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THR-149
Clinical update THR-149
THR-149, a highly potent plasma kallikrein inhibitor to treat DME In 2019, Oxurion announced positive topline data for the compound THR-149, a highly potent plasma kallikrein inhibitor to treat diabetic macular edema (DME). Not only was THR-149 safe and well-tolerated, the phase 1 clinical trial also showed fast onset of action in BCVA from day 1, following a single injection. “I am very encouraged to see signs of efficacy so early post-treatment, and to observe a clear durable benefit to the patient’s vision as measured by BCVA”, explains Dr. Pravin Dugel, M.D. Anti-VEGF is the standard of care for DME patients at the moment, but 40% has little or no benefit of these treatments. By targeting a VEGF independent pathway, an alternative treatment can be developed for poor or nonresponders to anti-VEGF treatment.
The macula is a very small, sensitive spot at the center of the retina. It is responsible for our central vision and color sight.
THR-149 is a plasma kallikrein (PKal) inhibitor, a preclinically well validated compound to prevent the induction of retinal vascular permeability (leading to edema), inflammation and the prevention of microhemorrhages. Literature data show that patients with DME have elevated levels of plasma kallikrein and that the vitreous level of plasma kallikrein varies less compared to VEGF, making it a potentially more effective target for the treatment of DME.
Vitreous chamber is located behind the lens and before the optic nerve. It is filled with a thick, clear gel-like substance called the vitreous body.
Study set-up The phase 1 clinical trial for THR-149 evaluated the safety of a single intravitreal injection of THR-149 in 12
Perspectives 2020
patients with visual impairment due to center-involved DME. Three doses were tested: 3 patients were injected with 0.005 mg (‘low dose’), 3 with the middle dose (0.021 mg), and 6 with a high dose (0.125 mg). All 12 completed the study and attended all study visits from day 0 to day 90.
The retina is a thin layer of tissue on the inside of the back of the eye. It absorbs light and sends visual signals to the brain, which processes them into images.
Safety confirmed In the phase 1 clinical trial for THR-149 no dose-limiting toxicities and no serious adverse events were reported, indicating THR-149 is safe to use and well-tolerated. This means THR-149 is safe to use and well-tolerated.