Preclinical research for Oxurion NV’s THR-687 was presented at the Association for Research in Ophthalmology (ARVO) last month, forecasting its promising potential within the DME space. However, Oxurion NV recently announced it would no longer pursue its Phase IIb INTEGRAL for THR-687 for the treatment of diabetic macular edema (DME), stating its decision to progress with its other therapy in the pipeline, THR-149, which has shown more promising Phase IIa results in the KALAHARI study. This drug may address a key unmet need for drugs with a new mechanism of action (MOA) reaching the ophthalmology market, says GlobalData, a leading data and analytics company.

DME treatment paradigms include VEGF inhibitor therapy, namely Bayer’s Eylea (aflibercept), or corticosteroid therapy, such as Allergan’s Ozurdex (dexamethasone LA). However, THR-149 is a plasma kallikrein inhibitor, which is new to the DME space.

Sara Reci, Pharma Analyst at GlobalData, comments: “While currently marketed pharmacotherapies cater to the needs of many patients, there is a subset of patients who do not respond well to, or are unable to comply with, existing treatments. This is largely due to DME patients being of working age and having comorbid conditions that they must also tend to. Thus, it is of paramount importance that unmet needs, such as therapies with a new MOA, are tackled to address these issues. Given the new MOA associated with THR-687, it was anticipated that this therapy could address this gap in the market.”

Some key opinion leaders (KOLs) interviewed by GlobalData have stated an unmet need for therapies with a new MOA that address inflammation and have also stressed the need for a therapy that combines the properties of anti-VEGF and anti-inflammatory therapies.

Reci continues: “Unlike currently marketed DME therapies, THR-687 showed promise in addressing these needs through inferring the prevention of both retinal vascular permeability and inflammation via its preclinical study, thereby mimicking an anti-VEGF and anti-inflammatory combination therapy approach. However, the company decided not to proceed with the drug due to it not meeting the efficacy endpoints for central subfield thickness (CST) and best-corrected visual acuity (BVCA) in the Phase 2a INTEGRAL trial.”

Despite news of the discontinuation of THR-687 clinical studies overshadowing the preclinical findings presented at the ARVO Annual Meeting, Oxurion NV’s decision to instead continue with the development of THR-149 into Phase IIb provides hope for the potential therapy with a new MOA reaching market.

Reci adds: “It is hoped that THR-149 will address a key unmet need within the DME space and related ophthalmological diseases, especially for the subset of patients who do not respond well to anti-VEGF therapies and corticosteroids.”