Diabetes, a worldwide epidemic, is the leading cause of blindness among working-age adults. Diabetic retinopathy (DR) is a diabetes complication that affects eyes, caused by chronic elevated blood sugar levels, and other metabolic problems. The condition can develop in anyone who has type 1 or type 2 diabetes. The longer you have diabetes and the less controlled your blood sugar is, the more likely you are to develop this eye complication. Diabetes leads to damage to the blood vessels of the light-sensitive tissue at the back of the eye (retina), which at first might cause no symptoms or only mild vision problems, but eventually it can cause blindness.
When DR is in its early stages, blood vessels in the retina are damaged and can begin to leak fluid into the retina, a problem called diabetic macular edema (DME). In advanced stages, new and abnormal blood vessels form which may break and bleed. Fluid and hemorrhage interfere with vision and may further cause irreversible visual impairment due to retinal scarring and even retinal detachment. Even though biologic injection therapies have been approved for DR and treatment is possible, patients with DR are not widely treated in this early stage of the disease.
We believe that APX3330’s oral delivery could be preferred over current invasive methods, and it has the potential to be used as monotherapy (non-proliferative or early proliferative stages of diabetic retinopathy) or as an adjunct therapy (advanced stages).
Diabetic Macular Edema
Diabetic Macular Edema (DME) is the most common cause of vision loss in people with DR. The pathogenesis of DME involves abnormal vascular leakage, accumulation of fluid in the macula, retinal ischemia, and release of vasoproliferative growth factors and inflammatory mediators. In DME, the primary drug therapies today are intravitreal anti-VEGF antibodies and intravitreal corticosteroids, which are given as injections into the white (sclera) of the eye every one to three months.
Earlier treatment options to prevent or delay vision loss for patients with diabetic eye disease are important. APX3330’s safety profile, pharmacokinetic properties, and molecular target engagement data observed in clinical trials and its drug exposure in the retina seen in mouse models, combined with a unique oral tablet formulation, suggest its potential to reduce the frequency of anti-VEGF treatments and increase compliance for better outcomes.
Other Indications: Wet Age-Related Macular Degeneration and Retinal Vein Occlusion
Wet age-related macular degeneration (wAMD) is the most severe form of AMD, and the leading cause of irreversible vision loss in industrialized nations for those ages 65 and above. Patients with wAMD develop choroidal neovascularization, retinal pigment epithelial detachment, subretinal hemorrhages and fibrovascular scarring. Currently, three types of innovative treatments have been demonstrated to limit or delay loss of vision in patients with wAMD: laser photocoagulation, photodynamic therapy and anti-VEGF.
Retinal vein occlusion (RVO) is a vascular disorder of the retina and one of the most common causes of vision loss worldwide. It is classified according to the occlusion location; central retinal vein occlusion (CRVO) at the level of the optic nerve and branch retinal vein occlusion (BRVO) at the level of any central vein branch. Although the exact etiology of RVO remains unclear, it is likely to follow a thrombotic event. The vein blockage leads to ischemia, vascular leakage, macular edema, inflammation and neovascularization.
Given APX3330’s similar anti-angiogenesis MOA and novel oral administration, future clinical studies to explore wAMD and RVO with a partner of interest.