Macular edema (ME), a disease caused by the build-up of fluid in the center of the retina, is the leading cause of blindness in the working-age population in the developed world. The disease most commonly affects diabetic patients and elderly patients with retinal vein occlusion. Current treatment focuses around the use of anti-vascular endothelial growth factor (VEGF) therapies, which although efficacious, have to be administered through frequent intravitreal (IVT) injections. Primary and secondary research conducted by GlobalData has identified less frequent anti-VEGF injections as one of the major unmet needs arising in the treatment of ME.
The introduction of anti-VEGF therapies revolutionized the treatment landscape of diabetic ME (DME) and ME following retinal vein occlusion (ME-RVO), causing a shift in the paradigm towards a pharmacological approach. There are currently two anti-VEGF therapies approved for the treatment of ME, Roche’s Lucentis (ranibizumab) and Regeneron’s Eylea (aflibercept). Roche’s anti-VEGF cancer treatment, Avastin (bevacizumab), is also widely used off-label due to its considerably lower price compared to Lucentis and Eylea.
Despite offering an efficacious and sight-altering treatment for patient with DME and ME-RVO, anti-VEGFs are not without fault. Anti-VEGFs are initially administered through three monthly loading IVT injections, after which, on average, patients receive an additional injection every five to six weeks, depending on the treatment regimen and anti-VEGF therapy used. Regardless of the frequency of injections, patients will still require monthly observational visits to their ophthalmologist. The frequency of visits, testing, and treatment expenses are a considerable burden for patients and physicians, and put a further strain on hospital and clinical resources. As such, therapies with a longer duration of action would greatly relieve the burden felt by patients and the healthcare system.
Regular visits to ophthalmologists are a considerable burden for DME patients, as they are in addition to the considerable number of visits and treatments required for the effective treatment of their diabetes. The same is applicable for ME-RVO patients, who are predominantly older individuals and as such may well be suffering from additional comorbidities. The therapy burden felt by these patients makes adherence to therapy difficult, proving detrimental to the patient’s health. The strict regimen required for anti-VEGF treatment means that when a patient misses any of their scheduled treatments, irreversible damage, such as fibrosis, can occur on the macula, resulting in further deterioration of vision. This means the patient will have to resume anti-VEGF treatment from a lower visual baseline, so that initially more frequent IVT injections will have to be given.
Given the burden associated with frequent anti-VEGF injections, it is unsurprising that the majority of R&D for ME focuses on reducing the need for such frequent injections. The majority of developers are looking to achieve this by prolonging the effect of anti-VEGF through the addition of a novel compound. For example, Allegro Ophthalmics is looking to combine Avastin with its novel integrin peptide, Luminate, and Clearside Biomedical is developing a suprachoroidal injection of triamcinolone acetonide, CLS-TA, in combination with Eylea. Roche and Regeneron are also looking to clash in the market again, as they try to develop compounds that target both the VEGF pathway and a novel angiopoietin-2, an inhibitor of the TIE-2 pathway. In addition to these therapies, an enhanced anti-VEGF, abicipar pegol, is being developed by Allergan for the treatment of DME.
The above therapies in development have the potential to reduce the high frequency of anti-VEGF injections, and key opinion leaders interviewed by GlobalData expressed optimism in their ability to do so. However, there is a growing feeling in the ME space that in the endeavor to reduce the therapy burden felt by patients, developers have lost sight of what may actually make a difference in terms of efficacy. Close to one third of patients do not show an adequate response to anti-VEGF therapy and therefore require treatment with less desirable corticosteroids. Even in patients who do show an adequate anatomical response to anti-VEGF therapy, a benefit may still not be felt in terms of visual acuity and vision improvement. Therefore, in many ways, there is a greater need for a more efficacious treatment in the first-line setting, which offers greater effects in terms of neuro-protection or neuro-improvement. A therapy that can provide this is much more likely to become a game-changer in the management of ME than a therapy with a longer-lasting duration of action. However, given current research trends, ophthalmologists and patients may have to settle, in the foreseeable future, for reduced injection frequency instead of improved efficacy outcomes.
GlobalData (2014). PharmaPoint: Macular Edema and Macular Degeneration – Global Drug Forecast and Market Analysis to 2023, October 2014, GDHC111PIDR.