Delivering next-generation treatments for back of the eye disorders, with focus on diabetic eye disease
Back of the eye
We tend to take our vision for granted. What many do not realize is that our eyes can suffer from several chronic disorders causing vision distortion or, in the most severe cases, vision loss. At Oxurion, we look to develop treatments for clinical conditions associated with the back of the eye, mainly the retina.
The retina absorbs light and sends visual signals to the brain, which processes them into images. The vitreous is a clear jelly-like substance in the eye that occupies the space behind the lens and in front of the retina. Back of the eye conditions such as diabetic eye disease, symptomatic vitreomacular adhesion/vitreomacular traction (sVMA/VMT), and dry AMD (age-related macular degeneration) are potentially sight-threatening and can impact a person’s daily activities and quality of life.
Chronic visual disorders have a large impact on people's life. Not being able to drive a car or go to work makes them lose their independence
Some 93 million adults worldwide are affected with DR, the leading cause of vision loss in the working population.* There are two types of DR: non-proliferative (NPDR) and proliferative (PDR). NPDR occurs in an early stage, when microaneurysms and leaking blood vessels (hyperpermeability) cause inflammation in the back of the eye.
As the disease progresses from moderate to severe NPDR, the patient may develop PDR, which is characterized by an abnormal growth of blood vessels in the vitreous or along the retina’s surface that eventually causes permanent damage through development of scar tissue (fibrosis).
Diabetic retinopathy has a major impact on patients’ quality of life and their ability to perform daily activities such as driving a car, working, and performing household chores. DR can cause blurry or cloudy vision or cause colors to look faded. If left untreated, DR can lead to blindness.
*Source(s): Yau 2012; Int’l Diabetes Federation and the Fred Hollows Foundation 2015; National Eye Institute 2015
Diabetic macular edema (DME)
Diabetic Eye Disease
DME is a complication of DR and is characterized by an accumulation of fluid in the macula. It can occur at any stage of the disease. The macula is responsible for the sharp vision and therefore swelling results into debilitating progressive vision loss that greatly affects patients’ quality of life (such as reading and driving).
Prevention and treatment
Diabetic eye disease often goes undetected: people with diabetes experience no symptoms of vision loss in early stages, so regular screening and eye exams with ophthalmoscopy, optical coherence tomography (OCT), or retinal photography are critical. Good management of diabetes is the key to preventing DR from progressing past the first stage.
There are currently no curative treatments [PB1] to restore vision loss in people with DR, but in its severe and sight-threatening phase, there are approaches to preserve vision. Treatments include:
laser therapy (photocoagulation)
intravitreal injections with anti-VEGF drugs and in some cases cortisone
surgical removal of the vitreous (vitrectomy)
Clinical and preclinical Oxurion programs
Current therapies are effective in preventing further vision loss and stabilizing vision, but all are fairly intrusive for patients. Injections with anti-VEGF drugs are today's standard of care for DME, and they must be repeated several times to ensure effectiveness. However, roughly half of the patients are not or suboptimally responding to classic anti-VEGF drugs, and surgery options are not preferred due to potential complications.
Therefore, there is still a high unmet need for novel therapies to improve the outcome for patients. At Oxurion we're working on three novel disease-modifying medicines to meet this medical need:
A PlGF antibody (THR-317) is in a Phase II clinical study in combination with anti-VEGF (Lucentis®).
A plasma kallikrein inhibitor (THR-149) is in a Phase I clinical study for treating DME.
An integrin antagonist (THR-687) is in late-stage preclinical development for treatment of DR and DME and is expected to reach clinics around mid-2018.
People who suffer from DME have leaking vessels in the back of the eye. This leakage leads to a thickening of the retina and causes vision problems. Close to 40% of patients don't respond optimally to current treatments. Moreover, the treatment burden of current therapies is high: patients have to have injections on a monthly basis. Oxurion strives to develop therapies that can serve as an alternative for patients who don't respond well to current treatments and to lower the burden of treatment.
Therapies that can stop the progression of DR at a very early stage, or novel treatments tackling several hallmarks simultaneously, would be very advantageous.
- Prof. Alan Stitt, Dean of Innovation & Impact and the McCauley Chair of Experimental Ophthalmology
Macular Telangiectasia (MacTel 1), or idiopathic macular telangiectasia, is a rare degenerative retinal disease with characteristic alterations of the retinal vasculature and macula degeneration. There are two distinct types of MacTel, describing distinct clinical entities: Type 1, “aneurysmal telangiectasia,” and Type 2, “perifoveal telangiectasia”.
MacTel 1 typically affects one eye and most commonly presents in men of 40 years to 50 years of age. In MacTel 1, capillaries of the macula become dilated and aneurysms form, causing swelling, disrupting blood flow and often leading to leakage from the blood vessels. Unlike in MacTel Type 2, neovascularisation as a result of this damage does not usually occur.
Age-related macular degeneration (AMD) is one of the world's leading causes of blindness. A study found that some 196 million people globally will likely be affected by AMD by 2020.* It is known that abnormal angiogenesis drives one sub-type of AMD, known as ‘wet’ AMD. But most AMD patients have the ‘dry’ form, in which retinal tissue slowly wastes away due to cell degeneration.
In its more advanced form, dry AMD may lead to geographic atrophy (GA). At Oxurion, we have a discovery program researching new pathways for treating dry AMD.
sVMA/VMT is caused when the vitreous adheres to the macula at the back of the eye in an abnormally strong manner. Because the macula provides central vision for everyday tasks like driving, reading and recognizing faces, the traction that results from this abnormally strong adherence, can cause symptoms like distorted or decreased vision. When it progresses, the traction may lead to formation of a hole in the macula (called a macular hole). For many years the only treatment option for patients with sVMA/VMT was surgical separation of the vitreous from the retina, a procedure called a vitrectomy.
This involves several risks and can lead to complications like bleeding, pain, post-operative inflammation and irritation, so the surgery is only performed after the patient’s vision has deteriorated significantly. Jetrea is the first and only non-surgical and pharmacological vitreolysis drug approved for the treatment of sVMA/VMT. Oxurion owns the global rights to Jetrea and is commercializing it worldwide.