Iluvien, United States of America

Iluvien is under investigation for the treatment of diabetic macular oedema, an eye disease that affects the retina. The drug delivery device was licensed in 2005 by Alimera Sciences from pSivida for development as a treatment for diabetic macular oedema.

Alimera began Phase III clinical trials on the drug in 2009. On 29 June 2010, the company submitted a new drug application to the US Food and Drug Administration (FDA) for the approval of the drug to treat diabetic macular oedema.

In July 2010, Alimera submitted a marketing authorisation application to the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK for the marketing approval of Iluvien.

Alimera has also submitted regulatory applications in Spain, Austria, Germany, Portugal, France and Italy.

On 23 December 2010, the FDA declined the new drug application and issued Alimera a complete response letter that requested further safety and efficacy data from the 36th month of the FAME study. Alimera's new drug application was based on the first 24 months of this study. The FDA also detected deficiencies in the current good manufacturing practices of Alimera's third-party manufacturers.

Alimera is currently preparing the safety and efficacy analysis the FDA has requested.

Alimera resubmitted the new drug application to the FDA in May 2011. The FDA review is expected to be completed in six months. The new application includes analysis of safety and efficacy data collected from the 36 month FAME trial. It also includes further information about the manufacturing, packaging and sterilisation specifications of the drug.

Diabetic macular oedema

Diabetic retinopathy causes blood vessel leakage within the macula, which is a vital part of the retina responsible for central vision. When this condition happens in people with diabetes, it is called diabetic macular oedema.

Diabetic macular oedema may cause blurring of central vision or complete loss of eyesight. The onset of the disease is painless, so it may go unidentified by the patient until it manifests with complete or partial loss of vision.

According to the study by Wisconsin Epidemiologic, it was observed that over a ten-year period, more than 19% of people with diabetes were diagnosed with diabetic macular oedema.

The World Health Organisation (WHO) estimates there are more than 150 million people worldwide with diabetes, about 24 million in the US alone. All people with diabetes are prone to the development of diabetic retinopathy. In the US, diabetic macular oedema is the main cause for 12,000 to 24,000 cases of vision loss a year.

The FDA has so far not approved any ophthalmic drugs for the treatment of diabetic macular oedema.

Targeting disease

Iluvien contains fluocinolone acetonide in small microgram levels, which can be delivered directly to the patient’s eye via an intravitreal insert. The drug is inserted in the posterior of the patient's eye through an inserter that employs a 25-gauge needle that creates a self-sealing wound. The Iluvien insert slowly releases corticosteroid into the eye for the treatment of diabetic macular oedema, and can give therapeutic effect for up to 36 months.

Clinical trials on Iluvien

Alimera conducted a Phase II study on Iluvien on the first human pharmacokinetic by enrolling 37 diabetic macular oedema patients in 2008. Low doses of the drug were administered to 20 patients and a high dose was given to 17 patients. The six-month study showed the best corrected visual acuity of 15 letters or more improved by 20% in the low-dose patients and 18% in the high-dose patients.

Alimera conducted two Phase III clinical trials on Iluvien between August 2007 and October 2010 in the FAME study. The research was conducted on 956 diabetic macular oedema patients from Canada, India, the US and Europe. The efficacy and safety of both low and high doses of the drug was tested for 36 months. The high dose of Iluvien administered to the patients was 0.45mg and the low dose 0.23mg a day.

The clinical trial was conducted using modified ART (all randomised and treated) methods in trials A and B. In trial A, 22.6% of the low-dose patients and 24.1% of the high-dose patients improved by 15 or more letters, compared to 12.6% of the control patients. In trial B, 29.7% of the low-dose and 29.3% of the high-dose patients improved by 15 or more letters compared to 13.3% of control patients.

The data collected during the first 24 months of the clinical trials indicated that the BCVA improved significantly, by more than 15 letters on diabetic macular oedema patients of both low and high-dosage categories.

The FAME study continued for a total of 36 months, concluding in October 2010 with the final patient visit at the three-year data point.

The FAME trial reported positive results in February 2011. The complete analysis consisted of 376 patients in ILUVIEN arm (including 190 patients in Trial A and 186 patients in Trial B) and 185 patients in the control arm. The response rates after 36 months were similar to those after 24 months.