic Goods Association was based on data generated by Dr. Keech and colleagues. They studied the effects of fenofibrate on heart disease in 10,000 patients with type 2 diabetes over an 8-year period and also evaluated its effect on retinal disease.
Dr. Keech led the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study conducted in Australia, Finland, and New Zealand. The researchers reported a 37% overall reduction in the need for laser surgery to prevent vision loss in 9795 patients with type 2 diabetes treated with fenofibrate (Lancet. 2007;370:1687-1697).
"We also reported a significant 79% slowing in the progression of photographic retinal vascular disease, a 2-step progression on [Early Treatment Diabetic Retinopathy Study] ETDRS score in subjects with existing retinopathy," he reported.
ACCORD Eye Study
A more recent study — the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye trial — detailed the beneficial effects of fenofibrate on diabetic retinopathy (N Engl J Med. 2010;363:233-244). Results showed a similar 40% reduction in progression of retinopathy with fenofibrate, as reported by Medscape Medical News. This provided 2 large trials with reproducible findings to support the new indication.
ACCORD investigated whether intensive glycemic control, combination therapy for dyslipidemia, and intensive blood-pressure control would limit the progression of diabetic retinopathy in patients with type 2 diabetes.
A total of 10,251 participants with type 2 diabetes received either intensive or standard treatment for glycemia (target glycated hemoglobin level, <6.0% vs 7.0% to 7.9%), for dyslipidemia (fenofibrate 160 mg/day plus simvastatin vs placebo plus simvastatin), or for systolic blood-pressure control (target, <120 vs <140 mm Hg). A subgroup of 2856 participants was evaluated for the effects of these interventions on the progression of diabetic retinopathy at 4 years.
The risk for progression of diabetic retinopathy was lower with intensive therapy than with standard therapy at 4 years for glycemia (7.3% vs 10.4%; P = .003) and for dyslipidemia (6.5% vs 10.2%; P = .006), but not for blood-pressure control (10.4% vs 8.8%; P = .29).
Class Effect or Fenofibrate-Specific?
Dr. Keech explained that statins did not appear to offer the benefit seen with fenofibrate in the Collaborative Atorvastatin Diabetes Study (CARDS). That study failed to show any significant reduction in progression of diabetic retinopathy or need for laser surgery. "As far as we can tell, this benefit is specific to fenofibrate. Other fibrates have not been tested in large numbers, but they have more problems when they are coprescribed with statins anyway, so such information would be less relevant," he added.
Fenofibrate is the only fibrate recommended by the US Food and Drug Administration and the European Medicines Agency for coprescription with statins because of its unique safety in combination.
It helps that "fenofibrate is a relatively cheap drug with a very good safety profile that has been used for other indications for decades," said Mark Gillies, MD, from the department of clinical ophthalmology and eye health at the University of Sydney. "Furthermore, numbers needed to treat are, in many cases, much less than those for commonly used therapies such as statins or antihypertensives."
Dr. Keech and his colleagues recently reported the main mechanisms by which fenofibrate seems to protect against eye disease (Diabetes. 2013;62:3968-3975).
Abbott is filing for approval in other areas of the world but could not specify where exactly at this stage.
Dr. Keech reports receiving funding from Laboratoires Fournier for the FIELD Study (now part of Abbott), and is listed on a patent application for the use of topical fenofibrate to treat diabetic retinopathy. Dr. Gillies has disclosed no relevant financial relationships.
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Cite this: World First Approval for Fenofibrate in Diabetic Retinopathy - Medscape - Nov 29, 2013.