Eylea (Aflibercept) for Treatment for Wet AMD, United States of America
Eylea (aflibercept), a recombinant fusion protein, is developed for the treatment of patients with wet age-related macular degeneration (AMD). It is jointly developed by Regeneron Pharmaceuticals and Bayer HealthCare.
Eylea was approved by the US Food and Drug Administration (FDA) in November 2011.
In March, 2012, Bayer received approval for Eylea from the Australian Therapeutic Goods Administration (TGA).
Bayer also submitted marketing authorisation applications for Eylea in Europe, Japan and other countries in 2011. In November 2012, the drug was approved by the European Commission. The drug has also been approved in Japan and Switzerland.
The drug was also tested beyond its wet AMD indication. Regeneron submitted a supplemental Biologics License Application (sBLA) to the FDA for use of Eylea in central retinal vein occlusion (CRVO). The drug was approved for this indication by the FDA in September 2012.
Bayer plans to submit a marketing authorisation application for CRVO in Europe towards the end of 2012.
Wet age-related macular degeneration (AMD) in older adults
Age-related macular degeneration (AMD) is frequently observed cause of blindness in older adults. Macula is a sensitive tissue present in the centre of the retina. It helps in viewing finer details clearly.
AMD occurs due to swelling caused by leaking of abnormal blood vessels growing under the retina, which leads to dysfunction of the retina creating blind spots in central vision.
It is the leading cause of blindness for people aged above 65 years in Europe and the US. It is estimated that about 15 million people in the US are affected by the disease. It is also reported that about 200,000 new cases of Wet AMD are diagnosed in North America every year.
Eylea mechanism of action
Vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF) proteins promote the growth of abnormal blood vessels under retina damaging the macula.
Eylea is an intravenous injection that contains recombinant fusion protein. The soluble decoy receptor present in the drug works by binding all forms of VEGF-A and PIGF proteins.
The drug inhibits the activation of the cognate VEGF receptors.
Clinical trials of Regeneron and Bayer HealthCare's recombinant fusion protein
Regeneron and Bayer jointly conducted Phase I clinical trials on Eylea between June 2005 and August 2008. The Phase I study was an exploratory study that found the safety and tolerability of the drug. The study enrolled 51 patients across the US. The primary outcome measure of the study was finding the safety, tolerability and biological effect of the drug. Secondary outcome measures included finding the effect of VGEF trap, extent of (Choroidal NeoVascularization) CNV leakage and plasma levels of VEGF trap.
Phase II clinical trials were conducted from April 2006 to August 2008. It was a randomised, controlled study which enrolled 159 patients with wet AMD. The primary outcome measure of the study was finding the mean change in central retinal / lesion thickness (CR/LT) from the baseline at week 12.
The secondary outcome measures included finding mean change of CR/LT, change in best corrected visual acuity (BCVA) and percentage of participants who gained at least 15 letters of vision.
Approval for Eylea in Australia was based on positive results of Phase III VIEW 1 and VIEW 2 clinical trials. The VIEW 1 study enrolled 1,217 patients across the US and Canada. The study was conducted by Regeneron. VIEW 2 enrolled 1,240 patients in Europe, Japan, Latin America and Asia-Pacific. The study was conducted by Bayer. The patients were administered with three different doses of Eylea regimens ranging between 0.5mg and 2mg.
Results of the study showed that Eylea which was used every other month after the initial three monthly injections was not found inferior to Genentech's wet AMD drug Lucentis that was dosed for every four weeks. The common adverse reaction found in Eylea-administered patients included cataracts, vitreous floaters, eye pain, vitreous detachment, increased intraocular pressure and haemorrhage.
Eylea is currently undergoing Phase III clinical studies for wet AMD in China.
Marketing commentary for wet AMD drugs and Eylea (aflibercept)
Jetrea (ocriplasmin) is a pharmacological agent developed by ThromboGenics, for the treatment of symptomatic vitreomacular adhesion (VMA). Jetrea was approved by the US Food and Drug Administration (FDA) for treating symptomatic VMA in October 2012.
Regeneron holds the exclusive rights for marketing Eylea in the US, where as Bayer markets the drug outside the US and both the companies share profits equally. Bayer plans to launch Eylea in Australia and other countries by the end of 2012 or in early 2013.
Other drugs approved by the FDA for the treatment of wet AMD include Visudyne, Macugen and lucentis, which were approved in 2000, 2004 and 2006 respectively.