ThromboGenics Enrolls First Patient in Phase II CIRCLE Trial Evaluating Multiple Doses of Ocriplasmin to Induce a Total Posterior Vitreous Detachment in Patients With Non-Proliferative Diabetic Retinopathy (NPDR)

LEUVEN, Belgium, January 13, 2016 /PRNewswire/ --

Assessing the potential of ocriplasmin to reduce risk of disease progression from NPDR to sight-threatening Proliferative Diabetic Retinopathy (PDR)  

ThromboGenics NV (Euronext Brussels: THR), an integrated biopharmaceutical company focused on developing and commercializing innovative treatments for diabetic eye disease, today announces that the first patient has been enrolled in its Phase II CIRCLE study evaluating the efficacy and safety of multiple doses of ocriplasmin in inducing total posterior vitreous detachment (PVD) in patients with non-proliferative diabetic retinopathy (NPDR). ThromboGenics hopes to be able to reduce the risk of disease progression to proliferative diabetic retinopathy (PDR) by inducing a total PVD using ocriplasmin. PDR is the major cause of blindness in patients with diabetes. Patients who progress to PDR are at high risk of experiencing severe vision loss or complete blindness.

The CIRCLE study is a Phase II, randomized, double-masked, sham-controlled, multi-center study that will evaluate the efficacy and safety of up to 3 intravitreal injections of either 0.125mg or 0.0625mg of ocriplasmin in subjects with moderately severe to very severe NPDR, to induce total PVD in order to reduce the risk of the patient developing sight-threatening PDR.

A total of 230 subjects will be recruited into the CIRCLE trial, approximately 92 in each ocriplasmin arm (0.125mg or 0.0625mg) and 46 in the sham arm, over the next 12 months. Patients will be accrued from sites across the US, Canada and EMEA.

The primary endpoint of the CIRCLE study is the percentage of patients with total PVD by the month 3 visit, confirmed by both B-scan ultrasound and SD-OCT.

The study has a number of exploratory secondary endpoints that are designed to provide further insight into ocriplasmin's potential in reducing the risk of progression of NPDR to PDR.

For each patient recruited, the CIRCLE study duration will be approximately 24 months from the first injection. The first results are anticipated to be available in the second half of 2017.

Research has suggested that total PVD, a complete separation of vitreous and retina, could prevent the progression of NPDR to PDR. This could be explained by total PVD leading to elimination of the scaffold needed for the development of new blood vessels and/or the improvement of oxygen supply to the retina, thereby reducing retinal ischemia, production of VEGF, vascular outgrowth and neovascularization.

Diabetic retinopathy (DR) is the leading cause of visual disability and blindness among professionally active adults ^[1]. Worldwide, the prevalence rate of vision-threatening PDR or diabetic macular edema (DME) was estimated to be 11.72% of the diabetic population in 2010 ^[2].

A recent report from the American Academy of Ophthalmology has projected that the prevalence of individuals with any form of diabetic retinopathy in the United States in the year 2020 will be 6 million people, of whom 1.34 million persons will have vision-threatening DR ^[3] (PDR or diabetic macular edema (DME)).

David Scales, MD - Principal Investigator at Foreseight Studies, LLC in San Antonio, Texas, USA for the Circle Study said, "I am delighted that we have recruited the first patient in this important study. There is a clear medical need for a treatment option that is able to prevent patients with NPDR progressing to PDR, a disease state that could result in them losing their sight. Achieving this, by using up to 3 doses of ocriplasmin to generate a total PVD pharmacologically, would be a major advance in the overall treatment of diabetic retinopathy."

Dr Patrik De Haes, CEO of ThromboGenics, commenting on today's announcement, "The start of the CIRCLE study is a major milestone for ThromboGenics as we focus our research efforts on delivering important advances in the treatment of diabetic eye disease. The CIRCLE trial is designed to show that multiple doses of either 0.125mg or 0.0625mg of ocriplasmin can generate total PVD in patients with NPDR. We hope that by using ocriplasmin to generate PVD, we can prevent a significant number of patients with NPDR experiencing their disease progressing to PDR, which could potentially lead to them losing their sight."

About Diabetic Retinopathy 

According to the World Health Organization (WHO), in 2014, 9% of adults 18 years and older had diabetes (WHO, 2015) ^[4].

Diabetic retinopathy (DR) is the leading cause of visual disability and blindness among professionally active adults (Cunha-Vaz, 1998; Fong et al., 1999). Worldwide, the prevalence rate of vision-threatening PDR or DME was estimated to be 11.72% of the diabetic population in 2010 (Yau et al., 2012).

DR progresses from mild, non-proliferative to more severe, or even proliferative stages. As DR progresses, there is a gradual closure of retinal vessels leading to impaired perfusion and retinal ischemia. When this progresses beyond certain thresholds, severe non-proliferative diabetic retinopathy (NPDR) is diagnosed.

