Among the drugs for ophthalmic diseases, anti-VEGF drugs are developing rapidly, and aflibercept is amplified rapidly. At the same time, the development of new targets, new drug delivery methods and bispecific antibodies has become a hot spot in the industry.
1.Anti-VEGF drugs are developing rapidly and become the mainstream
The formation of intraocular neovascularization is the pathological basis and clinical manifestation of many kinds of eye diseases. The irreversible damage caused by intraocular neovascularization to cornea, iris, choroid, retina and other eye tissues has become one of the important causes of blindness. The most common neovascular ophthalmopathy were wet age-related macular degeneration (wet-AMD), diabetic retinopathy (DR), diabetic macular edema (DME) and retinal vein occlusion (RVO).
Traditional treatment methods damage healthy tissues, anti-VEGF drugs came into being.
Traditional treatments such as vitrectomy, laser photocoagulation and photodynamic therapy can alleviate the progress of the disease, but inevitably damage healthy tissue. At present, with the continuous breakthrough and development of fundus therapy, anti-vascular endothelial growth factor (VEGF) drugs came into being, which has opened up a new direction for the treatment of neovascular ophthalmopathy.
Anti-VEGF drugs have developed rapidly and gradually become the mainstream.
Pegaptanib sodium, developed by Eyetech Pharmacy and Pfizer, was the first VEGF inhibitor to treat neovascular ophthalmopathy. FDA approved it in December 2004 for the treatment of age-related macular degeneration (AMD). However, in practical clinical application, it has been found that Pegaptanib sodium cannot stabilize the eyesight of patients and can only delay the progress. Many patients still lose their eyesight after treatment.
In 2006, Lucentis, developed by Roche’s Genentech and Novartis, was the first anti-VEGF antibody drug to treat neovascular ophthalmopathy in the United States. Lucentis was named one of the top 10 scientific breakthroughs of the year by Science in 2006 because of its excellent clinical manifestations, such as not only blocking the progress of the disease, but also improving or restoring patients’ eyesight.
In 2011, another VEGF antibody drug, Aflibercept was approved in the United States and has been approved in more than 100 countries. As the first fully humanized fusion protein, Aflibercept can bind to VEGF-A, VEGF-B and placental growth factor (PlGF).
2.Market analysis of antibody drugs for eye diseases: Aflibercept has expanded rapidly and become the TOP10 of global drug sales
As the first batch of ophthalmic monoclonal antibodies in the world for the treatment of neovascularization fundus diseases, Lucentis is safe, reliable and effective, and has attracted people’s attention since it was put on the market. Although the market has fallen slightly in recent years and hit by biological analogues and competitive products, it has maintained sales of more than $3 billion.
At present, the international market of Lucentis is gradually being eroded by Aflibercept, the main reasons are as follows: a. Lucentis is not a fully humanized protein, which is more likely to trigger immune response. b. Lucentis can only bind to VEGF-A, in contrast, Lucentis has more targets and more lasting effect.
The market has expanded rapidly since Aflibercept went on sale and has become a veritable blockbuster drug. Because of its excellent clinical manifestations, as well as the increasing number of indications and approved countries, its sales will continue to break through. Global sales in 2018 were $6.573 billion, well ahead of Lucentis ($3.705 billion), and its sales have not yet peaked, with a forecast future peak of nearly $10 billion.
3.Development trend of antibody drugs for eye diseases: new targets, new drug delivery methods and bispecific antibodies has become a hot spot
In the course of practical clinical application, Lucentis and Aflibercept will develop drug resistance after use for a period of time. The formation of intraocular neovascularization is a common pathological change of many eye diseases. Anti-VEGF is not the only pathogenesis of vascular hyperplasia. In addition, platelet derived growth factor (PDGF) and angiogenin (Angs) have been proved to be related to angiogenesis. At present, the targets of molecular mechanism of neovascularization, such as PGF, PIGF, Ang2, etc., are research focus, in order to achieve better therapeutic objectives through multi-target regulation.
Compared with the traditional treatment, although the listing of Lucentis and Aflibercept meet the clinical needs of neovascular ophthalmopathy, clinical experts believe that intravitreal injection of VEGF antibody has greater risk and poor compliance. Therefore, reducing the risk of VEGF antibody injection or developing oral drugs and eye drops will also become the main development direction of such drugs.
In addition, the development of bispecific antibodies is one of the current research hotspots. The combination of mature anti-VEGF antibodies with anti-pathogenic complement activation is expected to become a new scheme for the treatment of a variety of inflammation-related fundus diseases.