The more advanced stage, PDR, is characterized by the development of new blood vessels at the inner surface of the retina as a result of retinal ischemia. These new vessels are prone to bleed, resulting in vitreous hemorrhage. These new vessels may also undergo fibrosis and contraction, which may lead to epiretinal membrane formation, vitreoretinal traction bands, retinal tears and traction or retinal detachments.

PDR is considered high risk when the new vessels are accompanied by vitreous hemorrhage, or when they cover a significant area of the optic disc, even in the absence of vitreous hemorrhage, Patients with high risk PDR are at high risk of severe vision loss. The current treatment standard for PDR patients is laser photocoagulation (PRP) therapy. Lately, an increasing role for anti-VEGF treatments has also been demonstrated.

PDR patients may still progress to severe vision loss or even complete vision loss resulting from persistent or recurrent disease, even when receiving recurrent pan-retinal photocoagulation (PRP). In addition, recurrent treatment with PRP may lead to complications such as visual field loss or worsening of macular edema.^{[5] [6]}

About ThromboGenics 

ThromboGenics is an integrated biopharmaceutical company focused on developing and commercializing innovative treatments for diabetic eye disease.

The Company's first product, JETREA® (ocriplasmin), has been approved in 53 countries across the globe. In the US, ThromboGenics is commercializing JETREA® via its subsidiary ThromboGenics, Inc.  ThromboGenics signed an agreement with Alcon, a division of Novartis, for the commercialization of JETREA® outside the United States.

ThromboGenics is conducting the CIRCLE study, a Phase II clinical trial to assess ocriplasmin as a potential treatment for diabetic retinopathy In addition the Company is evaluating several other drug candidates that could potentially deliver a number of next generation treatments for diabetic eye disease.

ThromboGenics is headquartered in Leuven, Belgium, and has offices in Iselin, NJ (US) and Dublin, Ireland. The Company is listed on the NYSE Euronext Brussels exchange under the symbol THR.

More information is available at http://www.thrombogenics.com

Important information about forward-looking statements 

Certain statements in this press release may be considered "forward-looking". Such forward-looking statements are based on current expectations, and, accordingly, entail and are influenced by various risks and uncertainties. The Company therefore cannot provide any assurance that such forward-looking statements will materialize and does not assume an obligation to update or revise any forward-looking statement, whether as a result of new information, future events or any other reason. Additional information concerning risks and uncertainties affecting the business and other factors that could cause actual results to differ materially from any forward-looking statement is contained in the Company's Annual Report. 

This press release does not constitute an offer or invitation for the sale or purchase of securities or assets of ThromboGenics in any jurisdiction.  No securities of ThromboGenics may be offered or sold within the United States without registration under the U.S. Securities Act of 1933, as amended, or in compliance with an exemption therefrom, and in accordance with any applicable U.S. state securities laws.

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1. Cunha-Vaz J (1998). Lowering the risk of visual impairment and blindness. Diabet Med. 15 (Suppl 4): S47-50.

2. Yau JW, Rogers SL, Kawasaki R, Lamoureux EL, Kowalski JW, Bek T, Chen SJ, Dekker JM, Fletcher A, Grauslund J, Haffner S, Hamman RF, Ikram MK, Kayama T, Klein BE, Klein R, Krishnaiah S, Mayurasakorn K, O'Hare JP, Orchard TJ, Porta M, Rema M, Roy MS, Sharma T, Shaw J, Taylor H, Tielsch JM, Varma R, Wang JJ, Wang N, West S, Xu L, Yasuda M, Zhang X, Mitchell P, Wong TY; Meta-Analysis for Eye Disease (META-EYE) Study Group (2012). Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care 35 (3): 556-564.

3. http://www.aao.org/preferred-practice-pattern/diabetic-retinopathy-ppp--2014

4. World Health Organization (WHO). (2015). Diabetes. Fact sheet N°312. http://www.who.int/mediacentre/factsheets/fs312/en/   21 May 2015.

5. Bailey CC, Sparrow JM, Grey RH, Cheng H (1999). The National Diabetic Retinopathy Laser Treatment Audit. III. Clinical outcomes. Eye (Lond) 13 (Pt 2): 151-159.

6. Fong DS, Ferris FL 3rd, Davis MD, Chew EY (1999). Causes of severe visual loss in the early treatment diabetic retinopathy study: ETDRS report no. 24. Early Treatment Diabetic Retinopathy Study Research Group. Am J Ophthalmol. 127 (2): 137-141.

For further information please contact:

ThromboGenics
Wouter Piepers
Global Head of Corporate
Communications & IR
+32-16-75-13-10 / +32-478-33-56-32
wouter.piepers@thrombogenics.com

Citigate Dewe Rogerson
David Dible/Sylvie Berrebi
Tel: +44-(0)20-7282-2867
david.dible@citigatedr.co.uk